The Indications for Hepatectomy for Multinodular Hepatocellular Carcinoma: Experience from a Single Institution

Aims: This study was conducted in order to investigate the indications for hepatecomy for multinodular hepatocellular carcinoma (MNHCC) in single institution. Methods: We retrospectively analyzed the medical records from 55 MNHCC patients, mainly with Child-Pugh A liver function, who underwent hepatectomy from January 2006 to December 2008. Both short- and long-term outcomes were analyzed. In addition, the prognostic significance of clinicopathological factors on overall survival (OS) was investigated by univariate analysis using the log-rank test. A Cox proportional hazards model was used in a subsequent multivariate analysis. Results: The perioperative morbidity rate (grade II or higher) was 18.2% (n = 10), and the in-hospital mortality rate was 3.6%. The median OS was 23.9 months (range, 2.5-84 months), whereas the median disease-free survival was 8.75 months (range, 1-65 months). Independent prognostic risk factors of 5-year OS included the number of tumors >2 (p = 0.032) and gross morphology indicating multiple tumor nodules scattered throughout the liver (p = 0.009). Conclusions: The postoperative morbidity and mortality rates were acceptable. The number of tumors >2 and gross morphology indicating multiple tumor nodules scattered throughout the liver were independent prognostic risk factors for patients with MNHCC after hepatectomy. Patients with both of these features had a very poor prognosis and were not considered suitable for surgery.

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Risk Factors for Hepatocellular Carcinoma After Splenectomy in Liver Cirrhotic Patients

The American Surgeon ◽

10.1177/00031348211041562 ◽

2021 ◽

pp. 000313482110415

Author(s):

Naruhiko Honmyo ◽

Tsuyoshi Kobayashi ◽

Shintaro Kuroda ◽

Kentaro Ide ◽

Masahiro Ohira ◽

...

Keyword(s):

Risk Factors ◽

Hepatocellular Carcinoma ◽

Portal Hypertension ◽

Cox Regression ◽

Univariate Analysis ◽

Hemoglobin Level ◽

Rank Test ◽

Predictive Index ◽

Preoperative Hemoglobin ◽

Preoperative Hemoglobin Level

Background Splenectomy is sometimes indicated for portal hypertension caused by cirrhosis, which is a risk for hepatic carcinogenesis. This study aimed to identify risk factors for hepatocellular carcinoma (HCC) development after splenectomy. Methods This retrospective study included 65 patients who underwent splenectomy for portal hypertension between 2009 and 2017. Cox regression analyses were performed to identify factors related to HCC development after splenectomy. The predictive index for HCC development was constructed from the results of multivariate analysis, and 3 risk-dependent groups were defined. Discrimination among the groups was estimated using Kaplan-Meier curves and the log-rank test. Results Post-splenectomy, 36.9% of patients developed HCC. In the univariate analysis, the etiology of cirrhosis (hepatitis C virus antibody, P = .005, and hepatitis B surface antigen, P = .008, referring to non-B and non-C patients, respectively), presence of HCC history ( P < .001), and preoperative hemoglobin level ( P = .007) were related to HCC development, and the presence of HCC history ( P = .002) and preoperative hemoglobin level ( P = .022) were independent risk factors. The predictive index classified three groups at risk; the hazards in each group were significantly different (low vs middle risk, P = .035, and middle vs high risk, P = .011). Discussion The etiology of cirrhosis, presence of HCC history, and hemoglobin level were associated with HCC development after splenectomy. The predictive model may aid in HCC surveillance after splenectomy for patients with portal hypertension.

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Prognostic value of lemur tyrosine kinase-3 (LMTK3) polymorphism in Japanese (J) patients (PTS) with localized gastric adenocarcinoma (GAC).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.4088 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 4088-4088

Author(s):

Afsaneh Barzi ◽

Takeru Wakatsuki ◽

Wu Zhang ◽

Dongyun Yang ◽

Fotios Loupakis ◽

...

