Publications by authors named "Zhongguo Zhou"

32 Publications

Comparison Between Portal Vein Perfusion Chemotherapy and Neoadjuvant Hepatic Arterial Infusion Chemotherapy for Resectable Intermediate to Advanced Stage Hepatocellular Carcinoma.

Ann Surg Oncol 2021 Oct 12. Epub 2021 Oct 12.

Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.

Background: Patients with intermediate to advanced stage hepatocellular carcinoma (HCC; Barcelona Clinic Liver Cancer [BCLC] stage B/C) have few choices of curable treatments and thus suffer from dismal outcomes. Although surgical resection could prolong survival in certain selected patients with BCLC stage B/C HCC, the frequent postoperative recurrence and poor survival of these patients need to be improved by combining other therapies perioperatively.

Objective: This study was conducted to investigate the survival associations of adjuvant portal vein perfusion chemotherapy (PVC) and neoadjuvant hepatic arterial infusion chemotherapy (HAIC) in patients with resectable BCLC stage B/C HCC.

Methods: A retrospective study was conducted in consecutive patients who underwent R0 resection for intermediate to advanced stage HCC, combined with either PVC or HAIC perioperatively between January 2017 and December 2018. Patients treated with PVC or HAIC were analyzed according to intention-to-treat (ITT) and per protocol (PP) principles, respectively. The chemotherapy regimen of adjuvant PVC and neoadjuvant HAIC included 5-fluorouracil/leucovorin/oxaliplatin. Survival analysis and Cox regression for overall survival (OS) and event-free survival (EFS) were used to compare the outcomes.

Results: Among all 64 patients enrolled in this study, 28 received perioperative PVC and 36 received HAIC for ITT analysis. Age (median 44.00 vs. 46.50 years; p = 0.364), sex (male: 25/28 vs. 35/36; p = 0.435), and tumor size (median 9.55 vs. 8.10 cm; p = 0.178) were comparable between the two groups. In the ITT analysis, the median OS was significantly longer in patients in the HAIC group compared with the PVC group (median OS not reached vs. 19.47 months; p = 0.004); in the PP analysis, patients who received neoadjuvant HAIC followed by hepatectomy presented with much better EFS than patients in the PVC group (modified EFS 16.90 vs. 3.17 months; p = 0.022); and in the multivariate analysis, neoadjuvant HAIC presented as a significant predictor for enhanced EFS (hazard ratio [HR] 0.296; p = 0.007) and OS (HR 0.095; p = 0.007) for BCLC stage B/C HCC patients who received hepatectomy.

Conclusions: Compared with adjuvant PVC, neoadjuvant HAIC treatment was associated with better survival and fewer recurrences in HCC patients who received R0 resection at the intermediate to advanced stage. These results need to be further validated prospectively.
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http://dx.doi.org/10.1245/s10434-021-10903-4DOI Listing
October 2021

Preoperative Versus Postoperative Transarterial Chemoembolization on Prognosis of Large Hepatocellular Carcinoma.

J Cancer 2021 28;12(20):6231-6241. Epub 2021 Aug 28.

Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China.

Transarterial chemoembolization (TACE) has proven to be an effective adjuvant therapy with liver resection (LR) to treat patients with hepatocellular carcinoma (HCC). The aim of this study was to evaluate outcomes in patients with HCC larger than 5 cm, comparing those who had TACE before LR to those who had TACE after LR. A total of 320 consecutive patients who underwent LR in combination with TACE for HCC larger than 5 cm from January 2009 to December 2014 were enrolled in study. Patients were divided into two groups: preoperative TACE group (n=199) and postoperative TACE group (n=121). Overall survival (OS) and recurrence-free survival (RFS) of patients were compared between preoperative TACE and postoperative TACE groups by propensity score-matching (PSM). We determined prognostic factors for recurrence and death using multivariate cox regression analysis. Among the 320 patients, the median age was 48 (range, 18 to 75) years, and 285 (89.1%) patients were male. During the follow- up period, 88 (44.2%) patients in the preoperative TACE group and 69 (57.0%) patients in the postoperative TACE group died. Before PSM, both OS and RFS were significantly longer in the preoperative TACE group than those in the postoperative TACE group (=0.001 and <0.001, respectively). After PSM, compared to those received postoperative TACE, patients with preoperative TACE had significantly better OS (Hazard ratio [HR]=1.92; 95% confidence interval [CI], 1.22-3.02; =0.005) and RFS (HR=1.64; 95% CI, 1.16-2.32; =0.005). Patients with large HCC undergoing LR appear to derive greater disease control and survival benefit from a single preoperative TACE treatment than from postoperative TACE.
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http://dx.doi.org/10.7150/jca.55806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425190PMC
August 2021

A deep-learning pipeline for the diagnosis and discrimination of viral, non-viral and COVID-19 pneumonia from chest X-ray images.

Nat Biomed Eng 2021 06 15;5(6):509-521. Epub 2021 Apr 15.

Department of Medical Imaging and Deptartment of Cardiology, Xiangya Hospital, Central South University, Changsha, China.

Common lung diseases are first diagnosed using chest X-rays. Here, we show that a fully automated deep-learning pipeline for the standardization of chest X-ray images, for the visualization of lesions and for disease diagnosis can identify viral pneumonia caused by coronavirus disease 2019 (COVID-19) and assess its severity, and can also discriminate between viral pneumonia caused by COVID-19 and other types of pneumonia. The deep-learning system was developed using a heterogeneous multicentre dataset of 145,202 images, and tested retrospectively and prospectively with thousands of additional images across four patient cohorts and multiple countries. The system generalized across settings, discriminating between viral pneumonia, other types of pneumonia and the absence of disease with areas under the receiver operating characteristic curve (AUCs) of 0.94-0.98; between severe and non-severe COVID-19 with an AUC of 0.87; and between COVID-19 pneumonia and other viral or non-viral pneumonia with AUCs of 0.87-0.97. In an independent set of 440 chest X-rays, the system performed comparably to senior radiologists and improved the performance of junior radiologists. Automated deep-learning systems for the assessment of pneumonia could facilitate early intervention and provide support for clinical decision-making.
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http://dx.doi.org/10.1038/s41551-021-00704-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611049PMC
June 2021

Effect of prior cancer on survival of hepatocellular carcinoma: implications for clinical trial eligibility criteria.

