Jianguo Zhou

Prognostic value of the albumin-bilirubin grade in patients with hepatocellular carcinoma: validation in a Chinese cohort.

The prognostic value of the newly raised objective liver function assessment tool, the albumin–bilirubin (ALBI) grade, in patients with hepatocellular carcinoma has not been fully validated. We aimed to compare the performance of ALBI grade with the specific Child–Pugh (C‐P) score in predicting prognosis in this study.

Variants Identified by Hepatocellular Carcinoma and Chronic Hepatitis B Virus Infection Susceptibility GWAS Associated with Survival in HBV-Related Hepatocellular Carcinoma

Recent genome-wide association studies (GWAS) have identified several common susceptibility loci associated with the risk of hepatocellular carcinoma (HCC) or chronic hepatitis B infection (CHB). However, the relationship between these genetic variants and survival of patients with hepatitis B virus (HBV)-related HCC is still unknown. In this study, 22 single nucleotide polymorphisms (SNPs) were genotyped among 330 HBV-related HCC patients using the MassARRAY system from Sequenom. Cox proportional hazards regression was used to examine the effects of genotype on survival time under an additive model with age, sex, smoking status and clinical stage as covariates. We identified four SNPs on 6p21 (rs1419881 T>C, rs7453920 G>A,rs3997872 G>A and rs7768538 T>C), and two SNPs on 8p12 (rs2275959 C>T and rs7821974 C>T) significantly associated with survival time of HBV-related HCC patients. Our results suggest that HCC or CHB susceptibility loci might also affect the prognosis of patients with HBV-related HCC.

Evaluation of eight different clinical staging systems associated with overall survival of chinese patients with hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a common cancer in China, an area of high hepatitis B virus (HBV) infection. Although several staging systems are available, there is no consensus on the best classification to use because multiple factors, such as etiology, clinical treatment and populations could affect the survival of HCC patients. Methods: This study analyzed 743 HBV-related Chinese HCC patients who received surgery first and evaluated the predictive values of eight different commonly used staging systems in the clinic. Results: The overall 1-, 3-, 5-year survival rates and a median survival were 91.5%, 70.3%, 55.3% and 72 months respectively. Barcelona Clinic Liver Cancer (BCLC) staging systems had the best stratification ability and showed the lowest Akaike information criterion (AIC) values (2896.577), followed by tumor-node-metastasis 7th (TNM 7th) (AIC = 2899.980), TNM 6th (AIC = 2902.17), Japan integrated staging score (AIC = 2918.085), Tokyo (AIC = 2938.822), Cancer of the Liver Italian Program score (AIC = 2941.950), Chinese University Prognostic Index grade (AIC = 2962.027), and Okuda (AIC = 2979.389). Conclusions: BCLC staging system is a better staging model for HBV infection patients with HCC in Chinese population among the eight currently used staging systems. These identifications afford a large group of Chinese HCC patients with HBV infection and could be helpful to design a new staging system for a certain population.

Evaluation of seven different staging systems for alpha-fetoprotein expression in hepatocellular carcinoma after hepatectomy

Alpha-fetoprotein (AFP) represents the most important biomarker for hepatocellular carcinoma (HCC). The aim of this study was to identify the optimal staging system to predict the survival of AFP-negative and AFP-positive patients. This study analyzed the data of 431 AFP-negative HCC patients who had previously undergone surgery and 471 AFP-positive HCC candidates. Kaplan–Meier (K-M) survival estimates were plotted, and the P values were assessed using log-rank tests. The Akaike information criterion (AIC) was calculated using the results of a Cox’s regression to compare the overall assessment of the seven different staging systems. The AFP-positive group displayed characteristics of poor tumor biological behavior (tumor multiplicity [Pu2009=u20090.032], low grade differentiation [Pu2009=u20090.000] and carcinoma cell embolus [Pu2009=u20090.031]), poor liver function (Child–Pugh B classification [Pu2009=u20090.003], abnormal prothrombin time activity [Pu2009=u20090.037] and moderate/severe cirrhosis [Pu2009=u20090.000]) and increased operative difficulties (transfusion; Pu2009=u20090.001). TNM7th staging showed the lowest AIC value (1,279.528) for the AFP-negative group, while the Barcelona Clinic Liver Cancer (BCLC) staging system revealed the lowest AIC value (1,991.233) for the AFP-positive group. In conclusion, among the seven favorable staging systems, BCLC staging was superior for the AFP-positive group, while the TNM7th was a more appropriate staging model for the AFP-negative group.

