scholarly journals Reclassification of tumor size for solitary HBV-related hepatocellular carcinoma by minimum p value method: a large retrospective study

2020 ◽  
Author(s):  
Hongzhi Liu ◽  
Yuan Yang ◽  
Chuanchun Chen ◽  
Lei Wang ◽  
Qizhen Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Liver Cirrhosis ◽  
Tumor Size ◽  
Prognostic Significance ◽  
P Value ◽  
Tumor Differentiation ◽  
Clinicopathologic Characteristics ◽  
Large Retrospective Study

Abstract Background and Objectives Tumor size is one of the most important issues for hepatocellular carcinoma (HCC) treatment and prognosis but the classification of it still controversial. The aim of this study was to screen appropriate cutoffs for size of solitary HBV-related HCC. Methods A cohort of 1760 patients with solitary HBV-related HCC undergoing curative liver resection were divided into 11 groups based on tumor size in 1-cm intervals. The minimum p value method was used to screen the appropriate size cutoff according to overall survival (OS). Results There are 8 dichotomy, 8 trichotomy and 14 inquartation cutoffs were screened when classifying tumor sizes in accordance with OS. After reclassified patients into three new classifications: ≤ 3cm (n = 422), > 3 and ≤ 9cm (n = 1072), and > 9cm (n = 266). The comparison of clinicopathologic characteristics among these three classifications showed that the increase of tumor size was associated with the increase of α-fetoprotein (AFP), Microvascular invasion (MVI), tumor differentiation, and liver cirrhosis. And the comparison of the OS among three classifications showed statistical differences. Conclusions This study suggested that size criteria of 3cm and 9cm in solitary HBV-related HCC patients were appropriate based on biological characteristics and prognostic significance.

scholarly journals Reclassification of tumor size for solitary HBV-related hepatocellular carcinoma by minimum p value method: a large retrospective study

2020 ◽  
Author(s):  
Hongzhi Liu ◽  
Yuan Yang ◽  
Chuanchun Chen ◽  
Lei Wang ◽  
Qizhen Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Size ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Cox Proportional Hazards ◽  
P Value ◽  
Clinicopathologic Characteristics ◽  
B Virus ◽  
The Difference

Abstract Background and Objectives Tumor size is one of the most important issues for hepatocellular carcinoma (HCC) treatment and prognosis but the classification of it still controversial. The aim of this study was to screen appropriate cutoffs for size of solitary hepatitis B virus (HBV) related HCC.Methods A cohort of 1760 patients with solitary HBV-related HCC undergoing curative liver resection were divided into 11 groups based on tumor size in 1-cm interval. The minimum p value method was used to screen the appropriate size cutoff according to overall survival (OS). If multiple cutoffs meet the above standard, univariate analysis will be performed by using the Cox proportional hazards regression model, and hazard ratio (HR) will be considered as a criterion to assess the difference in survival.Results There are 8 dichotomy, 8 trichotomy and no inquartation cutoffs were screened when classifying tumor sizes in accordance with OS. The HR values of tumor size at these trichotomy cutoffs for OS were compared, the highest HR value is 2.79 when size cutoff is 3/9cm. Then, we reclassified patients into three new classifications: ≤ 3cm (n = 422), > 3 and ≤ 9cm (n = 1072), and > 9cm (n = 266). The comparison of clinicopathologic characteristics among these three classifications showed that the increase of tumor size was associated with the increase of α-fetoprotein (AFP), microvascular invasion (MVI), tumor differentiation, and liver cirrhosis. And the comparison of the OS among three classifications showed statistical differences. Conclusions This study suggested that size criteria of 3cm and 9cm in solitary HBV-related HCC patients were appropriate based on biological characteristics and prognostic significance.

Prognostic Significance of Globulin/Low-Density Lipoprotein Ratio In Patients With Hepatocellular Carcinoma After Local Ablative Therapy

2021 ◽  
Author(s):  
Wenying Qiao ◽  
Qi Wang ◽  
Jianjun Li ◽  
Chunwang Yuan ◽  
Dandan Guo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Tumor Size ◽  
Low Density Lipoprotein ◽  
Prognostic Significance ◽  
Density Lipoprotein ◽  
Low Density ◽  
Operating Characteristics ◽  
Tumor Number ◽  
Receiver Operating