BMC Cancer 2021 Feb 9;21(1):147. Epub 2021 Feb 9.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.

Background: Patients with cancer history are usually excluded from hepatocellular carcinoma (HCC) clinical trials. However, whether previous malignancy affects the oncological outcomes of HCC patients has not been fully assessed. This study aimed to evaluate whether prior cancer compromised the survival of HCC patients.

Methods: Patients with HCC were extracted from the Surveillance, Epidemiology, and End Results database between 2004 and 2015, and then they were classified into groups with and without prior cancer. The Kaplan-Meier and multivariate Cox regression analysis were adopted to evaluate whether prior cancer impacted clinical outcomes after propensity score matching (PSM) adjusting baseline differences. Validation was performed in the cohort from our institution.

Results: We identified 2642 HCC patients with prior cancer. After PSM, the median overall survival (OS) time were 14.5 and 12.0 months respectively for groups with and without prior cancer. Prior cancer did not compromise prognosis in patients with HCC (p = 0.49). The same tendency was found in subgroups stratified by tumor stages and cancer interval period: OS was similar between groups with and without prior cancer (both p values> 0.1). In the multivariate Cox regression model, prior cancer did not adversely impact patients' survival (HR: 1.024; 95% CI: 0.961-1.092). In the validation cohort from our institution, prior cancer had no significant association with worse outcomes (p = 0.48).

Conclusion: For HCC patients, prior cancer did not compromise their survival, regardless of tumor stage and cancer interval period. Exclusion criteria for HCC clinical trials could be reconsidered.
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http://dx.doi.org/10.1186/s12885-021-07870-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871582PMC
February 2021

Baseline HBV Loads Do Not Affect the Prognosis of Patients with Hepatocellular Carcinoma Receiving Anti-Programmed Cell Death-1 Immunotherapy.

J Hepatocell Carcinoma 2020 1;7:337-345. Epub 2020 Dec 1.

Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People's Republic of China.

Background: A high hepatitis B virus (HBV) load is a common exclusion criterion in hepatocellular carcinoma (HCC) clinical trials for anti-programmed cell death (PD)-1 immunotherapy. However, the validity of this criterion is barely verified. This study aimed to evaluate the impact of baseline HBV DNA levels and antiviral therapy on the oncological outcomes and liver functions of patients with HCC receiving anti-PD-1 immunotherapy.

Methods: We reviewed HCC trials related to anti-PD-(L)1 immunotherapy and whether they ruled out patients with increased HBV loads on clinicaltrials.gov. Then, for this retrospective study, we enrolled 253 HCC patients treated with anti-PD-1 blockade in our institution. Baseline information was compared between patients with low and high HBV loads. Overall survival (OS) and progression-free survival (PFS) were compared, and univariate and multivariate analyses were applied to identify potential risk factors for oncological outcomes and hepatic impairment.

Results: Among 76 HCC clinical trials including 13,927 patients receiving anti-PD-(L)1 blockade, 41 (53.9%) excluded patients with relatively high baseline HBV loads. The PFS and OS did not differ significantly between patients with baseline HBV loads ≤ 2000 IU/mL and those with viral loads >2000 IU/mL (p=0.615 and 0.982). The incidence of hepatic impairment showed no association with the baseline HBV load (p=0.319). Patients receiving antiviral therapy had a better OS than those without antiviral therapy in the high baseline HBV load group (p= 0.001).

Conclusion: High HBV loads did not compromise the clinical outcomes of HCC patients receiving anti-PD-1 blockade. Antiviral therapy could improve the OS of HCC patients with high HBV loads.
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http://dx.doi.org/10.2147/JHC.S278527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718972PMC
December 2020

The Postoperative Analgesic Effect of Ultrasound-Guided Bilateral Transversus Abdominis Plane Combined with Rectus Sheath Blocks in Laparoscopic Hepatectomy: A Randomized Controlled Study.

Ther Clin Risk Manag 2020 18;16:881-888. Epub 2020 Sep 18.

Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China.

Background: Our aim was to investigate the postoperative analgesic effect of ultrasound (US)-guided bilateral transversus abdominis plane (TAP) blocks combined with rectus sheath blocks (RSBs) in laparoscopic hepatectomy.

Patients And Methods: A total of 126 patients were allocated into two groups for analysis. Group 1 (n = 63) did not receive any local anesthetics. Group 2 (n = 63) received US-guided bilateral TAP blocks and RSBs using 20 mL 0.25% ropivacaine in each block. Postoperative pain scores, the dose of intraoperative remifentanil, 24 h consumption of oxycodone, adverse events such as postoperative dizziness, nausea and vomiting, and the length of postoperative hospital stay were recorded.

Results: In the postanesthesia care unit, patients in group 2 had significantly lower pain visual analog scale (VAS) scores at rest than those in group 1 ( < 0.001). The VAS scores both at rest and during movement were significantly lower in group 2 than in group 1 at 2, 4 and 6 h postoperatively (all < 0.001). There was no difference in VAS scores between the two groups at rest 24 h postoperatively ( = 0.477). However, the VAS score during movement at 24 h in group 2 was significantly lower than that in group 1 ( < 0.001). No significant differences in the incidence of adverse events or the dose of intraoperative remifentanil were observed between the two groups (all > 0.05). Patients in group 2 had a significantly lower 24 h consumption of oxycodone than patients in group 1 ( < 0.001). The mean length of postoperative hospital stay of group 2 was shorter than that of group 1 ( = 0.032).

Conclusion: US-guided bilateral TAP blocks combined with RSBs provide effective postoperative analgesia for laparoscopic hepatectomy, and they could shorten the postoperative hospital stay without increasing the incidence of adverse events from opioids.
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http://dx.doi.org/10.2147/TCRM.S267735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509310PMC
September 2020

Time-Frequency Analysis of Particulate Matter (PM) Concentration in Dry Bulk Ports Using the Hilbert-Huang Transform.

