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1
Ma, Hui, Zhongchen Li, Jia Yuan, Lan Zhang, Xiaoying Xie, Xin Yin, Rongxin Chen, and Zhenggang Ren. "Extrapolating Prognostic Factors of Primary Curative Resection to Postresection Recurrences Hepatocellular Carcinoma Treatable by Radiofrequency Ablation." Gastroenterology Research and Practice 2021 (January 2, 2021): 1–7. http://dx.doi.org/10.1155/2021/8878417.
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Objective. Recurrence after curative resection for hepatocellular carcinoma (HCC) is a major cause of death from this disease. Factors of primary curative resection are available and potential in the prognosis of follow-up treatment. Our aim was to assess the prognostic significance of primary curative resection factors in recurrent HCC patients undergoing radiofrequency ablation therapy (RFA). Methods. In this retrospective study, we assessed 235 patients who underwent limited RFA of HCC recurrences ( tumors ≤ 5 cm ; nodules ≤ 3 ) after primary curative resection. Factors of primary curative resection were collected, and overall survival and recurrence-free survival were evaluated by the Kaplan-Meier method. Univariate and multivariate analyses were used to identify significant prognostic factors. Results. After a median follow-up of 36 months, 54 patients died, and 128 patients had hepatic recurrence. On univariate analyses, patients whose primary tumors were less differentiated ( p = 0.032 and p = 0.048 ) and required less time to recur ( p = 0.013 and p = 0.001 ) after curative resection displayed poorer overall survival and higher recurrence rates following RFA. On multivariate analyses, the pathologic tumor grade ( p = 0.026 and p = 0.038 ) and recurrence-free survival after primary curative resection ( p = 0.028 and p < 0.001 ) emerged as independent risk factors of survival and HCC recurrence. Conclusions. Primary tumor differentiation and time to recurrence after curative resection are viable prognostic factors of overall survival and further recurrence risk in patients undergoing RFA of recurrent HCC.
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Zhu, Yu, Lingling Gu, Ting Chen, Guoqun Zheng, Chao Ye, and Weidong Jia. "Factors influencing early recurrence of hepatocellular carcinoma after curative resection." Journal of International Medical Research 48, no. 8 (August 2020): 030006052094555. http://dx.doi.org/10.1177/0300060520945552.
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Objective To identify the factors influencing early recurrence in patients with hepatocellular carcinoma (HCC) after curative resection. Methods Clinical data for 99 patients with HCC undergoing curative resection were analyzed. The clinicopathological factors influencing early recurrence were analyzed by Cox regression. Results Twenty-five of 99 patients (25.3%) suffered from early recurrence. There were significant differences between patients with and without recurrence in terms of tumor diameter, tumor capsular integrity, and preoperative alpha fetoprotein level. Cox regression analysis revealed that a tumor diameter >2.6 cm and preoperatively increased total bilirubin (TBL) level were risk factors for postoperative recurrence, while tumor capsular integrity had a protective effect on postoperative recurrence. After adjusting for preoperative TBL level and tumor capsular integrity, the risk of HCC recurrence was markedly increased in line with increasing tumor diameter in a non-linear manner. Conclusion Tumor diameter >2.6 cm and preoperatively increased TBL level are associated with a higher risk of early recurrence after curative resection in patients with HCC, while tumor capsular integrity is associated with a lower risk of early recurrence.
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Tsai, Yung-Fong, Fu-Chao Liu, Chun-Yu Chen, Jr-Rung Lin, and Huang-Ping Yu. "Effect of Mycophenolate Mofetil Therapy on Recurrence of Hepatocellular Carcinoma after Liver Transplantation: A Population-Based Cohort Study." Journal of Clinical Medicine 10, no. 8 (April 7, 2021): 1558. http://dx.doi.org/10.3390/jcm10081558.
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Hepatocellular carcinoma (HCC) recurrence after liver transplantation is associated with immunosuppressants. However, the appropriate immunosuppressant for HCC recipients is still debated. Data for this nationwide population-based cohort study were extracted from the National Health Insurance Research Database of Taiwan. A total of 1250 liver transplant recipients (LTRs) with HCC were included. We analyzed the risk factors for post-transplant HCC recurrences. Cumulative defined daily dose (cDDD) represented the exposure duration and was calculated as the amount of dispensed defined daily dose (DDD) of mycophenolate mofetil (MMF). The dosage effects of MMF on HCC recurrence and liver graft complication rates were investigated. A total of 155 LTRs, having experienced post-transplant HCC recurrence, exhibited low survival probability at 1-, 3-, 5-, and 10-year observations. Our results demonstrated increased HCC recurrence rate after liver transplantation (p = 0.0316) following MMF administration; however, no significant increase was demonstrated following cyclosporine, tacrolimus, or sirolimus administration. Notably, our data demonstrated significantly increased HCC recurrence rate following MMF administration with cDDD > 0.4893 compared with cDDD ≤ 0.4893 or no administration of MMF (p < 0.0001). MMF administration significantly increases the risk of HCC recurrence. Moreover, a MMF-minimizing strategy (cDDD ≤ 0.4893) is recommended for recurrence-free survival.
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Grasso, Alessandro, Alberto Quaglia, Paolo Montalto, Amar P. Dhillon, David Patch, Brian Davidson, Keith Rolles, et al. "HCC and liver transplantation (LT): risk factors for recurrence." Journal of Hepatology 36 (April 2002): 80. http://dx.doi.org/10.1016/s0168-8278(02)80274-4.
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Hayashi, Michihiro, Tetsunosuke Shimizu, Fumitoshi Hirokawa, Yoshihiro Inoue, Koji Komeda, Mitsuhiro Asakuma, Yoshiharu Miyamoto, Atsushi Takeshita, Yuro Shibayama, and Nobuhiko Tanigawa. "Clinicopathological Risk Factors for Recurrence within One Year after Initial Hepatectomy for Hepatocellular Carcinoma." American Surgeon 77, no. 5 (May 2011): 572–78. http://dx.doi.org/10.1177/000313481107700516.
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Hepatocellular carcinoma (HCC) shows a high rate of recurrence after hepatectomy; predictive factors for early recurrence would help determine optimal therapeutic and management strategies. Among 163 patients with HCC undergoing hepatectomy with curative intent, 46 patients developed recurrence within 1 year. Clinicopathological data were retrospectively analyzed to identify predictive parameters for early recurrence. Survival rates in cases of recurrence within 1 year were worse than those of no recurrence within 1 year or recurrence after 1 year. Protein induced by vitamin K absence/antagonist II (PIVKA-II) greater than 150, positive fucosylated alpha-fetoprotein (L3-AFP), and deviancy from Milan criteria (MC) on preoperative imaging were associated with high risk of early recurrence and total number of these three risk factors predicted the survival. With multivariate analysis, 1) preoperatively, positive factors of two or more among three items of PIVKA-II, L3-AFP, and deviancy from MC; 2) and postoperatively, pathological cancer spread (microscopic vascular invasion and/or intrahepatic metastasis) both represented risks for early recurrence. A combination of three preoperative factors, PIVKA-II, L3-AFP, and MC status, in conjunction with the postoperative factor of cancer spread status represents a significant indicator for recurrence within 1 year. Improving the prognosis of patients with HCC would depend on how to adequately treat those at high risk of early recurrence.
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Teng, Chiao-Fang, Tsai-Chung Li, Hsi-Yuan Huang, Wen-Ling Chan, Han-Chieh Wu, Woei-Cherng Shyu, Ih-Jen Su, and Long-Bin Jeng. "Hepatitis B virus pre-S2 deletion (nucleotide 1 to 54) in plasma predicts recurrence of hepatocellular carcinoma after curative surgical resection." PLOS ONE 15, no. 11 (November 25, 2020): e0242748. http://dx.doi.org/10.1371/journal.pone.0242748.
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Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Despite curative surgical resection, high recurrence of HCC after surgery results in poor patient survival. To develop prognostic markers is therefore important for better prevention and therapy of recurrent HCC to improve patient outcomes. Deletion mutations over the pre-S1 and pre-S2 gene segments of hepatitis B virus (HBV) have been closely associated with recurrence of HCC after curative surgical resection. In this study, we applied a next-generation sequencing-based approach to further evaluate the association of pre-S deletion regions with HCC recurrence. We demonstrated that the pre-S2 deletion (nucleotide 1 to 54) was the most predominant deletion regions of pre-S gene in plasma of HBV-related HCC patients. Moreover, patients with the pre-S2 deletion (nucleotide 1 to 54) exhibited a significantly higher risk of HCC recurrence after curative surgical resection than those without. The pre-S2 deletion (nucleotide 1 to 54) in plasma represented a prognostic factor that independently predicted HCC recurrence with greater performance than other clinicopathological and viral factors. Our data suggest that detection of the pre-S2 deletion (nucleotide 1 to 54) in plasma may be a promising noninvasive strategy for identifying patients at high risk for HCC recurrence after curative surgical resection.
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Bürger, Christin, Miriam Maschmeier, Anna Hüsing-Kabar, Christian Wilms, Michael Köhler, Martina Schmidt, Hartmut H. Schmidt, and Iyad Kabar. "Achieving Complete Remission of Hepatocellular Carcinoma: A Significant Predictor for Recurrence-Free Survival after Liver Transplantation." Canadian Journal of Gastroenterology and Hepatology 2019 (January 8, 2019): 1–7. http://dx.doi.org/10.1155/2019/5796074.
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Background. Liver transplantation (LT) is a curative treatment for hepatocellular carcinoma (HCC) and the underlying primary liver disease; however, tumor recurrence is still a major issue. Therefore, the aim of this study was to assess predictors and risk factors for HCC recurrence after LT in patients within and outside the Milan criteria with a special focus on the impact of different bridging strategies. Methods. All patients who underwent LT for HCC between 07/2002 and 09/2016 at the University Hospital of Muenster were consecutively included in this retrospective study. Database research was performed and a multivariable regression analysis was conducted to explore potential risk factors for HCC recurrence. Results. A total of 82 patients were eligible for the statistical analysis. Independent of bridging strategy, achieving complete remission (CR) was significantly associated with a lower risk for tumor recurrence (p = 0.029; OR = 0.426, 95% CI 0.198-0.918). A maximal diameter of lesion < 3 cm was also associated with lower recurrence rates (p = 0.040; OR = 0.140, 95% CI 0.022-0.914). Vascular invasion proved to be an independent risk factor for HCC recurrence (p = 0.004; OR = 11.357, 95% CI 2.142-60.199). Conclusion. Achieving CR prior to LT results in a significant risk reduction of HCC recurrence after LT independent of the treatment modalities applied.
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Yang, Jianming, Shijie Jiang, Yewu Chen, Jian Zhang, and Yinan Deng. "Adjuvant ICIs Plus Targeted Therapies Reduce HCC Recurrence after Hepatectomy in Patients with High Risk of Recurrence." Current Oncology 30, no. 2 (January 31, 2023): 1708–19. http://dx.doi.org/10.3390/curroncol30020132.
