• Investigative Magnetic Resonance Imaging
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• 제23권4호
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• pp.351-360
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• 2019

Purpose: To investigate noninvasive biomarkers for predicting treatment response in patients with locally advanced HCC who underwent concurrent chemoradiotherapy (CCRTx). Materials and Methods: Thirty patients (55.5 ± 10.2 years old, M:F = 24:6) who underwent CCRTx due to advanced HCC were enrolled. Contrast-enhanced US (CEUS) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) were obtained before and immediately after CCRTx. The third CEUS was obtained at one month after CCRTx was completed. Response was assessed at three months after CCRTx based on RECIST 1.1. Quantitative imaging biomarkers measured with CEUS and MRI were compared between groups. A cutoff value was calculated with ROC analysis. Overall survival (OS) was compared by the Breslow method. Results: Twenty-five patients were categorized into the non-progression group and five patients were categorized into the progression group. Peak enhancement of the first CEUS before CCRTx (PE1) was significantly lower in the non-progression group (median, 18.6%; IQR, 20.9%) than that in the progression group (median, 59.1%; IQR, 13.5%; P = 0.002). There was no significant difference in other quantitative biomarkers between the two groups. On ROC analysis, with a cutoff value of 42.6% in PE1, the non-progression group was diagnosed with a sensitivity of 90.9% and a specificity of 100%. OS was also significantly longer in patients with PE1 < 42.6% (P = 0.014). Conclusion: Early treatment response and OS could be predicted by PE on CEUS before CCRTx in patients with HCC.

• Radiation Oncology Journal
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• 제33권1호
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• pp.36-41
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• 2015

Purpose: To evaluate the incidence and risk factors of post-treatment intracranial hemorrhage of brain metastases from hepatocellular carcinoma (HCC). Materials and Methods: Medical records of 81 patients who have been diagnosed of brain metastases from HCC and underwent surgery, radiosurgery and/or whole brain radiotherapy (WBRT) between January 2000 and December 2013 were retrospectively reviewed. Results: Intracranial hemorrhage was present in 64 patients (79%) at the time of diagnosis. Median value of alpha-fetoprotein (AFP) level was 1,700 ng/mL. The Eastern Cooperative Oncology Group (ECOG) performance status for 20 patients was greater than 2. Fifty-seven patients underwent WBRT and the others were treated with surgery and/or radiosurgery without WBRT. During follow-up, 12 events of intracranial hemorrhage after treatment were identified. Three-month post-treatment hemorrhage rate was 16.1%. Multivariate analyses revealed that ECOG performance status, AFP, and WBRT were associated with post-treatment hemorrhage (p = 0.013, 0.013, and 0.003, respectively). Kaplan-Meier analysis showed that 3-month post-treatment hemorrhage rate of new lesion was higher in patients treated without WBRT, although statistical significance was not reached. (18.6% vs. 4.6%; p = 0.104). Ten of 12 patients with post-treatment hemorrhage died with neurologic cause. Conclusion: WBRT should be considered to prevent post-treatment hemorrhage in the treatment of brain metastases from HCC.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6257-6261
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• 2012

Objective: To investigate the safety and efficacy of transcatheter arterial chemoembolization (TACE), combined with portal vein embolization (PVE), and high intensity focused ultrasound (HIFU) sequential therapy in treating patients with hepatocellular carcinoma (HCC). Methods: Patients with inoperative HCC were treated by two methods: in the study group with TACE first, then PVE a week later, and then TACE+PVE every two months as a cycle, after 2~3 cycles finally HIFU was given; in the control group only TACE+PVE was given. Response (CR+PR), and disease control rate (CR+PR+SD), side effects, overall survival and time to progress were calculated. Results: Main side effects of both groups were nausea and vomiting. No treatment related death occurred. In the study group, 32 patients received TACE for overall 67 times, PVE 64 times, and HIFU 99 times; on average 2.1, 2 and 3.1 times for each patient, respectively. In the control group, 36 patients were given TACE 78 times and PVE 74 times, averaging 2.2 and 2.1 times per patient. Effective rate: 25.0% in study group and 8.3% in control group (p>0.05). Disease control rates were 71.9% and 44.4%, respectively (p<0.05). In patients with portal vein tumor thrombus, the rate reduced over 1/2 after treatment was 69.2%(9/13) in the study and 21.4%(3/14) in the control group (p<0.05). Rate of AFP reversion or decrease over 1/2 was 66.7%(16/24) in study and 37%(10/27) (p<0.05) in control group. Median survival time: 16 months in study and 10 months in control group. PFS was 7months in study and 3 months in control group. Log-rank test suggested that statistically significant difference exists between two groups (p=0.024). 1-, 2- and 3-year survival rates were 56.3%, 18.8% and 9.3% in study, while 30.6%, 5.6% and 0 in control group, respectively, with statistically significant difference between two groups (by Log-rank, p = 0.014). Conclusions: The treatment of TACE+PVE+HIFU sequential therapy for HCC increases response rate, prolong survival, and could thus be a safe and effective treatment for advanced cases.

