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Rohland O, Freye L, Schwenk L, Ali-Deeb A, Ardelt M, Bauschke A, Settmacher U, Rauchfuß F, Dondorf F. Liver Transplantation for Hepatocellular Carcinoma beyond the Milan Criteria: A Specific Role for Living Donor Liver Transplantation after Neoadjuvant Therapy. Cancers (Basel) 2024; 16:920. [PMID: 38473282 PMCID: PMC10930899 DOI: 10.3390/cancers16050920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 02/21/2024] [Accepted: 02/23/2024] [Indexed: 03/14/2024] Open
Abstract
PURPOSE This study was designed to elucidate the various new classifications and the use of LDLT and bridging therapy for HCC in this context beyond the Milan criteria (MC). METHODS The clinical data of patients with HCC outside the MC who underwent LT at Jena University between January 2007 and August 2023 were retrospectively analysed. Eligible patients were classified according to various classification systems. Clinicopathological features, overall and disease-free survival rates were compared between LT and LDLT within the context of bridging therapy. THE RESULTS Among the 245 patients analysed, 120 patients did not meet the MC, and 125 patients met the MC. Moreover, there were comparable overall survival rates between patients outside the MC for LT versus LDLT (OS 44.3 months vs. 28.3 months; 5-year survival, 56.4% vs. 40%; p = 0.84). G3 tumour differentiation, the presence of angioinvasion and lack of bridging were statistically significant risk factors for tumour recurrence according to univariate and multivariate analyses (HR 6.34; p = 0.0002; HR 8.21; p < 0.0001; HR 7.50; p = 0.0001). Bridging therapy before transplantation provided a significant survival advantage regardless of the transplant procedure (OS: p = 0.008; DFS: p < 0.001). CONCLUSIONS Patients with HCC outside the MC who underwent LT or LDLT had worse outcomes compared to those of patients who met the MC but still had a survival advantage compared to patients without transplantation. Nevertheless, such patients remain disadvantaged on the waiting list, which is why LDLT represents a safe alternative to LT and should be considered in bridged HCC patients because of differences in tumour differentiation, size and tumour marker dynamics.
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Affiliation(s)
- Oliver Rohland
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, 07747 Jena, Germany
- Interdisciplinary Center for Clinical Research (IZKF), Jena University Hospital, 07747 Jena, Germany
- Cancer Center Central Germany (CCCG), 04103 Leipzig, Germany
| | - Lea Freye
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, 07747 Jena, Germany
| | - Laura Schwenk
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, 07747 Jena, Germany
- Cancer Center Central Germany (CCCG), 04103 Leipzig, Germany
| | - Aladdin Ali-Deeb
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, 07747 Jena, Germany
- Cancer Center Central Germany (CCCG), 04103 Leipzig, Germany
| | - Michael Ardelt
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, 07747 Jena, Germany
- Cancer Center Central Germany (CCCG), 04103 Leipzig, Germany
| | - Astrid Bauschke
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, 07747 Jena, Germany
- Cancer Center Central Germany (CCCG), 04103 Leipzig, Germany
| | - Utz Settmacher
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, 07747 Jena, Germany
- Cancer Center Central Germany (CCCG), 04103 Leipzig, Germany
| | - Falk Rauchfuß
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, 07747 Jena, Germany
- Cancer Center Central Germany (CCCG), 04103 Leipzig, Germany
| | - Felix Dondorf
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, 07747 Jena, Germany
- Cancer Center Central Germany (CCCG), 04103 Leipzig, Germany
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Sun LY, Ouyang Q, Cen WJ, Wang F, Tang WT, Shao JY. A Model Based on Artificial Intelligence Algorithm for Monitoring Recurrence of HCC after Hepatectomy. Am Surg 2023; 89:1468-1478. [PMID: 34894786 DOI: 10.1177/00031348211063549] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND There is no satisfactory indicator for monitoring recurrence after resection of hepatocellular carcinoma (HCC). This retrospective study aimed to design and validate an HCC monitor recurrence (HMR) model for patients without metastasis after hepatectomy. METHODS A training cohort was recruited from 1179 patients with HCC without metastasis after hepatectomy between February 2012 and December 2015. An HMR model was developed using an AdaBoost classifier algorithm. The factors included patient age, TNM staging, tumor size, and pre/postoperative dynamic variations of alpha-fetoprotein (AFP). The diagnostic efficacy of the model was evaluated based on the area under the receiver operating characteristic curves (AUCs). The model was validated using a cohort of 695 patients. RESULTS In preoperative patients with positive or negative AFP, the AUC of the validation cohort in the HMR model was .8877, which indicated better diagnostic efficacy than that of serum AFP (AUC, .7348). The HMR model predicted recurrence earlier than computed tomography/magnetic resonance imaging did by 191.58 ± 165 days. In addition, the HMR model can predict the prognosis of patients with HCC after resection. CONCLUSIONS The HMR model established in this study is more accurate than serum AFP for monitoring recurrence after hepatectomy for HCC and can be used for real-time monitoring of the postoperative status in patients with HCC without metastasis.