Abstract Background: Low-density lipoprotein (LDL) and globulin have been found to be predictors for some malignant tumors, but their predictive value in hepatocellular carcinoma (HCC) has hardly to be elucidated. This study assessed the prognostic significance of globulin to low-density lipoprotein ratio (GLR) in HCC patients before ablation.Materials and methods: This study analyzed 312 HCC patients hospitalized and underwent ablative treatment in Beijing You 'an Hospital, Capital Medical University, from January 1, 2012 to January 1, 2017. Cox regression analysis was used to assess the factors independently associated with recurrence and survival. The optimal cut-off value and prognostic role of GLR and other markers were evaluated via the receiver operating characteristic-ROC curves and the Youden index. Overall survival (OS) and recurrence-free survival (RFS) were calculated by Kaplan-Meier analysis, and compared between groups using the log-rank.Result: Univariate and multivariate analysis found that the tumor number (HR: 1.676;95%CI: 1.113-2.526), tumor size (HR: 1.967;95%CI: 1.251-3.092), GLR (HR: 1.028;95%CI: 1.004-1.052) were independent risk factors of relapse; while etiology (HR: 1.328;95%CI: 1.052-1.677), tumor number (HR: 1.615;95%CI: 1.015-2.570), tumor size (HR: 2.061; 95%CI: 1.243-3.418), Fib (HR: 0.73; 95%CI: 0.535-0.996) and GLR (HR: 1.031;95%CI: 1.003-1.06) were related to overall survival. We classified the patients into groups with high and low levels of GLR based on the optimal cut-off value of GLR identified by generating receiver operating characteristics (ROC) curve. The cumulative 1-, 3-, and 5-year RFS rates in the low GLR group were 76.4%, 53.8% and 43.4%, while those in the high GLR group were 71%, 31% and 22%, respectively (P <0.001). Concerning OS, the low GLR group showed a 1-, 3- and 5-year OS of 99.5%, 92.0% and 80.2% versus 98%, 73% and 63% for the high GLR group (P <0.001). Finally, patients were stratified by GLR and tumor size. The outcomes revealed that patients in group A (GLR<16.54 and tumor size ≤30mm) showed better prognosis than group B (GLR≥16.54 and tumor size≤30mm or GLR<16.54 and tumor size >30mm) and group C (GLR≥16.54 and tumor size >30mm) (P <0.001). Conclusions: Preoperative GLR ratio could serve as a biomarker to predict prognosis in HCC patients who underwent complete ablation.

scholarly journals Hepatoblastoma: glutamine depletion hinders cell viability in the embryonal subtype but high GLUL expression is associated with better overall survival

2021 ◽  
Author(s):  
Andreas Schmidt ◽  
Angela Armento ◽  
Ovidio Bussolati ◽  
Martina Chiu ◽  
Verena Ellerkamp ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Growth Inhibition ◽  
Cell Viability ◽  
Cell Lines ◽  
Prognostic Significance ◽  
Asparagine Synthetase ◽  
Inhibition Of Proliferation ◽  
Its Gene ◽  
Glutamine Synthesis

Abstract Purpose Glutamine plays an important role in cell viability and growth of various tumors. For the fetal subtype of hepatoblastoma, growth inhibition through glutamine depletion was shown. We studied glutamine depletion in embryonal cell lines of hepatoblastoma carrying different mutations. Since asparagine synthetase was identified as a prognostic factor and potential therapeutic target in adult hepatocellular carcinoma, we investigated the expression of its gene ASNS and of the gene GLUL, encoding for glutamine synthetase, in hepatoblastoma specimens and cell lines and investigated the correlation with overall survival. Methods We correlated GLUL and ASNS expression with overall survival using publicly available microarray and clinical data. We examined GLUL and ASNS expression by RT-qPCR and by Western blot analysis in the embryonal cell lines Huh-6 and HepT1, and in five hepatoblastoma specimens. In the same cell lines, we investigated the effects of glutamine depletion. Hepatoblastoma biopsies were examined for histology and CTNNB1 mutations. Results High GLUL expression was associated with a higher median survival time. Independent of mutations and histology, hepatoblastoma samples showed strong GLUL expression and glutamine synthesis. Glutamine depletion resulted in the inhibition of proliferation and of cell viability in both embryonal hepatoblastoma cell lines. ASNS expression did not correlate with overall survival. Conclusion Growth inhibition resulting from glutamine depletion, as described for the hepatoblastoma fetal subtype, is also detected in established embryonal hepatoblastoma cell lines carrying different mutations. At variance with adult hepatocellular carcinoma, in hepatoblastoma asparagine synthetase has no prognostic significance.