Keyword(s):

Multivariate Analysis ◽

Univariate Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Gender Disparity ◽

Rank Test ◽

Tissue Samples ◽

Direct Dna Sequencing ◽

Estrogen Exposure ◽

Increased Risk

4088 Background: LMTK3 is an estrogen receptor α (ERα) regulator. Recent studies show that [rs808419(r8) and rs9989661(r9)] and LMTK3 expression are prognostic in breast and colon cancers. Our group demonstrated that r9AA is associated with shorter time to recurrence in Caucasian(C) and Hispanic(H) females(F) with GAC. We investigated the significance of LMTK3 polymorphism in J PTS with GAC. Methods: Blood or tissue samples of 169 J PTS who had surgery with/without adjuvant chemotherapy (ACT) were analyzed. Genomic DNA was extracted using the QIAmp kit; all samples were analyzed using PCR-based direct DNA-sequencing. The endpoints of the study were disease-free survival (DFS) and overall survival (OS). Kaplan-Meier curves and log-rank test were used for univariate analysis. Multivariate analysis was performed to test the interaction between polymorphism and gender adjusting for other variables. Results: 60 F and 109 males were enrolled in this study, 17% stage(s) IB, 31% s II, 36% s III, 17% s IV (AJCC-6). The median age was 67(31-88). 65% of PTS received S-1 based ACT. Median follow-up was 4 years(ys). Prognosis was worse in men with r9 AA than AG/GG, at 1 year 67% (95% CI 40-83%) with AA vs 99% (95% CI 91-99%) of AG/GG were alive (p= 0.039). Median survival was not reached in the AG/GG group; in the AA group median DFS and OS was 1yr (p= 0.03) and 2ys (p= 0.039) respectively. In the multivariate analysis adjusting for s, age, and ACT, males carrying AA had increased risk of disease recurrence (HR 3.84 95%CI 1.86-7.92, p< 0.001) and dying (HR 3.47 95%CI 1.58-7.62 p=0.002) compared to those with AG/GG (HR=1, reference). Conclusions: r9 AA was associated with significantly worse DFS and OS in J male with GAC. These results confirm our previous findings that LMTK3 is an independent prognostic factor for localized GAC; interestingly the relationship between gender and prognostic significance is the opposite in J vs. C/H. The gender disparity can be due to the differences in the etiology (histological subtypes), management strategies, allele frequency, and degree of estrogen exposure in the two populations. Additional studies are warranted to identify the underlying biological mechanism.

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Coexpression of PDGFR-Alpha, PDGFR-Beta and VEGF as a Prognostic Factor in Patients with Hepatocellular Carcinoma

The International Journal of Biological Markers ◽

10.5301/jbm.2011.8322 ◽

2011 ◽

Vol 26 (2) ◽

pp. 108-116 ◽

Cited By ~ 15

Author(s):

Li Chen ◽

Yan Shi ◽

Cheng-ying Jiang ◽

Li-xin Wei ◽

Ya-li Lv ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Growth Factor ◽

Proportional Hazards Model ◽

Cox Regression ◽

Univariate Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Hazard Ratio ◽

Cox Proportional Hazards Model ◽

Cox Regression Analysis

Aims To evaluate the prognostic value of vascular endothelial growth factor (VEGF), platelet-derived growth factor receptor-alpha (PDGFR-α) and beta (PDGFR-β) expression in patients with hepatocellular carcinoma (HCC). Methods The expression of PDGFR-α, PDGFR-β and VEGF in 63 HCC patients who underwent curative resection was examined by immunohistochemistry (IHC). The correlations between the expression of these biomarkers and the clinicopathological characteristics were analyzed. Patient survival was analyzed by univariate analysis and Cox proportional hazards model. Results Univariate survival analysis showed that PDGFR-α or PDGFR-β overexpression was of no prognostic significance in predicting disease-free survival (DFS) and overall survival (OS) (p>0.05), while VEGF overexpression and PDGFR-α/PDGFR-β/VEGF coexpression were significantly correlated with worse DFS and poorer OS in HCC patients (P<0.05). More importantly, PDGFR-α/PDGFR-β/VEGF coexpression was an independent prognostic marker for poor survival as indicated by multivariate Cox regression analysis (DFS, hazard ratio 3.122, p=0.001; OS, hazard ratio 4.260, p=0.000). Conclusions Coexpression of PDGFR-α, PDGFR-β and VEGF could be considered an independent prognostic biomarker for predicting DFS and OS in HCC patients. This result could be used to identify patients at a higher risk of tumor recurrence and poor prognosis, and help to select therapeutic schemes for the treatment of HCC.