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Background: The high recurrence rate of hepatocellular carcinoma (HCC) after hepatectomy usually results in poor prognosis. To the best of our knowledge, no study has reported the efficacy of immune checkpoint inhibitors (ICIs) plus targeted therapies on preventing HCC recurrence after hepatectomy. Thus, the aim of this study was to investigate the benefits and safety of applying adjuvant ICIs plus targeted therapies after hepatectomy for patients at high risk of HCC recurrence. Methods: A total of 196 patients with any risk factors for recurrence who underwent hepatectomy for HCC were reviewed in this retrospective study. Results: Compared with the control group (n = 158), ICIs plus targeted therapies (n = 38) had a significantly higher recurrence-free survival (RFS) rate in univariate analysis (HR, 0.46; 95% confidence interval [CI], 0.24–0.90; p = 0.020), multivariate analysis (adjusted HR, 0.62; 95%CI, 0.49–0.79; p < 0.001) and propensity score-matched analysis (HR, 0.35; 95%CI, 0.16–0.75; p = 0.005). Subgroup analyses also showed that postoperative adjuvant ICIs plus targeted therapies might reduce HCC recurrence in patients with the most of risk factors. Conclusion: Postoperative adjuvant ICI plus targeted therapies may reduces early HCC recurrence in patients with a high risk of recurrence, and the treatments are well tolerated.
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Yoshizumi, Tomoharu, Toru Ikegami, Shohei Yoshiya, Takashi Motomura, Yohei Mano, Jun Muto, Rumi Matono, et al. "Impact of up-to-seven criteria and neutrophil-to-lymphocyte ratio in liver transplantation for patients who received pretreatment for hepatocellular carcinoma." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e14536-e14536. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e14536.
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e14536 Background: There is currently no consensus on how to manage patients with hepatocellular carcinoma (HCC) while awaiting liver transplantation (LT). The guideline published in UK states that locoregional therapy should be considered for all listed patients with HCC. Living donor LT (LDLT) is a choice for treating HCC patients in organ shortage era. The aim of the present study is to clarify the risk factors of tumor recurrence after LDLT in patients who had received pre-transplant treatments (pre-Tx) for HCC. Methods: One hundred two adult patients (39 females and 63 males) who had undergone LDLT due to end-stage liver disease with recurrent HCC after pre-Tx were enrolled. The primary end-point of this study was HCC recurrence after LDLT. Recurrence-free survival rates after LDLT were calculated. Risk factors of tumor recurrence were identified using univariate and multivariate analysis. Results: The 1-, 3-, and 5-year recurrence-free survival rates were 89.4%, 80.7%, and 78.8%, respectively. Seventy-four of 102 patients underwent pre-Tx more than twice. Moreover, the times of pre-Tx, the interval between the first treatment and LDLT, and the interval between the last treatment and LDLT did not affect the outcome of LDLT. On univariate analysis, the factors affecting recurrence-free survival were exceeding the up-to-seven criteria (p<0.0001), exceeding the Kyushu University criteria (p<0.0001), neutrophil-to-lymphocyte ratio (NLR) > 4 (p=0.0001), Alpha-fetoprotein > 400 ng/ml (p<0.0001), and bilobar tumor distribution (p=0.047). A multivariate analysis identified independent risk factors for post-LDLT tumor recurrence were exceeding the up-to-seven criteria (p=0.001) and NLR > 4 (p=0.002). The 1- and 3-year recurrence-free survival rates in the recipients with exceeding the up-to-seven criteria and NLR > 4 were 30.0% and 15.0%, respectively. Conclusions: The kind or duration of pre-Tx did not affect the outcome of LDLT, but LDLT should not be performed for the patients with exceeding the up-to-seven criteria and NLR more than 4 after pre-Tx for HCC to prevent tumor recurrence.
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Cho, Wei-Ru, Chih-Chi Wang, Meng-Yun Tsai, Chen-Kai Chou, Yueh-Wei Liu, Yi-Ju Wu, Ming-Tsung Lin, et al. "Impact of metformin use on the recurrence of hepatocellular carcinoma after initial liver resection in diabetic patients." PLOS ONE 16, no. 3 (March 4, 2021): e0247231. http://dx.doi.org/10.1371/journal.pone.0247231.
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Background Metformin is proposed to have chemopreventive effect of various cancer currently. However, the anti-cancer effect of metformin for diabetic patients with hepatocellular carcinoma (HCC) undergoing liver resection remains unclear. The aim of our cohort study was to assess whether metformin influence the recurrence of HCC. Methods We retrospectively enrolled 857 HCC patients who received primary resection from April 2001 to June 2016. 222 patients were diagnosed with diabetes mellitus (DM) from medical record. Factors influence the overall survival (OS) and recurrence-free survival (RFS) were analyzed by multivariate analysis. Results During the follow-up period (mean, 75 months), 471 (54.9%) patients experienced recurrence, and 158 (18.4%) patients died. Multivariate analysis revealed that DM (p = 0.015), elevated AST (p = 0.006), hypoalbuminemia (p = 0.003), tumor number (p = 0.001), tumor size (p < 0.001), vascular invasion (p <0.001), high Ishak fibrosis score (p <0.001), hepatitis B (p = 0.014), hepatitis C (p = 0.001) were independent predictors for RFS. In diabetic patients, only HbA1c>9% (p = 0.033), hypoalbuminemia (p = 0.030) and vascular invasion (p = 0.001) were independent risk factors for HCC recurrence; but the metformin use revealed no significance on recurrence. DM is a risk factor of HCC recurrence after resection. Adequate DM control can reduce the recurrence of HCC. However, the use of metformin does not reduce the risk of HCC recurrence in diabetic patient after initial resection. Hence, metformin may not have protective influences on HCC recurrence in diabetic patients who undergo initial liver resection.
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Bzeizi, Khalid I., Maheeba Abdullah, Kota Vidyasagar, Saleh A. Alqahthani, and Dieter Broering. "Hepatocellular Carcinoma Recurrence and Mortality Rate Post Liver Transplantation: Meta-Analysis and Systematic Review of Real-World Evidence." Cancers 14, no. 20 (October 19, 2022): 5114. http://dx.doi.org/10.3390/cancers14205114.
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Background: liver transplantation (LT) is the best curative option for eligible patients with hepatocellular carcinoma (HCC), however recurrence remains a major concern. This meta-analysis aimed to investigate the prevalence and risk factors of HCC recurrence. Methods: studies were selected using PubMed, Epistemonikas, and Google Scholar databases published from inception to 15 May 2022 and a meta-analysis of the proportions was conducted. Observational studies reporting the prevalence of recurrent HCC after an LT were included, with the analysis being stratified by an adherence to the Milan criteria (MC), geographical region, AFP levels, and donor type. Results: out of 4081 articles, 125 were included in the study. The prevalence of recurrent HCC was 17% (CI: 15–19). Patients beyond the MC were more likely to recur than patients within the MC. Asian populations had the greatest prevalence of HCC recurrence (21%; CI: 18–24), whereas North American populations had the lowest recurrence (10%; CI: 7–12). The mortality rate after HCC recurrence was 9%; CI: 8–11. North American populations had the greatest prevalence of mortality with 11% (CI: 5–17). Conclusions: the recurrence, overall survival, and mortality rates among patients with HCC post-LT remains high, with substantial differences between regions.
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Yoshimasu, Yu, Yoshihiro Furuichi, Yoshitaka Kasai, Hirohito Takeuchi, Katsutoshi Sugimoto, Ikuo Nakamura, and Takao Itoi. "Predictive Factors for Hepatocellular Carcinoma Occurrence or Recurrence after Direct-Acting Antiviral Agents in Patients with Chronic Hepatitis C." Journal of Gastrointestinal and Liver Diseases 28, no. 1 (March 1, 2019): 63–71. http://dx.doi.org/10.15403/jgld.2014.1121.281.hpc.
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Background & Aims: Direct-acting antiviral agents (DAAs) and the risk of hepatocellular carcinoma (HCC) is controversially reported in the literature. The primary endpoints of this study were to clarify the cumulative incidence and recurrence rate of HCC after DAA treatment. The secondary endpoints were to identify the factors associated with the occurrence or recurrence of HCC after DAAs treatment.Methods: Of 234 HCV patients, 211 with no history of HCC (no-HCC-history group) and 23 with previous treated HCC history (HCC-history group) were treated with DAAs and followed for more than 24 weeks to determine the incidence of HCC. Platelet count, albumin, α-fetoprotein (AFP) level, L3%, the FIB-4 index and APRI scores were analyzed as possible factors associated with HCC occurrence and recurrence. An intergroup comparison was made of the cumulative incidence of HCC. Cox proportional hazards regression was used to determine associations between blood test values and risk of HCC.Results: The median observation period was 21 months. Cumulative incidence of HCC was higher in the HCChistory group than in the no-HCC-history group (p < 0.0001, 19.0 and 0.52 per 100 patient-years, respectively). Univariate analysis revealed platelet count, albumin, α-fetoprotein (AFP) level, AFP-L3%, and FIB-4 index and APRI scores at the end of DAA treatment as being significantly associated with occurrence/recurrence of HCC. Multivariate analysis revealed that AFP levels before and after the administration of DAAs and AFP-L3% after DAA were independently associated with the occurrence/recurrence of HCC (p = 0.045, 0.043, 0.005, respectively).Conclusion: The HCC occurrence rate after DAA treatment was very low, and the recurrence rate lower than that in previous interferon reports. The AFP level and AFP-L3% were identified as important factors in predicting occurrence/recurrence of HCC. Careful observation is needed when increased levels of AFP or AFP-L3% after DAAs treatment are observed.
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Lee, Chern-Horng, Chien-Heng Shen, Cho-Li Yen, Tzung-Hai Yen, and Sen-Yung Hsieh. "Discontinuing Hepatitis Activity Reduced Hepatocellular Carcinoma Recurrence after Primary Curative Therapy." Journal of Personalized Medicine 13, no. 3 (February 24, 2023): 397. http://dx.doi.org/10.3390/jpm13030397.
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Background: Hepatocellular carcinoma (HCC) tends to recur after curative treatment. This study aimed to identify the clinical factors associated with HCC recurrence after initial curative therapy. Methods: We retrospectively included patients with early stage HCC Barcelona Clinic Liver Cancer (BCLC) stages 0 and A who received curative surgical resection or local ablation at three different Chang Gung Memorial Hospitals in Taiwan (527 patients from Linkou, 150 patients from Keelung, and 127 patients from Chiayi) from 2000 to 2009. Pretreatment clinical data were subjected to univariate and multivariate logistic analyses to identify the risk factors for HCC recurrence within five years after the primary curative treatment. Recurrence and survival rates were assessed using Kaplan–Meier curves and log-rank tests. Results: Patients with a history of nucleoside analog or peg-interferon treatment for hepatitis B or hepatitis C infection had lower HCC recurrence rates than did those without such treatment. By contrast, alcohol drinking habits (p = 0.0049, hazard ratio (HR): 1.508, 95%CI: 1.133–2.009), a platelet count of < 14 × 104/μL (p = 0.003, HR: 1.533, 95%CI: 1.155–2.035), and a serum alanine aminotransferase level > 40 U/L (p = 0.0450, HR: 1.305, 95%CI: 1.006–1.694) were independent risk factors for HCC recurrence. The five-year HCC recurrence rates did not differ between patients who received either local radiofrequency ablation or surgical resection at BCLC stages 0 and A. Conclusions: Factors contributing to persistent hepatitis activity and advanced fibrosis precipitate tumor recurrence. Active intervention to discontinue liver injury or hepatitis could reduce HCC recurrence.
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Vidal, Raphael Iglesias de Oliveira, Edison Iglesias de Oliveira Vidal, Basilio de Bragança Pereira, Cachimo Combo Assane, Alexandre Ribeiro, Emilia Matos do Nascimento, Fernando Gomes Romeiro, and Joaquim Ribeiro Filho. "Risk Factors for Hepatocellular Carcinoma Recurrence and Survival after Liver Transplantation in Patients with HCV-Related Cirrhosis." BioMed Research International 2020 (October 17, 2020): 1–8. http://dx.doi.org/10.1155/2020/1487593.