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Affiliation(s)
- Li-Yue Sun
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Qing Ouyang
- Department of Hepatobiliary, General Hospital of Southern Theatre Command of PLA, Guangzhou, China
| | - Wen-Jian Cen
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Fang Wang
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wen-Ting Tang
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jian-Yong Shao
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
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Pathology of Combined Hepatocellular Carcinoma-Cholangiocarcinoma: An Update. Cancers (Basel) 2023; 15:cancers15020494. [PMID: 36672443 PMCID: PMC9856551 DOI: 10.3390/cancers15020494] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 01/08/2023] [Accepted: 01/11/2023] [Indexed: 01/15/2023] Open
Abstract
Combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer that is composed of both hepatocellular and cholangiocellular differentiated cells. It is slightly more common in men and among Asian and Pacific islanders. Overall, risk factors are similar to classic risk factors of hepatocellular carcinoma (HCC). The classification has significantly evolved over time. The last WHO classification (2019) mainly emphasized diagnosis on morphological basis with routine stainings, discarded previously recognized classifications with carcinomas with stem cell features, introduced intermediate cell carcinoma as a specific subtype and considered cholangiolocarcinoma as a subtype of cholangiocellular carcinoma. Immunohistochemical markers may be applied for further specification but have limited value for diagnosis. Recent discoveries in molecular pathway regulation may pioneer new therapeutic approaches for this poor prognostic and challenging diagnosis.
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Combined Hepatocellular-Cholangiocarcinoma: An Update on Pathology and Diagnostic Approach. Biomedicines 2022; 10:biomedicines10081826. [PMID: 36009374 PMCID: PMC9405224 DOI: 10.3390/biomedicines10081826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 07/19/2022] [Accepted: 07/20/2022] [Indexed: 12/04/2022] Open
Abstract
Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver carcinoma displaying both hepatocytic and cholangiocytic differentiation within the same tumor. Relative to classic hepatocellular carcinoma (HCC), cHCC-CCA has more aggressive behavior and a poorer prognosis. Though recent advances have improved our understanding of the biology underlying cHCC-CCAs, they remain diagnostically challenging for pathologists because of their morphologic and phenotypic diversity. Accurate diagnosis of cHCC-CCA is important for patient management and prognostication. Herein, we review recent updates on cHCC-CCA, focusing on tumor classification, pathology, and diagnostic approach.
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Zhang F, Hu KS, Lu SX, Li M, Chen RX, Ren ZG, Shi YH, Yin X. Prognostic significance of preoperative systemic immune-inflammation index in combined hepatocellular-cholangiocarcinoma. Cancer Biomark 2021; 31:211-225. [PMID: 33896819 DOI: 10.3233/cbm-200643] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Inflammation-based prognostic scores have been increasingly used for prognosis prediction in malignant tumors. However, no existing study has comprehensively evaluated these scores in combined hepatocellular-cholangiocarcinoma (cHCC-CCA). OBJECTIVE This study aimed to identify a robust inflammation-based prognostic predictor for cHCC-CCA. METHODS We retrospectively analyzed 220 patients pathologically confirmed as Allen type C cHCC-CCA. The univariate and multivariate analyses were used to explore the associations between clinical variables and prognosis of cHCC-CCA. The propensity score-matching (PSM) was performed to reduce the effects of potential cofounders and selection bias. Finally, the predictive values of different inflammation-based indices were compared by using time-dependent receiver operating characteristic (ROC) curves. RESULTS The systemic immune-inflammation index (SII) and aspartate aminotransferase to platelet ratio index (APRI) were identified as independent prognostic predictors in multivariate analysis. After PSM, the survival differences were still significant between SII-high group and SII-low group (P= 0.016 for RFS and P= 0.001 for OS). Further ROC analysis showed that the SII harbored the largest 1-, 3- and 5-year area under the curves (AUC) values as compared with other scores. CONCLUSIONS The SII may serve as a preferable predictor of both recurrence-free survival (RFS) and overall survival (OS) in patients with cHCC-CCA.