• 한국간담췌외과학회지
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• 제26권1호
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• pp.58-68
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• 2022

Backgrounds/Aims: Mechanisms for the development of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected patients remain unclear. The aim of the present study was to identify genes and pathways involved in the development of HBV-associated HCC. Methods: The GSE121248 gene dataset, which included 70 HCCs and 37 adjacent liver tissues, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) in HCCs and adjacent liver tissues were identified. Gene ontology and Kyoto Encyclopedia of Genes and Genome pathway enrichment analyses were then performed. Results: Of 134 DEGs identified, 34 were up-regulated and 100 were down-regulated in HCCs. The 34 up-regulated DEGs were mainly involved in nuclear division, organelle fission, spindle and midbody formation, histone kinase activity, and p53 signaling pathway, whereas the 100 down-regulated DEGs were involved in steroid and hormone metabolism, collagen-coated extracellular matrix, oxidoreductase activity, and activity on paired donors, including incorporation or reduction of molecular oxygen, monooxygenase activity, and retinol metabolism. Analyses of protein-protein interaction networks with a high degree of connectivity identified significant modules containing 14 hub genes, including ANLN, ASPM, BUB1B, CCNB1, CDK1, CDKN3, ECT2, HMMR, NEK2, PBK, PRC1, RACGAP1, RRM2, and TOP2A, which were mainly associated with nuclear division, organelle fission, spindle formation, protein serine/threonine kinase activity, p53 signaling pathway, and cell cycle. Conclusions: This study identified key genes and carcinogenic pathways that play essential roles in the development of HBV-associated HCC. This may provide important information for the development of diagnostic and therapeutic targets for HCC.

• Radiation Oncology Journal
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• 제28권2호
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• pp.85-90
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• 2010

목 적: 크기가 작은 5 cm 미만의 재발성 간세포암 환자를 대상으로 소분할 방사선치료 후 종양의 반응, 국소제어율 및 소분할 방사선치료와 연관된 부작용을 평가하였다. 대상 및 방법: 2006년부터 2007년까지 국소요법으로 치료한 후 재발한 간세포암 환자 중 구제치료로 소분할 방사선치료를 받은 12명의 환자를 대상으로 후향적 분석을 시행하였다. 소분할 방사선치료의 적용기준은 종양의 크기가 5 cm 미만이고, 중요 정상조직에 인접하지 않으면서, 간세포암에 의한 간문맥 종양 혈전증이 없으며, 처방된 방사선량의 50%가 조사되는 정상 간 용적이 15% 미만인 경우로 제한하였다. 소분할 방사선치료의 1회 조사량은 5 Gy였고, 주 5회 치료하여 2주 동안 총 50 Gy를 조사하였다. 종양의 반응도는 방사선치료 종료 후 3개월에 시행된 간 컴퓨터단층촬영으로 평가하였다. 치료와 연관된 부작용은 Common Terminology Criteria for Adverse Events version 3.0으로 평가하였다. 방사선치료 종료 후 추적관찰기간은 8~33개월(중앙값 18개월)이었다. 결 과: 방사선치료 후 3개월에 시행한 간 컴퓨터단층촬영에서 완전관해율은 41.7%였고 추적관찰기간에 확인한 전체 완전관해율은 58.3%였다. 방사선치료 부위 내 국소제어율은 83.3%였다. 두 명을 제외한 모든 환자에서 간 내 재발이 발생하였다. 전체 환자의 1년 및 2년 생존율은 각각 90.0%, 67.5%였다. 치료와 연관된 부작용은 3명의 환자가 치료 중 1도의 오심, 식욕부진이 발생하였고 방사선치료 종료 후 복수가 진행한 환자가 1명 있었다. 3도 이상의 중대한 부작용은 없었다. 결 론: 작은 크기의 재발성 간세포암의 구제 치료로서 소분할 방사선치료는 58.3%의 완전관해율과 83.3%의 국소 제어율을 보여주었다. 소분할 방사선치료로 5 Gy씩 총 50 Gy를 조사하는 것은 치료와 연관된 심각한 독성 없이 비교적 안전하고 효과적인 방법으로 판단된다.