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Purpose. We aimed to identify prognostic factors for survival and recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) for patients with HCC and hepatitis C virus-related cirrhosis (HCV-cirrhosis). Methods. This retrospective cohort study followed all adult patients with HCV-cirrhosis who underwent LT because of HCC or had incidental HCC identified through pathologic examination of the explanted liver at a university hospital in Rio de Janeiro, Brazil, over 11 years (1998-2008). We used Cox regression models to assess the following risk factors regarding HCC recurrence or death after LT: age, Model for End-stage Liver Disease score, Child-Pugh classification, alpha-fetoprotein (AFP), whether patients had undergone locoregional treatment before transplantation, the number of packed red blood cell units (PRBCU) transfused during surgery, the number and size of HCC lesions in the explanted liver, and the presence of microvascular invasion and necrotic areas within HCC lesions. Results. Seventy-six patients were followed up for a median (interquartile range (IQR)) of 4.4 (0.7-6.6) years. Thirteen (17%) patients had HCC recurrence during the follow-up period, and 26 (34%) died. The median survival time was 6.6 years (95% CI: 2.4-12.0), and the 5-year survival was 52.5% (95% CI: 42.3-65.0%). The final regression model for overall survival included four variables: age (hazard ratio (HR): 1.02, 95% CI: 0.96-1.08, P = 0.603 ), transplantation waiting time (HR: 1.00, 95% CI: 1.00-1.00, P = 0.190 ), preoperative AFP serum levels (HR: 1.01, 95% CI: 1.00-1.02, P = 0.006 ), and whether >4 PRBCU were transfused during surgery (HR: 1.15, 95% CI: 1.05-1.25, P = 0.001 ). The final cause-specific Cox regression model for HCC recurrence included only microvascular invasion (HR: 14.86, 95% CI: 4.47-49.39, P < 0.001 ). Conclusion. In this study of LT for HCV-cirrhosis, preoperative AFP levels and the number of PRBCU transfused during surgery were associated with overall survival, whereas microvascular invasion with HCC recurrence.
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Yu, Liang-He, Nan Li, and Shu-Qun Cheng. "The Role of Antiviral Therapy for HBV-Related Hepatocellular Carcinoma." International Journal of Hepatology 2011 (2011): 1–8. http://dx.doi.org/10.4061/2011/416459.
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Hepatocellular carcinoma (HCC) is a highly prevalent and lethal cancer worldwide; despite the curative treatment for HCC, the rate of tumor recurrence after hepatectomy remains high. Tumor recurrence can occur early (<2 years) or late (>2 years) as metastases or de novo tumors. Several tumor factors were associated with HCC recurrence; high hepatitis B virus (HBV) load is the major risk factor for late recurrence of HCC after resection. Preoperative antiviral therapy improves liver function, and postoperative reduce HCC recurrence. In this paper, we focus on antiviral treatment to improve the liver function, prevent recurrence, and lengthen the overall survival for HBV-related HCC.
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Gruttadauria, Salvatore, Floriana Barbera, Pier Giulio Conaldi, Duilio Pagano, Rosa Liotta, Enrico Gringeri, Roberto Miraglia, et al. "Clinical and Molecular-Based Approach in the Evaluation of Hepatocellular Carcinoma Recurrence after Radical Liver Resection." Cancers 13, no. 3 (January 29, 2021): 518. http://dx.doi.org/10.3390/cancers13030518.
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Background: Hepatic resection remains the treatment of choice for patients with early-stage HCC with preserved liver function. Unfortunately, however, the majority of patients develop tumor recurrence. While several clinical factors were found to be associated with tumor recurrence, HCC pathogenesis is a complex process of accumulation of somatic genomic alterations, which leads to a huge molecular heterogeneity that has not been completely understood. The aim of this study is to complement potentially predictive clinical and pathological factors with next-generation sequencing genomic profiling and loss of heterozygosity analysis. Methods: 124 HCC patients, who underwent a primary hepatic resection from January 2016 to December 2019, were recruited for this study. Next-generation sequencing (NGS) analysis and allelic imbalance assessment in a case-control subgroup analysis were performed. A time-to-recurrence analysis was performed as well by means of Kaplan–Meier estimators. Results: Cumulative number of HCC recurrences were 26 (21%) and 32 (26%), respectively, one and two years after surgery. Kaplan–Meier estimates for the probability of recurrence amounted to 37% (95% C.I.: 24–47) and to 51% (95% C.I.: 35–62), after one and two years, respectively. Multivariable analysis identified as independent predictors of HCC recurrence: hepatitis C virus (HCV) infection (HR: 1.96, 95%C.I.: 0.91–4.24, p = 0.085), serum bilirubin levels (HR: 5.32, 95%C.I.: 2.07–13.69, p = 0.001), number of nodules (HR: 1.63, 95%C.I.: 1.12–2.38, p = 0.011) and size of the larger nodule (HR: 1.11, 95%C.I.: 1.03–1.18, p = 0.004). Time-to-recurrence analysis showed that loss of heterozygosity in the PTEN loci (involved in the PI3K/AKT/mTOR signaling pathway) was significantly associated with a lower risk of HCC recurrence (HR: 0.35, 95%C.I.: 0.13–0.93, p = 0.036). Conclusions: multiple alterations of cancer genes are associated with HCC progression. In particular, the evidence of a specific AI mutation presented in 20 patients seemed to have a protective effect on the risk of HCC recurrence.
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Lee, Soon Kyu, Sung Won Lee, Jeong Won Jang, Si Hyun Bae, Jong Young Choi, and Seung Kew Yoon. "Immunological Markers, Prognostic Factors and Challenges Following Curative Treatments for Hepatocellular Carcinoma." International Journal of Molecular Sciences 22, no. 19 (September 24, 2021): 10271. http://dx.doi.org/10.3390/ijms221910271.
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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortalities worldwide. Patients with early-stage HCC are eligible for curative treatments, such as surgical resection, liver transplantation (LT) and percutaneous ablation. Although curative treatments provide excellent long-term survival, almost 70–80% of patients experience HCC recurrence after curative treatments. Tumor-related factors, including tumor size, number and differentiation, and underlying liver disease, are well-known risk factors for recurrence following curative therapies. Moreover, the tumor microenvironment (TME) also plays a key role in the recurrence of HCC. Many immunosuppressive mechanisms, such as an increase in regulatory T cells and myeloid-derived suppressor cells with a decrease in cytotoxic T cells, are implicated in HCC recurrence. These suppressive TMEs are also modulated by several factors and pathways, including mammalian target of rapamycin signaling, vascular endothelial growth factor, programmed cell death protein 1 and its ligand 1. Based on these mechanisms and the promising results of immune checkpoint blockers (ICBs) in advanced HCC, there have been several ongoing adjuvant studies using a single or combination of ICB following curative treatments in HCC. In this review, we strive to provide biologic and immunological markers, prognostic factors, and challenges associated with clinical outcomes after curative treatments, including resection, LT and ablation.
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Imai, Kenji, Koji Takai, Takao Miwa, Toshihide Maeda, Tatsunori Hanai, Makoto Shiraki, Atsushi Suetsugu, and Masahito Shimizu. "Increased Visceral Adipose Tissue and Hyperinsulinemia Raise the Risk for Recurrence of Non-B Non-C Hepatocellular Carcinoma after Curative Treatment." Cancers 13, no. 7 (March 26, 2021): 1542. http://dx.doi.org/10.3390/cancers13071542.
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We investigated the factors affecting recurrence-free survival in patients with non-B non-C hepatocellular carcinoma (HCC) who received curative treatment. Decision-tree analysis was performed in 72 curative cases of non-B non-C HCC to extract the risk factors for recurrence. The reliability of the extracted risk factors was evaluated using the Kaplan–Meier method and the Cox proportional hazards model. The decision-tree analysis extracted three factors—visceral adipose tissue (VAT) index (VATI; <71 and ≥71 cm2/m2), which was the cross-sectional areas of VAT on the computed tomographic image at the umbilical level, normalized by the square of the height, fasting immunoreactive insulin (FIRI; <5.5 and ≥5.5 µU/mL), and alpha-fetoprotein (AFP; <11 and ≥11 ng/mL). The Cox proportional hazards model showed that VATI (hazard ratio (HR): 2.556, 95% confidence interval (CI): 1.191–5.486, p = 0.016), FIRI (HR: 3.149, 95% CI: 1.156–8.575, p = 0.025), and AFP (HR: 3.362, 95% CI: 1.550–7.288, p = 0.002) were all independent risk factors for HCC recurrence. Non-B non-C HCC patients with a higher VATI (≥71 cm2/m2) or higher FIRI (≥5.5 µU/mL) and AFP (≥11 ng/mL) if VATI was <71 cm2/m2 are prone to recurrence after curative treatment.
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Chen, Hsin-Yeh, Sheng-Nan Lu, Chao-Hung Hung, Jing-Houng Wang, Chien-Hung Chen, Yi-Hao Yen, Yuan-Hung Kuo, and Kwong-Ming Kee. "Predicting outcomes for recurrent hepatocellular carcinoma within Milan criteria after complete radiofrequency ablation." PLOS ONE 15, no. 11 (November 10, 2020): e0242113. http://dx.doi.org/10.1371/journal.pone.0242113.
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Background Intrahepatic distant recurrence (IDR) is a significant problem for patients who have undergone radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). The objective of the study was to investigate risk factors and to predict outcomes of recurrent IDR within Milan criteria after complete RFA for primary early-stage HCC. Method This retrospective study reviewed 449 patients with intrahepatic distant recurrent HCC after complete RFA for early-stage HCC. After excluding 100 patients who were beyond Milan criteria, with incomplete lab data, or had follow-up less than three months, a total of 349 patient cases were compiled and their baseline characteristics, further treatment modalities after tumor recurrence and survival were analyzed. Results After a median follow-up of 36.2 months, 92 patients had expired. The majority of patients were male (59.9%) with a median age of 64.3 years (range:38–88). The cumulative 5-year overall survival (OS) rates after treatment for recurrent HCC was 67.2%. On multivariate analysis, end-stage renal disease(Hazard ratio (H.R.) = 2.33, p = 0.021), m-ALBI grade 2a (H.R. = 2.86, p = 0.003) and m-ALBI grades 2b or 3 (H.R. = 2.30, p = 0.009), APRI greater than 1 (H.R. = 1.92, p = 0.036) and 2nd recurrence occurring within 1 year (H.R. = 2.69, p<0.001) were significantly associated with worse survival. The cumulative 5-year 2nd recurrence rate was 87.4%. On multivariate analysis, male gender (H.R. = 1.47, p = 0.01), age greater than 65 years (H.R. = 1.72, p<0.001), an alpha fetoprotein level greater than 20ng/ml (H.R. = 1.41, p = 0.016), surgical treatment for recurrent HCC (H.R. = 0.25, p = 0.007), tumor number greater than 1 (H.R. = 1.35, p = 0.046), and IDR developing within 2 years (H.R. = 1.67, p = 0.001) were prognostic factors for 2nd recurrence. Conclusion Our study suggested that presence of end-stage renal disease, m-ALBI grades 2 and 3, APRI >1 and time to 2nd HCC recurrence were all associated with overall survival while the 2nd HCC recurrence was associated with male gender, age ≥65 years, α-fetoprotein level >20 ng/mL, non-surgical therapy, time to IDR, and tumor number> 1.