Int J Environ Res Public Health 2020 08 9;17(16). Epub 2020 Aug 9.

College of Science, Hohai University, No.1, Xikang Road, Nanjing 210098, China.

To analyze the time-frequency characteristics of the particulate matter (PM) concentration, data series measured at dry bulk ports were used to determine the contribution of various factors during different periods to the PM concentration level so as to support the formulation of air quality improvement plans around port areas. In this study, the Hilbert-Huang transform (HHT) method was used to analyze the time-frequency characteristics of the PM concentration data series measured at three different sites at the Xinglong Port of Zhenjiang, China, over three months. The HHT method consists of two main stages, namely, empirical mode decomposition (EMD) and Hilbert spectrum analysis (HSA), where the EMD technique is used to pre-process the HSA in order to determine the intrinsic mode function (IMF) components of the raw data series. The results show that the periods of the IMF components exhibit significant differences, and the short-period IMF component provides a modest contribution to all IMF components. Using HSA technology for these IMF components, we discovered that the variations in the amplitude of the PM concentration over time and frequency are discrete, and the range of this variation is mainly concentrated in the low-frequency band. We inferred that long-term influencing factors determine the PM concentration level in the port, and short-term influencing factors determine the difference in concentration data at different sites. Therefore, when formulating PM emission mitigation strategies, targeted measures must be implemented according to the period of the different influencing factors. The results of this study can help guide recommendations for port authorities when formulating the optimal layout of measurement devices.
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http://dx.doi.org/10.3390/ijerph17165754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460512PMC
August 2020

Stereotactic Body Radiotherapy as a Salvage Therapy after Incomplete Radiofrequency Ablation for Hepatocellular Carcinoma: A Retrospective Cohort Study.

J Oncol 2020 28;2020:4835653. Epub 2020 May 28.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, China.

Residual tumor tissue after radiofrequency ablation (RFA) is inevitable in clinical practice, and the optimal management of residual tumor after RFA has not been established. To evaluate the efficiency and toxicity of stereotactic body radiotherapy (SBRT) as a salvage therapy after incomplete RFA for hepatocellular carcinoma (HCC), we retrospectively included 32 HCC patients with an initial incomplete response (iIR) to RFA from May 2011 to August 2018. An iIR was defined as the presence of residual enhancement on CT or MRI one month after RFA treatment. The primary endpoint was local tumor control (LTC); the secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. All patients fulfilled 6 fractions of SBRT as planned, with dosages ranging from 30 Gy to 54 Gy. The objective response rate (ORR) was 50.0%. The 1- and 2-year LTC rates were 86.6% (95% CI, 74.3% to 98.9%) and 74.7% (95% CI, 55.9% to 93.5%), respectively. Fewer times of prior treatments was associated with better LTC (HR = 11.7, =0.026). The 1- and 2-year PFS rate were 69.9% (95% CI, 53.4% to 86.4%) and 52.7% (95% CI, 33.1% to 72.3%), respectively. A higher Child-Pugh score was the only independent risk factor for tumor progression (HR = 5.17, =0.012). The 1- and 3-year OS rate were 85.6% and 67.1%, respectively. Only two patients suffered grade 3 adverse events, and none experienced grade 4 or 5 events. In conclusion, for HCC patients confirmed to have an iIR to prior RFA, with compensated liver function, SBRT provided favorable LTC and OS along with acceptable toxicity.
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http://dx.doi.org/10.1155/2020/4835653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275213PMC
May 2020

Clinically Applicable AI System for Accurate Diagnosis, Quantitative Measurements, and Prognosis of COVID-19 Pneumonia Using Computed Tomography.

Cell 2020 06 4;181(6):1423-1433.e11. Epub 2020 May 4.

The First People's Hospital of Yunnan Province, Kunmin, China.

Many COVID-19 patients infected by SARS-CoV-2 virus develop pneumonia (called novel coronavirus pneumonia, NCP) and rapidly progress to respiratory failure. However, rapid diagnosis and identification of high-risk patients for early intervention are challenging. Using a large computed tomography (CT) database from 3,777 patients, we developed an AI system that can diagnose NCP and differentiate it from other common pneumonia and normal controls. The AI system can assist radiologists and physicians in performing a quick diagnosis especially when the health system is overloaded. Significantly, our AI system identified important clinical markers that correlated with the NCP lesion properties. Together with the clinical data, our AI system was able to provide accurate clinical prognosis that can aid clinicians to consider appropriate early clinical management and allocate resources appropriately. We have made this AI system available globally to assist the clinicians to combat COVID-19.
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http://dx.doi.org/10.1016/j.cell.2020.04.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196900PMC
June 2020

Single versus multiple port laparoscopic left lateral sectionectomy for hepatocellular carcinoma: A retrospective comparative study.

Int J Surg 2020 May 13;77:15-21. Epub 2020 Mar 13.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, PR China; Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, PR China. Electronic address:

Background: Single port laparoscopic hepatectomy has been applied in some surgeries. We aimed to describe our experience with single port laparoscopic left lateral sectionectomy (SPLS) and to compare the safety and feasibility of this technique with those of conventional multi-port laparoscopic left lateral sectionectomy (MPLS) in the treatment of hepatocellular carcinoma (HCC).

Methods: A total of 72 consecutive patients who underwent SPLS (n = 33) and MPLS (n = 39) for HCC were enrolled. The peri-operative parameters of safety and feasibility, as well as the short-term oncological outcomes were compared.

Results: The length of postoperative hospital stay (LOS) was significantly shorter in the SPLS group than in the MPLS group (4.12 vs. 4.59 days, P = 0.043). No significant difference between the two groups was found in the operation time (104.58 vs. 95.69 min in the SPLS group and MPLS group respectively, P = 0.353) or the amount of blood loss (62.73 vs. 68.46 ml, P = 0.595). The 1-year recurrence-free survival rate was 77.9% in the SPLS group and 70.7% in the MPLS group (P = 0.82). Subgroup analysis showed that for patients without cirrhosis, the LOS was shorter in the SPLS group than in the MPLS group (P = 0.033), while for patients with cirrhosis, the LOS was not significantly different between the two groups (P = 0.201), although it was shorter in the SPLS group.