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The Predictive Value of Vessels Encapsulating Tumor Clusters in Treatment Optimization for Recurrent Early-Stage Hepatocellular Carcinoma

10.21203/rs.3.rs-84444/v1 ◽

2020 ◽

Author(s):

Zhi-Yuan Chen ◽

Zhi-Xing Guo ◽

Liang-He Lu ◽

Jie Mei ◽

Wen-Ping Lin ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Predictive Value ◽

Early Stage ◽

Univariate Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Survival Outcomes ◽

Treatment Optimization ◽

Initial Hepatectomy ◽

Significant Difference

Abstract Background. The vessels encapsulating tumor clusters (VETC) pattern is an effective predictor of survival in patients with hepatocellular carcinoma (HCC) after resection. The predictive value of VETC in recurrent early-stage HCC remains unclear. Therefore, the aim of the present study was to investigate the prognostic significance of VETC in patients with recurrent early-stage HCC after repeat hepatic resection (RHR) or radiofrequency ablation (RFA). Methods. From December 2005 to December 2016, 138 patients who underwent RHR and 188 patients who underwent RFA were enrolled. VETC was evaluated by immunohistochemical staining for CD34. The survival outcomes of treatment for patients with or without the VETC pattern was investigated. Results. Among VETC-positive HCC patients, 50 patients underwent RHR, and 69 patients underwent RFA; among VETC-negative HCC patients, 88 patients underwent RHR, and 119 patients underwent RFA. There was no significant difference between the RHR and RFA groups in disease-free survival (DFS) or overall survival (OS) as determined by univariate analysis of the whole cohort. In the subgroup analysis of the VETC-positive cohort, the patients in the RHR group had a longer median DFS time compared to those in the RFA group (15.0 vs 5.0 months, P=0.001). Similarly, the patients in the RHR group had a longer median OS time compared to those in the RFA group (39.5 vs 19 months, P=0.001). In the VETC-negative cohort, there was no significant difference in DFS and OS rates between the RHR and RFA groups (P>0.05).Conclusions. The results of our study suggested that RHR was relatively safe and superior to RFA in improving survival outcomes for recurrent early-stage HCC after initial hepatectomy. Furthermore, the VETC pattern may represent a reliable marker for selecting HCC patients who may benefit from RHR.

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PD-L1+NEUT, Foxp3+Treg, and NLR as New Prognostic Marker with Low Survival Benefits Value in Hepatocellular Carcinoma

Technology in Cancer Research & Treatment ◽

10.1177/15330338211045820 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110458

Author(s):

Lin Zhou ◽

Jing Wang ◽

Shao-cheng Lyu ◽

Li-chao Pan ◽

Xian-jie Shi ◽

...