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Chen, Yu-Syuan, Kuo-Hsuan Huang, Pei-Ming Wang, Ching-Hui Chuang, Chee-Chien Yong, Yueh-Wei Liu, Pao-Yuan Huang, Chih-Chien Yao, Yen-Po Lin, and Ming-Chao Tsai. "The Impact of Direct-Acting Antiviral Therapy on the Risk of Recurrence after Curative Resection in Patients with Hepatitis-C-Virus-Related Early Stage Hepatocellular Carcinoma." Medicina 58, no. 2 (February 9, 2022): 259. http://dx.doi.org/10.3390/medicina58020259.
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Background and Objectives: The impact of direct-acting antiviral (DAA)-based regimens on the recurrence of hepatocellular carcinoma (HCC) after successful curative hepatectomy is controversial. Aims: This study aimed to assess the association between DAAs treatment and recurrence risk in HCC after resection. Materials and Methods: We retrospectively assessed 152 cases of early stage (BCLC stage 0/A) hepatitis C virus (HCV)-related HCC (HCV-HCC) that underwent resection with curative intent between 2001 and 2019 at Kaohsiung Chang Gung Memorial Hospital; 48 cases achieved a sustained virological response (SVR) by DAA, and 104 cases were not treated with any antiviral therapy (non-treatment group). Recurrence-free survival (RFS) following curative resection was analyzed by using the log-rank test and Kaplan–Meier method. A Cox proportional hazards model was used to analyze the factors that impacted RFS and OS. Results: Five patients (10.4%) experienced HCC recurrence after DAA therapy. The cumulative HCC recurrence rate was significantly lower in the DAA group than the non-treatment group (p < 0.001). Multivariate analysis revealed a significant difference in RFS between the non-treatment group and DAA group (p = 0.001; hazard ratio (HR), 4.978; 95% CI, 1.976–12.542); liver cirrhosis (p = 0.005; HR, 2.062; 95% CI, 1.247–3.410), microvascular invasion (p = 0.001; HR, 2.331; 95% CI, 1.408–3.860) and AFP > 15 ng/mL (p = 0.022; HR, 1.799; 95% CI, 1.089–2.970) were also independent factors for HCC recurrence. ALBI stage II/III (p = 0.005; HR, 3.249; 95% CI, 1.418–7.443) and microvascular invasion (p < 0.001; HR, 4.037 95% CI, 2.071–7.869) were independent factors for OS; no significant difference in OS was observed between the DAA and no DAA treatment groups. Conclusions: DAA treatment could reduce the risk of recurrence after curative treatment for early stage HCC.
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Jin, Hongmei, Hui Wang, Guanghao Li, Qingshun Hou, Wei Wu, and Fuhui Liu. "Risk factors for early postoperative recurrence in single and small hepatitis B virus-associated primary hepatocellular carcinoma." Journal of International Medical Research 48, no. 10 (October 2020): 030006052096126. http://dx.doi.org/10.1177/0300060520961260.
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Objective To investigate the risk factors of early postoperative recurrence in patients with single and small (≤3 cm) hepatitis B virus-associated primary hepatocellular carcinoma (HBV-HCC). Methods This retrospective study analyzed patients with single and small HBV-HCC. All patients were followed up for 1 year after surgery. Results Among 182 patients, 54 patients had early recurrence within 1 year. The recurrence group had higher proportions of men, drinking history, Child–Turcotte–Pugh (CTP) class C, patients who underwent transarterial chemoembolization (TACE), and serum alpha-fetoprotein (AFP) >10 ng/mL as well as higher gamma-glutamyl transpeptidase (GGT) levels and lower total protein (TP) and CD8+ T lymphocyte levels than the no recurrence group. Cox multivariate regression analysis demonstrated that drinking history (HR, 1.312; 95% CI, 1.042–1.652), CTP class C (HR, 1.236; 95% CI, 1.037–1.473), TACE treatment (HR, 1.241; 95% CI, 1.026–1.501), GGT (HR, 1.138; 95% CI, 1.042–1.243), TP (HR, 0.729; 95% CI, 0.555–0.957), and AFP (HR, 2.519; 95% CI, 1.343–4.726) were independently associated with early postoperative recurrence. Conclusion Drinking history, CTP class C, TACE, serum AFP, GGT, and TP levels were independently associated with early postoperative recurrence in patients with single and small HBV-HCC.
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Shehata, Mona A. H., Nabeel El-Kady, Maha Hasaballah, Loai Mansour, Nabila El-Gazzar, and Sherief Abd-Elsalam. "Hypervascular Nodules and Stiffer Liver are Associated with Recurrence after Microwave Ablation in Patients with Hepatocellular Carcinoma: A Double-Center Analysis." South Asian Journal of Cancer 09, no. 03 (July 2020): 153–57. http://dx.doi.org/10.1055/s-0041-1723102.
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Abstract Background and Aims The aim of this study was to detect the most important risk factors for recurrence after microwave ablation (MWA) of hepatocellular carcinoma (HCC). Methods A total of 92 patients with 110 HCC focal lesions (FLs) underwent MWA therapy. All the patients underwent triphasic CT before and after 1 and 3 months of MWA therapy. Complete ablation and recurrence rates were recorded, and the risk factors associated with recurrence were analyzed. Results Regarding the 110 HCC FLs that were detected pre-MWA, adequate ablation was recorded post-MWA procedure in 88 FLs (80%) and incomplete ablation in 22 FLs (showed residual contrast enhancement). However, there were newly detected lesions (17 FLs). The rate of recurrence was significantly higher in patients with multiple larger (> 4 cm) sized and hypervascular nodules. Diabetics were significantly associated with a higher recurrence rate of HCC. The rate of recurrence was significantly higher in patients with baseline level of serum alfa-fetoprotein (AFP) ≥200 ng/mL. Stiffer liver> 25 kPa had higher incidence for recurrence after ablation. Conclusion Meticulous follow-up is mandatory in diabetic patients, patients with AFP > 200 ng/dL starting value, hypervascular large hepatic FL, and in stiffer liver> 25 kPa, as these patients have higher incidence for recurrence after ablation.
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He, Ling-Ling, Xiao-Li Liu, Shuan Zhang, Meng-Ge Li, Xian-Bo Wang, Yu-Yong Jiang, and Zhi-Yun Yang. "Independent risk factors for disease recurrence after surgery in patients with hepatitis B virus-related hepatocellular carcinoma ≤3 cm in diameter." Gastroenterology Report 7, no. 4 (March 30, 2019): 250–57. http://dx.doi.org/10.1093/gastro/goz009.
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Abstract Background Post-operative recurrence rates are high for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). This study aimed to explore the factors associated with post-operative 1-year recurrence rate in patients with HBV-related HCC who had a single small primary tumor (≤3 cm in diameter). Methods This was a retrospective study of 203 (training cohort) and 64 (validation cohort) patients newly diagnosed with HBV-related HCC who had a single small primary tumor. The first year of post-operative follow-up was examined. Factors potentially associated with HCC recurrence were identified using Cox regression analyses. A model was constructed based on the factors identified and the prognostic value of the model was evaluated using receiver operating characteristic (ROC) curve analysis and calculation of the area under the ROC curve (AUC). Results A history of alcoholism and serum levels of α-fetoprotein, total protein and γ-glutamyl transpeptidase (GGT) were independently associated with 1-year recurrence rate after surgery. A predictive model based on these four factors had an AUC of 0.711 (95% confidence interval, 0.643–0.772) in the training cohort and 0.727 (95% confidence interval, 0.601–0.831) in the validation cohort. The 1-year recurrence rate was significantly lower in the low-risk group than in the high-risk group in both the training cohort (17.0% vs. 49.5%, P < 0.001) and the validation cohort (43.2% vs. 74.1%, P = 0.031). Conclusion A history of alcoholism and serum levels of α-fetoprotein, total protein and γ-glutamyl transpeptidase were independently associated with post-operative 1-year recurrence rate in patients with HBV-related HCC who had a single small primary tumor (≤3 cm in diameter).
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Chen, Kuan-Yang, Yi-Hsiang Huang, Wan-Huai Teo, Ching-Wen Chang, Yu-Syuan Chen, Yi-Chen Yeh, Chieh-Ju Lee, and Jeng-Fan Lo. "Loss of Tid1/DNAJA3 Co-Chaperone Promotes Progression and Recurrence of Hepatocellular Carcinoma after Surgical Resection: A Novel Model to Stratify Risk of Recurrence." Cancers 13, no. 1 (January 4, 2021): 138. http://dx.doi.org/10.3390/cancers13010138.
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Tid1, a mitochondrial co-chaperone protein, acts as a tumor suppressor in various cancer types. However, the role of Tid1 in hepatocellular carcinoma (HCC) remains unclear. First, we found that a low endogenous Tid1 protein level was observed in poorly differentiated HCC cell lines. Further, upregulation/downregulation of Tid1 abrogated/promoted the malignancy of human HCC cell lines, respectively. Interestingly, Tid1 negatively modulated the protein level of Nrf2. Tissue assays from 210 surgically resected HCC patients were examined by immunohistochemistry (IHC) analyses. The protein levels of Tid1 in the normal and tumor part of liver tissues were correlated with the clinical outcome of the 210 HCC cases. In multivariate analysis, we discovered that tumor size > 5 cm, multiple tumors, presence of vascular invasion, low Tid1 expression in the non-tumor part, and high Nrf2 expression in the non-tumor part were significant factors associated with worse recurrence-free survival (RFS). A scoring system by integrating the five clinical and pathological factors predicts the RFS among HCC patients after surgical resection. Together, Tid1, serving as a tumor suppressor, has a prognostic role for surgically resected HCC to predict RFS.
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Iwamoto, Takayuki, Yasuharu Imai, Takumi Igura, Sachiyo Kogita, Yoshiyuki Sawai, Kazuto Fukuda, Yoshitaka Yamaguchi, et al. "Non-Hypervascular Hypointense Hepatic Nodules during the Hepatobiliary Phase of Gadolinium-Ethoxybenzyl-Diethylenetriamine Pentaacetic Acid-Enhanced MRI as a Risk Factor of Intrahepatic Distant Recurrence after Radiofrequency Ablation of Hepatocellular Carcinoma." Digestive Diseases 35, no. 6 (2017): 574–82. http://dx.doi.org/10.1159/000480185.
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Background: Non-hypervascular hypointense hepatic nodules during the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI have been reported to be associated with intrahepatic distant recurrence (IDR) after hepatectomy or radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). IDR is categorized into hypervascular transformation of non-hypervascular hypointense hepatic nodules and new intrahepatic recurrence. The aim of this study was to evaluate the relationship between non-hypervascular hypointense hepatic nodules on Gd-EOB-DTPA-enhanced MRI and IDR after RFA, focusing on new intrahepatic recurrence. Methods: Ninety-one consecutive patients with 115 HCCs undergoing pretreatment Gd-EOB-DTPA-enhanced MRI and RFA for treatment of HCC were enrolled. Results: Of the 91 patients who underwent RFA for HCC, 24 had non-hypervascular hypointense hepatic nodules on pretreatment Gd-EOB-DTPA-enhanced MRI. Recurrences were observed in 15 and 19 patients with and without non-hypervascular hypointense hepatic nodules, respectively. Of the 15 recurrences in patients with non-hypervascular hypointense hepatic nodules, 10 patients had new intrahepatic recurrences. The cumulative incidence of new intrahepatic recurrence was significantly higher in patients with non-hypervascular hypointense hepatic nodules than in those without non-hypervascular hypointense hepatic nodules (p < 0.0001). Multivariate analysis revealed that the presence of non-hypervascular hypointense hepatic nodules and Child-Pugh score were independent risk factors for new intrahepatic recurrence. Conclusions: Non-hypervascular hypointense hepatic nodules during the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI were a useful predictive factor for IDR, particularly for new intrahepatic recurrence, after RFA.
