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Szeto W, Mannan R. Other Primary Epithelial Neoplasms of the Liver. Adv Anat Pathol 2025:00125480-990000000-00146. [PMID: 40202295 DOI: 10.1097/pap.0000000000000494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/10/2025]
Abstract
Primary liver carcinoma (PLC) is the sixth most common malignancy worldwide and the third leading cause of cancer-related mortalities. Hepatocellular carcinoma (HCC) is the most prevalent form of PLC, followed by intrahepatic cholangiocarcinoma (iCCA). In addition, there is a group of rarer PLCs that do not fit neatly into the HCC or iCCA categories. This review explores this heterogeneous group, including combined hepatocellular-cholangiocarcinoma (cHCC-CCA), intermediate cell carcinoma (ICC), mixed hepatocellular-neuroendocrine carcinoma, and undifferentiated primary liver carcinoma. cHCC-CCA is a rare subtype of PLC, characterized by both hepatocytic and cholangiocytic differentiation within the same tumor. The latest WHO classification (2019, fifth edition) redefined cHCC-CCA by eliminating the "stem cell subtypes" and emphasized that diagnosis should primarily rely on morphologic features, supported by immunohistochemical staining to better define subtypes. Intermediate cell carcinoma is a subtype of cHCC-CCA and is comprised of monomorphic tumor cells that exhibit characteristics intermediate between hepatocytes and cholangiocytes, with immunohistochemical expression of hepatocytic and cholangiocytic markers within the same cell. Another rare entity, combined HCC and neuroendocrine carcinoma (NEC), contains an admixture of HCC and NEC components within the same tumor. Undifferentiated primary liver carcinoma, on the other hand, lacks definitive lineage differentiation beyond an epithelial phenotype. These heterogeneous PLCs pose diagnostic challenges owing to their mixed/unusual histologic features and overlapping immunohistochemical markers. They tend to have poor prognoses, highlighting the critical importance of accurate and timely diagnosis.
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Affiliation(s)
- Wai Szeto
- Department of Pathology, City of Hope National Medical Center, Duarte, CA
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Nolasco F, Fonseca GM, de Mello ES, Kruger JAP, Jeismann VB, Makdissi FF, Coelho FF, Alves VAF, Herman P. Prognostic Impact of the Cholangiolar Component in Combined Hepatocellular-Cholangiocarcinoma: Insights From a Western Single-Center Study. J Surg Oncol 2025; 131:427-434. [PMID: 39410740 DOI: 10.1002/jso.27955] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 09/23/2024] [Accepted: 10/02/2024] [Indexed: 05/02/2025]
Abstract
INTRODUCTION Primary liver malignancies, such as hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular-cholangiocarcinoma (cHCC-CCA), represent significant contributors to global cancer-related mortality. The diagnostic challenges associated with distinguishing cHCC-CCA from HCC and ICC stem from their rarity and overlapping histological features. OBJECTIVES This study aimed to reclassify primary liver tumors resected at a Western center and to compare clinicopathological features and prognosis among patients with HCC, ICC, and cHCC-CCA. METHODS A retrospective analysis was conducted on patients undergoing resection for HCC, ICC, or cHCC-CCA between 2007 and 2017. Clinical and perioperative data were collected, and pathological specimens were reclassified by a specialized pathologist. Statistical analysis was employed to compare clinical features and survival outcomes among the different tumor types. RESULTS Out of the initially identified 192 patients, 140 were included in the analysis. Following reclassification, 71.42% were diagnosed with HCC, 12.14% with ICC, and 16.42% with cHCC-CCA. Patients with HCC were predominantly male and exhibited a higher incidence of isolated liver recurrence. ICC patients more frequently underwent open procedures. Additionally, patients with HCC and cHCC-CCA showed higher rates of cirrhosis, elevated alpha-fetoprotein levels, and extrahepatic recurrence, while those with ICC and cHCC-CCA demonstrated elevated CA 19-9 levels. Overall survival and disease-free survival were longer for HCC compared to cases with a cholangiolar component (ICC and cHCC-CCA). CONCLUSIONS Histological evaluation should actively incorporate the search for a cholangiolar component in primary liver tumors to prevent misdiagnosis, as its presence indicates a poorer prognosis.
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Affiliation(s)
- Francisco Nolasco
- Liver Surgery Unit, Department of Gastroenterology, Digestive Surgery Division, University of Saão Paulo Medical School, São Paulo, Brazil
| | - Gilton Marques Fonseca
- Liver Surgery Unit, Department of Gastroenterology, Digestive Surgery Division, University of Saão Paulo Medical School, São Paulo, Brazil
| | - Evandro S de Mello
- Departament of Pathology, University of São Paulo Medical School, São Paulo, Brazil
| | - Jaime Arthur Pirolla Kruger
- Liver Surgery Unit, Department of Gastroenterology, Digestive Surgery Division, University of Saão Paulo Medical School, São Paulo, Brazil
| | - Vagner Birk Jeismann
- Liver Surgery Unit, Department of Gastroenterology, Digestive Surgery Division, University of Saão Paulo Medical School, São Paulo, Brazil
| | - Fabio Ferrari Makdissi
- Liver Surgery Unit, Department of Gastroenterology, Digestive Surgery Division, University of Saão Paulo Medical School, São Paulo, Brazil
| | - Fabricio Ferreira Coelho
- Liver Surgery Unit, Department of Gastroenterology, Digestive Surgery Division, University of Saão Paulo Medical School, São Paulo, Brazil
| | - Venancio A F Alves
- Departament of Pathology, University of São Paulo Medical School, São Paulo, Brazil
| | - Paulo Herman