Conclusions: SPLS was a feasible and safe surgical approach for the treatment of HCC on left lateral section.
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http://dx.doi.org/10.1016/j.ijsu.2020.03.003DOI Listing
May 2020

Expression of hepatitis B surface antigen in liver tissues can serve as a predictor of prognosis for hepatitis B virus-related hepatocellular carcinoma patients after liver resection.

Eur J Gastroenterol Hepatol 2021 01;33(1):76-82

Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center.

Background: Hepatitis B surface antigen (HBsAg) is a detectable index after hepatitis B virus (HBV) infection, which is a risk factor of hepatocellular carcinoma (HCC). However, few studies have focused on the expression of HBsAg in HCC patients' liver tissues. This study aimed to explore the potential utility of using HBsAg protein expression in normal liver tissues as a prognostic factor for HCC patients who underwent liver resection.

Study Design: The study enrolled 100 HCC patients with seropositivity for HBsAg. The liver tissues were collected, and tissue microarrays were constructed. The expression of HBsAg in liver tissues were measured by immunohistochemistry (IHC). Relevant clinical data and follow-up records were collected for analysis.

Results: HBsAg expressions was detected in 29 patients (positive group) and was unable to be detected in the remaining 71 patients (negative group). The patients in the positive group had higher HBV DNA levels (P < 0.05) than the patients in the negative group. The overall survival (OS) rate of the positive group was worse than the OS rate of the negative group (P = 0.013). The OS rates after resection at 1 and 2 years in negative group were 90.1% and 85.7%, respectively, while the value in the positive group were 79.3% and 65.5%, respectively. Multivariate analysis showed that HBsAg expression in liver tissues, ascites and alpha-fetoprotein levels were independent factors influencing OS. Similarly, after propensity score matching (PSM), the OS was worse in the positive group than in the negative group, and HBsAg expression could also serve as a predictor for OS (P = 0.039). The OS rates after resection and PSM at 1 and 2 years were 93.2% and 85.9% in the negative group, while the value in the positive group were 79.3% and 65.5%.

Conclusion: As determined according to grouping based on immunohistochemistry staining results for HBsAg, this study indicated that HBsAg expression in liver tissues could predict the OS of HBV-related HCC patients after liver resection.
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http://dx.doi.org/10.1097/MEG.0000000000001698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704243PMC
January 2021

Single-Port Laparoscopic Hepatectomy for Liver Tumor: Operative Steps (With Video).

Surg Laparosc Endosc Percutan Tech 2019 Dec;29(6):e98-e101

Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center.

Background: The single-port laparoscopic technique has been widely applied in abdominal surgery. We introduce a single-port laparoscopic hepatectomy for liver tumor in a single center.

Materials And Methods: This study included 37 patients who underwent single-port laparoscopic liver resection for liver tumor in the segments II, III, IV, and V between October 2017 and November 2018. Their perioperative course and operative techniques were retrospectively evaluated.

Results: All patients underwent single-port laparoscopic hepatectomy for liver tumor. None of the cases was converted to open surgery. The median procedure duration was 100 minutes (39 to 240 min), and the median blood loss volume was 50 mL (30 to 300 mL). No postoperative complications >3 grades were observed during the perioperative period. The median postoperative hospital stay was 4 days (3 to 7 d).

Conclusions: Single-port laparoscopic hepatectomy is a safe, feasible, and minimal incision, especially for tumors in the left lobe.
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http://dx.doi.org/10.1097/SLE.0000000000000724DOI Listing
December 2019

Sorafenib Plus Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin vs Sorafenib Alone for Hepatocellular Carcinoma With Portal Vein Invasion: A Randomized Clinical Trial.

JAMA Oncol 2019 07;5(7):953-960

Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Importance: Sorafenib is the first-line treatment for hepatocellular carcinoma with portal vein invasion; however, it has shown unsatisfactory survival benefit. Sorafenib plus hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown promising results for these patients in a previous phase 2 study.

Objective: To investigate the efficacy and safety of sorafenib plus HAIC compared with sorafenib for hepatocellular carcinoma with portal vein invasion.

Design, Setting, And Participants: This randomized, open-label clinical trial enrolled 818 screened patients. Of the 818 participants, 247 with hepatocellular carcinoma and portal vein invasion were randomly assigned (1:1) via a computer-generated sequence to receive sorafenib plus HAIC or sorafenib. This trial was conducted at 5 hospitals in China and enrolled patients from April 1, 2016, to October 10, 2017, with a follow-up period of 10 months.

Interventions: Randomization to receive 400 mg sorafenib twice daily (sorafenib group) or 400 mg sorafenib twice daily plus HAIC (SoraHAIC group) (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2400 mg/m2 for 46 hours, every 3 weeks).

Main Outcomes And Measures: The primary endpoint was overall survival by intention-to-treat analysis. Safety was assessed in patients who received at least 1 dose of study treatment.

Results: For 247 patients (median age, 49 years; range, 18-75 years; 223 men and 24 women), median overall survival was 13.37 months (95% CI, 10.27-16.46) in the SoraHAIC group vs 7.13 months (95% CI, 6.28-7.98) in the sorafenib group (hazard ratio [HR], 0.35; 95% CI, 0.26-0.48; P < .001). The SoraHAIC group showed a higher response rate than the sorafenib group (51 [40.8%] vs 3 [2.46%]; P < .001), and a longer median progression-free survival (7.03 [95% CI, 6.05-8.02] vs 2.6 [95% CI, 2.15-3.05] months; P < .001). Grade 3/4 adverse events that were more frequent in the SoraHAIC group than in the sorafenib group included neutropenia (12 [9.68%] vs 3 [2.48%]), thrombocytopenia (16 [12.9%] vs 6 [4.96%]), and vomiting (8 [6.45%] vs 1 [0.83%]).

Conclusions And Relevance: Sorafenib plus HAIC of FOLFOX improved overall survival and had acceptable toxic effects compared with sorafenib in patients with hepatocellular carcinoma and portal vein invasion.