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Grąt, Michał, Maciej Krasnodębski, Marek Krawczyk, Jan Stypułkowski, Marcin Morawski, Michał Wasilewicz, Zbigniew Lewandowski, Karolina Grąt, Waldemar Patkowski, and Krzysztof Zieniewicz. "Extremes of Liver Transplantation for Hepatocellular Carcinoma." Journal of Clinical Medicine 8, no. 6 (June 3, 2019): 787. http://dx.doi.org/10.3390/jcm8060787.
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The aim of this retrospective observational study was to evaluate outcomes of patients with extremely advanced hepatocellular carcinoma (HCC) after liver transplantation. A total of 285 HCC patients after liver transplantation were screened for eligibility based on either intrahepatic dissemination (≥10 tumors) or macrovascular invasion. Tumor recurrence was the primary end-point. The study cohort comprised 26 patients. Median recurrence-free survival was 23.2 months with hepatitis B virus (HBV) infection (p = 0.038), higher AFP model score (p = 0.001), prolonged graft ischemia (p = 0.004), and younger donor age (p = 0.016) being significant risk factors. Median recurrence-free survival of HBV-negative and HBV-positive patients was 29.8 and 9.3 months, respectively (p = 0.053). In patients with macrovascular invasion, recurrence-free survival at 3 years was 46.3% with no specific predictors. Tumor size (p = 0.044), higher AFP model score (p = 0.019), prolonged graft ischemia (p = 0.016), and younger donor age (p = 0.041) were significant risk factors in patients with intrahepatic dissemination. Superior 3-year outcomes were observed in patients with intrahepatic dissemination and tumor size <3.5 cm (83.3%, p = 0.027) and HBV-negative patients with ischemia <9.7 h (85.7%, p = 0.028). In conclusion, patients with extremely advanced HCCs are remarkably heterogeneous with respect to their profile of tumor recurrence risk. This heterogeneity is largely driven by factors other than standard predictors of post-transplant HCC recurrence.
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Teng, Chiao-Fang, Tsai-Chung Li, Hsi-Yuan Huang, Jia-Hui Lin, Wen-Shu Chen, Woei-Cherng Shyu, Han-Chieh Wu, Cheng-Yuan Peng, Ih-Jen Su, and Long-Bin Jeng. "Next-Generation Sequencing-Based Quantitative Detection of Hepatitis B Virus Pre-S Mutants in Plasma Predicts Hepatocellular Carcinoma Recurrence." Viruses 12, no. 8 (July 24, 2020): 796. http://dx.doi.org/10.3390/v12080796.
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Hepatocellular carcinoma (HCC) is among the most common and lethal human cancers worldwide. Despite curative resection, high recurrence of HCC remains a big threat, leading to poor patient outcomes. Hepatitis B virus (HBV) pre-S mutants, which harbor deletions over pre-S1 and pre-S2 gene segments of large surface proteins, have been implicated in HCC recurrence. Therefore, a reliable approach for detection of pre-S mutants is urgently needed for predicting HCC recurrence to improve patient survival. In this study, we used a next-generation sequencing (NGS)-based platform for quantitative detection of pre-S mutants in the plasma of HBV-related HCC patients and evaluated their prognostic values in HCC recurrence. We demonstrated that the presence of deletions spanning the pre-S2 gene segment and the high percentage of pre-S2 plus pre-S1 + pre-S2 deletions, either alone or in combination, was significantly and independently associated with poor recurrence-free survival and had greater prognostic performance than other clinicopathological and viral factors in predicting HCC recurrence. Our data suggest that the NGS-based quantitative detection of pre-S mutants in plasma represents a promising approach for identifying patients at high risk for HBV-related HCC recurrence after surgical resection in a noninvasive manner.
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Seehofer, Daniel, Robert Öllinger, Timm Denecke, Moritz Schmelzle, Andreas Andreou, Eckart Schott, and Johann Pratschke. "Blood Transfusions and Tumor Biopsy May Increase HCC Recurrence Rates after Liver Transplantation." Journal of Transplantation 2017 (2017): 1–9. http://dx.doi.org/10.1155/2017/9731095.
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Introduction. Beneath tumor grading and vascular invasion, nontumor related risk factors for HCC recurrence after liver transplantation (LT) have been postulated. Potential factors were analyzed in a large single center experience. Material and Methods. This retrospective analysis included 336 consecutive patients transplanted for HCC. The following factors were analyzed stratified for vascular invasion: immunosuppression, rejection therapy, underlying liver disease, age, gender, blood transfusions, tumor biopsy, caval replacement, waiting time, Child Pugh status, and postoperative complications. Variables with a potential prognostic impact were included in a multivariate analysis. Results. The 5- and 10-year patient survival rates were 70 and 54%. The overall 5-year recurrence rate was 48% with vascular invasion compared to 10% without (p<0.001). Univariate analysis stratified for vascular invasion revealed age over 60, pretransplant tumor biopsy, and the application of blood transfusions as significant risk factors for tumor recurrence. Blood transfusions remained the only significant risk factor in the multivariate analysis. Recurrence occurred earlier and more frequently in correlation with the number of applied transfusions. Conclusion. Tumor related risk factors are most important and can be influenced by patient selection. However, it might be helpful to consider nontumor related risk factors, identified in the present study for further optimization of the perioperative management.
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Montalti, R., G. Rompianesi, M. Masetti, L. Losi, F. Di Benedetto, N. De Ruvo, A. Pierini, et al. "Risk factors and patterns of HCC recurrence: Experience after 116 liver transplantation." Digestive and Liver Disease 39, no. 10 (October 2007): A40. http://dx.doi.org/10.1016/j.dld.2007.07.031.
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Kishta, Sara, Ashraf Tabll, Tea Omanovic Kolaric, Robert Smolic, and Martina Smolic. "Risk Factors Contributing to the Occurrence and Recurrence of Hepatocellular Carcinoma in Hepatitis C Virus Patients Treated with Direct-Acting Antivirals." Biomedicines 8, no. 6 (June 25, 2020): 175. http://dx.doi.org/10.3390/biomedicines8060175.
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Although hepatitis C virus (HCV) RNA may be eliminated from blood circulation by direct-acting antivirals (DAA) therapy as assessed by real-time polymerase chain reaction (PCR), HCV RNA can still be present in liver tissue, and this is known as occult HCV. There has been a lot of controversy surrounding the recurrence of hepatocellular carcinoma (HCC) after DAA treatment of hepatic cells infected with chronic HCV. One of the main risk factors that leads to de novo HCC is the chronicity of HCV in hepatic cells. There are many studies regarding the progression of HCV-infected hepatic cells to HCC. However, there is a lack of research on the different molecular mechanisms that lead to the progression of chronic HCV infection to HCC, as well as on the effect of HCV on the alteration of DNA ploidy, which eventually leads to a recurrence of HCC after DAA treatment. In this review article, we will address some risk factors that could lead to the development/recurrence of HCC after treatment of HCV with DAA therapy, such as the role of liver cirrhosis, the alteration of DNA ploidy, the reactivation of hepatitis B virus (HBV), the role of cytokines and the alteration of the immune system, concomitant non- alcoholic fatty liver disease (NAFLD), obesity, alcohol consumption and also occult HCV infection/co-infection. Clinicians should be cautious considering that full eradication of hepatocarcinogenesis cannot be successfully accomplished by anti-HCV treatment alone.
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Li, Shen, Antonio Saviano, Derek J. Erstad, Yujin Hoshida, Bryan C. Fuchs, Thomas Baumert, and Kenneth K. Tanabe. "Risk Factors, Pathogenesis, and Strategies for Hepatocellular Carcinoma Prevention: Emphasis on Secondary Prevention and Its Translational Challenges." Journal of Clinical Medicine 9, no. 12 (November 25, 2020): 3817. http://dx.doi.org/10.3390/jcm9123817.
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Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality globally. Given the limited therapeutic efficacy in advanced HCC, prevention of HCC carcinogenesis could serve as an effective strategy. Patients with chronic fibrosis due to viral or metabolic etiologies are at a high risk of developing HCC. Primary prevention seeks to eliminate cancer predisposing risk factors while tertiary prevention aims to prevent HCC recurrence. Secondary prevention targets patients with baseline chronic liver disease. Various epidemiological and experimental studies have identified candidates for secondary prevention—both etiology-specific and generic prevention strategies—including statins, aspirin, and anti-diabetic drugs. The introduction of multi-cell based omics analysis along with better characterization of the hepatic microenvironment will further facilitate the identification of targets for prevention. In this review, we will summarize HCC risk factors, pathogenesis, and discuss strategies of HCC prevention. We will focus on secondary prevention and also discuss current challenges in translating experimental work into clinical practice.
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Ko, Chih-Jan, Su-Yu Chien, Chen-Te Chou, Li-Sheng Chen, Mei-Ling Chen, and Yao-Li Chen. "Factors Affecting the Prognosis of Small Hepatocellular Carcinoma in Taiwanese Patients Following Hepatic Resection." Canadian Journal of Gastroenterology 25, no. 9 (2011): 485–91. http://dx.doi.org/10.1155/2011/790528.
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BACKGROUND: Small hepatocellular carcinoma (HCC) affects millions of individuals worldwide. Surveillance of high-risk patients increases the early detection of small HCC.OBJECTIVE: To identify prognostic factors affecting the overall survival (OS) and recurrence-free survival (RFS) of patients with small HCC.METHODS: The present prospective study enrolled 140 Taiwanese patients with stage I or stage II small HCC. Clinical parameters of interest included operation type, tumour size, tumour histology, Child-Pugh class, presence of hepatitis B surface antigen and liver cirrhosis, hepatitis C status, alpha-fetoprotein, total bilirubin and serum albumin levels, and administration of antiviral and salvage therapies.RESULTS: Tumour size correlated significantly with poorer OS in patients with stage I small HCC (P=0.014); however, patients with stage II small HCC experienced a significantly poorer RFS (P=0.033). OS rates did not differ significantly between patients with stage I and stage II small HCC. Tumour margins, tumour histology and cirrhosis did not significantly affect OS or RFS (P>0.05).DISCUSSION: Increasing tumour size has generally been associated with poorer prognoses in cases of HCC. The present study verified the relationship between small HCC tumour size and OS; however, a reduction in OS with increasing tumour size was demonstrated for patients with stage I – but not for stage II – small HCC.CONCLUSION: Patients with stage II small HCC may benefit from aggressive surveillance for tumour recurrence and appropriate salvage treatment. Further studies are needed for additional stratification of stage I patients to identify those at increased risk of death.
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Morisson-Sarapak, Kornelia, Maciej Wrzesiński, Samir Zeair, and Marta Wawrzynowicz-Syczewska. "Late Recurrence of Hepatocellular Carcinoma in a Patient 10 Years after Liver Transplantation Unrelated to Transplanted Organ." Case Reports in Oncology 14, no. 3 (December 10, 2021): 1754–60. http://dx.doi.org/10.1159/000520535.