Prognostic factors of carcinoma of the ampulla of Vater after surgery

The purpose of this study was to investigate the prognostic factors of carcinoma of the ampulla of Vater (CAV) after surgery. The clinicopathological factors related to the recurrence and prognosis of 162 CAV patients after surgical resection were retrospectively analyzed using univariate and multivariate methods. The in-hospital mortality rate was 4.32xa0% and the 5-year disease-free survival and overall survival of the 162 subjects were 55.1 and 51.7xa0%, respectively. Univariate analysis revealed that an advanced T stage (Pu2009=u20090.002), lymph nodal metastasis (Pu2009=u20090.002), poor differentiation (Pu2009=u20090.006), tumor size (Pu2009=u20090.033), tumor stage (Pu2009=u20090.001), carbohydrate antigen (CA) 199 serum levels (Pu2009=u20090.000), pancreatic invasion (Pu2009=u20090.001), chemotherapy/radiation therapy (Pu2009=u20090.006), and jaundice (Pu2009=u20090.012) were factors that significantly affected the prognosis of CAV. Multivariate analysis showed that the pancreatic invasion (Pu2009=u20090.009), lymph nodal metastasis (Pu2009=u20090.009), and increased CA199 serum level (Pu2009=u20090.001) were independent risk factors of recurrence. The pancreatic invasion, lymph nodal metastasis, and increased CA199 serum level are key prognostic factors of CAV after surgery.

Total tumor volume predicts survival following liver resection in patients with hepatocellular carcinoma

Assessing the prognosis of patients with hepatocellular carcinoma (HCC) by the number and size of tumors is sometimes difficult. The main purpose of the study was to evaluate the prognostic value of total tumor volume (TTV), which combines the two factors, in patients with HCC who underwent liver resection. We retrospectively reviewed 521 HCC patients from January 2001 to December 2008 in our center. Patients were categorized using the tertiles of TTV. The prognostic value of TTV was assessed. With a median follow-up of 116xa0months, the 1-, 3-, and 5-year overall survival (OS) rates of the patients were 93.1u2009, 69.9, and 46.3xa0%, respectively. OS was significantly differed by TTV tertile groups, and higher TTV was associated with shorter OS (Pu2009<u20090.001). Multivariate analysis revealed that TTV was an independent prognostic factor for OS. Larger TTV was significantly associated with higher alpha-fetoprotein level, presence of macrovascular invasion, multiple tumor lesions, larger tumor size, and advanced tumor stages (all Pu2009<u20090.05). Within the first and second tertiles of TTV (TTVu2009≤u200973.5xa0cm3), no significant differences in OS were detected in patients within and beyond Milan criteria (Pu2009=u20090.183). TTV-based Cancer of the Liver Italian Program (CLIP) score gained the lowest Akaike information criterion value, the highest χ2 value of likelihood ratio test, and the highest C-index among the tested staging systems. Our results suggested that TTV is a good indicator of tumor burden in patients with HCC. Further studies are warranted to validate the prognostic value of TTV.

RIPK1 Binds MCU to Mediate Induction of Mitochondrial Ca2+ Uptake and Promotes Colorectal Oncogenesis

The receptor-interacting protein kinase 1 (RIPK1) is an essential signaling molecule in pathways for cell survival, apoptosis, and necroptosis. We report here that RIPK1 is upregulated in human colorectal cancer and promotes cell proliferation when overexpressed in a colon cancer cell line. RIPK1 interacts with mitochondrial Ca2+ uniporter (MCU) to promote proliferation by increasing mitochondrial Ca2+ uptake and energy metabolism. The ubiquitination site of RIPK1 (RIPK1-K377) was critical for this interaction with MCU and function in promoting cell proliferation. These findings identify the RIPK1-MCU pathway as a promising target to treat colorectal cancer.Significance: RIPK1-mediated cell proliferation through MCU is a central mechanism underlying colorectal cancer progression and may prove to be an important therapeutic target for colorectal cancer treatment. Cancer Res; 78(11); 2876-85. ©2018 AACR.

Interaction of margin status and tumour burden determines survival after resection of colorectal liver metastases: A retrospective cohort study

