Hepatocellular Carcinoma with Bone Metastases: Incidence, Prognostic Significance, and Management—Single-Center Experience

Bhatia, Ruchi; Ravulapati, Sravanthi; Befeler, Alex S.; Dombrowski, John; Gadani, Sameer; Poddar, Nishant

doi:10.1007/s12029-017-9998-6

Cited by 40 publications

(34 citation statements)

References 18 publications

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“…However, the morbidity and mortality of HCC were still high. Widespread metastases remain to be a major challenge for HCC therapy and contributed to the poor prognosis of HCC [2,3]. Therefore, identifying novel regulators related to HCC tumorigenesis, progression and metastasis is still an urgent need.…”

Section: Introductionmentioning

confidence: 99%

Exosomal circRNA-100338 promotes hepatocellular carcinoma metastasis via enhancing invasiveness and angiogenesis

Huang

et al. 2020

J Exp Clin Cancer Res

285

198

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Background: Exosomes play crucial roles in regulating the crosstalk between normal and cancer cells in the tumor microenvironment, and in regulating cancer proliferation, migration and invasion through their cargo molecules. Methods: We analyzed the pro-invasiveness of exosomal circRNA-100,338 in HCC using the transwell invasion assay. The co-culture of human umbilical vein endothelial cells (HUVEC) and exosomes derived from HCC cell lines were used to evaluate the impact of HCC derived exosomes on HUVEC. Nude mice models were used to validate the findings in vitro. Clinically, quantitative RT-PCR was used to quantify the expression of serum exosomal circRNA-100,338 in HCC patients at both pre-surgery within one week and post-surgery within three weeks. Results: We aim to investigate the pro-invasive role of exosomal circRNA-100,338 in HCC metastasis. We for the first time demonstrated that circRNA-100,338 was highly expressed in both highly metastatic HCC cells and their secreted exosomes. The transwell invasion assay showed that the overexpression or knockdown of exosomal circRNA-100,338 significantly enhanced or reduced the invasive abilities of HCC cells. Subsequently, in vitro and in vivo assays showed that exosomal circRNA-100,338 affected the cell proliferation, angiogenesis, permeability, and vasculogenic mimicry (VM) formation ability of human umbilical vein endothelial cells (HUVEC), and tumor metastasis. Furthermore, we also observed that the persistent high expression of exosomal circRNA-100,338 in serum of HCC patients who underwent curative hepatectomy may be a risk indicator of pulmonary metastasis and poor survival. Conclusions: Our findings indicated that metastatic ability of HCC cells could be enhanced by transferring exosomal circRNA-100,338 to recipient HUVECs, which could affect proangiogenic activity by regulating angiogenesis.

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Section: Introductionmentioning

confidence: 99%

Exosomal circRNA-100338 promotes hepatocellular carcinoma metastasis via enhancing invasiveness and angiogenesis

Huang

et al. 2020

J Exp Clin Cancer Res

285

198

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“…From our 10-year study, only 6% of patients with HCC were found to have spinal metastases with a median survival time of 79 days, which was relatively short compared with that of other common metastatic tumors to the spine such as lung cancer (11.3 months) [12], breast cancer (21.7 months) [13], prostate cancer (58.3 months for hormone naïve and 5 months for hormone refractory [14,15]), thyroid cancer (15.4 months) [16], and cholangiocarcinoma (3 months) [17]. In comparison with other reports on the survival of patients with HCC-derived spinal metastasis [6,18,19], the median survival time after metastasis was also shorter in our study. This could be explained by the lower rate of primary surgical resection and higher rate of palliative treatment and best supportive care in our study.…”

Section: Discussionmentioning

confidence: 88%

Natural disease progression and novel survival prediction model for hepatocellular carcinoma with spinal metastases: a 10-year single-center study