Trial Registration: ClinicalTrials.gov identifier: NCT02774187.
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http://dx.doi.org/10.1001/jamaoncol.2019.0250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512278PMC
July 2019

Tumor Location Influences Oncologic Outcomes of Hepatocellular Carcinoma Patients Undergoing Radiofrequency Ablation.

Cancers (Basel) 2018 Oct 10;10(10). Epub 2018 Oct 10.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou 510060, Guangdong, China.

Radiofrequency ablation (RFA) is recommended as a first-line therapy for small hepatocellular carcinoma (HCC). Tumor location is a potential factor influencing the procedure of RFA. To compare oncologic outcomes of RFA for different tumor locations, this retrospective study enrolled 194 patients with small HCC who had undertaken RFA. The HCC nodules were classified as peri-hepatic-vein (pHV) or non-pHV, peri-portal-vein (pPV) or non-pPV, and subcapsular or non-subcapsular HCC. The regional recurrence-free survival (rRFS), overall survival (OS), recurrence-free survival (recurrence in any location, RFS) and distant recurrence-free survival (dRFS) were compared. Operation failures were recorded in five pPV HCC patients, which was more frequent than in non-pPV HCC patients ( = 0.041). The 1-, 3-, and 5-year rRFS was 68.7%, 53.7%, and 53.7% for pHV patients and 85.1%, 76.1%, and 71.9% for non-pHV patients, respectively ( = 0.012). After propensity score matching, the 1-, 3-, and 5-year rRFS was still worse than that of non-pHV patients ( = 0.013). The OS, RFS, and dRFS were not significantly different between groups.

Conclusions: A pHV location was a risk factor for the regional recurrence after RFA in small HCC patients. The tumor location may not influence OS, RFS, and dRFS. Additionally, a pPV location was a potential high-risk factor for incomplete ablation.
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http://dx.doi.org/10.3390/cancers10100378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210710PMC
October 2018

A novel inflammation-based nomogram system to predict survival of patients with hepatocellular carcinoma.

Cancer Med 2018 10 27;7(10):5027-5035. Epub 2018 Sep 27.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer, Guangzhou, China.

Background And Aim: The existed staging systems were limited in the accuracy of prediction for overall survival (OS) of hepatocellular carcinoma (HCC) patients. The aim of this study is to establish a novel inflammation-based prognostic system with nomogram for HCC patients.

Methods: A prospective cohort of patients was recruited and assigned to the training cohort (n = 659) and validation cohort (n = 320) randomly. Different inflammation-based score systems were evaluated to select the best one predicting overall survival (OS). The inflammation-based score system with the highest predicting value and the parameters best reflecting tumor burden identified by multivariate analysis were selected to construct a novel predicting nomogram system. The predictive accuracy and discriminative ability of the nomogram were evaluated by concordance index (C-index) and calibration curve and compared with conventional staging systems.

Results: With a highest C-index and areas under the receiver operating characteristic curve (AUC), C-reactive protein/albumin ratio (CAR) was selected to construct the novel system, along with tumor number, tumor size, macrovascular invasion and extra-hepatic metastases. The C-index of the nomogram was 0.813 (95% CI, 0.789-0.837) in the training cohort and 0.794 (95% CI, 0.756-0.832) in the validation cohort. The calibration curve for predicting probability of survival showed that the nomogram had a high consistency with follow-up data. The C-index of the novel system was higher than other conventional staging systems (P < 0.001).

Conclusions: The novel inflammation-based nomogram, developed from prospectively collected data in the present study, predicted the OS of HCC patients.
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http://dx.doi.org/10.1002/cam4.1787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198220PMC
October 2018

High expression of TACC2 in hepatocellular carcinoma is associated with poor prognosis.

Cancer Biomark 2018 ;22(4):611-619

Department of Hepatobiliary Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.

Background: Transforming acidic coiled-coil protein 2 (TACC2) is a member of TACC family proteins which is mainly involved in the stabilization of spindles and regulation of microtubule dynamics through interactions with molecules involved in centrosomes/microtubules. TACC2 is involved in tumorigenesis of variety of cancers but the clinical significance of TACC2 protein in hepatocellular carcinoma (HCC) is still unclear.

Objective: This study aims to investigate the expression of TACC2 in HCC and determine if clinical significance and prognostic relevance exists.

Methods: We performed quantitative PCR (qPCR) and western blot to examine TACC2 mRNA and protein expression in paired HCC tissues and matched adjacent non-cancerous tissues. Immunohistochemistry was performed in 106 postoperative HCC samples.

Results: There was higher expression of TACC2 protein and mRNA in HCC tissue. Immunohistochemistry analysis showed high expression of TACC2 in HCC tissue and was significantly associated with the capsular extension, tumor recurrence and shortened overall and disease free survival. The Cox regression analysis suggested that a high expression of TACC2 was an independent prognostic factor for HCC patients.

Conclusion: This finding suggests that TACC2 may be a useful tool as a candidate biomarker to predict the recurrence and prognosis of HCC.
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http://dx.doi.org/10.3233/CBM-170091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130418PMC
November 2018

Sorafenib Monotherapy Versus Sorafenib Combined with Regional Therapies for Hepatocellular Carcinoma Patients with Pulmonary Oligometastases: A Propensity Score-matched Analysis.

J Cancer 2018 19;9(10):1745-1753. Epub 2018 Apr 19.

Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.