- Liver Surgery Unit, Department of Gastroenterology, Digestive Surgery Division, University of Saão Paulo Medical School, São Paulo, Brazil
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Zhu Z, Yang C, Zeng M, Zhou C. Prognostic Impact of CCA Components in Combined Hepatocellular Carcinoma-Cholangiocarcinoma. J Hepatocell Carcinoma 2024; 11:2483-2492. [PMID: 39712948 PMCID: PMC11663380 DOI: 10.2147/jhc.s491243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Accepted: 12/14/2024] [Indexed: 12/24/2024] Open
Abstract
Purpose To investigate the differences of combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) patients with a cholangiocarcinoma (CCA) component ≥ 30% or < 30% versus intrahepatic cholangiocarcinoma (iCCA) patients in recurrence-free survival (RFS) and overall survival (OS) prognoses. Methods Patients with cHCC-CCA and iCCA after surgery were recruited. All cHCC-CCA patients were divided into two subgroups (CCA components ≥ 30% and < 30%). Then, Kaplan-Meier survival analysis and Cox regression analysis were used to investigate and compare the differences of cHCC-CCAs with a CCA component ≥ 30% or < 30% versus iCCAs in RFS and OS prognoses, respectively. The differences of MRI features between cHCC-CCAs with a CCA component ≥ 30% and < 30% were also compared. Results One hundred sixty-four cHCC-CCAs and 146 iCCAs were enrolled. Compared with iCCAs, cHCC-CCAs with a CCA component < 30% had better OS prognosis (HR: 2.888, p = 0.045). However, Cox regression analysis revealed that cHCC-CCAs with a CCA component ≥ 30% had poorer RFS (HR: 0.503, p < 0.001) and OS (HR: 0.58, p = 0.033) prognoses than iCCAs. In addition, rim APHE (OR = 0.286, p < 0.001), targetoid diffusion restriction (OR = 0.316, p = 0.019), corona enhancement (OR = 0.481, p = 0.033), delayed enhancement (OR = 0.251, p = 0.001), and LR-M (OR = 1.586, p < 0.001) were significant factors associated with cHCC-CCAs with a CCA component ≥ 30%. Multivariable regression analyses showed that only LR-M (OR = 1.522, p = 0.042) was a significantly independent predictor for cHCC-CCAs with a CCA component ≥ 30%. Conclusion cHCC-CCAs with a CCA component ≥ 30% had worse prognoses than iCCAs. Therefore, we suggest that the postoperative treatment of cHCC-CCAs with a CCA component ≥ 30% can be based on the treatment strategy for iCCAs.
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Affiliation(s)
- Zhu Zhu
- Department of Radiology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, People’s Republic of China
| | - Chun Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Changwu Zhou
- Department of Radiology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, People’s Republic of China
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Lin RY, Kahramangil D, Ozer M, George TJ, Nassour I, Hughes SJ, Zarrinpar A, Sahin I. Patient Outcomes in Resected Combined Hepatocellular Cholangiocarcinoma (cHCC-ICC) and Intrahepatic Cholangiocarcinoma: A Single Center Study. Cancers (Basel) 2024; 16:3878. [PMID: 39594833 PMCID: PMC11592994 DOI: 10.3390/cancers16223878] [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: 11/04/2024] [Revised: 11/16/2024] [Accepted: 11/18/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND/OBJECTIVES Combined hepatocellular cholangiocarcinoma (cHCC-ICC) is a rare malignancy that involves a combination of features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma (ICC) and exhibits a more aggressive clinical course; however, its risk factors and outcomes remain largely undefined. METHODS This study is a single-center retrospective study of 82 patients diagnosed with ICC or cHCC-ICC who underwent surgical resection from June 2011 to January 2023. Our analysis included 70 patients with resected ICC and 12 with resected cHCC-ICC. RESULTS The overall survival (OS) for the entire cohort was 21.6 months, with a recurrence-free survival (RFS) of 11.8 months. The cHCC-ICC group had significantly higher levels of AST and ALT (AST median 206 U/L vs. 46 U/L; ALT median 165.5 U/L vs. 48 U/L; p = 0.012 and p = 0.013, respectively), whereas the ICC group had higher alkaline phosphatase (median 66 U/L vs. 104 U/L; p = 0.03). CA 19-9 values (76 U/mL vs. 22 U/mL; p = 0.02) were higher in the ICC group, while AFP values were higher in the cHCC-ICC group (7.3 ng/mL vs. 3.2 ng/mL; p = 0.0004). The cHCC-ICC group had a significantly higher rate of recurrence (83% vs. 47%, p = 0.028) with a significantly decreased RFS (4.7 months vs. 12.4 months; log-rank p = 0.007). In multivariate analysis, patients with resected ICC had a significantly reduced risk of recurrence by 73% compared to their counterparts (HR 0.27 [0.10-0.73], p = 0.01). CONCLUSIONS cHCC-ICC is a rare entity that needs to be further studied to improve patient outcomes. Further studies are warranted and may suggest the need for more aggressive initial treatment strategies in patients diagnosed with cHCC-ICC.
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Affiliation(s)
- Rick Y. Lin
- Department of Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA;
| | - Doga Kahramangil
- Department of Medicine, Division of Hematology and Oncology, College of Medicine, University of Florida, Gainesville, FL 32610, USA; (D.K.); (T.J.G.)
| | - Muhammet Ozer
- Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA;
| | - Thomas J. George
- Department of Medicine, Division of Hematology and Oncology, College of Medicine, University of Florida, Gainesville, FL 32610, USA; (D.K.); (T.J.G.)
| | - Ibrahim Nassour
- Department of Surgery, University of Florida, Gainesville, FL 32610, USA; (I.N.); (S.J.H.); (A.Z.)
| | - Steven J. Hughes
- Department of Surgery, University of Florida, Gainesville, FL 32610, USA; (I.N.); (S.J.H.); (A.Z.)
| | - Ali Zarrinpar
- Department of Surgery, University of Florida, Gainesville, FL 32610, USA; (I.N.); (S.J.H.); (A.Z.)