Keyword(s):

Risk Factors ◽

Hepatocellular Carcinoma ◽

Peripheral Blood ◽

Cox Regression ◽

Disease Free Survival ◽

Rank Test ◽

Cancer Tissue ◽

Cox Regression Analysis ◽

Poorly Differentiated ◽

Independent Risk Factors

Background: This presented study was aimed to evaluate the diagnostic and prognostic value of PD-L1+Neutrophils (PD-L1+NEUT) and neutrophil to lymphocyte ratio (NLR) based on our previous experience of Foxp3+Treg in transplantation. Methods: the NLR cutoff value of 1.79 was used to include 136 cases from the 204 patients with hepatocellular carcinoma (HCC) confirmed by clinical pathology, which were divided into highly-moderately and poorly differentiated HCC groups. The expressions of PD-L1+NEUT and Foxp3+Treg in peripheral blood and cancer tissue were detected with flow cytometry, meanwhile, PD-L1 and Foxp3 expressed in carcinoma and para-carcinoma tissues were marked by immunohistochemistry. Survival rates, including overall survival and disease-free survival, were calculated by the Kaplan–Meier curve and evaluated with the log-rank test. Finally, Cox risk regression model was used to analyze the independent risk factors for prognostic survival. Results: The level of PD-L1+NEUT, Foxp3+Treg, and NLR in peripheral blood of patients with poorly differentiated HCC were significantly increased (all P < .001). Both PD-L1+NEUT and NLR were positively correlated with Foxp3+Treg ( r = 0.479, P = .0017; r = 0.58, P < .0001). The level of PD-L1+NEUT and Foxp3+Treg as well as PD-L1 and Foxp3 in cancer tissue and patients with poorly differentiated HCC were obviously increased (all P < .01), respectively. Cox regression analysis indicated that PD-L1+NEUT, NLR, and Foxp3+Treg were independent risk factors for the prognosis ( P = .000, .000, .006) with a RR and 95%CI of 2.704-(2.155-3.393), 3.139-(2.361-4.173), 1.409-(1.105-1.798), respectively. Conclusion: PD-L1+NEUT, NLR, and Foxp3+Treg are independent risk factors for prognosis which maybe new marker of lower survival benefits.

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Expression of GRK2 and IGF1R in hepatocellular carcinoma: clinicopathological and prognostic significance

Journal of Clinical Pathology ◽

10.1136/jclinpath-2016-203998 ◽

2017 ◽

Vol 70 (9) ◽

pp. 754-759 ◽

Cited By ~ 10

Author(s):

Song-Bai Lin ◽

Li Zhou ◽

Zhi-Yong Liang ◽

Wei-Xun Zhou ◽

Ye Jin

Keyword(s):

Hepatocellular Carcinoma ◽

Prognostic Value ◽

Univariate Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

The Cancer Genome Atlas ◽

Potential Marker ◽

Tumour Node Metastasis Stage ◽

Clinicopathological Significance ◽

Igf1r Expression

AimIt has been shown that G-protein-coupled receptor kinase 2 (GRK2) negatively regulates the insulin-like growth factor 1 receptor (IGF1R) signalling pathway in hepatocellular carcinoma (HCC). The aim of this study was to evaluate the clinicopathological and prognostic significance of GRK2 and IGF1R in HCC.MethodsExpression of GRK2 and IGF1R was first detected by tissue microarray-based immunohistochemistry in 156 patients with HCC. Staining results, termed the H-score, were then correlated with clinicopathological variables and patient survival. Finally, the prognostic value of GRK2 and IGF1R was validated in the publically available TCGA (The Cancer Genome Atlas) RNA-sequencing database.ResultsThe H-score of GRK2 staining (which was significantly lower in tumour than non-tumour tissue) was negatively associated with that of IGF1R with a reverse trend. No clinicopathological significance of the proteins was found except for a relationship between tumoral IGF1R expression and tumour–node–metastasis stage. In univariate analysis, high IGF1R expression predicted poor overall and disease-free survival, whereas GRK2 was not prognostic. In multivariate analysis, IGF1R was significant for overall survival. Furthermore, IGF1R was also of prognostic value in the TCGA database.ConclusionsOur data indicate that GRK2 and IGF1R show a negative correlation in HCC. IGF1R could be a potential marker of poor prognosis for this malignancy.