Efficacy and prognostic significance of triflurodine/tipiracil beyond oxaliplatin and irinotecan based chemotherapy in patients with refractory metastatic colorectal cancer: An observational multicenter study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15586-e15586
Author(s):  
Mohamed Alghamdi ◽  
Shouki Bazarbashi ◽  
Elsamany Shereef ◽  
Mervat Mahrous ◽  
Omar Al shaer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Saudi Arabia ◽  
Neutrophil Count ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
P Value ◽  
Second Line ◽  
First Line ◽  
Free Survival

e15586 Background: In Saudi Arabia, the incidence of colorectal cancer has been increased over the past few years. The optimal treatment beyond the second line is not fully understood. To the best of our knowledge, the efficacy and disease outcomes of triflurodine/tipiracil in Saudi patients with refractory metastatic colorectal cancer(mCRC) has not been studied yet. Our study is a real-life practice evaluation of the efficacy of triflurodine/tipiracil in patients with refractory mCRC. Moreover, the prognosis and the prognostic significance of the different clinical variables have been analyzed. Methods: A retrospective, multi-centers ( 5 centers representative of Saudi Arabia )observational study in patients with mCRC who have received triflurodine/tipiracil beyond oxaliplatin & Irinotecan-based chemotherapy between December 2018-December 2020.We aimed to assess the response to triflurodine/tipiracil, to evaluate the progression-free survival (PFS ), the overall survival (OS), and the associated factors of prognostic significance. Results:The data of 100 patients with refractory mCRC who has received triflurodine/tipiracil have been analyzed. The mean age was 55.2 +11.8 years. Forty-two patients were (42%) females and 58 (58%) were male patients. Sigmoid was the most common primary site of cancer in 35 (35%) patients, followed by rectum 29 (29%). Peritoneal metastasis was present in 17 (23.3%) patients ,liver in 51(56.6%) and lung in 39 (50.7%). Metastatic sites were ≥ 2 in 45 (45%) patients. Metastatic lesions were ≥ 5 in 65 (65%) patients. Xelox chemotherapy regimen was the most commonly used first-line chemotherapy which represents 43%, while Folfiri or Xeliri combination was the most used second line in 57 (60%). For the third line, Folfox or Xelox was used in 81 (83.5%) patients. The fourth line was given to 49 (67.1%). For first-line biological agents, Cetuximab was used most frequently 31 (46.3%).Evaluation of the response to treatment with triflurodine/tipiracil revealed one patient (1%) with a complete response,3 patients (3%) with partial response, 28 (28%) patients with stable disease, and 66 (66%) showed progressive disease. The estimated median progression-free survival was 5 months ( 3.839 - 6.161) and the median overall survival was 12 months (9.732-14.268). The log-rank analysis showed that the baseline neutrophils ≤ 75 % ( P-value= 0.0092) and low hemoglobin level (P-value= 0.0245) were strongly associated with a higher survival. By multivariate Cox regression analysis, the neutrophil count ≤ 75 % was the only independent predictor for survival. Conclusions: Trifluridine/tipiracil is effective in patients with refractory mCRC. The low neutrophil count might predict a better overall survival.

scholarly journals A Nomogram Based on a Three-Gene Signature Derived from AATF Coexpressed Genes Predicts Overall Survival of Hepatocellular Carcinoma Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Jun Liu ◽  
Jianjun Lu ◽  
Zhanzhong Ma ◽  
Wenli Li
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Clinical Practice ◽  
Correlation Coefficient ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Gene Signature ◽  
Cancer Genome ◽  
Survival Prediction

Background. Hepatocellular carcinoma (HCC) is a common cancer with an extremely high mortality rate. Therefore, there is an urgent need in screening key biomarkers of HCC to predict the prognosis and develop more individual treatments. Recently, AATF is reported to be an important factor contributing to HCC. Methods. We aimed to establish a gene signature to predict overall survival of HCC patients. Firstly, we examined the expression level of AATF in the Gene Expression Omnibus (GEO), the Cancer Genome Atlas (TCGA), and the International Union of Cancer Genome (ICGC) databases. Genes coexpressed with AATF were identified in the TCGA dataset by the Poisson correlation coefficient and used to establish a gene signature for survival prediction. The prognostic significance of this gene signature was then validated in the ICGC dataset and used to build a combined prognostic model for clinical practice. Results. Gene expression data and clinical information of 2521 HCC patients were downloaded from three public databases. AATF expression in HCC tissue was higher than that in matched normal liver tissues. 644 genes coexpressed with AATF were identified by the Poisson correlation coefficient and used to establish a three-gene signature (KIF20A, UCK2, and SLC41A3) by the univariate and multivariate least absolute shrinkage and selection operator Cox regression analyses. This three-gene signature was then used to build a combined nomogram for clinical practice. Conclusion. This integrated nomogram based on the three-gene signature can predict overall survival for HCC patients well. The three-gene signature may be a potential therapeutic target in HCC.

