• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5995-6000
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• 2013

Background: Nausea and vomiting after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) are common in clinical practice, but few studies have reported the incidence and risk factors of such events. Objective: The purpose of this study was to analyze the incidence and risk factors of nausea and vomiting after TACE for HCC. Methods: This study was a single-center retrospective analysis of a prospectively maintained database. Between May 2010 and October 2012, 150 patients with HCC were analyzed for incidence and preprocedural risk factors. Results: The incidence of postembolization nausea and vomiting was 38.8% and 20.9%, respectively, in patients with HCC. Patients who developed nausea had lower levels (<100 IU/L) of serum alkaline phosphatase (ALP) compared to those without nausea ($123.04{\pm}69.38$ vs. $167.41{\pm}138.95$, respectively, p=0.044). Female gender correlated to a higher incidence of nausea as well (p=0.024). Patients who developed vomiting, compared to those who did not, also had lower levels (<100 IU/L) of serum ALP ($112.52{\pm}62.63$ vs. $160.10{\pm}127.80$, respectively, p=0.010), and serum alanine transferase (ALT) ($35.61{\pm}22.87$ vs. $4.97{\pm}29.62$, respectively, p=0.045). There were no statistical significances in the incidences of nausea and vomiting between male patients over 50 years old and female patients who have entered menopause (p=0.051 and p=0.409, respectively). Multivariate analysis by logistic regression analysis demonstrated that female gender and ALP>100 IU/L were the most independent predictive factors of postembolization nausea (odds ratio (OR): 3.271, 95% CI: 1.176-9.103, p=0.023 and OR: 0.447, 95% CI: 0.216-0.927, p=0.030, respectively). ALP>100 IU/L was also the most independent predictive risk factor of postembolization vomiting (OR: 0.389, 95% CI: 0.159-0.952, p=0.039). Conclusions: Postembolizaiton nausea and vomiting are common in patients with HCC. Recognition of the risk factors presented above before TACE is important for early detection and proper management of postembolization nausea and vomiting. Nevertheless, future studies are required.

• Investigative Magnetic Resonance Imaging
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• v.17 no.1
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• pp.8-18
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• 2013

Purpose : The purpose of this study was to find and categorize the various magnetic resonance imaging (MRI) findings of spinal metastases that correlate with the type of primary cancer. Materials and Methods: We retrospectively reviewed gadolinium-enhanced magnetic resonance images of 30 patients with 169 spinal metastatic lesions from lung cancer (n = 56), breast cancer (n = 29), colorectal cancer (n = 20), hepatocellular carcinoma (HCC) (n = 17), and stomach cancer (n = 47). The size, location, extent of invasion, signal intensity, margin, enhancement pattern, and osteoblastic or osteolytic characteristics of each metastatic tumor were analyzed. Results: The metastatic lesions from HCC were larger than those from the other primary tumors (P < 0.05) except for colorectal cancer (P = 0.268). Well-defined metastatic tumor margins were more frequently seen in lung cancer and breast cancer (P < 0.01). All but HCC showed a tendency to invade the vertebral body rather than the posterior elements (P < 0.02). Colorectal cancer and HCC showed a tendency toward extraosseous invasion without statistical significance. HCC showed a characteristic enhancement pattern of 'worms-in-a-bag'. Rim enhancement with a sclerotic center was only seen in spinal metastases from stomach cancer. Conclusion: Despite many overlapping imaging features, spinal metastases of various primary tumors display some characteristic MRI findings that can help identify the primary cancer.