PURPOSEnWe sought to determine the impact of surgical margin status on overall survival (OS) and recurrence pattern stratified by tumor burden.nnnMATERIALS AND METHODSnData were collected from patients undergoing resection for colorectal liver metastases (CRLM). Tumor burden was calculated according to a newly proposed Tumor Burden Score (TBS) system, defined as the distance from the origin on a Cartesian plane that incorporated maximum tumor size and number of liver lesions. Patients were divided into low tumor burden group and high tumor burden group accordingly, and the impact of resection margin on overall survival was examined.nnnRESULTSnA total of 286 patients were available, among which R1 resection was observed in 88 patients. The median TBS for the entire cohort was 3.84. Metastases in the R1 group were characterized by more advanced disease and more complex resections. Compared with a R0 resection, a R1 resection offered an lower 5-year overall survival rate (46.8% vs. 22.1%, pxa0=xa00.001). Multivariate analysis identified R1 resection (pxa0=xa00.03), high TBS (pxa0=xa00.002), lymph nodes metastases (pxa0=xa00.003) and lymphovascular invasion (pxa0=xa00.03) of the primary colorectal tumor as the factors independently associated with worse survival. The survival benefit associated with negative margins was greater in patients with low TBS (55.7% vs. 21.7%, pxa0=xa00.021) than in patients with high TBS (31.8% vs. 24.5%, pxa0=xa00.116). R1 resection was associated with an increased true margin recurrence rate in patients with low TBS (32.3% vs. 13.4%; pxa0=xa00.014) and an increased risk of new intrahepatic metastases in patients with high TBS (43.9% vs. 26.7%; pxa0=xa00.034).nnnCONCLUSIONSnNegative margin is an important determinant of survival. The impact of positive margins is more pronounced in patients with low tumor burden.

Metastasis associated genomic aberrations in stage II rectal cancer

Genomic aberrations of rectal carcinoma, especially DNA copy number changes associated with metastasis were largely unclear. We aim to identify the metastasis associated biomarkers in stage II rectal cancer. Formalin-fixed, paraffin-embedded primary tumor tissues of stage II rectal carcinoma were analyzed by array-based comparative genomic hybridization, and genomic aberrations were identified by Genomic Workbench and SAM software. Copy number changes and mRNA expressions were validated by Real-time PCR in an independent rectal cancer samples. The results showed that the most frequent gains in stage II rectal cancer were at 1q21.2-q23.1, 3p21.31, 11q12.2-q23.3, 12q24.11-q24.31, 12q13.11-q14.1 and losses in 18q11.2-q23, 17q21.33-q22, 13q31.1-q31.3, 21q21.1-q21.3, 8p23.3-p23.1 and 4q22.1-q23. Twenty-two amplifications and five homozygous deletions were also identified. We further found that S100A1 (1q21.3-q23.1), MCM7 (7q22.1) and JUND (19p13.11) were amplified and overexpressed in stage II rectal cancer. Interestingly, the genomic aberrations affected 14 signaling pathways including VEGF signaling pathway and fatty acid metabolism. Most importantly, loss of 13q31.1-q34 and gain of 1q44 were associated with distant metastasis. Our results indicated that these metastasis associated genomic changes may be useful to reveal the pathogenesis of rectal cancer metastasis and identify candidate biomarkers.

A Low Neutrophil to Lymphocyte Ratio Before Preoperative Chemotherapy Predicts Good Outcomes After the Resection of Colorectal Liver Metastases

BackgroundThe neutrophil to lymphocyte ratio (NLR) is a marker of inflammation and is associated with poor outcomes. We aimed to evaluate the role of the pretreatment NLR in predicting the outcomes after preoperative chemotherapy in patients with colorectal liver metastases (CRLM).MethodsA retrospective review was performed for 183 patients with CRLM. The NLR was measured before chemotherapy, and a receiver operating characteristic (ROC) curve was used to estimate the cutoff value. Logistic regressions were applied to analyze potential predictors of the pathological response. The Cox proportional hazard method was used to analyze survival.ResultsThe pre-chemotherapy NLR was 2.4u2009±u20091.1, whereas the post-chemotherapy NLR was 2.1u2009±u20091.6 (pu2009<u20090.001). The pretreatment NLR of 2.3 was a significant predictive marker for the pathological response. The pathological response rates were 67.1% in the patients with an NLRxa0≤xa02.3 and 48.1% in patients with an NLRu2009>u20092.3 (pu2009=u20090.01). Multivariate analysis revealed that the factors independently associated with pathological responses were a low pretreatment NLR (pu2009=u20090.043), radiological response to chemotherapy (pu2009<u20090.001), first-line chemotherapy (pu2009=u20090.001), and targeted therapy (pu2009=u20090.002). The median overall survival (OS) and recurrence-free survival (RFS) were worse in the increased NLR cohort than in the low NLR cohort (OS: 31.1 vs. 43.1xa0months, pu2009=u20090.012; RFS: 6.5 vs. 9.4xa0months, pu2009=u20090.06). According to multivariate analyses, a high pretreatment NLR was a significant predictor for both worse OS (HRu2009=u20092.43, 95%CIu2009=u20091.49–3.94, pu2009<u20090.001) and RFS (HRu2009=u20091.53, 95%CIu2009=u20091.08–2.18, pu2009=u20090.017).ConclusionsAn increased pretreatment NLR was a significant predictor of a poor pathological response and worse prognosis after preoperative chemotherapy. The NLR is a simple biomarker for assessing chemotherapy efficacy.