• Radiation Oncology Journal
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• 제32권1호
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• pp.14-22
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• 2014

Purpose: To evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) followed by radiotherapy (RT) in treatment-na$\ddot{i}$ve patients with locally advanced hepatocellular carcinoma (HCC). Materials and Methods: Eligibility criteria were as follows: newly diagnosed with HCC, the Barcelona Clinic Liver Cancer stage C, Child-Pugh class A or B, and no prior treatment for HCC. Patients with extrahepatic spread were excluded. A total of 59 patients were retrospectively enrolled. All patients were treated with TACE followed by RT. The time interval between TACE and RT was 2 weeks as per protocol. A median RT dose was 47.25 $Gy_{10}$ as the biologically effective dose using the ${\alpha}/{\beta}$ = 10 (range, 39 to 65.25 $Gy_{10}$). Results: At 1 month, complete response was obtained in 3 patients (5%), partial response in 27 patients (46%), stable disease in 13 patients (22%), and progressive disease in 16 patients (27%). The actuarial one- and two-year OS rates were 60.1% and 47.2%, respectively. The median OS was 17 months (95% confidence interval, 5.6 to 28.4 months). The median time to progression was 4 months (range, 1 to 35 months). Grade 3 or greater liver enzyme elevation occurred in only two patients (3%) after RT. Grade 3 gastroduodenal toxicity developed in two patients (3%). Conclusion: The combination treatment of TACE followed by RT with two-week interval was safe and it showed favorable outcomes in treatment-na$\ddot{i}$ve patients with locally advanced HCC. A prospective randomized trial is needed to validate these results.

• Korean Journal of Radiology
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• 제22권2호
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• pp.179-188
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• 2021

Objective: This study aimed to prospectively compare the efficacy, safety, and mid-term outcomes of dual-switching monopolar (DSM) radiofrequency ablation (RFA) to those of conventional single-switching monopolar (SSM) RFA in the treatment of hepatocellular carcinoma (HCC). Materials and Methods: This single-center, two-arm, parallel-group, randomized controlled study was approved by the Institutional Review Board. Written informed consent was obtained from all patients upon enrollment. A total of 80 patients with 94 HCC nodules were randomized into either the DSM-RFA group or SSM-RFA group in a 1:1 ratio, using a blocked randomization method (block size 2). The primary endpoint was the minimum diameter of the ablation zone per unit time. The secondary endpoints included other technical parameters, complication rate, technique efficacy, and 2-year clinical outcomes. Results: Significantly higher ablation energy per unit time was delivered to the DSM-RFA group than to the SSM-RFA group (1.7 ± 0.2 kcal/min vs. 1.2 ± 0.3 kcal/min; p < 0.001). However, no significant differences were observed between the two groups for the analyzed variables, including primary endpoint, regarding size of the ablation zone and ablation time. Major complication rates were 4.9% in the DSM-RFA group and 2.6% in the SSM-RFA group (p = 1.000). The 2-year local tumor progression (LTP) rates of the HCC nodules treated using DSM-RFA and SSM-RFA were 8.5% and 4.7%, respectively (p = 0.316). The 2-year LTP-free survival rates of patients in the DSM-RFA and SSM-RFA groups were 90.0% and 94.4%, respectively (p = 0.331), and the 2-year recurrence-free survival rates were 54.9% and 75.7%, respectively (p = 0.265). Conclusion: Although DSM-RFA using a separable clustered electrode delivers higher ablation energy than SSM-RFA, its effectiveness failed to show superiority over SSM-RFA in the treatment of HCC.