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The Predictive Value of Vessels Encapsulating Tumor Clusters in Treatment Optimization for Recurrent Early-stage Hepatocellular Carcinoma

10.21203/rs.3.rs-228188/v1 ◽

2021 ◽

Author(s):

Zhi-Yuan Chen ◽

Zhi-Xing Guo ◽

Liang-He Lu ◽

Jie Mei ◽

Wen-Ping Lin ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Predictive Value ◽

Early Stage ◽

Univariate Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Survival Outcomes ◽

Treatment Optimization ◽

Initial Hepatectomy ◽

Significant Difference

Abstract Background: The predictive value of vessels encapsulating tumor clusters (VETC) in recurrent early-stage Hepatocellular Carcinoma (HCC) remains unclear. Therefore, the aim of the present study was to investigate the prognostic significance of VETC in patients with recurrent early-stage HCC after repeat hepatic resection (RHR) or radiofrequency ablation (RFA). Methods: From December 2005 to December 2016, 138 patients receiving RHR and 188 patients receiving RFA were recruited. VETC was evaluated by immunohistochemical staining for CD34. The survival outcomes of patients with VETC pattern or not were investigated. Results: There was no significant difference between the RHR and RFA groups in disease-free survival (DFS) or overall survival (OS) as determined by univariate analysis of the whole cohort. In the subgroup analysis of the VETC-positive cohort, the patients in the RHR group showed a longer median DFS time in contrast to those in the RFA group (15.0 vs 5.0 months, P=0.001). Similarly, the patients in the RHR group showed a longer median OS time in contrast to those in the RFA group (39.5 vs 19 months, P=0.001). In the VETC-negative cohort, no significant differences in DFS and OS rates between the RHR and RFA groups were observed (P>0.05).Conclusions: The results of our study suggested that RHR was relatively safe and superior to RFA in improving survival outcomes for recurrent early-stage HCC after initial hepatectomy. Furthermore, the VETC pattern may represent a reliable marker for selecting HCC patients who may benefit from RHR.

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Transcript levels of spindle and kinetochore-associated complex 1/3 as prognostic biomarkers correlated with immune infiltrates in hepatocellular carcinoma

Scientific Reports ◽

10.1038/s41598-021-89628-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

De-Chen Yu ◽

Xiang-Yi Chen ◽

Xin Li ◽

Hai-Yu Zhou ◽

De-Quan Yu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Protein Complex ◽

Immune Cell ◽

Prognostic Significance ◽

Tumor Development ◽

Disease Free Survival ◽

Tumor Grade ◽

Tumor Stage ◽

Prognostic Biomarkers ◽

High Expression

AbstractThe spindle and kinetochore-associated protein complex (Ska) is an essential component in chromosome segregation. It comprises three proteins (Ska1, Ska2, and Ska3) with theorized roles in chromosomal instability and tumor development, and its overexpression has been widely reported in a variety of tumors. However, the prognostic significance and immune infiltration of Ska proteins in hepatocellular carcinoma (HCC) are not completely understood. The bioinformatics tools Oncomine, UALCAN, gene expression profiling interactive analysis 2 (GEPIA2), cBioPortal, GeneMANIA, Metascape, and TIMER were used to analyze differential expression, prognostic value, genetic alteration, and immune cell infiltration of the Ska protein complex in HCC patients. We found that the mRNA expression of the Ska complex was markedly upregulated in HCC. High expression of the Ska complex is closely correlated with tumor stage, patient race, tumor grade, and TP53 mutation status. In addition, high expression of the Ska complex was significantly correlated with poor disease-free survival, while the high expression levels of Ska1 and Ska3 were associated with shorter overall survival. The biological functions of the Ska complex in HCC primarily involve the amplification of signals from kinetochores, the mitotic spindle, and (via a MAD2 invasive signal) unattached kinetochores. Furthermore, the expression of the complex was positively correlated with tumor-infiltrating cells. These results may provide new insights into the development of immunotherapeutic targets and prognostic biomarkers for HCC.

