Impact of Hepatic Steatosis on Disease-Free Survival in Patients with Non-B Non-C Hepatocellular Carcinoma Undergoing Hepatic Resection

Nishio, Toshikazu; Hatano, Etsuro; Sakurai, Takaki; Taura, Kojiro; Okuno, Masayuki; Kasai, Yosuke; Seo, Satoru; Yasuchika, Kentaro; Mori, Akira; Kaido, Toshimi; Üemoto, Shinji

doi:10.1245/s10434-014-4181-9

Cited by 20 publications

(14 citation statements)

References 34 publications

(29 reference statements)

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“…Furthermore, AFP levels >1000 ng/mL, preoperative tumor rupture, local extrahepatic disease, poor tumor differentiation, cirrhosis, and steatosis did not significantly distinguish short-term from long-term survivors. These findings were consistent with some, but not all, prior studies 8,19–27 . This is likely due to the heterogeneity of HCC patients and thus it is difficult to identify prognostic factors that are widely applicable.…”

Section: Discussionsupporting

confidence: 93%

Actual 10-Year Survivors After Resection of Hepatocellular Carcinoma

et al. 2016

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Background Resection of hepatocellular carcinoma (HCC) offers a chance of cure, but recurrence is common and survival is often limited. The clinical and pathological characteristics of long-term survivors have not been well studied. Methods We retrospectively reviewed 212 patients who underwent partial hepatectomy for HCC with curative intent from 1992 to 2006. Fifty patients who survived beyond 10 years were compared with 109 patients who died of recurrence within 10 years. Results Multivariate analysis showed that tumors <5cm (OR=2.3, p=0.04), solitary tumors (OR=3.2, p=0.01), and absence of vascular invasion (OR=2.3, p=0.04) were independently associated with actual 10-year survival. However, more than 20% of long-term survivors also possessed established poor prognostic factors, including α-fetoprotein >1000 ng/mL, unfavorable serum inflammatory indices, tumor size >10cm, microvascular invasion, poor tumor differentiation, cirrhosis, and metabolic syndrome. None of the 10-year survivors had an R1 resection. While 77% of the short-term survivors developed recurrence within 2 years, 42% of the 10-year survivors developed recurrence during their decade of follow-up, although most of the recurrences among 10-year survivors were intrahepatic and amenable to further treatment. Among patients who survived beyond 10 years, 42% remained alive without recurrence. Conclusions In this largest Western series of actual 10-year survivors after HCC resection, almost one in four patients survived over a decade, even though nearly half of this subset had developed recurrence. While many well known variables were associated with a poor outcome, only a positive microscopic margin precluded long-term survival.

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Section: Discussionsupporting

confidence: 93%

Actual 10-Year Survivors After Resection of Hepatocellular Carcinoma

et al. 2016

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“…The effects of tumor diameter, multiple tumor nodes, and vascular invasion, which are relevant to aggressive behavior of a tumor, on the prognosis of HCC have been reported in many previous literatures. 6,9,[22][23][24][25] In addition, several studies demonstrated the unfavorable effect of these factors in NBNC-HCC, 9,22 which is consistent with our results. GGT, a cost-effective and easily accessible serum biomarker, has been reported to have diagnostic and prognostic effects in various malignancies.…”

Section: Discussionsupporting

confidence: 92%

<p>Development and Validation of a Prognostic Nomogram to Predict the Long-Time Prognosis in Non-B, Non-C Hepatocellular Carcinoma</p>