• Radiation Oncology Journal
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• 제23권2호
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• pp.92-97
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• 2005

목적 : 원발성 간암에서 근치적 목적의 방사선치료 결과엔 대한 문헌상 보고는 드물다. 이에 저자들이 경험한 원발성 간암의 분할 정위방사선치료에 대한 결과를 보고하고자 하였다. 대상 및 방법 : 1999년 7월부터 2002년 3월까지 원발성 간암으로 조직학적 진단을 받은 후 분할 정위방사선치료를 시행한 20명을 대상으로 후향적 분석을 하였다. 종양의 장경은 $2~6.5\;cm$ (평균: 3.8 cm)였다. 분할 정위방사선치료는 1회 조사량으로 5와 10 Gy였고 선량은 계획용 표적체적(planning target volume)에 맞추어 처방하였으며 회전중심점 선량의 $85\~90\%$등선량 곡선에 치료를 하였다. 주 $3\~5$회 치료하여 2주 동안 총 50 Gy를 조사하였다(중앙선량: 50 Gy). 추적관찰기간은 $3\~55$개월(중간 추적관찰기간: 23개월)이었다. 결과 : 전체 치료 반응률은 $60\%$이었으며 완전 반응 4명($20\%$), 부분 반응 8명($40\%$), 안정성 병변이 8명($40\%$)이었다. 전체 환자의 1년 및 2년 생존율은 각각 $70\%$, $43.1\%$이었으며 중앙 생존기간은 20개월이었다. 1년 및 2년 무병 생존율은 각각 $65\%$, $32.5\%$이었으며 중앙 무병생존기간은 19개월이었다. 치료 부작용으로 소화장애가 16명($60\%$), 오심/구토가 8명($40\%$), 간 기능 저하가 6명($30\%$)에서 발생하였으나 부작용에 의한 사망은 없었다. 결론 : 원발성 간암의 분할 정위방사선치료는 비교적 안전하고 효과적인 방법이었다. 따라서 단일 병변이면서 비교적 종양의 크기가 작은 간암에서 내과적으로 수술이 불가능하거나 수술을 거부하는 환자에서 국소 치료방법으로 고려할 수 있을 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2923-2927
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• 2014

Background: Hepatocellular cancer (HCC) is one of the important health problems in Turkey, being very common and highly lethal. The aim of this study was to determine clinical, demographic features and risk factors. Materials and Methods: Nine hundred and sixth-three patients with HCC from 13 cities in Turkey were included in this study. Results: Only 205 (21%) of the 963 patients were women, with a male:female predominance of 4.8:1 and a median age of 61 years. The etiologic risk factors for HCC were hepatitis B in 555 patients (57.6%), 453 (81%) in men, and 102 (19%) in women, again with male predominance, hepatitis C in 159 (16.5%), (14.9% and 22.4%, with a higher incidence in women), and chronic alcohol abuse (more than ten years) in 137 (14.2%) (16.8% and 4.9%, higher in males). The Child-Pugh score paralleled with advanced disease stage amd also a high level of AFP. Conclusions: According to our findings the viral etiology (hepatitis B and hepatitis C infections) in the Turkish population was the most important factor in HCC development, with alcohol abuse as the third risk factor. The Child-Pugh classification and AFP levels were determined to be important prognostic factors in HCC patients.

• Molecular & Cellular Toxicology
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• 제5권3호
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• pp.193-197
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• 2009

Suppressors of cytokine signaling (SOCS) proteins were originally identified as negative feedback regulators of cytokine signaling and include the Janus kinase/Signal transducer and activator of transcription (JAK/STAT) pathways. Recent studies have shown that SOCS proteins negatively regulate the receptor tyrosine kinase (RTK) pathway including the insulin receptor (IR), EGFR, and KIT signaling pathways. In addition, SOCS1 and SOCS3 have been reported to have anti-tumor effects in human hepatocellular carcinoma (HCC). However, it is uncertain whether other members of the SOCS family are associated with tumor development and progression. In this study, to investigate whether SOCS6 is aberrantly regulated in HCC, we examined the expression level of SOCS6 in HCC by Western blot analysis and immunohistochemical staining. The results showed that SOCS6 was down-regulated in all examined HCCs compared to the corresponding normal tissues. In addition, expression of SOCS6 was observed in the cytoplasm of most normal and precancerous tissue, but not in the HCCs by immunohistochemical staining. This is first report to demonstrate that SOCS6 is aberrantly regulated in HCC. These findings suggest that underexpression of SOCS6 is involved in hepatocarcinogenesis, and SOCS6 may play a role, as a tumor suppressor, in HCC development and progression.