| | - Ilyas Sahin
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
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Zhou C, Yang C, Zeng M. Is it necessary to distinguish between combined hepatocellular carcinoma-cholangiocarcinoma with less than 10% of cholangiocarcinoma components versus hepatocellular carcinoma? Hepatol Int 2024:10.1007/s12072-024-10730-1. [PMID: 39298106 DOI: 10.1007/s12072-024-10730-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 09/06/2024] [Indexed: 09/21/2024]
Abstract
PURPOSE Whether there are differences in recurrence-free survival (RFS) prognosis between combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) cases with a small proportion of CCA components and HCC cases remains unknown. We aim to investigate the differences in RFS prognosis between cHCC-CCAs with a small proportion of CCA components and HCCs. METHODS Patients with malignant liver neoplasms who underwent MRI and surgery were prospectively recruited. All cHCC-CCA patients were divided into different groups according to the ratio of CCA components. The primary end point was recurrence-free-survival. Cox regression analysis and Kaplan-Meier survival analysis was used to investigate and compare RFS prognosis. RESULTS One hundred sixty-four cHCC-CCA cases and 271 HCC cases were enrolled. There was no significant difference in RFS prognosis between cHCC-CCA cases with a CCA component of < 10% and HCC cases (log rank p = 0.169). There were no significant differences in some major HCC-favoring MR features, such as nonrim APHE (85.7% vs. 81.5%, p = 0.546), nonperipheral washout (80.0% vs. 84.1%, p = 0.534), and enhancing capsule (62.9% vs. 45.4%, p = 0.051) between them. In addition, some clinicopathological findings had no significant differences between cHCC-CCAs with a CCA component of < 10% and HCCs (all p > 0.05). CONCLUSIONS There were no significant differences in RFS prognosis, major HCC-favoring MRI features, and clinicopathological findings between cHCC-CCAs with a CCA component of < 10% and HCCs. Therefore, we suggest that cHCC-CCAs with pathological diagnosis of less than 10% of CCA components may be treated as HCCs in clinical setting.
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Affiliation(s)
- Changwu Zhou
- Department of Radiology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Chun Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
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Zhang YZ, Liu YC, Su T, Shi JN, Huang Y, Liang B. Current advances and future directions in combined hepatocellular and cholangiocarcinoma. Gastroenterol Rep (Oxf) 2024; 12:goae031. [PMID: 38628397 PMCID: PMC11018545 DOI: 10.1093/gastro/goae031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 03/17/2024] [Accepted: 03/24/2024] [Indexed: 04/19/2024] Open
Abstract
The low incidence of combined hepatocellular cholangiocarcinoma (cHCC-CCA) is an important factor limiting research progression. Our study extensively included nearly three decades of relevant literature and assembled the most comprehensive database comprising 5,742 patients with cHCC-CCA. We summarized the characteristics, tumor markers, and clinical features of these patients. Additionally, we present the evolution of cHCC-CCA classification and explain the underlying rationale for these classification standards. We reviewed cHCC-CCA diagnostic advances using imaging features, tumor markers, and postoperative pathology, as well as treatment options such as surgical, adjuvant, and immune-targeted therapies. In addition, recent advances in more effective chemotherapeutic regimens and immune-targeted therapies were explored. Furthermore, we described the molecular mutation features and potential specific markers of cHCC-CCA. The prognostic value of Nestin has been proven, and we speculate that Nestin will also play a role in classification and diagnosis. However, further research is needed. Moreover, we believe that the possibility of using machine learning liquid biopsy for preoperative diagnosis and establishing a scoring system are directions for future research.
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Affiliation(s)
- Yu-Zhu Zhang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, Jiangxi, P. R. China
- The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, Jiangxi, P. R. China
| | - Yu-Chen Liu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, Jiangxi, P. R. China
- Queen Mary School, Jiangxi Medical College of Nanchang University, Nanchang, Jiangxi, P. R. China
| | - Tong Su
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, Jiangxi, P. R. China
- The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, Jiangxi, P. R. China
| | - Jiang-Nan Shi
- The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, Jiangxi, P. R. China
| | - Yi Huang
- The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, Jiangxi, P. R. China
| | - Bo Liang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, Jiangxi, P. R. China
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Zhang J, Dong W, Liu W, Fu J, Liao T, Li Y, Huo L, Jia N. Preoperative evaluation of MRI features and inflammatory biomarkers in predicting microvascular invasion of combined hepatocellular cholangiocarcinoma. Abdom Radiol (NY) 2024; 49:710-721. [PMID: 38112787 PMCID: PMC10909765 DOI: 10.1007/s00261-023-04130-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 11/07/2023] [Accepted: 11/12/2023] [Indexed: 12/21/2023]
Abstract
PURPOSE Microvascular invasion (MVI) is a significant prognostic factor in combined hepatocellular cholangiocarcinoma (cHCC-CCA). However, its diagnosis relies on postoperative histopathologic analysis. This study aims to identify preoperative inflammatory biomarkers and MR-imaging features that can predict MVI in cHCC-CCA. METHODS This retrospective study enrolled 119 patients with histopathologically confirmed cHCC-CCA between January 2016 and December 2021. Two radiologists, unaware of the clinical data, independently reviewed all MR image features. Univariable and multivariable analyses were performed to determine the independent predictors for MVI among inflammatory biomarkers and MRI characteristics. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the diagnostic performance. RESULTS Multivariable logistic regression analysis identified four variables significantly associated with MVI (p < 0.05), including two inflammatory biomarkers [albumin-to-alkaline phosphatase ratio (AAPR) and aspartate aminotransferase-to-neutrophil ratio index (ANRI)] and two MRI features (non-smooth tumor margin and arterial phase peritumoral enhancement). A combined model for predicting MVI was constructed based on these four variables, with an AUC of 0.802 (95% CI 0.719-0.870). The diagnostic efficiency of the combined model was higher than that of the imaging model. CONCLUSION Inflammatory biomarkers and MRI features could be potential predictors for MVI in cHCC-CCA. The combined model, derived from inflammatory biomarkers and MRI features, showed good performance in preoperatively predicting MVI in cHCC-CCA patients.
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Affiliation(s)
- Juan Zhang
- Department of Radiology, Eastern Hepatobiliary Surgery Hospital, Third Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Wei Dong
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Third Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Wanmin Liu
- Department of Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Jiazhao Fu
- Department of Organ Transplantation, Changhai Hospital, First Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Tian Liao
- Department of Ultrasound, Changsha Hospital of Traditional Chinese Medicine, Changsha, China
| | - Yinqiao Li
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China
| | - Lei Huo
- Department of Radiology, Eastern Hepatobiliary Surgery Hospital, Third Affiliated Hospital of Naval Medical University, Shanghai, China.
| | - Ningyang Jia
- Department of Radiology, Eastern Hepatobiliary Surgery Hospital, Third Affiliated Hospital of Naval Medical University, Shanghai, China.