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Affiliation(s)
- Feng Zhang
- Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Ke-Shu Hu
- Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Shen-Xin Lu
- Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Miao Li
- Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Rong-Xin Chen
- Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Zheng-Gang Ren
- Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Ying-Hong Shi
- Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Xin Yin
- Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
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Sun LY, He Y, Liu Q, Wang F. Effect of delta α-fetoprotein on the detection of liver cancer recurrence. Transl Cancer Res 2020; 9:6263-6274. [PMID: 35117236 PMCID: PMC8798164 DOI: 10.21037/tcr-20-1874] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Accepted: 09/12/2020] [Indexed: 11/24/2022]
Abstract
BACKGROUND We explored the ability of delta α-fetoprotein (ΔAFP) to detect recurrence in patients with liver cancer treated with hepatectomy. METHODS A total of 1,846 patients diagnosed with local liver cancer who underwent hepatectomy at Sun Yat-sen University Cancer Center were enrolled in the present study. Receiver operating characteristic curve analysis was used to determine the cutoff value of ΔAFP at the last follow-up or recurrence. RESULTS Recurrence occurred in 51.5% (950/1,846) of liver cancer patients. The cutoff value of ΔAFP was 1.295 ng/mL in our model. Sensitivity in our model was higher than the normal range for AFP level for detecting recurrence (59.8% vs. 43.8%), but specificity was similar (98.4% vs. 99.8%). ΔAFP in preoperative AFP-positive patients (77.16% vs. 63.28%) and AFP-negative patients (31.20% vs. 11.70%) was more sensitive than normal AFP. ΔAFP was superior to AFP in the early (78.13% vs. 63.75%) or late recurrence (56.08% vs. 39.75%) of liver cancer. Moreover, in 18.3% of patients with recurrence (174/950), ΔAFP detected recurrence earlier than computed tomography/magnetic resonance imaging by 158.33 days. ΔAFP during follow-up indicated a worse prognosis after hepatectomy. CONCLUSIONS The cutoff value of ΔAFP is more sensitive for monitoring recurrence than a normal AFP level in liver cancer patients.
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Affiliation(s)
- Li-Yue Sun
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yuan He
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Qing Liu
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Fang Wang
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
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Zhang J, Wang X, Zhang L, Yao L, Xue X, Zhang S, Li X, Chen Y, Pang P, Sun D, Xu J, Shi Y, Chen F. Radiomics predict postoperative survival of patients with primary liver cancer with different pathological types. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:820. [PMID: 32793665 PMCID: PMC7396247 DOI: 10.21037/atm-19-4668] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Background Radiomics can be used to determine the prognosis of liver cancer, but it might vary among cancer types. This study aimed to explore the clinicopathological features, radiomics, and survival of patients with hepatocellular carcinoma (HCC), mass-type cholangiocarcinoma (MCC), and combined hepatocellular-cholangiocarcinoma (CHCC). Methods This was a retrospective cohort study of patients with primary liver cancer operated at the department of hepatobiliary surgery of the First Affiliated Hospital of Zhejiang University from 07/2013 to 11/2015. All patients underwent preoperative liver enhanced MRI scans and diffusion-weighted imaging (DWI). The radiomics characteristics of DWI and the enhanced equilibrium phase (EP) images were extracted. The mRMR (minimum redundancy maximum relevance) was applied to filter the parameters. Results There were 44 patients with MCC, 59 with HCC, and 33 with CHCC. Macrovascular invasion, tumor diameter, positive ferritin preoperatively, positive AFP preoperatively, positive CEA preoperatively, Correlation, Inverse Difference Moment, and Cluster Prominence in model A (DWI and clinicopathological parameters) were independently associated with overall survival (OS) (P<0.05). Lymphadenopathy, gender, positive ferritin preoperatively, positive AFP preoperatively, positive CEA preoperatively, Uniformity, and Cluster Prominence in model B (EP and clinicopathological parameters) were independently associated with OS (P<0.05). Macrovascular invasion, lymphadenopathy, gender, positive ferritin preoperatively, positive CEA preoperatively, Uniformity_EP, GLCMEnergy_DWI, and Cluster Prominence_EP in model C (image texture and clinicopathological parameters) were independently associated with OS (P<0.05). Those factors were used to construct three nomograms to predict OS. Conclusions Clinicopathological and radiomics features are independently associated with the OS of patients with primary liver cancer.