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Liver transplantation (LTx) is an accepted method of hepatocellular carcinoma (HCC) treatment in cirrhotic patients; however, it has many limitations, and there is a substantial risk of recurrence. Most relapses occur within the first 2 posttransplant years. We aimed to present a late extrahepatic recurrence of HCC 10 years after LTx, and we discuss the possible risk factors and ways to improve transplantation results. A 68-year-old patient with liver cirrhosis and HCC on the background of chronic HCV and past HBV infection was transplanted urgently due to the rapid decompensation. Anti-HCV treatment before surgery was unsuccessful. Pretransplant computed tomography showed 1 focal 4.5 cm lesion consistent with HCC. Histopathology of the explanted organ showed 2 nodules outside the Milan criteria. Angioinvasion was not found. The patient achieved a sustained viral response to pegylated interferon and ribavirin 2 years post-LTx. Eight years were uneventful. CT of the abdomen performed occasionally was normal. Ten years after LTx, the patient unexpectedly presented with shortness of breath, fatigue, and weight loss. Two metastatic nodules of HCC in the lungs and pelvis were found. Although late HCC recurrence post-LTx is rare, it should be always considered, especially when risk factors such as viral infections and underestimation of tumor advancement were identified. We advocate that oncological surveillance of HCC relapse has to be continued during the whole posttransplant period. High AFP levels, the unfavorable neutrophil to lymphocyte ratio, and better estimation of primary tumor size seem to be useful in the identification of good candidates for transplantation.
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Wu, Zheng, Zheng Wang, Lei Zhang, Xiaojing Song, Xilin Du, and Kai Tan. "Preliminary results of the phase II ALTER-H004: Anlotinib combined with TACE as adjuvant therapy in hepatocellular carcinoma patients at high risk of post surgery recurrence." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e16125-e16125. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e16125.
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e16125 Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high incidence and mortality worldwide. Presumably, adjuvant therapy is an efficient treatment for reducing recurrence in patients (pts) with hepatectomy, especially in those with high recurrence factors. Transarterial chemoembolization (TACE) can block the blood supply of the tumor, besides, high concentration of chemotherapeutic drugs can be accumulated within the tumor. It is recommended in several guidelines prophylactic TACE for pts with high recurrence risk factors after hepatectomy, which mainly include grade 1-2 microvascular invasion (M1-2) and portal vein tumor thrombus resection. Moreover, angiogenic inhibitors based therapy has constituted the crucial treatment strategy in HCC. As a novel multitarget tyrosine kinase inhibitor, anlotinib was demonstrated to be an effective first and second-line monotherapy for pts with advanced or recurrent HCC in China. The aim of this phase II trial was to evaluate the efficacy and safety of anlotinib as maintenance adjuvant treatment following inductional TACE in pts with HCC. Methods: A total of 48 histologically confirmed HCC pts who undertook hepatectomy within 1-2 months will be enrolled. The recruited pts who did not recieve any previous tumor-related treatment must have any of the following high risk factors: ≥5cm and <10cm of tumor diameter, tumor number ≥3, tumor microvascular invasion M1 or M2, portal vein tumor thrombus resection (Cheng’s classification Ⅰ/Ⅱ). Enrolled pts were received conventional TACE treatment with pirarubicin or epirubicin and platinum within 1-2 months after hepatectomy. On the 4th day after TACE treatment, oral anlotinib (12mg, qd, 2 weeks on 1 week off) was given until disease recurrence or unacceptable toxicity. The primary endpoint was disease free survival (DFS). Secondary endpoints included 1-year DFS rate, time to recurrence and safety. Results: By the cutoff date of January 26, 2021, 10 pts were enrolled and received at least once tumor assessment. According to RECIST version 1.1, 9 of them did not progress and 1 relapsed, in whom the DFS was 2.4 months. Most of treatment-related adverse events (TRAEs) were rash (20.0% Grade≤2), pain (20.0% Grade=1) and hypertension (10.0% Grade=1). Only one patient had grade 3 TRAE which was leukocytopenia (10.0%). No more grade 3 or above TRAEs occurred. Conclusions: The current results indicated that anlotinib combined with TACE as adjuvant therapy in HCC pts at high recurrence risk exhibited preliminary and implicational anti-tumor efficacy and manageable toxicity. The conclusion should be validated in more pts consecutively. Clinical trial information: NCT04213118.
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Yang, Modan, Winyen Tan, Xinyu Yang, Jianyong Zhuo, Zuyuan Lin, Beini Cen, Zhengxing Lian, et al. "Homocysteine: A novel prognostic biomarker in liver transplantation for alpha-fetoprotein- negative hepatocellular carcinoma." Cancer Biomarkers 29, no. 2 (October 9, 2020): 197–206. http://dx.doi.org/10.3233/cbm-201545.
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BACKGROUND: Precise recipient selection optimizes the prognosis of liver transplantation (LT) for hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is the most commonly used biomarker for diagnosis and prognosis of HCC in the clinical context. As a crucial molecule in methionine cycle, homocysteine (Hcy) level has been proved to be related to HCC progression and metastasis. OBJECTIVE: We aimed to explore the prognostic capacity of pre-transplant serum Hcy level in LT for HCC. METHODS: This study retrospectively enrolled 161 HCC patients who had underwent LT from donation after cardiac death (DCD) in the First Affiliated Hospital of Zhejiang University from 2015.01.01 to 2018.09.01. Pre-transplant serum Hcy level was incorporated into statistical analysis together with other clinical parameters and pathological features. RESULTS: From an overall perspective, significant difference was observed in Hcy level between recurrence (n= 61) and non-recurrence group (n= 100) though subsequent analysis showed unsatisfactory predicting performance. In the whole cohort, multivariate analysis showed that lnAFP (p= 0.010) and Milan criteria (MC, p< 0.001) were independent risk factors of HCC recurrence after LT. MA score based on MC and lnAFP performed well in predicting post-LT tumor recurrence with the AUROC at 0.836 (p< 0.001) and 3-year recurrence-free survival rate at 96.8% (p< 0.001) in the low risk group (n= 69). According to the clinical practice, serum concentration lower than 20 μg/L is considered as normal range of AFP. Elevated pre-transplant serum AFP (> 20 μg/L) predicts high HCC recurrence after LT. We further divided the 161 recipients into AFP- group (n= 77, AFP ⩽ 20 μg/L) and AFP+ group (n= 84, AFP > 20 μg/L). MA score was still well presented in the AFP+ group and the AUROC for tumor recurrence was 0.823 (p< 0.001), whereas the predicting accuracy was reduced in AFP- group (AUROC: 0.754, P< 0.001). After subsequent analysis, we found that elevated pre-transplant Hcy level (> 12.75 μmol/L) predicted increased tumor recurrence risk in AFP- group. The 3-year recurrence-free survival rates were 92.0% and 53.7% (p< 0.001) in low Hcy subgroup (n= 40) and high Hcy subgroup (n= 37) respectively. Multivariate analysis showed that Hcy (p= 0.040) and Milan criteria (p= 0.003) were independent risk factors for post-transplant tumor recurrence in AFP- group. Further combination of Hcy level and Milan criteria identified a subgroup of AFP- recipients with acceptable outcomes even though beyond Milan criteria (3-year recurrence-free survival rate: 77.7%, p< 0.001). CONCLUSION: As a classic predictor in HCC prognosis, AFP performed well in our study cohort when combined with Milan criteria. Homocysteine was an effective prognostic biomarker in LT for AFP- hepatocellular carcinoma. In recipients exceeding Milan criteria, acceptable post-transplant outcome could be seen in those with low Hcy and AFP level.
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Ruan, Dan-Yun, Yang Li, Nan Jiang, Ze-Xiao Lin, XiangBo Wan, Xing Li, Xiang-Yuan Wu, and Guihua Chen. "A prognostic model for early recurrence prediction in hepatocellular carcinoma after liver resection." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e15021-e15021. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e15021.
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e15021 Background: Recurrence resulting in high morbidity of hepatocellular carcinoma (HCC) patients received radical liver resection, the majority of which occur within 1 to 3 years. The study aims to find risk factors and set up a prognostic model predicting early recurrence of HCC. Methods: From 2003 to 2010, 196 HCC patients underwent liver resection were retrospectively analyzed. Univariate and multivariate analyses were used to assess variables. A recurrence risk model was developed with independent prognostic factors. Area under the ROC curve (AUC) was carried out to evaluate its predictive value. Results: The median follow-up time was 33 months (1-103M), median RFS was 22 months. Total tumor volume (TTV), hepatitis B, Child-Pugh score, and portal vein tumor thrombus were independent factors of recurrence. Patients with TTV>115cm3 had worse RFS (28.9% vs 51.7%, p<0.000) and OS (64.4% vs 80.1%, p=0.032) than those TTV≤115cm3. We established a risk model consisted of the 4 parameters, and classified patients into four stages. There were significant differences between each stage, especially for the 1st year. (1-yr RFS: 80.1% vs 47.8% vs 28.6% vs 0%, p=0.000, AUC 0.682). Compared to four currently used staging systems (BCLC, TNM, CLIP, and Okuda), the new model could well predict patient’s survival with the largest AUC in both RFS and OS (Table). Conclusions: TTV has been found a preferable description of tumor burden and a prognostic factor in HCC. This prognostic model predicts early tumor recurrence and survival of patients received radical liver resection and might contributes to the selection of patients who may benefit from surgery. [Table: see text]
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Hossain, SM Shakhwat, Md Mahboob Hasan, and Md Mahbubur Rahman. "Outcome of Oligonodular Hepatocellular Carcinoma after Hepatectomy." Journal of Armed Forces Medical College, Bangladesh 15, no. 1 (August 20, 2020): 55–57. http://dx.doi.org/10.3329/jafmc.v15i1.48643.
Full textAbstract:
Introduction: Hepatocellular carcinoma (HCC) is a common cancer and is the third most common cause of cancer-related death worldwide. Frequent recurrence of HCC after resection is a major surgical limitation. Early recurrence is the most disappointing outcome after surgery for multinodular HCC. Several studies found good results after hepatectomy for oligonodular (2 or 3 nodules) HCC.
Objectives: To observe the recurrence rate three months after hepatectomy for oligonodular HCC and study the possible risk factors.
Materials and Methods: The study population consisted of 102 patients with oligonodular HCC and received hepatectomy in Combined Military Hospital (CMH) between July 2011 and July 2017 according to the following criteria: (1) numbers of tumour nodules determined by preoperative imaging (computed tomography or magnetic resonance imaging) and intraoperative exploration; (2) diagnosis of HCC confirmed by postoperative histopathology; (3) incision margins negative; (4) complete clinicopathologic data; (5) adjuvant chemotherapy advised one month after operation. Multicentric occurrence (MO) and intrahepatic metastasis (IM) were determined in each patient according to the histopathologic examination.
Results: Among 102 patients, 43(42.2%) had small tumor stain three months after surgery, 22(21.6%) and 21(20.6%) were definded as single and multiple recurrence respectively. The recurrence rate of patients with microvascular involvement was higher (64.3%) than those without (33.8%), (p<0.05). IM or MO, complete tumor capsule or not, number of tumors (2 versus 3), liver condition (cirrhosis versus chronic hepatitis) showed no significant difference.
Conclusion: There was a high rate of very early recurrence for patients with oligonodular HCC three months ater hepatectomy, and the hepatic resection seems no-account for these patients regardless of very early recurrence or not a curative resection. Microvascular involvement was a risk factor while IM or MO is not.
Journal of Armed Forces Medical College Bangladesh Vol.15 (1) 2019: 55-57
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Ho, Cheng-Maw, Rey-Heng Hu, Yao-Ming Wu, Ming-Chih Ho, and Po-Huang Lee. "Cross-Match as an Immuno-Oncological Risk Factor for Hepatocellular Carcinoma Recurrence and Inferior Survival After Living Donor Liver Transplantation: A Call for Further Investigation." Clinical Medicine Insights: Oncology 14 (January 2020): 117955492096877. http://dx.doi.org/10.1177/1179554920968774.