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Amory B, Goumard C, Laurent A, Langella S, Cherqui D, Salame E, Barbier L, Soubrane O, Farges O, Hobeika C, Kawai T, Regimbeau JM, Faitot F, Pessaux P, Truant S, Boleslawski E, Herrero A, Mabrut JY, Chiche L, Di Martino M, Rhaiem R, Schwarz L, Resende V, Calderaro J, Augustin J, Caruso S, Sommacale D, Hofmeyr S, Ferrero A, Fuks D, Vibert E, Torzilli G, Scatton O, Brustia R. Combined hepatocellular-cholangiocarcinoma compared to hepatocellular carcinoma and intrahepatic cholangiocarcinoma: Different survival, similar recurrence: Report of a large study on repurposed databases with propensity score matching. Surgery 2024; 175:413-423. [PMID: 37981553 DOI: 10.1016/j.surg.2023.09.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 09/06/2023] [Accepted: 09/26/2023] [Indexed: 11/21/2023]
Abstract
BACKGROUND Combined hepatocholangiocarcinoma is a rare cancer with a grim prognosis composed of both hepatocellular carcinoma and intrahepatic cholangiocarcinoma morphologic patterns in the same tumor. The aim of this multicenter, international cohort study was to compare the oncologic outcomes after surgery of combined hepatocholangiocarcinoma to hepatocellular carcinoma and intrahepatic cholangiocarcinoma. METHODS Patients treated by surgery for combined hepatocholangiocarcinoma, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma from 2000 to 2021 from multicenter international databases were analyzed retrospectively. Patients with combined hepatocholangiocarcinoma (cases) were compared with 2 control groups of hepatocellular carcinoma or intrahepatic cholangiocarcinoma, sequentially matched using a propensity score based on 8 preoperative characteristics. Overall and disease-free survival were compared, and predictors of mortality and recurrence were analyzed with Cox regression after propensity score matching. RESULTS During the study period, 3,196 patients were included. Propensity score adjustment and 2 sequential matching processes produced a new cohort (n = 244) comprising 3 balanced groups was obtained (combined hepatocholangiocarcinoma = 56, intrahepatic cholangiocarcinoma = 66, and hepatocellular carcinoma = 122). Kaplan-Meier overall survival estimations at 1, 3, and 5 years were 67%, 45%, and 28% for combined hepatocholangiocarcinoma, 92%, 75%, and 55% for hepatocellular carcinoma, and 86%, 53%, and 42% for the intrahepatic cholangiocarcinoma group, respectively (P = .0014). Estimations of disease-free survival at 1, 3, and 5 years were 51%, 25%, and 17% for combined hepatocholangiocarcinoma, 63%, 35%, and 26% for the hepatocellular carcinoma group, and 51%, 31%, and 28% for the intrahepatic cholangiocarcinoma group, respectively (P = .19). Predictors of mortality were combined hepatocholangiocarcinoma subtype, metabolic syndrome, preoperative tumor markers alpha-fetoprotein and carbohydrate antigen 19-9, and satellite nodules, and recurrence was associated with satellite nodules rather than cancer subtype. CONCLUSION Despite data limitations, overall survival among patients with combined hepatocholangiocarcinoma was worse than both groups and closer intrahepatic cholangiocarcinoma, whereas disease-free survival was similar among the 3 groups. Future research on immunophenotypic profiling may hold more promise than traditional nonmodifiable clinical characteristics (as found in this study) in predicting recurrence or response to salvage treatments.
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Affiliation(s)
- Boris Amory
- Department of Digestive and Hepato-pancreatic-biliary Surgery, AP-HP, Hôpital Henri-Mondor, Paris Est Créteil University, UPEC, France; Assistance Publique-Hôpitaux de Paris, Créteil, France
| | - Claire Goumard
- Department of Hepatobiliary and Liver Transplantation Surgery, AP-HP, Hôpital Pitié Salpêtrière, CRSA, Sorbonne Université, Paris, France
| | - Alexis Laurent
- Department of Digestive and Hepato-pancreatic-biliary Surgery, DMU CARE, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, Créteil, France; Paris Est Créteil University, UPEC, France; Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers," INSERM U955, Créteil, France; Assistance Publique-Hôpitaux de Paris, Créteil, France
| | - Serena Langella
- Department of General and Oncological Surgery, Ospedale Mauriziano, Torino, Italy
| | - Daniel Cherqui
- Center Hepato-Biliaire, AP-HP Paul Brousse Hospital, Paris-Saclay University, Villejuif, France
| | - Ephrem Salame
- Department of Digestive Surgery and Liver Transplantation, University Hospital of Tours, University of Tours, France; FHU Support, Tours, France
| | - Louise Barbier
- Department of Digestive Surgery and Liver Transplantation, University Hospital of Tours, University of Tours, France; FHU Support, Tours, France
| | - Olivier Soubrane
- Department of Digestive, Oncological, and Metabolic Surgery, Institut Mutualiste Montsouris, Paris, France
| | - Olivier Farges
- Department of HPB Surgery and Liver Transplantation, AP-HP Beaujon Hospital, University of Paris, Clichy, France
| | - Christian Hobeika
- Department of HPB Surgery and Liver Transplantation, AP-HP Beaujon Hospital, University of Paris, Clichy, France
| | - Takayuki Kawai
- Department of Surgery, Medical Research Institute, Kitano Hospital, Osaka and Graduate School of Medicine, Kyoto University, Japan
| | - Jean-Marc Regimbeau
- SSPC (Simplification of Surgical Patients Care) - Clinical Research Unit, University of Picardie Jules Verne, Amiens, France; Department of Digestive Surgery, Amiens University Medical Center, France
| | - François Faitot
- Service de Chirurgie Hépato-Biliaire et Transplantation Hépatique, Hôpital de Hautepierre, Strasbourg, France