• Korean Journal of Radiology
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• v.22 no.2
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• pp.213-224
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• 2021

Objective: Clinical outcomes of patients who undergo transarterial chemoembolization (TACE) for single small hepatocellular carcinoma (HCC) are not consistent, and may differ based on certain imaging findings. This retrospective study was aimed at determining the efficacy of pre-TACE CT or MR imaging findings in predicting survival outcomes in patients with small HCC upon being treated with TACE. Besides, the study proposed to build a risk prediction model for these patients. Materials and Methods: Altogether, 750 patients with functionally good hepatic reserve who received TACE as the first-line treatment for single small HCC between 2004 and 2014 were included in the study. These patients were randomly assigned into training (n = 525) and validation (n = 225) sets. Results: According to the results of a multivariable Cox analysis, three pre-TACE imaging findings (tumor margin, tumor location, enhancement pattern) and two clinical factors (age, serum albumin level) were selected and scored to create predictive models for overall, local tumor progression (LTP)-free, and progression-free survival in the training set. The median overall survival time in the validation set were 137.5 months, 76.1 months, and 44.0 months for low-, intermediate-, and high-risk groups, respectively (p < 0.001). Time-dependent receiver operating characteristic curves of the predictive models for overall, LTP-free, and progression-free survival applied to the validation cohort showed acceptable areas under the curve values (0.734, 0.802, and 0.775 for overall survival; 0.738, 0.789, and 0.791 for LTP-free survival; and 0.671, 0.733, and 0.694 for progression-free survival at 3, 5, and 10 years, respectively). Conclusion: Pre-TACE CT or MR imaging findings could predict survival outcomes in patients with small HCC upon treatment with TACE. Our predictive models including three imaging predictors could be helpful in prognostication, identification, and selection of suitable candidates for TACE in patients with single small HCC.

• Journal of the Korean Society of Radiology
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• v.82 no.5
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• pp.1218-1230
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• 2021

Purpose To compare the per-patient diagnostic performance of simulated abbreviated MRI (AMRI) to that of conventional MRI (CMRI) with full-sequence dynamic gadoxetic acid (GA) enhancement for early-stage hepatocellular carcinoma (HCC) screening in high-risk patients. Materials and Methods A total of 201 consecutive patients at high-risk for HCC, who underwent 3T liver MRI, were included in this retrospective study. The AMRI protocol comprised T2-weighted imaging, hepatobiliary phase imaging after GA injection, and diffusion-weighted imaging. For each patient, two AMRI and CMRI image sets were independently reviewed by two radiologists. Inter-reader agreement was assessed using Cohen's kappa value. A composite reference standard was used to determine the diagnostic performance of each image set for each reader. Results A total of 93 HCCs were detected in 79 patients. The inter-reader agreement was almost perfect for both image sets (κ = 0.839, 0.948). In AMRI, the per-patient sensitivity and negative predictive values (NPV) were 94.9% and 96.4%, respectively. In CMRI, the per-patient sensitivity and NPV were 96.2% and 97.5%, respectively. Conclusion AMRI, using only three sequences, had a comparable diagnostic performance to CMRI in screening early-stage HCC. AMRI could be an alternative HCC screening tool for high-risk HCC patients.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.28 no.2
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• pp.134-143
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• 2024

Backgrounds/Aims: The hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is classified as the advanced stage (BCLC stage C) with extremely poor prognosis, and in current guidelines is recommended for systemic therapy. This study aimed to evaluate the surgical outcomes and long-term prognosis after hepatic resection (HR) for patients who have HCC combined with PVTT. Methods: We retrospectively analyzed 332 patients who underwent HR for HCC with PVTT at ten tertiary referral hospitals in South Korea. Results: The median overall and recurrence-free survival after HR were 32.4 and 8.6 months, while the 1-, 3-, and 5-year overall survival rates were 75%, 48%, and 39%, respectively. In multivariate analysis, tumor number, tumor size, AFP, PIVKA-II, neutrophil-to-lymphocyte ratio, and albumin-bilirubin (ALBI) grade were significant prognostic factors. The risk scoring was developed using these seven factors-tumor, inflammation and hepatic function (TIF), to predict patient prognosis. The prognosis of the patients was well stratified according to the scores (log-rank test, p < 0.001). Conclusions: HR for patients who have HCC combined with PVTT provided favorable survival outcomes. The risk scoring was useful in predicting prognosis, and determining the appropriate treatment strategy for those patients who have HCC with PVTT.