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Background: The success of immunotherapy for patients with hepatocellular carcinoma (HCC) suggests that immune dysregulation occurs in HCC patients. This warrants an immuno-oncological risk assessment in the platform of liver transplantation. Methods: This retrospective single-center study analyzed risk factors for—particularly cross-matching performed through conventional complement-dependent cytotoxicity cross-match tests—and the outcomes of HCC recurrence following living donor liver transplant. Results: A total of 71 patients were included. The median follow-up period was 29.1 months; 17 (23.9%) patients had posttransplant HCC recurrence, and their 1-, 3-, and 5-year-survival rates were 70.6%, 25.7%, and 17.1%, respectively, which were inferior to those of patients without HCC recurrence (87.0%, 80.7%, and 77.2%, respectively; P < .001). In addition to microvascular invasion, positive cross-match results for B cells at 37°C (B- 37°C) or T cells at 4°C (T- 4°C) were associated with inferior overall survival in multivariable analysis after adjustment for tumor status beyond Milan criteria and elevated alpha-fetoprotein levels. Rejection alone cannot be the mechanism underlying the effects of positive cross-match results on patient outcomes. Adjusted survival curves suggested that positive cross-match B- 37°C or T- 4°C was associated with inferior recurrence-free and patient survival, but the robustness of the finding was limited by insufficient power. Conclusions: Additional large-scale studies are required to validate positive cross-match as an immuno-oncological factor associated with HCC recurrence and inferior patient survival.
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Bae, Bong Kyung, Hee Chul Park, Gyu Sang Yoo, Moon Seok Choi, Joo Hyun Oh, and Jeong Il Yu. "The Significance of Systemic Inflammation Markers in Intrahepatic Recurrence of Early-Stage Hepatocellular Carcinoma after Curative Treatment." Cancers 14, no. 9 (April 21, 2022): 2081. http://dx.doi.org/10.3390/cancers14092081.
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Systemic inflammatory markers (SIMs) are known to be associated with carcinogenesis and prognosis of hepatocellular carcinoma (HCC). We evaluated the significance of SIMs in intrahepatic recurrence (IHR) of early-stage HCC after curative treatment. This study was performed using prospectively collected registry data of newly diagnosed, previously untreated HCC between 2005 and 2017 at a single institution. Inclusion criteria were patients with Barcelona Clinic Liver Cancer stage 0 or A, who underwent curative treatment. Pre-treatment and post-treatment values of platelet, neutrophil, lymphocyte, monocyte, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lymphocyte/monocyte ratio (LMR) were analyzed with previously well-known risk factors of HCC to identify factors associated with IHR-free survival (IHRFS), early IHR, and late IHR. Of 4076 patients, 2142 patients (52.6%) experienced IHR, with early IHR in 1018 patients (25.0%) and late IHR in 1124 patients (27.6%). Pre-treatment platelet count and PLR and post-treatment worsening of NLR, PLR, and LMR were independently associated with IHRFS. Pre-treatment platelet count and post-treatment worsening of NLR, PLR, and LMR were significantly related to both early and late IHR. Pre-treatment values and post-treatment changes in SIMs were significant factors of IHR in early-stage HCC, independent of previously well-known risk factors of HCC.
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Liang, Tingbo, Zongli Zhang, Jinfang Zheng, Yijun Wang, Jialin Zhang, Bo Li, Tao Ma, et al. "Abstract CT546: A phase 2, multicenter study to evaluate the efficacy and safety of TACE sequential tislelizumab as adjuvant therapy in patients with HCC at high risk of recurrence after curative resection." Cancer Research 82, no. 12_Supplement (June 15, 2022): CT546. http://dx.doi.org/10.1158/1538-7445.am2022-ct546.
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Abstract Background: Surgical resection is one of the most important radical treatment in hepatocellular carcinoma (HCC). However, the 5-year recurrence rate of HCC after surgery is up to 70%, hampering further improvement in the prognosis of HCC patients. Risk factors for recurrence include microvascular invasion (MVI), multiple lesion and solitary tumor ≥ 5 cm, etc. Postoperative adjuvant treatment with transarterial chemoembolization (TACE) can reduce the recurrence rate and improve overall survival (OS) for patients with high risk of recurrence to some extent. TACE treatment promotes the release of tumor related antigen and the recruitment of immune cells by killing tumor cells, thereby promoting the anti-tumor immune response; it may have a potential synergistic effect with PD-1 blockade. Currently, there is no ongoing study on TACE combined with immunotherapy as postoperative adjuvant therapy for HCC. This is an open-label, multicenter, phase II study to evaluate the efficacy and safety of TACE sequential tislelizumab as adjuvant therapy in HCC patients with high risk of recurrence after curative resection (NCT04981665). Trial design: Eligible patients are ≥18 y, ECOG PS 0 or 1, Child-Pugh class A, diagnosed with HCC confirmed by histopathology or cytology, with no prior systematic treatment and locoregional therapy for HCC, and have received a curative resection with high risk of recurrence fulfilling one of the following criteria: (1) a solitary tumor > 5 cm, (2) solitary tumor > 2 cm and ≤ 5 cm with MVI, (3) 2-3 lesions. 50 pts will receive TACE treatment once (4±1 w) after curative resection, then followed by tislelizumab 200 mg IV Q3W (5±2 d). Tislelizumab will be administered until disease recurrence, intolerable toxicity, death, withdrawal of consent or completion of a maximum of 17 cycles of tislelizumab. Primary endpoint is 2-year recurrence-free survival rate (2-year RFS rate). Secondary endpoints include RFS, time to recurrence, OS, 1-year RFS rate, 1-year and 2-year OS rate, and safety. Exploratory endpoints include biomarkers related to the response and prognosis of adjuvant TACE sequential tislelizumab therapy. Citation Format: Tingbo Liang, Zongli Zhang, Jinfang Zheng, Yijun Wang, Jialin Zhang, Bo Li, Tao Ma, Yunfei Xu, Changxiong Wu, Quan Sun, Yiman Meng, Xiaoli Yang. A phase 2, multicenter study to evaluate the efficacy and safety of TACE sequential tislelizumab as adjuvant therapy in patients with HCC at high risk of recurrence after curative resection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT546.
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Kashyap, R., S. Safadjou, G. Connolly, S. Ramalingam, S. Agarwal, M. Vetter, L. Grinnell-Merrick, et al. "METABOLIC RISK FACTORS - INFLUENCE ON SURVIVAL AND RECURRENCE OF HCC POST LIVER TRANSPLANT." Transplantation Journal 90 (July 2010): 801. http://dx.doi.org/10.1097/00007890-201007272-01557.
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Toubert, Cyprien, Boris Guiu, Bader Al Taweel, Eric Assenat, Fabrizio Panaro, François-Regis Souche, Jose Ursic-Bedoya, Francis Navarro, and Astrid Herrero. "Prolonged Survival after Recurrence in HCC Resected Patients Using Repeated Curative Therapies: Never Give Up!" Cancers 15, no. 1 (December 30, 2022): 232. http://dx.doi.org/10.3390/cancers15010232.
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Surgical resection is the optimal treatment for HCC, despite a high risk of recurrence. Few data are available on patient’s survival after resection. This is a retrospective study of tumor recurrence occurring after hepatectomy for HCC from 2000 to 2016. Univariate and multivariate analyses were performed to identify prognostic factors of survival after recurrence (SAR). Among 387 patients, 226 recurred (58.4%) with a median SAR of 26 months. Curative treatments (liver transplantation, repeat hepatectomy, thermal ablation) were performed for 44.7% of patients. Independent prognostic factors for SAR were micro-vascular invasion on the primary surgical specimen, size of the initial tumor >5 cm, preoperative AFP, albumin and platelet levels, male gender, number, size and localization of tumors at recurrence, time to recurrence, Child–Pugh score and treatment at recurrence. In subgroup analysis, early recurrence (46%) was associated with a decrease in SAR, by contrast with late recurrence. However, the overall survival (OS) of patients with early recurrence and curative treatment did not significantly differ from that of non-recurring patients. For late recurrence, OS did not significantly differ from that of non-recurring patients, regardless of the proposed treatment. Aggressive and repeat treatments are therefore key to improve prognosis of patients with HCC.
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Kondili, L. A., A. Lala, B. Gunson, S. Hubscher, S. Olliff, S. Bramhall, and D. Mutimer. "255 Primary hepatocellular cancer (HCC) in the explanted liver: Outcome of transplantation and risk factors for HCC recurrence." Journal of Hepatology 40 (January 2004): 80. http://dx.doi.org/10.1016/s0168-8278(04)90255-3.
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Cai, Huayong, Yu Zhang, Fanyu Meng, Chao Cui, Hao Li, Minghao Sui, Haoyun Zhang, and Shichun Lu. "Preoperative Serum IL6, IL8, and TNF-α May Predict the Recurrence of Hepatocellular Cancer." Gastroenterology Research and Practice 2019 (October 20, 2019): 1–10. http://dx.doi.org/10.1155/2019/6160783.
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Purpose. As we all know, curative resection remains the only effective treatment for hepatocellular cancer (HCC). However, systemic inflammatory response syndrome always correlates with surgery, which may impose an impact on the clinical outcome of HCC patients who had undergone curative treatment. The present study is aimed at exploring the correlation between perioperative inflammatory mediators and recurrence risk of HCC. Methods. This study retrospectively included 157 histologically confirmed single HCC patients (88 patients developed HCC again) who had received radical hepatectomy between January 2016 and May 2018 at the Department of Hepatobiliary Surgery, the People’s Liberation Army General Hospital (PLAGH), China. The cut-off values for predicting recurrence were determined by receiver operating characteristic (ROC) curve analysis with estimation of the Youden index. Recurrence-free survival (RFS) was assessed using the Kaplan-Meier method, and the difference was compared between groups by the log-rank test. Univariate/multivariate analysis was performed to identify independent risk factors of postoperative tumor recurrence. Results. The perioperative serum IL1, IL2, and IL10 levels showed no difference between groups, whereas the serum IL6, IL8, and TNF-α levels showed significant differences between groups. High preoperative serum IL6, IL8, and TNF-α levels were significantly associated with shorter RFS. Multivariate analysis revealed that preoperative serum IL6>8.45 pg/ml, preoperative serum IL8>68 pg/ml, preoperative serum TNF−α>14.9 pg/ml, microvascular invasion (MVI), and maximum tumor size>6 cm were independent predictors of RFS. Conclusions. The present study confirmed that high preoperative serum IL6, IL8, and TNF-α levels were distinctly correlated with the postoperative tumor recurrence risk of HCC patients.
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Rinaldi, Luca, Riccardo Nevola, Gianluigi Franci, Alessandro Perrella, Giusy Corvino, Aldo Marrone, Massimiliano Berretta, et al. "Risk of Hepatocellular Carcinoma after HCV Clearance by Direct-Acting Antivirals Treatment Predictive Factors and Role of Epigenetics." Cancers 12, no. 6 (May 26, 2020): 1351. http://dx.doi.org/10.3390/cancers12061351.