| | - Patrick Pessaux
- Unité Chirurgie HBP, Pôle hépato-digestif Nouvel Hôpital Civil, Strasbourg, France; Institut of Viral and Liver Disease, Inserm U1110, Strasbourg, France
| | - Stéphanie Truant
- Department of Digestive Surgery and Transplantation, University Hospitals, Lille, France
| | - Emmanuel Boleslawski
- Department of Digestive Surgery and Transplantation, University Hospitals, Lille, France
| | - Astrid Herrero
- Department of HBP Surgery and Liver Transplantation, Montpellier University Hospital, University of Montpellier, France
| | - Jean-Yves Mabrut
- Croix Rousse University Hospital, Department of General Surgery and Liver Transplantation, Lyon, France; Cancer Research Center of Lyon, INSERM U1052, France
| | - Laurence Chiche
- Department of Hepato-Bilio-Pancreatic Surgery and Liver Transplantation, Haut Lévêque Hospital, Center Hospitalier Universitaire de Bordeaux, France; Inserm UMR 1312-Team 3 "Liver Cancers and Tumoral Invasion," Bordeaux Institute of Oncology, University of Bordeaux, France
| | - Marcello Di Martino
- HPB Unit, Department of General and Digestive Surgery, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Madrid, Spain
| | - Rami Rhaiem
- Department of Hepatobiliary, Pancreatic, and Digestive Surgery, Robert Debré University Hospital, Reims, France; University Reims Champagne-Ardenne, France
| | - Lilian Schwarz
- Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, Rouen University Hospital, UNIROUEN, UMR 1245 INSERM, Normandie Rouen University, France
| | - Vivian Resende
- Federal University of Minas Gerais School of Medicine, Belo Horizonte, Brazil
| | - Julien Calderaro
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France; Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Pathology, Créteil, France; Inserm, U955, Team 18, Créteil, France
| | - Jérémy Augustin
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France; Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Pathology, Créteil, France; Inserm, U955, Team 18, Créteil, France
| | - Stefano Caruso
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France; Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Pathology, Créteil, France; Inserm, U955, Team 18, Créteil, France
| | - Daniele Sommacale
- Department of Digestive and Hepato-pancreatic-biliary Surgery, DMU CARE, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, Créteil, France; Paris Est Créteil University, UPEC, Créteil, France; Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers," INSERM U955, Créteil, France; Assistance Publique-Hôpitaux de Paris, Créteil, France
| | - Stefan Hofmeyr
- Division of Surgery, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Academic Hospital, Cape Town, South Africa
| | - Alessandro Ferrero
- Department of General and Oncological Surgery, Ospedale Mauriziano, Torino, Italy
| | - David Fuks
- Department of Hepato-Pancreatic-Biliary and Endocrine Surgery, Hopital Cochin, Assistance Publique-Hôpitaux de Paris, France; Université Paris Cité, France
| | - Eric Vibert
- Center Hepato-Biliaire, AP-HP Paul Brousse Hospital, Paris-Saclay University, Villejuif, France
| | - Guido Torzilli
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Research Hospital - IRCCS, Humanitas University, Rozzano, Milan, Italy
| | - Olivier Scatton
- Department of Hepatobiliary and Liver Transplantation Surgery, AP-HP, Hôpital Pitié Salpêtrière, CRSA, Sorbonne Université, Paris, France
| | - Raffaele Brustia
- Department of Digestive and Hepato-pancreatic-biliary Surgery, DMU CARE, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, Créteil, France; Paris Est Créteil University, UPEC, France; Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers," INSERM U955, Créteil, France; Assistance Publique-Hôpitaux de Paris, Créteil, France.
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9
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Ye L, Schneider JS, Ben Khaled N, Schirmacher P, Seifert C, Frey L, He Y, Geier A, De Toni EN, Zhang C, Reiter FP. Combined Hepatocellular-Cholangiocarcinoma: Biology, Diagnosis, and Management. Liver Cancer 2024; 13:6-28. [PMID: 38344449 PMCID: PMC10857821 DOI: 10.1159/000530700] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 04/03/2023] [Indexed: 01/04/2025] Open
Abstract
BACKGROUND Combined hepatocellular-cholangiocarcinoma (cHCC-iCCA) is a rare type of primary liver cancer displaying characteristics of both hepatocytic and cholangiocytic differentiation. SUMMARY Because of its aggressive nature, patients with cHCC-iCCA exhibit a poorer prognosis than those with HCC. Surgical resection and liver transplantation may be considered curative treatment approaches; however, only a minority of patients are eligible at the time of diagnosis, and postoperative recurrence rates are high. For cases that are not eligible for surgery, locoregional and systemic therapy are often administered based on treatment protocols applied for HCC or iCCA. Owing to the rarity of this cancer, there are still no established standard treatment protocols; therefore, the choice of therapy is often personalized and guided by the suspected predominant component. Further, the genomic and molecular heterogeneity of cHCC-iCCA can severely compromise the efficacy of the available therapies. KEY MESSAGES In the present review, we summarize the latest advances in cHCC-iCCA and attempt to clarify its terminology and molecular biology. We provide an overview of the etiology of cHCC-iCCA and present new insights into the molecular pathology of this disease that could contribute to further studies aiming to improve the patient outcomes through new systemic therapies.