Sorafenib has been recommended as the standard therapy for advanced HCC with extrahepatic metastasis. The purpose of this retrospective study was to investigate the difference in overall survival (OS) between treatments with sorafenib combined with regional therapies versus sorafenib monotherapy in hepatocellular carcinoma (HCC) patients with pulmonary oligometastases. The study retrospectively enrolled 95 consecutive patients who underwent sorafenib therapy. A combined group (CG) of 40 patients received regional therapy in addition to sorafenib, and a monotherapy group (MG) of 55 patients received only sorafenib. OS was the primary endpoint, and time to progression (TTP) was the secondary endpoint. Subgroup analysis was further performed to evaluate the differences between the two groups. A propensity score-matched analysis was performed to overcome the bias. Median OS was significantly longer in the CG than in the MG (18.37 vs. 7.13 months; = 0.002). Multivariate analysis identified three baseline characteristics that were prognostic indicators of OS: macrovascular invasion, regional therapy, and alpha-fetoprotein. Median TTP was significantly longer in the CG than in the MG (2.93 vs. 2.23 months; = 0.004). Further multivariate analysis showed alpha-fetoprotein, total bilirubin, and regional therapy as prognostic indicators of TTP. After propensity score matching, 34 paired patients constituted each group. Patients in the adjusted CG showed a longer OS and TTP than those in the adjusted MG (OS: 18.37 vs. 7.37 months, = 0.015; TTP: 3.12 vs. 2.265 months, = 0.009). Multivariate analysis showed that combining regional therapies was still a prognostic indicator of OS ( = 0.01) and TTP ( = 0.001). Sorafenib combined with regional therapies may be associated with prolonged OS and TTP in HCC patients with pulmonary oligometastases compared with sorafenib monotherapy.
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http://dx.doi.org/10.7150/jca.24568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968762PMC
April 2018

The mutation of hepatitis B virus and the prognosis of hepatocellular carcinoma after surgery: a pilot study.

Cancer Manag Res 2018 27;10:599-611. Epub 2018 Mar 27.

Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.

Background: Although hepatitis B virus (HBV) is still one of the most common etiological factors for hepatocellular carcinoma (HCC), the association between the HBV mutations and the clinical characteristics and prognosis of HBV-related HCC patients (HBV-HCC) after surgical resection remains largely unknown.

Materials And Methods: A cohort of 131 consecutive patients who received hepatectomy for HBV-HCC were retrospectively enrolled. The HBV genotype and 14 genomic mutations, which have been reported to relate to HCC in liver samples, were sequenced. The associations between the genomic mutations and clinical characteristics and outcomes were analyzed.

Results: Both A1762T/G1764A mutation and Pre S deletion related to worse overall survival (OS, =0.040 and <0.001, respectively) and disease-free survival (DFS, =0.040 and <0.001, respectively), G1899A mutation related to worse OS (=0.030), A1762T/G1764A mutation correlated with tumor size (=0.204, =0.019), G1899A mutation correlated with vascular invasion (=0.332, <0.001), and Pre S deletion correlated with alpha-fetoprotein (AFP; =0.254, =0.003) positively. Multivariate analysis with Cox proportional hazards model revealed that both A1762T/G1764A mutation and Pre S deletion were independent prognostic factors for OS (hazard ratio [HR]=3.701, 95% CI=1.390-9.855, =0.009, and HR=4.816, 95% CI=2.311-10.032, <0.001, respectively) and DFS (HR=3.245, 95% CI=1.400-7.521, =0.006, and HR=2.437, 95% CI=1.311-4.530, <0.001, respectively), and patients with dual mutations were found to have the worst OS and DFS (<0.001 and <0.001, respectively). Patients with A1762T/G1764A mutation or Pre S deletion were more likely to have early recurrence (=0.042 and =0.019, respectively).

Conclusion: HBV DNA genomic mutations in A1762T/G1764A and Pre S deletion were associated with worse prognoses and early recurrence for HBV-HCC patients after surgery.
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http://dx.doi.org/10.2147/CMAR.S160047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877868PMC
March 2018

Genetic variations in the PI3K/PTEN/AKT/mTOR pathway predict tumor response and disease-free survival in locally advanced rectal cancer patients receiving preoperative chemoradiotherapy and radical surgery.

J Cancer 2018 28;9(6):1067-1077. Epub 2018 Feb 28.

Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine Guangzhou, 510060, P.R. China.

Although preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) is the standard treatment for locally advanced rectal cancer (LARC), the clinical efficacy differs among patients. This study was conducted to determine the association between genetic variations in the PI3K/PTEN/AKT/mTOR pathway and clinical outcomes in LARC patients. Sixteen tagging single-nucleotide polymorphisms (SNPs) in five core genes (PIK3CA, PTEN, AKT1, AKT2, and FRAP1) were genotyped. The associations of these SNPs with tumor response to preoperative CRT, postoperative disease-free survival (DFS) and overall survival (OS) were identified. Crude odds ratios (ORs) and hazard ratios (HRs) were adjusted by age, sex, clinical stage, tumor differentiation, tumor location, cycles of preoperative chemotherapy and time interval from CRT completion to surgery. In an analysis of 97 LARC patients, the G/T+G/G genotype of AKT1:rs2498804 was associated with an increased tumor response rate (adjusted OR = 2.909, 95% confidence interval (CI), 1.127-7.505, P = 0.027). At a median of 65.7 months of follow-up, the G/C+C/C genotype of AKT2:rs8100018 was associated with a reduced risk of postoperative recurrence (adjusted HR = 0.414; 95% CI, 0.187-0.914, P = 0.029). Patients carrying the G/C+C/C genotype in AKT2:rs8100018 presented a higher 5-year DFS rate than those with the wild-type genotype (79.2% vs. 62.3%, P = 0.038). None of the SNPs were significantly associated with pathological complete response (pCR) or 5-year OS. The current study indicates that genetic variations within the PI3K/ PTEN/AKT/mTOR signaling pathway are associated with the clinical outcomes of LARC patients undergoing preoperative CRT followed by radical surgery.
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http://dx.doi.org/10.7150/jca.23538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868174PMC
February 2018

Overexpression of LAMC1 predicts poor prognosis and enhances tumor cell invasion and migration in hepatocellular carcinoma.

J Cancer 2017 25;8(15):2992-3000. Epub 2017 Aug 25.

Department of Hepatobiliary Surgery, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China.