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Affiliation(s)
- Jiahui Zhang
- Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Department of Radiology, Hangzhou Third Hospital, Hangzhou, China
| | - Xiaoli Wang
- Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lixia Zhang
- Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Linpeng Yao
- Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xing Xue
- Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Siying Zhang
- Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xin Li
- GE China Medical Life Sciences Division Core Image Senior Application Team, Guangzhou, China
| | - Yuanjun Chen
- GE China Medical Life Sciences Division Core Image Senior Application Team, Guangzhou, China
| | - Peipei Pang
- GE China Medical Life Sciences Division Core Image Senior Application Team, Guangzhou, China
| | | | - Juan Xu
- Medical Big Data, AliHealth, Hangzhou, China
| | - Yanjun Shi
- Department of Hepatobiliary and Pancreas Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Feng Chen
- Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Jiang XX, Huang XT, Huang CS, Chen LH, Liang LJ, Yin XY. Long-term outcome and prognostic factors of combined hepatocellular carcinoma and cholangiocarcinoma after curative resection. Gastroenterol Rep (Oxf) 2020; 8:134-142. [PMID: 32280473 PMCID: PMC7136721 DOI: 10.1093/gastro/goaa003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 01/09/2020] [Accepted: 01/13/2020] [Indexed: 02/06/2023] Open
Abstract
Background Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is a rare subtype of primary liver cancers. Its prognostic factors remain unclear. The study aimed to evaluate its long-term outcome and prognostic factors by retrospectively reviewing the series of cHCC-CC after curative resection from our institute. Methods A total of 55 pathologically confirmed cHCC-CC patients undergoing curative resections between January 2003 and January 2018 at the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) were included. The clinicopathological and follow-up data were retrieved. Overall survival (OS) and recurrence-free survivals (RFS) were analysed by Kaplan–Meier curve. The independent prognostic factors were determined by using univariate and multivariate Cox analyses. Results There were 41 males and 14 females, with a median age of 51.0 (interquartile range, 44.0–60.0) years. The 1-, 3-, and 5-year OS and RFS rates in cHCC-CC were 80.0%, 25.5%, and 16.4%, respectively, and 52.7%, 21.8%, and 10.9%, respectively. The median OS and RFS were 24.9 and 14.5 months, respectively. Univariate and multivariate analyses revealed that elevated alpha-fetal protein (AFP) and/or CA19-9, vascular invasion, local extra-hepatic invasion, and lymph-node metastasis (LNM) were independent unfavorable prognostic factors for OS and RFS (all P < 0.005). Furthermore, elevated AFP and/or CA19-9 were independent unfavorable prognostic factors in various subgroups of cHCC-CC, including patients aged <60 years, positive hepatitis B surface antigen, cirrhosis, single tumor, tumor size ≥5 cm, no vascular invasion, no LNM, and no local extra-hepatic invasion (all P < 0.05). Conclusions Elevated AFP and/or CA19-9, vascular invasion, local extra-hepatic invasion, and LNM were independent unfavorable prognostic factors for long-term survival of cHCC-CC undergoing curative resections. Patients with normal levels of AFP and CA19-9 had better prognosis.