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Affiliation(s)
- Liangtao Ye
- Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Julia S. Schneider
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Najib Ben Khaled
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | | | - Carolin Seifert
- Institute for Pathology, University Würzburg, Würzburg, Germany
| | - Lea Frey
- Institute for Pathology, University Würzburg, Würzburg, Germany
| | - Yulong He
- Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Andreas Geier
- Division of Hepatology, Department of Medicine II, University Hospital Würzburg, Würzburg, Germany
| | - Enrico N. De Toni
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Changhua Zhang
- Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Florian P. Reiter
- Division of Hepatology, Department of Medicine II, University Hospital Würzburg, Würzburg, Germany
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10
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Lv TR, Hu HJ, Ma WJ, Liu F, Jin YW, Li FY. Meta-analysis of prognostic factors for overall survival and disease-free survival among resected patients with combined hepatocellular carcinoma and cholangiocarcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:107279. [PMID: 38000116 DOI: 10.1016/j.ejso.2023.107279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 11/09/2023] [Accepted: 11/15/2023] [Indexed: 11/26/2023]
Abstract
BACKGROUND Combined hepatocellular carcinoma and cholangiocarcinoma (CHCC-CC) is a rare subtype of primary liver malignancy and has been treated equally as intra-hepatic cholangiocarcinoma (IHCC) according to the 8th AJCC staging system. Owing to its rarity, its prognostic factors have been rarely explored and defined. METHODS PubMed, EMBASE, the Cochrane Library and Web of Science were searched up till January 1st, 2023 and eligible studies were restricted to studies reported prognostic factors of resected CHCC-CC. Standard Parmar modifications were used to determine pooled univariable hazard ratios (HRs). RESULTS A total of eleven studies with 1286 patients with resected classical CHCC-CC were finally included. Pooled results indicated that serum tumor biomarkers, including AFP, CA199, and CEA, were prognostic factors for postoperative overall survival (OS) and disease-free survival (DFS). Moreover, liver cirrhosis (P = 0.010), HBV infection (P = 0.030), and HCV infection (P < 0.001) were prognostic factors for OS. Age (HR = 1.03, P = 0.005) was a prognostic factor for DFS. Tumor size (OS: HR = 2, P < 0.001, DFS: HR = 2.15, P < 0.001), tumor number (OS: HR = 2.05, P < 0.001; DFS: HR = 1.96, P = 0.006), surgical margin (OS: HR = 2.33, <0.001001; DFS: HR = 2.35, P < 0.001), node metastasis (OS: HR = 2.96, P < 0.001; DFS: HR = 2.1, P < 0.001), vascular invasion (OS: HR = 2.17, P < 0.001; DFS: HR = 2.64, P < 0.001), and postoperative prophylactic trans-arterial chemotherapy embolization (PPTACE) (OS: HR = 1.67, P = 0.04; DFS: HR = 2.31, P < 0.001) were common prognostic factors for OS and DFS. CONCLUSION Various risk factors unmentioned in the 8th AJCC staging system were identified. These promising findings would facilitate a more personalized predictive model and help clinicians to stratify patients with different survival outcomes.
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Affiliation(s)
- Tian-Run Lv
- Department of Biliary Tract Surgery, General Surgrey, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Hai-Jie Hu
- Department of Biliary Tract Surgery, General Surgrey, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Wen-Jie Ma
- Department of Biliary Tract Surgery, General Surgrey, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Fei Liu
- Department of Biliary Tract Surgery, General Surgrey, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Yan-Wen Jin
- Department of Biliary Tract Surgery, General Surgrey, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Fu-Yu Li
- Department of Biliary Tract Surgery, General Surgrey, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
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11
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van der Meeren PE, de Wilde RF, Sprengers D, IJzermans JNM. Benefit and harm of waiting time in liver transplantation for HCC. Hepatology 2023:01515467-990000000-00646. [PMID: 37972979 DOI: 10.1097/hep.0000000000000668] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 10/26/2023] [Indexed: 11/19/2023]
Abstract
Liver transplantation is the most successful treatment for limited-stage HCC. The waiting time for liver transplantation (LT) can be a critical factor affecting the oncological prognosis and outcome of patients with HCC. Efficient strategies to optimize waiting time are essential to maximize the benefits of LT and to reduce the harm of delay in transplantation. The ever-increasing demand for donor livers emphasizes the need to improve the organization of the waiting list for transplantation and to optimize organ availability for patients with and without HCC. Current progress in innovations to expand the donor pool includes the implementation of living donor LT and the use of grafts from extended donors. By expanding selection criteria, an increased number of patients are eligible for transplantation, which necessitates criteria to prevent futile transplantations. Thus, the selection criteria for LT have evolved to include not only tumor characteristics but biomarkers as well. Enhancing our understanding of HCC tumor biology through the analysis of subtypes and molecular genetics holds significant promise in advancing the personalized approach for patients. In this review, the effect of waiting time duration on outcome in patients with HCC enlisted for LT is discussed.
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Affiliation(s)
- Pam Elisabeth van der Meeren
- Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Roeland Frederik de Wilde
- Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Dave Sprengers
- Department of Gastroenterology & Hepatology, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Jan Nicolaas Maria IJzermans
- Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
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12
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Jang YJ, Kim EJ, Kim HD, Kim KP, Ryu MH, Park SR, Choi WM, Lee D, Choi J, Shim JH, Kim KM, Lim YS, Lee HC, Ryoo BY, Yoo C. Clinical outcomes of immune checkpoint inhibitors in unresectable or metastatic combined hepatocellular-cholangiocarcinoma. J Cancer Res Clin Oncol 2023; 149:7547-7555. [PMID: 36971796 DOI: 10.1007/s00432-023-04704-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Accepted: 03/17/2023] [Indexed: 03/29/2023]
Abstract
PURPOSE Immune checkpoint inhibitors (ICIs) have been demonstrated to be effective for unresectable or metastatic hepatocellular carcinoma (HCC) or cholangiocarcinoma (CCA) in prior prospective trials. However, the clinical outcomes of ICIs in patients with combined HCC-CCA (cHCC-CCA) have not been investigated. Accordingly, we retrospectively evaluated the effectiveness and safety of ICIs in patients with unresectable or metastatic cHCC-CCA. METHODS Among 101 patients with histologically documented cHCC-CCA who received systemic therapy, 25 received ICIs between January 2015 and September 2021 and were included in the current analysis. Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were retrospectively evaluated. RESULTS The median age was 64 years (range 38-83) and 84% (n = 21) of patients were males. Most patients had Child-Pugh A liver function (n = 22, 88%) and hepatitis B virus infection (17, 68%). Nivolumab (n = 17, 68%) was the most frequently used ICI, followed by pembrolizumab (n = 5, 20%), atezolizumab plus bevacizumab (n = 2, 8%), and ipilimumab plus nivolumab (n = 1, 4%). All patients, except one, had previously received systemic therapy; median two lines (1-5 lines) of systemic therapy were administered prior to ICIs. With a median follow-up duration of 20.1 months (95% CI 4.9-35.2 months), the median PFS was 3.5 months (95% CI 2.4-4.8 months), and the median OS was 8.3 months (95% CI 6.8-9.8 months). The ORR was 20.0% (n = 5, nivolumab for 2 patients, pembrolizumab for 1, atezolizumab plus bevacizumab for 1, and ipilimumab plus nivolumab for 1) and the duration of response was 11.6 months (95% CI 11.2-12.0 months). CONCLUSIONS ICIs displayed clinical anti-cancer effectiveness, aligning with the results of prior prospective studies for HCC or CCA. Further international studies are required to define the optimal strategies for managing unresectable or metastatic cHCC-CCA.