• BMB Reports
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• v.52 no.8
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• pp.520-525
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• 2019

Dihydroartemisinin (DHA) has been reported to possess anti-cancer activity against many cancers. However, the pharmacologic effect of DHA on HBV-positive hepatocellular carcinoma (HCC) remains unknown. Thus, the objective of the present study was to determine whether DHA could inhibit the proliferation of HepG2.2.15 cells and uncover the underlying mechanisms involved in the effect of DHA on HepG2.2.15 cells. We found that DHA effectively inhibited HepG2.2.15 HCC cell proliferation both in vivo and in vitro. DHA also reduced the migration and tumorigenicity capacity of HepG2.2.15 cells. Regarding the underlying mechanisms, results showed that DHA induced cellular senescence by up-regulating expression levels of proteins such as p-ATM, p-ATR, ${\gamma}-H_2AX$, P53, and P21 involved in DNA damage response. DHA also induced autophagy (green LC3 puncta gathered together and LC3II/LC3I ratio increased through AKT-mTOR pathway suppression). Results also revealed that DHA-induced autophagy was not linked to senescence or cell death. TPP1 (telomere shelterin) overexpression could not rescue DHA-induced anticancer activity (cell proliferation). Moreover, DHA down-regulated TPP1 expression. Gene knockdown of TPP1 caused similar phenotypes and mechanisms as DHA induced phenotypes and mechanisms in HepG2.2.15 cells. These results demonstrate that DHA might inhibit HepG2.2.15 cells proliferation through inducing cellular senescence and autophagy.

• Journal of Korean Neurosurgical Society
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• v.62 no.4
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• pp.467-475
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• 2019

Objective : There is a lack of knowledge regarding whether decompression is necessary in treating patients with epidural spinal cord compression (ESCC) grade 2. The purpose of this study was to compare the outcomes of minimally invasive surgery (MIS) without decompression and conventional open surgery (palliative laminectomy) for patients with hepatocellular carcinoma (HCC) spinal metastasis of ESCC grade 2. Methods : Patients with HCC spinal metastasis requiring surgery were retrospectively reviewed. Patients with ESCC grade 2, medically intractable mechanical back pain, a Nurick grade better than 3, 3-6 months of life expectancy, Tomita score ${\geq}5$, and Spinal Instability Neoplastic Score ${\geq}7$ were included. Patients with neurological deficits, other systemic illnesses and less than 1 month of life expectancy were excluded. Thirty patients were included in the study, including 17 in the open surgery group (until 2008) and 13 in the MIS group (since 2009). Results : The MIS group had a significantly shorter operative time ($94.2{\pm}48.2minutes$ vs. $162.9{\pm}52.3minutes$, p=0.001), less blood loss ($140.0{\pm}182.9mL$ vs. $1534.4{\pm}1484.2mL$, p=0.002), and less post-operative intensive care unit transfer (one patient vs. eight patients, p=0.042) than the open surgery group. The visual analogue scale for back pain at 3 months post-operation was significantly improved in the MIS group than in the open surgery group ($3.0{\pm}1.2$ vs. $4.3{\pm}1.2$, p=0.042). The MIS group had longer ambulation time ($183{\pm}33days$ vs. $166{\pm}36days$) and survival time ($216{\pm}38days$ vs. $204{\pm}43days$) than the open surgery group without significant difference (p=0.814 and 0.959, respectively). Conclusion : MIS without decompression would be a good choice for patients with HCC spinal metastasis of ESCC grade 2, especially those with limited prognosis, mechanical instability and no neurologic deficit.