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Affiliation(s)
- Xing-Xing Jiang
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.,Department of Hepatobiliary Surgery, The Affiliated Xinyu Hospital, Nanchang University, Xinyu, Jiangxi, P. R. China
| | - Xi-Tai Huang
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Chen-Song Huang
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Liu-Hua Chen
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Li-Jian Liang
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Xiao-Yu Yin
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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Competing risk analyses of overall survival and cancer-specific survival in patients with combined hepatocellular cholangiocarcinoma after surgery. BMC Cancer 2019; 19:178. [PMID: 30813928 PMCID: PMC6391817 DOI: 10.1186/s12885-019-5398-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Accepted: 02/20/2019] [Indexed: 12/15/2022] Open
Abstract
Background Our objective was to identify risk factors affecting overall survival (OS) and cancer-specific survival (CSS) and build nomograms to predict survival based on a large population-based cohort. Methods Two hundred and thirty patients diagnosed with CHCC between 2004 and 2015 were retrospectively extracted from the Surveillance, Epidemiology, and End Results (SEER) database as a training cohort. In addition, Ninety-nine patients diagnosed with CHCC between 2000 and 2017 were retrospectively extracted from Sun Yat-Sen University Cancer Center (SYSUCC) as an external validation. Nomograms for predicting probability of OS and CSS were established. Performance of the nomograms was measured by concordance index (C-index) and the area under receiver operating characteristic (ROC) curve (AUC). Results In training cohort, the 1-, 2 and 3-year OS were 67.7, 46.8 and 37.9%, and the 1-, 2 and 3-year CSS were 73.1, 52.0 and 43.0%, respectively. The established nomograms were well calibrated in both training and validation cohort, with concordance indexes (C-index) of 0.652 and 0.659, respectively for OS prediction; 0.706 and 0.763, respectively for CSS prediction. Nomograms also displayed better discriminatory compared with 8th edition tumor-node-metastasis (TNM) stage system for predicting OS and CSS. Conclusion We constructed nomograms to predict OS and CSS based on a relatively large cohort. The established nomograms were well validated and could serve to improve predictions of survival risks and guide management of patients with CHCC after surgery.
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Li DB, Si XY, Wang SJ, Zhou YM. Long-term outcomes of combined hepatocellular-cholangiocarcinoma after hepatectomy or liver transplantation: A systematic review and meta-analysis. Hepatobiliary Pancreat Dis Int 2019; 18:12-18. [PMID: 30442549 DOI: 10.1016/j.hbpd.2018.10.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 10/17/2018] [Indexed: 02/05/2023]
Abstract
BACKGROUND Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare primary liver malignancy. We conducted a systematic review and meta-analysis to assess the evidence available on the long-term outcomes of cHCC-CC patients after either hepatectomy or liver transplantation (LT). DATA SOURCES Relevant studies published between January 2000 and January 2018 were identified by searching PubMed and Embase and reviewed systematically. Data were pooled using a random-effects model. RESULTS A total of 42 observational studies involving 1691 patients (1390 for partial hepatectomy and 301 for LT) were included in the analysis. The median tumor recurrence and 5-year overall survival (OS) rates were 65% (range 38%-100%) and 29% (range 0-63%) after hepatectomy versus 54% (range 14%-93%) and 41% (range 16%-73%) after LT, respectively. Meta-analysis found no significant difference in OS and tumor recurrence between LT and hepatectomy groups. CONCLUSION Hepatectomy rather than LT should be considered as the prior treatment option for cHCC-CC.
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Affiliation(s)
- De-Bang Li
- Department III of General Surgery, the First Hospital of Lanzhou University, Lanzhou 730000, China
| | - Xiao-Ying Si
- Department of Hepatobiliary & Pancreatovascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003, China
| | - Shi-Jie Wang
- Department of Hepatobiliary & Pancreatovascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003, China
| | - Yan-Ming Zhou
- Department of Hepatobiliary & Pancreatovascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003, China.
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Nugroho A, Lee KW, Lee KB, Kim HS, Kim H, Yi NJ, Suh KS. Adrenal metastasis in sequentially developed combined hepatocellular carcinoma-cholangiocarcinoma: A case report. Ann Hepatobiliary Pancreat Surg 2018; 22:287-291. [PMID: 30215052 PMCID: PMC6125274 DOI: 10.14701/ahbps.2018.22.3.287] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Revised: 05/16/2018] [Accepted: 05/24/2018] [Indexed: 12/15/2022] Open
Abstract
The incidence of combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CC) in a single patient accounts for only 0.4 to 14% of all primary liver cancer. However, the prognosis of its intrahepatic cholangiocarcinoma (ICC) component is poor. We experienced a unique case of a sequentially developed cHCC-CC with adrenal metastasis as the primary presentation and a hidden primary hepatocellular carcinoma. A 65-year-old female with a history of jaundice and abdominal discomfort was diagnosed with S4 ICC measuring 5 cm in diameter, and characterized histologically as papillary adenocarcinoma with intraductal growth, but without any evidence of malignant hepatocyte. S4 segmentectomy with hepaticojejunostomy revealed no additional masses. A follow-up CT scan 3 months after surgery showed a right adrenal mass with markedly increased serum AFP (4950 ng/mL), which was treated with right adrenalectomy. Histopathology revealed a metastatic hepatocellular carcinoma testing positive for AFP, glypican-3, and hepatocytes, but negative for CD-10, inhibin-α, EMA, S-100, and cytokeratin-7. Serum AFP level immediately plummeted to 4.1 ng/mL upon adrenal mass removal. A recurrent S7 liver mass was suspected 1 year later with serum AFP value of 7.6 ng/mL, and characteristic CT imaging of HCC. TACE was performed with good response. Adrenal metastasis may manifest as the primary focus of hepatocellular carcinoma in sequentially developed cHCC-CC patients with hidden primary HCC. cHCC-CC should be considered in the differential diagnosis of cholangiocarcinoma with elevated AFP.