LAMC1 encodes an extracellular matrix protein, laminin γ1 chain, which is involved in several biological and pathological processes including tissue development, tumor cell invasion and metastasis. In present study, we demonstrated that both LAMC1 protein and mRNA levels were elevated in HCC tissue samples compared with non-cancerous tissue samples according to western blot analyses, immunohistochemistry (IHC) and microarray. Moreover, high LAMC1 expression was positively correlated with incomplete encapsulation (=0.014), poor overall (OS, =0.02) and disease-free survival (DFS, =0.014). Using cell lines, we demonstrated that the levels of LAMC1 mRNA and protein were significantly higher in HCC cell lines than that in LO2 cell line. After the expression of LAMC1 was depressed by siRNA technique, the cell proliferation, migration and invasion were depressed significantly. Taken together, these data suggest that LAMC1 is enriched in HCC; overexpression of LAMC1 predicts poor prognosis, and enhances tumor cell invasion and migration. LAMC1 might be a new biomarker predictive of HCC prognosis and might also be a useful treatment target.
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http://dx.doi.org/10.7150/jca.21038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604451PMC
August 2017

Transcatheter arterial chemoembolization (TACE) versus hepatectomy in hepatocellular carcinoma with macrovascular invasion: a meta-analysis of 1683 patients.

J Cancer 2017 25;8(15):2984-2991. Epub 2017 Aug 25.

Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China.

For hepatocellular carcinoma (HCC) patients with macrovascular invasion (MaVI), hepatectomy and transcatheter arterial chemoembolization (TACE) remain the main treatment options in Asia. However, which could achieve better survivals remains controversial. In present study, we conducted a meta-analysis to clarify the survival benefits and safety of hepatectomy versus TACE in HCC patients with MaVI. The PubMed, Cochrane Library and Web of Science databases were searched for eligible studies. There were no prospective studies identified. 8 retrospective studies from Asia with 1683 patients met our inclusion criteria were included in meta-analysis. The overall survival (OS) is higher in hepatectomy group than TACE group (HR=1.61, 95%CI=1.23-2.10, =0.0005). Hepatectomy was superior over TACE in 1-year (OR=2.27, 95%CI=1.26-4.08, =0.006) and 3-year (OR=3.04, 95%CI=2.17-4.26, <0.00001) respectively, but not in 5-year (OR=7.34, 95%CI=0.78-68.16, =0.08) survival rate. Subgroup analysis demonstrated that hepatectomy was superior over TACE for patients with PVTT (HR=1.50, 95%CI=1.14-1.98, =0.004), but not for patients with HVTT/IVC (HR=2.39, 95%CI=0.88-6.49, =0.09). There was not significantly difference between two groups in peri-operative mortality. Our results indicated that, compared to TACE, hepatectomy might be a better treatment option for resectable HCC patients with MaVI. Being lack of high-quality studies, more well-designed multi-center randomized trials are needed to confirm our finding.
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http://dx.doi.org/10.7150/jca.20978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604450PMC
August 2017

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

Ultrasound Med Biol 2017 11 12;43(11):2522-2529. Epub 2017 Aug 12.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China; Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China. Electronic address:

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).
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http://dx.doi.org/10.1016/j.ultrasmedbio.2017.07.003DOI Listing
November 2017

Derived neutrophil to lymphocyte ratio predicts prognosis for patients with HBV-associated hepatocellular carcinoma following transarterial chemoembolization.

Oncol Lett 2016 May 21;11(5):2987-2994. Epub 2016 Mar 21.

Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China; Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China.

The derived neutrophil to lymphocyte ratio (dNLR) has been proposed as an easily determinable prognostic factor for cancer patients, but the prognostic significance of the dNLR in hepatocellular carcinoma (HCC) has not been investigated. The present study aimed to validate the prognostic power of the NLR and dNLR in HCC patients undergoing transarterial chemoembolization (TACE). The data of 279 consecutive patients who underwent TACE for unresectable HBV-associated HCC between September 2009 and November 2011 at the Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center (Guangzhou, China) were retrieved from a prospective database. The cut-off values for the NLR and dNLR were determined by receiver operating characteristic (ROC) analysis. The association between the NLR and dNLR and the clinicopathological characteristics and overall survival (OS) rates and times of patients was analyzed. The area under the curve (AUC) was calculated to evaluate the discriminatory ability of the NLR and dNLR. The median follow-up period was 446 days, the 1, 2 and 3-year OS rates were 38.8, 18.5 and 11.1% respectively, and the median OS time was 264 days. The cut-off values were determined as 2.6 and 1.8 for the NLR and dNLR, respectively. The NLR and dNLR were each associated with patient age, presence of vascular invasion, tumor size, AST level and ALP level. Multivariate analysis showed that the NLR, dNLR, ALT level and AFP level were independent prognostic factors for OS. An elevated NLR or dNLR was associated with a poor prognosis (P=0.001 and P=0.002, respectively). The prognostic power of NLR [AUC=0.539; 95% confidence interval (CI), 0.423-0.656] and dNLR (AUC=0.522; 95% CI, 0.406-0.638) was similar. Elevated dNLR predicted poor prognosis for patients with HBV-associated HCC undergoing TACE, with similar prognostic power to NLR. The dNLR may be used as an alternative to the NLR, as it is easily available and inexpensive.
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http://dx.doi.org/10.3892/ol.2016.4359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840749PMC
May 2016

Expression of Pim-3 in colorectal cancer and its relationship with prognosis.

Tumour Biol 2016 Jul 14;37(7):9151-6. Epub 2016 Jan 14.

State Key Laboratory of Southern China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China.

There is increasing evidence suggesting that the establishment of Pim-3 is involved in tumorigenesis. This study aimed to investigate the expression and clinicopathological significance of Pim-3 in colorectal cancer (CRC). Clinical pathology data were collected from 410 CRC patients who received radical resection and were pathologically confirmed at the Sun Yat-Sen University Cancer Center between October 2002 and December 2008. We compared the expression Pim-3 in the primary focus and liver metastasis and investigated the correlations with other clinical-pathological factors. Multivariate analysis showed that perioperative blood transfusion, local invasion, lymph node and liver metastasis, and Pim-3 expression were independent prognostic factors. The expression of Pim-3 in CRC was higher than that in normal tissues. Patients with positive expression had significant decreases in 5-year survival. Pim-3 expression showed a positive correlation with tumor cell differentiation, local infiltration, and lymph node and liver metastasis. In conclusion, Pim-3 might serve as a novel target and prognosis factor for colorectal cancer.
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http://dx.doi.org/10.1007/s13277-016-4806-7DOI Listing
July 2016

A monocyte/granulocyte to lymphocyte ratio predicts survival in patients with hepatocellular carcinoma.