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Direct-acting antivirals (DAAs) induce a rapid virologic response (SVR) in up to 99% of chronic hepatitis C patients. The role of SVR by DAAs on the incidence or recurrence of hepatocellular carcinoma (HCC) is still a matter of debate, although it is known that SVR does not eliminate the risk of HCC. In this review, we made an updated analysis of the literature data on the impact of SVR by DAAs on the risk of HCC as well as an assessment of risk factors and the role of epigenetics. Data showed that SVR has no impact on the occurrence of HCC in the short–medium term but reduces the risk of HCC in the medium–long term. A direct role of DAAs in the development of HCC has not been demonstrated, while the hypothesis of a reduction in immune surveillance in response to the rapid clearance of HCV and changes in the cytokine pattern influencing early carcinogenesis remains to be further elucidated. HCV induces epigenetic alterations such as modifications of the histone tail and DNA methylation, which are risk factors for HCC, and such changes are maintained after HCV clearance. Future epigenetic studies could lead to identify useful biomarkers and therapeutic targets. Cirrhosis has been identified as a risk factor for HCC, particularly if associated with high liver stiffness and α-fetoprotein values, diabetes and the male sex. Currently, considering the high number and health cost to follow subjects’ post-HCV clearance by DAAs, it is mandatory to identify those at high risk of HCC to optimize management.
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Au, Kin-Pan, James Yan-Yue Fung, Wing-Chiu Dai, Albert Chi-Yan Chan, Chung-Mau Lo, and Kenneth Siu-Ho Chok. "Impact of Tumour Biology on Outcomes of Radical Therapy for Hepatocellular Carcinoma Oligo-Recurrence after Liver Transplantation." Journal of Clinical Medicine 11, no. 15 (July 28, 2022): 4389. http://dx.doi.org/10.3390/jcm11154389.
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It is uncertain whether tumour biology affects radical treatment for post-transplant hepatocellular carcinoma (HCC) oligo-recurrence, i.e. recurrence limited in numbers and locations amendable to radical therapy. We conducted a retrospective study on 144 patients with post-transplant HCC recurrence. Early recurrence within one year after transplant (HR 2.53, 95% CI 1.65–3.88, p < 0.001), liver recurrence (HR 1.74, 95% CI 1.12–2.68, p = 0.01) and AFP > 200 ng/mL upon recurrence (HR 1.62, 95% CI 1.04–2.52, p = 0.03) predicted mortality following recurrence. In patients with early recurrence and liver recurrence, radical treatment was associated with improved post-recurrence survival (early recurrence: median 18.2 ± 1.5 vs. 9.2 ± 1.5 months, p < 0.001; liver recurrence: median 28.0 ± 4.5 vs. 11.6 ± 2.0, p < 0.001). In patients with AFP > 200 ng/mL, improvement in survival did not reach statistical significance (median 18.2 ± 6.5 vs. 8.8 ± 2.2 months, p = 0.13). Survival benefits associated with radical therapy were reduced in early recurrence (13.6 vs. 9.0 months) and recurrence with high AFP (15.4 vs. 9.3 months) but were similar among patients with and without liver recurrence (16.9 vs. 16.4 months). They were also diminished in patients with multiple biological risk factors (0 risk factor: 29.0 months; 1 risk factor: 19.7 months; 2–3 risk factors: 3.4 months): The survival benefit following radical therapy was superior in patients with favourable biological recurrence but was also observed in patients with poor tumour biology. Treatment decisions should be individualised considering the oncological benefits, quality of life gain and procedural morbidity.
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Chen, Yu-Syuan, Shih-Yu Yang, Pei-Ming Wang, Chih-Chi Wang, Chee-Chien Yong, Ding-Wei Chen, Yueh-Wei Liu, et al. "Concurrent Cholecystectomy Is Associated with a Lower Risk of Recurrence after Curative Resection in Early-Stage Hepatocellular Carcinoma: A 10 Year Observational Single-Center Study." Journal of Personalized Medicine 11, no. 12 (November 30, 2021): 1261. http://dx.doi.org/10.3390/jpm11121261.
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Background: Cholecystectomy has been reported to be associated with increased risk of developing hepatocellular carcinoma (HCC). However, there is little information about the impact of cholecystectomy on the outcome of HCC. Aims: To evaluate the long-term effect of concurrent cholecystectomy on recurrence and overall survival in HCC after curative hepatectomy. Patients and Methods: We retrospectively enrolled 857 patients with BCLC stage 0 or A HCC who underwent primary resection from January 2001 to June 2016. The impact of concurrent cholecystectomy on overall survival (OS) and recurrence-free survival (RFS) were analyzed by Cox’s proportional hazards models after one-to-one propensity score matching (PSM). Results: Of the 857 patients, 539 (62.9%) received concurrent cholecystectomy (cholecystectomy group) and 318 (37.1%) did not (non-cholecystectomy group). During the mean follow-up period of 75.0 months, 471 (55.0%) patients experienced recurrence, and 321 (37.5%) died. RFS and OS were not significantly different between the groups. After PSM, a total of 298 patients were enrolled in each group. RFS was significantly higher in the cholecystectomy than non-cholecystectomy group (p = 0.044). In multivariate analysis, age (p = 0.022), serum AFP (p = 0.008), liver cirrhosis (p < 0.001), diabetes (p = 0.004), tumor number (p = 0.005), tumor size (p = 0.002), histological grade (p = 0.001), microvascular invasion (p < 0.001) and cholecystectomy (p = 0.021) were independent risk factors for HCC recurrence. However, there were no significant differences in OS between the cholecystectomy and non-cholecystectomy groups. Conclusions: Concurrent cholecystectomy may reduce recurrence in early-stage HCC after curative resection. Further studies are needed to validate our results.
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Force, Madison, Grace Park, Divya Chalikonda, Christopher Roth, Micah Cohen, Dina Halegoua-DeMarzio, and Hie-Won Hann. "Alpha-Fetoprotein (AFP) and AFP-L3 Is Most Useful in Detection of Recurrence of Hepatocellular Carcinoma in Patients after Tumor Ablation and with Low AFP Level." Viruses 14, no. 4 (April 8, 2022): 775. http://dx.doi.org/10.3390/v14040775.
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Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is a leading cause of mortality worldwide. While there are many risk factors for HCC including alcohol, obesity, and diabetes, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection still account for the majority of HCC worldwide. Globally, HBV is the leading risk factor for HCC. Patients with chronic hepatitis B (CHB) and advanced liver disease are at high risk for HCC. Screening for HCC is done routinely with ultrasound with or without alpha-fetoprotein (AFP) at six-month intervals. The combination of ultrasound and AFP has been shown to provide some additional detection of 6–8% of cases compared to ultrasound alone; however, this also increases false-positive results. This is because AFP can be elevated not only in the setting of HCC, but also in chronic hepatitis, liver cirrhosis, or ALT flare in CHB, which limits the specificity of AFP. AFP-L3 is a subfraction of AFP that is produced by malignant hepatocytes. The ratio of AFP-L3 to total AFP is reported as a percentage, and over 10% AFP-L3 is consistent with a diagnosis of HCC. Here, we review five cases of patients with CHB, cirrhosis, and HCC, and their levels of AFP and the AFP-L3% at various stages of disease including ALT flare, cirrhosis, initial diagnosis of HCC, and recurrence of HCC. These cases emphasize the utility of AFP-L3% in identifying early, new or recurrent HCC prior to the presence of imaging findings.
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He, Aiwu Ruth, Fung-Lung Chung, Monika Aggarwal, Zizhao Zhu, Sophie Gould, Kevin Zhang, Mark Kuo, et al. "Detection of DNA adduct γ-OHPdG in circulating tumor cells (CTCs) and its use as a prognostic biomarker in patients with hepatocellular carcinoma (HCC)." Journal of Clinical Oncology 41, no. 4_suppl (February 1, 2023): 594. http://dx.doi.org/10.1200/jco.2023.41.4_suppl.594.
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594 Background: A blood-based biomarker to predict the risk of hepatocellular carcinoma (HCC), and its recurrence is needed. Previously, we showed that γ-OHPdG, a mutagenic DNA adduct formed by lipid peroxidation, in liver biopsies from HCC patients, as detected by IHC, is inversely associated with overall survival (p<0.0001) and recurrence-free survival (p<0.007) after surgical resection. This finding suggests that γ-OHPdG may serve as a prognostic biomarker of HCC and its recurrence. A non-invasive method to detect γ-OHPdG is needed. Liquid biopsy is preferred over tissue biopsy because it is non-invasive, allows repeated sampling, lower risk to patient, and lower medical care cost. We developed a non-invasive method for detecting and quantifying γ-OHPdG using CTCs from HCC patient. Methods: The method involved following steps. First, CTCs from blood samples were isolated using a RosetteSep CD45 Depletion Cocktail and Ficoll Paque-based method. Isolated cells were identified as liver CTCs using asialoglycoprotein receptor 1 (ASGPR1), a cell surface protein expressed solely on the surface of hepatic cells, and γ-OHPdG by immunocytochemistry. The percentage of ASGPR1 and γ-OHPdG-positive stained CTCs and γ-OHPdG staining intensity was quantified using Metamorph software. The staining intensities in livers CTCs will be compared with that found in liver biopsies by IHC. Results: To determine the sensitivity and specificity of testing -γ-OHPdG level in circulating tumor cells using an-anti γ-OHPdG antibody, we showed that the proportion of γ-OHPdG-positively stained cells and staining intensity increased in HepG2 liver cancer cells upon acrolein treatment at increasing concentration. Furthermore, when the HepG2 was used to spike blood of healthy volunteers’, the recovery rate of γ-OHPdG positivity was > 50-60%. CTCs from 32 HCC patients, detected at a positivity rate of ~97%, were tested for γ-OHPdG levels using the method developed in this project. The clinical factors including demographics, risk factors, alpha-fetoprotein (AFP), HCC size, multifocality, vascular invasion, extrahepatic metastasis have been correlated with the levels of γ-OHPdG in CTCs. Conclusions: The CTC method developed for detecting and quantifying γ-OHPdG warrant validations as a prognostic biomarker for predicting HCC risk and recurrence in clinical trials.
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Kaseb, A. O., M. Bansal, I. Wollner, V. Shah, D. Moonka, G. Divine, and M. Abouljoud. "A 10-year retrospective analysis of risk factors, patterns of cancer recurrence, and survival after liver transplant for cirrhosis and hepatocellular carcinoma." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 4617. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.4617.
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4617 Introduction: Determining eligible patients who are likely to have better outcomes following orthotopic liver transplant (OLT) for cirrhosis and hepatocellular carcinoma (HCC) is an ongoing challenge. In addition, tumor recurrence represents a major limitation of long-term survival in this setting. Patients and Methods: The study analyzed 72 OLT recipients for cirrhosis and HCC, between 1996–2006. The endpoints were frequency, patterns, localization, and risk factors of recurrence. Survival from time of OLT to recurrence was compared with primary tumor and patient characteristics, and type of treatment received pre- and post-OLT using univariate and multivariate analyses. Survival was estimated using Kaplan-Meier plots. Results: 13 recurrences (18%) occurred after a median of 33.4 months follow up (6–123 months). 11/13 (84.6%) were distant metastases. Using cox regression analysis and log-rank p-value; bilobar involvement, a tumor number of =3, tumor grade 2 or 3, size >3 cm, vascular invasion, and elevated AFP at diagnosis were all positively associated with recurrence (either distant or any). Tumors that met Milan criteria were associated with a lower likelihood of recurrence. In addition, Pre and post-OLT treatments were not found to be associated with significantly improved disease-free survival. Conclusions: Our analyses confirmed that advanced pathologic features are independently associated with significantly shorter disease-free survival. Pre- and post-OLT treatment modalities were not observed to improve disease-free survival for patients with bad prognostic indicators. However, this is limited due to our small sample size and our univariate anaylsis. We conclude that careful patient selection based on prognostic indicators would maximize benefit from use of this expensive and limited resource. [Table: see text] No significant financial relationships to disclose.