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Prognostic Implications of Numb Immunoreactivity in Salivary Gland Carcinomas

International Journal of Immunopathology and Pharmacology ◽

10.1177/039463200702000414 ◽

2007 ◽

Vol 20 (4) ◽

pp. 779-789 ◽

Cited By ~ 29

Author(s):

E. Maiorano ◽

G. Favia ◽

S. Pece ◽

L. Resta ◽

P. Maisonneuve ◽

...

Keyword(s):

Salivary Gland ◽

Univariate Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Ki 67 ◽

Cell Fate Decisions ◽

Ductal Cells ◽

Adenoid Cystic ◽

Pathologic Features ◽

Salivary Gland Carcinomas

The gene numb encodes for a protein (Numb) involved in cell fate decisions in Drosophila, with proposed endocytic and developmental functions in mammalians. The distribution pattern of Numb in human tissues however, has not been fully characterized. We set out to explore the immunohistochemical expression of Numb in normal and neoplastic (28 adenoid cystic and 34 mucoepidermoid carcinomas) salivary glands, and correlated the results with the clinico-pathologic features of the neoplasms. Intense Numb immunoreactivity was detected in normal ductal cells and in a subset of acinar cells. In salivary carcinomas, we detected diffuse and intense Numb immunostaining in 5 adenoid cystic and 8 mucoepidermoid carcinomas. By contrast, the majority of adenoid cystic and mucoepidermoid cancers showed only moderate (14 and 5 cases) or focal staining (9 and 21 cases), respectively. The corresponding expression of Numb mRNA was documented in normal parotid gland and adenoid cystic carcinoma. Numb immunoreactivity was inversely correlated with the histological grade and Ki-67 immunoreactivity of both adenoid cystic and mucoepidermoid carcinomas. In addition, while tumor grade, stage, Ki-67 and Numb immunoreactivity were associated with disease-free survival in univariate analysis, only Numb and Ki-67 immunoreactivities retained independent prognostic significance in multivariate analysis. These data suggest that loss of Numb is implicated in aberrant differentiation programs of salivary gland carcinomas and may serve as a prognostic indicator in patients treated for these neoplasms.

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Is It The Time That We Can Depend on Bioscore as a New Staging System in Non-Metastatic Breast Cancer to Predict the Disease-Free Survival?

10.21203/rs.3.rs-1068006/v1 ◽

2021 ◽

Author(s):

Rehab Farouk Mohamed ◽

Donia Hussein Abd El Hameed ◽

Mohamed Alaa Eldeen Hassan

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Prognostic Value ◽

Univariate Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Metastatic Breast ◽

Her2 Status ◽

Free Survival ◽

Disease Free

Abstract Purpose: Novel molecular characterization of breast cancer with cellular markers has allowed a new classification that offers prognostic value. This study investigates the prognostic value of the Bioscore among non-metastatic breast cancer patients with respect to disease free survival (DFS).Methods: This study included 317 patients with non-metastatic surgically treated breast cancer; they were identified in the period from January 2015 to December 2018 at Clinical Oncology Department of Assiut University Hospital. Many variables were used; pathologic stage (PS), T stage (T), nodal stage (N), grade (G), estrogen receptor (ER), progesterone receptors (PR), and human epidermal growth factor receptor (HER2) status. Univariate & two multivariate analyses were performed to identify which of these variables are associated with disease-free survival (DFS). Results: The only significant factors in the Univariate analysis were PS3, T2, T3, T4, N3, G2, G3, ER -ve, PR -ve, and HER2 –ve. The factors which were significant in the first multivariate analysis; PS3, G3, ER –ve, and in the second one were; T2, T4, N3, G3, and ER –ve. Two sets of models were built to determine the utility of combining variables. Models incorporating G and E status had the highest C-index (0.72) for T+N + G + ER in comparison with (0.69) for (PS+ G + ER) and the lowest AIC (953.01) for T + N + G + E and (966.9) for PS + G + E. Conclusions: This study confirms the prognostic significance of bioscore in non-metastatic breast cancer in concerning DFS.

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