Lin¹,

Huang²,

Huo³

et al. 2020

CMAR

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To develop and validate a nomogram for individualized prediction of the longterm prognosis of patients with non-B, non-C hepatocellular carcinoma (NBNC-HCC) who underwent hepatectomy. Materials and Methods: Five hundred ninety-four patients who met the criteria were included in the research and randomly categorized into the training or validation cohort. The nomogram was constructed on the basis of the independent risk variables that were acquired via multivariate Cox proportional hazard regression analysis. Several complementary methods included the Harrell c-index, time-dependent areas under the receiver operating characteristic curve (tdAUC), and calibration plot, and the Kaplan-Meier curve with Log rank test were used to test predictive performance of the model. The clinical utility of the model was tested by the decision cure analysis (DCA). Results: Tumor diameter, tumor number, elevated serum gamma-glutamyl transpeptidase (GGT) level, microvascular invasion (MVI), and macrovascular invasion were independent risk factors of prognosis of NBNC-HCC. C-indexes of the nomogram were 0.702 (95% confidence interval [CI], 0.662-0.741) in the training cohort and 0.700 (95% CI, 0.643-0.758) in the validation cohort, and median tdAUC values of the nomogram were 0.743 (range, 0.736-0.775) in the training cohort and 0.751 (range, 0.686-0.793) in the validation cohort, which were both higher than those in the conventionally used Barcelona Clinic Liver Cancer staging system, American Joint Committee on Cancer, and eighth edition and the model of Zhang et al. The calibration plot depicted a good consistency between prediction of the model and observed outcome. The Kaplan-Meier curve analysis showed that the model was able to separate patients into three distinct risk subgroups. The DCA analysis also demonstrated that the nomogram was clinically useful. Conclusion: We developed and validated a nomogram that was accurate and clinically useful in patients with NBNC-HCC who underwent hepatectomy.

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“…Although we found that MVI does not influence patient outcome after LDLT [ 1 ], 77.8% of patients with HCC recurrence presented with distant metastasis, of which 66.7% were associated with MVI in the explanted liver ( Table 1 ). Given that circulation biomarkers have been previously identified from peripheral blood, it is likely that MVI influences recurrence after LDLT [ 25 – 26 ]. A recent study showed that higher VEGF plasma levels before liver transplantation may influence HCC recurrence [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Repeated-Measures Implication of Hepatocellular Carcinoma Biomarkers in Living Donor Liver Transplantation

et al. 2015

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ObjectiveHepatocellular carcinoma (HCC) and its recurrence are major problems in living donor liver transplantation (LDLT). Several biomarkers have been used to investigate this event. We conducted a prospective controlled study to determine the activities of the basic fibroblast growth factor (FGF-2), survivin, Ki67, endostatin, and vascular endothelial growth factor (VEGF) in different conditions before, early after, and late after LDLT with and without HCC recurrence.MethodsFifty patients with virus-related HCC who underwent LDLT were enrolled in this 2-year cross-sectional study. During the study period, recurrent HCC was identified in 9 patients (study group, n = 9) and 41 patients (control group, n = 41) had no recurrence after LDLT. The mean time to HCC recurrence was 587.11 ± 398.64 days (range, 90–1352 days). Microvascular invasion (MVI) was found in 66.7% (6/9) of the recipients, as determined on pathological examination. The serum biomarkers were investigated by using enzyme-linked immunosorbent assay at the different LDLT stages.ResultsThe serum levels of the biomarkers significantly correlated with LDLT and HCC recurrence in the repeated-measures analysis (F = 31.676, P = 0.000). Significant differences were observed in the effects of all biomarkers (F = 85.313, P = 0.000) and the time to HCC recurrence after LDLT (F = 3.178, P = 0.046). The biomarkers, ordered by the observed power of the test for HCC recurrence after LDLT, were FGF-2 (1.000) > survivin (0.999) > Ki67 (0.949) > endostatin (0.411) > VEGF (0.305).ConclusionsDifferent biomarker activities may be implicated in the pathogenesis of HCC recurrence after LDLT. Oncogenes may not exist in the new graft but may still be present in the peripheral blood. The timing of HCC recurrence and impact of MVI in the explanted liver requires confirmation in larger studies with a longer follow-up.

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Impact of Hepatic Steatosis on Disease-Free Survival in Patients with Non-B Non-C Hepatocellular Carcinoma Undergoing Hepatic Resection

Abstract: The prognosis of NBNC HCC was similar to that of BC HCC. Among NBNC HCC patients, NAFLD-associated HCC patients had a relatively low recurrence risk. Absence of steatosis in hepatic parenchyma had a significant impact on disease-free survival in NBNC HCC patients.

Cited by 20 publications

References 34 publications

Actual 10-Year Survivors After Resection of Hepatocellular Carcinoma

Actual 10-Year Survivors After Resection of Hepatocellular Carcinoma

<p>Development and Validation of a Prognostic Nomogram to Predict the Long-Time Prognosis in Non-B, Non-C Hepatocellular Carcinoma</p>

Repeated-Measures Implication of Hepatocellular Carcinoma Biomarkers in Living Donor Liver Transplantation

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