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Affiliation(s)
- Adianto Nugroho
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.,Department of Surgery, Fatmawati General Hospital, Jakarta, Indonesia
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Bun Lee
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - Hyo-Shin Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hyeyoung Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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Zhou H, Xu J, Wang S, Peng J. Role of cantharidin in the activation of IKKα/IκBα/NF‑κB pathway by inhibiting PP2A activity in cholangiocarcinoma cell lines. Mol Med Rep 2018; 17:7672-7682. [PMID: 29620225 PMCID: PMC5983964 DOI: 10.3892/mmr.2018.8860] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Accepted: 02/08/2018] [Indexed: 12/15/2022] Open
Abstract
Cantharidin (CAN), a potent inhibitor of serine/threonine‑protein phosphatase 2A (PP2A), is widely used in clinical practice, particularly in the treatment of advanced cancer due to its specific action on these types of cancer. In the present study, the inhibitory effect of CAN was examined in two cholangiocarcinoma cell lines (QBC939 and Hucc‑t1). Following treatment with CAN, cell viability was effectively reduced in QBC939 and Hucc‑t1 cells and normal human intrahepatic biliary epithelial cells. However, a slight increase in reactive oxygen species levels in QBC939 cells treated with CAN was observed post‑treatment. CAN significantly inhibited cell migration and invasion in a dose‑dependent manner. Western blot analysis demonstrated that the nuclear factor‑κB (NF‑κB) pathway was stimulated by CAN, which was confirmed by the upregulated phosphorylation levels of inhibitor of NF‑κB kinase subunit α (IKKα) and NF‑κB inhibitor α (IκBα) in cells, and an increased NF‑κB p65 subunit level in the nucleus. The expression levels of 72 kDa type IV collagenase (MMP2) and matrix metalloproteinase 9 (MMP9) were downregulated by CAN. Notably, there was a negative association between MMP2 and MMP9 expression levels, and NF‑κB p65, although NF‑κB p65 regulates the expression of MMP2 and MMP9 and has a positive association with these proteins in various types of cancer. Notably, it was observed that CAN exerted specific inhibition on PP2A activity and thereby resulted in the activation of the IKKα/IκBα/NF‑κB pathway. Therefore, CAN‑induced cell inhibition maybe partially dependent on the activation of the IKKα/IκBα/NF‑κB pathway. In conclusion, it was demonstrated that CAN selectively and effectively inhibited cholangiocarcinoma cell migration and invasion. The present study may provide a novel insight into the use of CAN as a therapeutic candidate in the treatment of cholangiocarcinoma.