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Affiliation(s)
- Yoon Jung Jang
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
- Department of Hematology/Oncology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Eo Jin Kim
- Department of Hematology/Oncology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyung-Don Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Kyu-Pyo Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Min-Hee Ryu
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Sook Ryun Park
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Danbi Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jonggi Choi
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ju Hyun Shim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kang Mo Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Han Chu Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Baek-Yeol Ryoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
| | - Changhoon Yoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
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13
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Shen YT, Yue WW, Xu HX. Non-invasive imaging in the diagnosis of combined hepatocellular carcinoma and cholangiocarcinoma. Abdom Radiol (NY) 2023; 48:2019-2037. [PMID: 36961531 DOI: 10.1007/s00261-023-03879-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 02/28/2023] [Accepted: 03/02/2023] [Indexed: 03/25/2023]
Abstract
Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare type of primary liver cancer. It is a complex "biphenotypic" tumor type consisting of bipotential hepatic progenitor cells that can differentiate into cholangiocytes subtype and hepatocytes subtype. The prognosis of patients with cHCC-CC is quite poor with its specific and more aggressive nature. Furthermore, there are no definite demographic or clinical features of cHCC-CC, thus a clear preoperative identification and accurate non-invasive imaging diagnostic analysis of cHCC-CC are of great value. In this review, we first summarized the epidemiological features, pathological findings, molecular biological information and serological indicators of cHCC-CC disease. Then we reviewed the important applications of non-invasive imaging modalities-particularly ultrasound (US)-in cHCC-CC, covering both diagnostic and prognostic assessment of patients with cHCC-CC. Finally, we presented the shortcomings and potential outlooks for imaging studies in cHCC-CC.
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Affiliation(s)
- Yu-Ting Shen
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, 200032, China
| | - Wen-Wen Yue
- Department of Medical Ultrasound, Center of Minimally Invasive Treatment for Tumor, Shanghai Tenth People's Hospital, Ultrasound Research and Education Institute, Clinical Research Center for Interventional Medicine, School of Medicine, Tongji University, Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment, Shanghai, 200072, China.
| | - Hui-Xiong Xu
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, 200032, China.
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14
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Goodwin B, Lou J, Butchy M, Wilson T, Atabek U, Spitz F, Hong Y. Hepatocellular-Cholangiocarcinoma Collision Tumors: An Update of Current Management Practices. Am Surg 2023; 89:2685-2692. [PMID: 36031932 DOI: 10.1177/00031348221124323] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/28/2023]
Abstract
Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare form of primary hepatic collision tumor, with an incidence ranging from 0.4 to 14.2%. Given the diagnostic challenges and lack of randomized trials, standardized treatment has yet to be established. We aim to review the literature to summarize the diagnosis, molecular characteristics, current treatment modalities, and challenges for cHCC-CC. A literature review was performed using PubMed. We included studies investigating and describing cHCC-CC, focusing on surgical, medical, and radiologic treatments. Overall prognosis is poor, with a 5-year survival rate under 30%. Minor or major hepatectomy with R0 resection is the only curative treatment; however, recurrence is likely (as high as 50% within 5 years). The role of liver transplantation is also highly debated given the biliary nature of these tumors, with cHCC-CC as a relative contraindication for liver transplantation. Although gemcitabine-based treatments had higher progression-free survival over sorafenib, there is no standard chemotherapy regimen. Treatment with gemcitabine and platinum demonstrates improved disease control rates compared to gemcitabine in conjunction with 5-fluorouracil (78.4% verse 38.5% respectively). Additionally, platinum-containing chemotherapy regimens exhibit a higher overall response rate than non-platinum regimens (21.4% verse 7.0% respectively). These molecular-directed therapies have prolonged survival for HCC, but further investigation needs to be done to assess their utility in patients with cHCC-CC. cHCC-CC is a rare and complex subset of primary hepatic neoplasms with a dismal prognosis and unstandardized treatment options. Further trials need to be performed to investigate systemic chemotherapy and immunotherapy options for patients with unresectable disease.
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Affiliation(s)
- Brandon Goodwin
- Rowan University School of Osteopathic Medicine, Stratford, NJ, USA
| | | | | | - Traeden Wilson
- Cooper Medical School of Rowan University, Camden, NJ, USA
| | | | | | - Young Hong
- Cooper University Hospital, Camden, NJ, USA
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15
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Zhang J, Dong W, Li Y, Fu J, Jia N. Prediction of microvascular invasion in combined hepatocellular-cholangiocarcinoma based on preoperative contrast-enhanced CT and clinical data. Eur J Radiol 2023; 163:110839. [PMID: 37121101 DOI: 10.1016/j.ejrad.2023.110839] [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: 02/15/2023] [Revised: 04/11/2023] [Accepted: 04/14/2023] [Indexed: 05/02/2023]
Abstract
OBJECTIVE Microvascular invasion (MVI) is significantly associated with prognosis in combined hepatocellular-cholangiocarcinoma (cHCC-CCA) patients. The study aimed to explore the value of preoperative contrast-enhanced CT (CECT) features and clinical data in predicting MVI of cHCC-CCA. METHODS A total of 33 patients with MVI-positive and 27 with MVI-negative were enrolled, and underwent preoperative CECT imaging from January 2016 to December 2021. Preoperative clinical data and CECT imaging features were retrospectively analyzed. Univariable and multivariable logistic regression analysis were performed to identify potential predictors of MVI in cHCC-CCA. The diagnostic performance was evaluated by the receiver operating characteristic (ROC) curve and its area under the curve (AUC) value. RESULTS The mean age of the patients was 54.0 ± 10.3 years, and 53 of the 60 patients (88.3%) were male. Preoperative imaging features on CECT (non-smooth contour and arterial phase peritumoral enhancement) and clinical data (hepatitis B virus (HBV) infection and protein induced by vitamin K absence or antagonist-II (PIVKA-II)) were highly distinct between those in MVI-positive group and MVI-negative group. On multivariable logistic analysis, arterial phase peritumoral enhancement (odds ratio (OR), 6.514; 95% confidence interval (CI), 1.588-26.728, p = 0.012) and high serum PIVKA-II level (OR, 6.810; 95% CI, 1.796-25.820, p = 0.005) were independent predictors associated with MVI of cHCC-CCA. The combination of these two predictors had high sensitivity (31/33, 93.9%; 95% CI, 80.4% - 98.3%) in the prediction of MVI with an area under the receiver operating characteristic (ROC) curve of 0.763 (95% CI, 0.635-0.863). CONCLUSIONS The findings indicated that arterial phase peritumoral enhancement on preoperative CECT and high serum PIVKA-II level were identified as potential predictors for MVI in cHCC-CCA patients.