Sci Rep 2015 Oct 21;5:15263. Epub 2015 Oct 21.

Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China.

Conflict that the derived neutrophil lymphocyte (dNLR) has prognostic value in patients with a variety of cancers exists. The aim of the present study was to devise a monocyte/granulocyte to lymphocyte ratio (M/GLR) which counts as (white cell count - lymphocyte count) to lymphocyte count, and verify its prognostic value in patients with hepatocellular carcinoma (HCC). 1061 HCC patients were retrieved and the associations between M/GLR/NLR/dNLR and clinicopathological variables and survivals (OS and RFS) were analyzed. The area under the curve (AUC) was calculated to evaluate the discriminatory ability of M/GLR/NLR/dNLR. The median follow-up period was 947 days, the 1, 3, 5 year OS was 64%, 51%, and 46% respectively, and the median OS was 842 days. The cut-off values were determined by ROC as 2.8, 1.6, and 3.2 for NLR, dNLR, M/GLR respectively. Elevated M/GLR/NLR/dNLR was associated with poor prognosis (P = 0.001, P = 0.009 and P = 0.022 respectively). By time-dependent ROC, the AUC of M/GLR was higher than that of NLR or dNLR, either in whole group or in subgroups according to TNM stages or different treatments. We concluded that elevated M/GLR predicted poor prognosis for patients with HCC and the M/GLR can be used as an alternative to NLR and dNLR.
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http://dx.doi.org/10.1038/srep15263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4614102PMC
October 2015

The cell cycle regulator 14-3-3σ opposes and reverses cancer metabolic reprogramming.

Nat Commun 2015 Jul 16;6:7530. Epub 2015 Jul 16.

Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Extensive reprogramming of cellular energy metabolism is a hallmark of cancer. Despite its importance, the molecular mechanism controlling this tumour metabolic shift remains not fully understood. Here we show that 14-3-3σ regulates cancer metabolic reprogramming and protects cells from tumorigenic transformation. 14-3-3σ opposes tumour-promoting metabolic programmes by enhancing c-Myc poly-ubiquitination and subsequent degradation. 14-3-3σ demonstrates the suppressive impact on cancer glycolysis, glutaminolysis, mitochondrial biogenesis and other major metabolic processes of tumours. Importantly, 14-3-3σ expression levels predict overall and recurrence-free survival rates, tumour glucose uptake and metabolic gene expression in breast cancer patients. Thus, these results highlight that 14-3-3σ is an important regulator of tumour metabolism, and loss of 14-3-3σ expression is critical for cancer metabolic reprogramming. We anticipate that pharmacologically elevating the function of 14-3-3σ in tumours could be a promising direction for targeted anticancer metabolism therapy development in future.
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http://dx.doi.org/10.1038/ncomms8530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4507299PMC
July 2015

Antiviral therapy in the improvement of survival of patients with hepatitis B virus-related hepatocellular carcinoma treated with sorafenib.

J Gastroenterol Hepatol 2015 Jun;30(6):1032-9

Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Background And Aim: To evaluate the role of antiviral therapy with nucleoside analogs (NAs) in sorafenib-treated patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).

Methods: A retrospective cohort study was done in 151 HBV-related HCC patients treated with sorafenib at Sun Yat-sen University Cancer Center between 2007 and 2012. Overall survival (OS), progression-free survival and adverse events were compared in patients treated with/without NAs. Subgroup analysis and Cox regression analysis were performed to determine the efficiency of NAs and prognostic factors for OS.

Results: HBV-related HCC patients (n=151) were identified from our database of HCC patients treated with sorafenib. Patients treated with NAs (antiviral group, n=88) had significantly improved OS compared with the patients who received no NAs (non-antiviral group, n=63; median OS: 16.47 months vs 13.10 months, P=0.03). Patients in the antiviral group had a significant risk reduction of death compared with the non-antiviral group (hazard ratio: 0.67, 95% confidence interval: 0.46-0.98, P=0.04). By subgroup analysis, patients of Barcelona Clinic Liver Cancer (BCLC) stage C and patients with higher presorafenib HBV-DNA level achieved better survival improvement. Antiviral therapy with NAs was one of the independent prognostic factors for OS of HBV-related HCC patients who were treated with sorafenib.

Conclusion: Antiviral therapy with NAs improved OS of HBV-related HCC patients treated with sorafenib, especially in patients with BCLC stage C disease and higher HBV-DNA level.
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http://dx.doi.org/10.1111/jgh.12910DOI Listing
June 2015

CSN6 drives carcinogenesis by positively regulating Myc stability.

Nat Commun 2014 Nov 14;5:5384. Epub 2014 Nov 14.

Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.

Cullin-RING ubiquitin ligases (CRLs) are critical in ubiquitinating Myc, while COP9 signalosome (CSN) controls neddylation of Cullin in CRL. The mechanistic link between Cullin neddylation and Myc ubiquitination/degradation is unclear. Here we show that Myc is a target of the CSN subunit 6 (CSN6)-Cullin signalling axis and that CSN6 is a positive regulator of Myc. CSN6 enhanced neddylation of Cullin-1 and facilitated autoubiquitination/degradation of Fbxw7, a component of CRL involved in Myc ubiquitination, thereby stabilizing Myc. Csn6 haplo-insufficiency decreased Cullin-1 neddylation but increased Fbxw7 stability to compromise Myc stability and activity in an Eμ-Myc mouse model, resulting in decelerated lymphomagenesis. We found that CSN6 overexpression, which leads to aberrant expression of Myc target genes, is frequent in human cancers. Together, these results define a mechanism for the regulation of Myc stability through the CSN-Cullin-Fbxw7 axis and provide insights into the correlation of CSN6 overexpression with Myc stabilization/activation during tumorigenesis.
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http://dx.doi.org/10.1038/ncomms6384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234183PMC
November 2014
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