Expression of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Human Pancreatic Adenocarcinomas: Clinicopathologic and Prognostic Significance of Matrilysin Expression

2001 ◽  
Vol 19 (4) ◽  
pp. 1118-1127 ◽  
Author(s):  
Hiroyuki Yamamoto ◽  
Fumio Itoh ◽  
Shouhei Iku ◽  
Yasushi Adachi ◽  
Hiroshi Fukushima ◽  
...  
Keyword(s):  
Overall Survival ◽  
Matrix Metalloproteinases ◽  
Pancreatic Carcinoma ◽  
Prognostic Significance ◽  
Carcinoma Cells ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Invasive Front ◽  
Clinicopathologic Characteristics ◽  
Tissue Inhibitors

PURPOSE: A disruption in the balance between the matrix metalloproteinases (MMPs) and their natural inhibitors, tissue inhibitors of metalloproteinases (TIMPs), has been implicated in the progression of many types of cancer. The aim of this study was to determine whether a specific MMP or TIMP has clinicopathologic and prognostic significance in pancreatic carcinoma. PATIENTS AND METHODS: Using immunohistochemistry, we analyzed 70 pancreatic ductal adenocarcinoma tissues for expression of MMP-1, MMP-2, MMP-3, MMP-7 (matrilysin), MMP-9, MT1-MMP, TIMP-1, and TIMP-2. The results were matched with clinicopathologic characteristics and patients’ survival. The effects of the suppression of a specific MMP on in vitro invasiveness of pancreatic carcinoma cells were also examined. RESULTS: Expression of MMP-1, MMP-2, MMP-3, matrilysin, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 was detected in either tumor cells or tumor stromal cells, or in both components, at varying frequencies. Among MMPs, matrilysin showed a unique distribution in the tumor nests; its expression was usually most pronounced at the invasive front of the tumors. Sections with immunostaining signals in more than 30% of carcinoma cells at the invasive front, which were observed in 40 cases (57%), were judged to be positive for matrilysin. Matrilysin positivity was significantly correlated with pT, pN, and pM categories and with more advanced pathologic tumor-node-metastasis stages. Patients with matrilysin-positive carcinoma had a significantly shorter overall survival time than did those with matrilysin-negative carcinoma. Matrilysin was a significant independent prognostic factor for overall survival in multivariate analysis. In contrast, there was no correlation between the presence of other MMPs or TIMPs and clinicopathologic characteristics, nor was the presence of individual MMPs or TIMPs related to survival. Antisense matrilysin-transfected CFPAC-1 cells expressed reduced levels of matrilysin and demonstrated a similar growth potential but were less invasive in vitro compared with neotransfected CFPAC-1 cells. CONCLUSION: Our results suggest that matrilysin may play a key role in progression of pancreatic carcinoma and thereby contribute to a poor prognosis. Because different synthetic MMP inhibitors affect different types of MMPs to a different degree, examination of the expression of MMPs, especially that of matrilysin, may serve as an indicator for selecting the most effective MMP inhibitor.

Overall survival modeling and association with serum biomarkers in durvalumab-treated patients with head and neck cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6549-6549
Author(s):  
Vadryn Pierre ◽  
Xiang Guo ◽  
Ignacio Gonzalez-Garcia ◽  
Nassim Morsli ◽  
Alejandro Javier Yovine ◽  
...  
Keyword(s):  
Overall Survival ◽  
Head And Neck ◽  
Tumor Size ◽  
Tumor Burden ◽  
P Value ◽  
Plasminogen Activator Inhibitor 1 ◽  
Term Survival ◽  
Baseline Serum ◽  
Neutrophil Lymphocyte Ratio ◽  
Pai 1