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Affiliation(s)
- Huijiang Zhou
- Department of General Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, P.R. China
| | - Jiangfeng Xu
- Department of General Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, P.R. China
| | - Shuai Wang
- Department of General Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, P.R. China
| | - Jinfeng Peng
- Department of General Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, P.R. China
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Ma MC, Chen YJ, Chiu TJ, Lan J, Liu CT, Chen YC, Tien HH, Chen YY. Positive expression of Midkine predicts early recurrence and poor prognosis of initially resectable combined hepatocellular cholangiocarcinoma. BMC Cancer 2018; 18:227. [PMID: 29486735 PMCID: PMC5830052 DOI: 10.1186/s12885-018-4146-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Accepted: 02/19/2018] [Indexed: 12/13/2022] Open
Abstract
Background Post-surgical prognosis is usually poor for combined hepatocellular cholangiocarcinoma (CHCC-CC), a rare primary liver cancer. Although midkine (MK) is a prognostic biomarker for several known cancers, it is not known whether it can be used as such in resectable CHCC-CC. This study examined whether MK expression can predict recurrence and survival in patients with resectable CHCC-CC. Methods We retrospectively enrolled 52 patients with resectable CHCC-CC who had received curative hepatic resections. MK expression was assessed in post-surgical immunohistochemical studies of specimens in paraffin blocks. Clinical outcomes were analyzed from medical records. Results Two-year disease-free and three-year overall survival rates were 42.1% and 44.6%. MK was expressed in 30 patients. Univariate analysis showed patients positively expressing MK had a significantly poorer 2-year disease free and three-year overall survival. Multivariate analysis found positive MK expression independently predicted recurrence. Conclusions Positive expression of MK predicts poor prognosis in patients with resectable CHCC-CC.
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Affiliation(s)
- Ming-Chun Ma
- Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niaosong District, Kaohsiung, 833, Taiwan.,Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Ju Chen
- Department of Anatomic Pathology, E-Da hospital, I-Shou University, Kaohsiung, Taiwan
| | - Tai-Jan Chiu
- Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niaosong District, Kaohsiung, 833, Taiwan.,Chang Gung University College of Medicine, Kaohsiung, Taiwan.,Kaohsiung Chang Gung Cholangiocarcinoma and Pancreatic Cancer Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.,Institute of Clinical Medical Sciences, Chang Gung University, Kaohsiung, 833, Taiwan
| | - Jui Lan
- Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Ting Liu
- Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niaosong District, Kaohsiung, 833, Taiwan.,Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Ching Chen
- Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niaosong District, Kaohsiung, 833, Taiwan.,Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Hsin-Ho Tien
- Department of Nursing, Kaohsiung Chang Gung Memorial Hospital Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Yen-Yang Chen
- Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niaosong District, Kaohsiung, 833, Taiwan. .,Chang Gung University College of Medicine, Kaohsiung, Taiwan. .,Kaohsiung Chang Gung Cholangiocarcinoma and Pancreatic Cancer Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
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Zhou YM, Zhang XF, Wu LP, Sui CJ, Yang JM. Risk factors for combined hepatocellular-cholangiocarcinoma: A hospital-based case-control study. World J Gastroenterol 2014; 20:12615-12620. [PMID: 25253966 PMCID: PMC4168099 DOI: 10.3748/wjg.v20.i35.12615] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2014] [Revised: 05/22/2014] [Accepted: 06/17/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To identify risk factors contributing to the development of combined hepatocellular-cholangiocarcinoma (CHC) in China.
METHODS: One hundred and twenty-six patients with CHC and 4:1 matched healthy controls were interviewed during the period from February 2000 to October 2012. Logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for each risk factor.
RESULTS: Univariate analysis showed that the significant risk factors for CHC development were hepatitis B virus (HBV) infection, heavy alcohol consumption, a family history of liver cancer, and diabetes mellitus. Multivariate stepwise logistic regression analysis showed that HBV infection (OR = 19.245, 95%CI: 13.260-27.931) and heavy alcohol consumption (OR = 2.186, 95%CI: 1.070-4.466) were independent factors contributing to the development of CHC.
CONCLUSION: HBV infection and heavy alcohol consumption may play a role in the development of CHC in China.
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Sanada Y, Kawashita Y, Okada S, Azuma T, Matsuo S. Review to better understand the macroscopic subtypes and histogenesis of intrahepatic cholangiocarcinoma. World J Gastrointest Pathophysiol 2014; 5:188-199. [PMID: 25133021 PMCID: PMC4133518 DOI: 10.4291/wjgp.v5.i3.188] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2014] [Revised: 03/18/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
Intrahepatic cholangiocarcinoma is macroscopically classified into three subtypes, mass-forming-type, periductal infiltrating-type, and intraductal growth-type. Each subtype should be preoperatively differentiated to perform the valid surgical resection. Recent researches have revealed the clinical, radiologic, pathobiological characteristics of each subtype. We reviewed recently published studies covering various aspects of intrahepatic cholangiocarcinoma (ICC), focusing especially on the macroscopic subtypes and stem cell features to better understand the pathophysiology of ICC and to establish the valid therapeutic strategy.
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