• YAKHAK HOEJI
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• v.55 no.1
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• pp.75-79
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• 2011

The replication competent adenoviral vector (AV), AdLPCDIRESE1A was generated and reported previously to have cytotoxic effects in some cell lines. In AdLPCDIRESE1A, the expression of cytosine deaminse (CD) and E1A genes are under the control of tumor-specific L-plastin promoter. CD enzyme can deaminate the nontoxic prodrug 5-fluorocytosine (5-FC) to the toxic 5-fluorouracil (5-FU). E1A gene is essential for viral replication. Primary liver cancer, most of which is hepatocellular carcinoma (HCC), is the third common leading cancer in Korea. Thus, we have conducted in vitro preclinical study to evaluate effectiveness of AdLPCDIRESE1A on HCC. The efficacy of cytotoxicity was measured by generation of cytopathic effect (CPE) and cell counting. We infected HepG2 cells with various MOI of vector alone or concurrent with 5-FC. Exposure of cells to AdLPCDIRESE1A generated a significant cytotoxic effect as compared to the control. Almost 83% of the cell had manifested the characteristic cytotoxic effect on day 9 after infection of cells with 10 MOI of vector. We also observed the additive cytotoxic effects when AdLPCDIRESE1A vector had been coadministrated with 5-FC. The results suggest that the use of AdLPCDIRESE1A/5FC may be value in treatment of liver cancer. Further animal studies are needed for clinical trial.

• Microbiology and Biotechnology Letters
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• v.49 no.4
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• pp.594-602
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• 2021

The NLRP3 (nucleotide-binding domain, leucine-rich repeat family pyrin domain containing 3) inflammasome plays an important role in the initiation of inflammatory responses, through the recognition of pathogen-associated molecular patterns and tumor progression, including tumor growth and metastasis. In this study, we examined the effects of defective NLRP3 on the growth, migration, and invasiveness of hepatocellular carcinoma (HCC) SK-Hep1 cell. First, HCC SK-Hep1 cells were transfected with human NLRP3 targeting LentiCRISPRv2 vector using the CRISPR-Cas9 system, and NLRP3 deficiency was confirmed by RT-qPCR and western blotting. NLRP3 deficient SK-Hep1 cells showed delayed cell growth and decreased protein expression of PI3K, p-AKT, and pNF-κB when compared to NLRP3 complete SK-Hep1 cells. In addition, NLRP3 deficiency arrested the cell cycle at G1 phase through an increase in p21 and a reduction in CDK6. NLRP3 deficient SK-Hep1 cells also showed significantly delayed cell migration, invasion, and wound healing. The expression of epithelial-mesenchymal transition signaling molecules, such as N-cadherin and MMP-9, was found to be dramatically decreased in NLRP3 deficient SK-Hep1 cells compared to NLRP3 complete SK-Hep1 cells.

• Radiation Oncology Journal
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• v.33 no.3
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• pp.179-187
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• 2015

Purpose: The purpose of this study was to investigate the predictable value of pretreatment $^{18}F$-fluorodeoxyglucose positron emission tomography-computed tomography ($^{18}F$-FDG PET-CT) in radiotherapy (RT) for patients with hepatocellular carcinoma (HCC) or portal vein tumor thrombosis (PVTT). Materials and Methods: We conducted a retrospective analysis of 36 stage I-IV HCC patients treated with RT. $^{18}F$-FDG PET-CT was performed before RT. Treatment target was determined HCC or PVTT lesions by treatment aim. They were irradiated at a median prescription dose of 50 Gy. The response was evaluated within 3 months after completion of RT using the Response Evaluation Criteria in Solid Tumors (RECIST). Response rate, overall survival (OS), and the pattern of failure (POF) were analyzed. Results: The response rate was 61.1%. The statistically significant prognostic factor affecting response in RT field was maximal standardized uptake value (maxSUV) only. The high SUV group (maxSUV ${\geq}5.1$) showed the better radiologic response than the low SUV group (maxSUV < 5.1). The median OS were 996.0 days in definitive group and 144.0 days in palliative group. Factors affecting OS were the %reduction of alpha-fetoprotein (AFP) level in the definitive group and Child-Pugh class in the palliative group. To predict the POF, maxSUV based on the cutoff value of 5.1 was the only significant factor in distant metastasis group. Conclusion: The results of this study suggest that the maxSUV of $^{18}F$-FDG PET-CT may be a prognostic factor for treatment outcome and the POF after RT. A %reduction of AFP level and Child-Pugh class could be used to predict OS in HCC.