6549 Background: Optimal patient selection for immunotherapy remains a challenge as most patients fail to respond. We aim to assess baseline factors for association with long-term survival from durvalumab treatment in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC)1,2. Methods: Pooled longitudinal tumor size, survival, and dropout data from four trials (1108: NCT01693562, CONDOR: NCT02319044 , HAWK: NCT02207530, and EAGLE: NCT02369874) involving 467 HNSCC patients were used to develop tumor size-driven hazard models. A panel of 66 serum protein biomarkers at baseline and 4 relevant clinical markers from 346 out of 413 patients treated with durvalumab (all studies except 1108) were initially screened to select a pool of 21 candidate covariates. The criteria for dimensionality reduction comprised correlation strength between biomarkers and pharmacological hypotheses pertaining to a prior analysis3 (inflammation, immunomodulation, tumor burden and angiogenesis). Results: The final tumor model highlighted that high tumor burden, elevated LDH and neutrophil-lymphocyte ratio were associated with faster tumor growth while patients with lower baseline tumor burden had an increase in net tumor shrinkage. For overall survival, the model suggested that high levels of immunomodulators (IL23, Osteocalcin), low inflammation (IL6, NLR), low tumor burden, and low angiogenesis factors (von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1)) were associated with survival benefits for patients treated with durvalumab. Specifically, these patients had baseline serum IL23 > 2.1 pg/mL and Osteocalcin > 32 pg/mL or serum PAI-1 < 229 pg/mL and serum IL6 < 5.4 pg/mL which corresponded to a hazard ratio estimate (HR and 95%CI) of 0.36 (0.27- 0.47), logrank p-value: 2.3x10−14. The median (n, 95%CI) overall survival time for the patients with favorable biomarker profile was 14.6 months (n = 129, 11.2-21.4) vs. 4.4 months (n = 217, 3.6-5.3). Conclusions: Our results corroborate the prior hypothesis highlighting the prognostic value of inflammation, disease burden, tumor angiogenesis, and immunomodulatory factors on the clinical outcomes of HNSCC patients treated with durvalumab3. Collectively, we identified a serum biomarker profile of HNSCC patients with median survival times exceeding 1 year which may potentially be used for patient enrichment following further validation in prospective studies. References: 1Yanan CPT 2017, 2Baverel, 2018 ENA, 3Guo, X, 2019 Asco P6048 Clinical trial information: NCT01693562, NCT02319044, NCT02207530, NCT02369874 .

scholarly journals The Clinicopathological and Prognostic Significance of the Gross Classification of Hepatocellular Carcinoma

2018 ◽  
Vol 52 (2) ◽  
pp. 85-92 ◽  
Author(s):  
Yangkyu Lee ◽  
Hyunjin Park ◽  
Hyejung Lee ◽  
Jai Young Cho ◽  
Yoo-Seok Yoon ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Significance

scholarly journals Sub-Classification of Cirrhosis Affects Surgical Outcomes for Early Hepatocellular Carcinoma Independent of Portal Hypertension

2021 ◽  
Vol 11 ◽  
Author(s):  
Er-lei Zhang ◽  
Jiang Li ◽  
Jian Li ◽  
Wen-qiang Wang ◽  
Jin Gu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Portal Hypertension ◽  
Surgical Outcomes ◽  
Early Stage ◽  
Surgical Mortality ◽  
Tumor Capsule ◽  
B Virus ◽  
Independent Risk Factors

Severity of liver cirrhosis is distinct from clinical portal hypertension because there exist different degrees of liver cirrhosis in hepatocellular carcinoma (HCC) patients without significant clinical portal hypertension. Whether severity of cirrhosis affects surgical outcomes for HCC patients in absence of portal hypertension or not remains unclear. This study aims to analyze the effect of cirrhotic severity on surgical outcomes for HCC patients with hepatitis B virus (HBV) infection in absence of portal hypertension. This retrospective study enrolled 166 patients who underwent curative resection for a single HCC ≤5 cm in absence of portal hypertension between February 2011 and December 2013. Liver cirrhosis was sub-classified into no/mild (no/F4A) and moderate/severe (F4B/F4C) according to the Laennec scoring system. The surgical outcomes and complications were analyzed. The surgical mortality was zero in this study. Major complications were apparently higher in the F4B/F4C group than in the no/F4A group (17.0% vs 7.4%, p &lt;0.001). The 1-year, 3-year and 5-year overall survival (OS) rates were 98.5, 88.1 and 80%, respectively, in the no/F4A group, which were significantly higher than those in the F4B/F4C group (98.0, 69.2 and 54.7%, p = 0.001). Microscopic vascular invasion, absence of tumor capsule and severity of liver cirrhosis were independent risk factors of surgical outcomes for HCC patients without portal hypertension. In conclusion, severity of liver cirrhosis affected surgical outcomes for early-stage HCC patients independent of portal hypertension.

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