et al. 2020

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Background: Individual prediction of life expectancy in patients with spinal metastases from hepatocellular carcinoma (HCC) is key for optimal treatment selection, especially when identifying potential candidates for surgery. Most reported prognostic tools provide categorical predictions, and only a few include HCC-related factors. This study aimed to investigate the natural progression of the disease and develop a prognostic tool that is capable of providing individualized predictions. Methods: Patients with HCC-derived metastatic spinal disease were identified from a retrospective cohort of patients with spinal metastases who were diagnosed at Chiang Mai University Hospital between 2006 and 2015. Kaplain-Meier methods and log-rank tests were used to statistically evaluate potential factors. Significant predictors from the univariable analysis were included in the flexible parametric survival regression for the development of a prognostic prediction model. Results: Of the 1143 patients diagnosed with HCC, 69 (6%) had spinal metastases. The median survival time of patients with HCC after spinal metastases was 79 days. In the multivariable analysis, a total of 11 potential clinical predictors were included. After backward elimination, four final predictors remained: patients aged > 60 years, Karnofsky Performance Status, total bilirubin level, and multifocality of HCC. The model showed an acceptable discrimination at C-statistics 0.73 (95% confidence interval 0.68-0.79) and fair calibration. Conclusion: Four clinical parameters were used in the development of the individual survival prediction model for patients with HCC-derived spinal metastases of Chiang Mai University or HCC-SM CMU model. Prospective external validation studies in a larger population are required prior to the clinical implication of the model.

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“…From our 10year study, only six percent of patients with HCC were found to have spinal metastases with a median survival time of 79 days, which was relatively short compared with that of other common metastatic tumor to the spine such as lung cancer (11.3 months) [12], breast cancer (21.7 months) [13], prostate cancer (58.3 months for hormone naïve and 5 months for hormone refractory [14,15]), thyroid cancer (15.4 months) [16], and cholangiocarcinoma (3 months) [17]. In comparison with other reports on the survival of patients with HCC-derived spinal metastasis [6,18,19], the median survival time after metastasis was also shorter in our study. This could be explained by the lower rate of primary surgical resection and higher rate of palliative treatment and best supportive care in our study.…”

Section: Discussionmentioning

confidence: 89%

Natural disease progression and novel survival prediction model for hepatocellular carcinoma with spinal metastases: a 10-year single-center study

Phinyo

Boonyanaruthee

Paholpak

et al. 2020

Preprint

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Background: Individual prediction of life expectancy in patients with spinal metastases from hepatocellular carcinoma (HCC) is key for optimal treatment selection, especially when identifying potential candidates for surgery. Most reported prognostic tools provide categorical predictions, and only a few include HCC-related factors. This study aimed to investigate the natural progression of the disease and develop a prognostic tool that is capable of providing individualized predictions.Methods: Patients with HCC-derived metastatic spinal disease were identified from a retrospective cohort of patients with spinal metastases who were diagnosed at Chiang Mai University Hospital between 2006 and 2015. Kaplain–Meier methods and log-rank tests were used to statistically evaluate potential factors. Significant predictors from univariable analysis were included in the flexible parametric survival regression for the development of a prognostic prediction model. Results: Of the 1,143 patients diagnosed with HCC, 69 (6%) had spinal metastases. The median survival time of patients with HCC after spinal metastases was 79 days. In the multivariable analysis, a total of 11 potential clinical predictors were included. After backward elimination, four final predictors remained: patients aged > 60 years, Karnofsky Performance Status, total bilirubin level, and multifocality of HCC. The model showed acceptable discrimination at C-statistics 0.73 (95% Confidence interval 0.68–0.79) and fair calibration. Conclusion: Four clinical parameters were used in the development of the individual survival prediction model for patients with HCC-derived spinal metastases of Chiang Mai University or HCC-SM CMU model. Prospective external validation studies in a larger population are required prior to the clinical implication of the model.

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Hepatocellular Carcinoma with Bone Metastases: Incidence, Prognostic Significance, and Management—Single-Center Experience

Abstract: Bone metastases in HCC are very rare and aggressive. Due to its rarity, optimal treatment strategies are not well defined. Early diagnosis is important for optimal therapy and improved survival.

Cited by 40 publications

References 18 publications

Exosomal circRNA-100338 promotes hepatocellular carcinoma metastasis via enhancing invasiveness and angiogenesis

Exosomal circRNA-100338 promotes hepatocellular carcinoma metastasis via enhancing invasiveness and angiogenesis

Natural disease progression and novel survival prediction model for hepatocellular carcinoma with spinal metastases: a 10-year single-center study

Natural disease progression and novel survival prediction model for hepatocellular carcinoma with spinal metastases: a 10-year single-center study

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