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Affiliation(s)
- Juan Zhang
- Department of Radiology, Eastern Hepatobilliary Surgery Hospital, Third Affiliated Hospital of Naval Medical University, Shanghai 200438, China
| | - Wei Dong
- Department of Pathology, Eastern Hepatobilliary Surgery Hospital, Third Affiliated Hospital of Naval Medical University, Shanghai 200438, China
| | - Yinqiao Li
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Jiazhao Fu
- Department of Organ Transplantation, Changhai Hospital, First Affiliated Hospital of Naval Medical University, Shanghai 200433, China.
| | - Ningyang Jia
- Department of Radiology, Eastern Hepatobilliary Surgery Hospital, Third Affiliated Hospital of Naval Medical University, Shanghai 200438, China.
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16
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Zhao J, Stephan-Falkenau S, Schuler M, Arndt B. Management of Locally Advanced or Metastatic Combined Hepatocellular Cholangiocarcinoma. Cancers (Basel) 2023; 15:988. [PMID: 36765942 PMCID: PMC9913543 DOI: 10.3390/cancers15030988] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 01/25/2023] [Accepted: 02/01/2023] [Indexed: 02/09/2023] Open
Abstract
Combined hepatocellular cholangiocarcinoma (cHCC-CC) is a rare primary liver malignancy that comprises features of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Due to the rarity of this tumor, the treatment of choice has not yet been defined. For resectable disease, liver resection is the mainstay treatment. However, most patients relapse or display advanced disease and were not surgical candidates. Although the majority of patients are either primarily or secondarily treated in palliative intent, no guideline recommendations or prospective trial reports exist to allow reliable evaluation of debated treatment options. We review different locoregional or medical treatment options for advanced combined hepatocellular cholangiocarcinoma (cHCC-CC) in the neoadjuvant, adjuvant, or palliative setting and discuss the possibility of predictive biomarker-guided therapeutic options.
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Affiliation(s)
- Jemmy Zhao
- National Center of Tumor Diseases, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
| | - Susann Stephan-Falkenau
- Institute of Pathology, Medizinisches Versorgungszentrum am Helios Klinikum Emil von Behring, Walterhöferstr. 11, 14165 Berlin, Germany
| | - Markus Schuler
- Onkologischer Schwerpunkt am Oskar-Helene Heim, Clayallee 225a, 14195 Berlin, Germany
| | - Börge Arndt
- Department of Hematology and Oncology, Helios Klinikum Emil von Behring, Walterhöferstr. 11, 14165 Berlin, Germany
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17
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Xiao Y, Zheng X, Zhou C, Huang P, Wu F, Yang C, Zeng M. Combined hepatocellular carcinoma-cholangiocarcinoma with a predominant HCC component: better survival and MRI-based prediction. Eur Radiol 2023; 33:1412-1421. [PMID: 36112193 DOI: 10.1007/s00330-022-09131-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 07/22/2022] [Accepted: 08/29/2022] [Indexed: 02/03/2023]
Abstract
OBJECTIVES To determine the optimal cutoff value of HCC% for predicting the outcome of patients with combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) and to investigate how preoperative MR features based on the Liver Imaging Reporting and Data System (LI-RADS ver. 2018) are related to the HCC% in cHCC-CCA. METHODS The study enrolled 107 patients pathologically confirmed to have single cHCC-CCA according to the 2019 WHO classification. A receiver operating characteristic (ROC) curve was used to find the optimal cutoff value of HCC% based on overall survival (OS). The preoperative MR imaging features and clinicopathological findings were retrospectively evaluated and compared between the high HCC% and low HCC% groups. RESULTS In total, 107 patients (mean age, males vs. females: 56.6 ± 10.7 years vs. 54.2 ± 12.8 years) were evaluated. Analysis of the relationship between HCC% and OS by ROC curve suggested that the optimal cutoff value was 65%, by which 51 (47.7%) patients were assigned to the high HCC% group. LI-RADS categorization (OR = 3.657, p = 0.006 vs. OR = 4.075, p = 0.004) and serum carcinoembryonic antigen (CEA) >5 ng/mL (OR = 0.348, p = 0.089 vs. OR = 0.298, p = 0.040) were significant predictors for HCC% in cHCC-CCA in both univariate and multivariate analysis. CONCLUSIONS cHCC-CCA patients with HCC components higher than 65% tend to exhibit better overall survival, and MRI-based LI-RADS categorization and serum CEA level are valuable for identifying HCC% in cHCC-CCA preoperatively. KEY POINTS • cHCC-CCA patients with HCC components higher than 65% tend to exhibit better overall survival. • MRI-based LI-RADS categorization and serum CEA level were significant predictors for HCC% in cHCC-CCA in both univariate and multivariate analyses and valuable for identifying HCC% in cHCC-CCA preoperatively.
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Affiliation(s)
- Yuyao Xiao
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Xinde Zheng
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Changwu Zhou
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.,Shanghai Institute of Medical Imaging, Shanghai, China
| | - Peng Huang
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Fei Wu
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
| | - Chun Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China. .,Shanghai Institute of Medical Imaging, Shanghai, China. .,Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
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Zhang HY, Zong RQ, Wu FX, Li YR. Bioinformatics Analysis Identifies ASCL1 as the Key Transcription Factor in Hepatocellular Carcinoma Progression. DISEASE MARKERS 2023; 2023:3560340. [PMID: 36755802 PMCID: PMC9902118 DOI: 10.1155/2023/3560340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 10/12/2022] [Accepted: 11/25/2022] [Indexed: 01/31/2023]
Abstract
Methods Differentially transcription factors (DETFs) were identified from differentially expressed genes (DEGs) in GSE62232 and transcription factors. Then, they were analyzed by regulatory networks, prognostic risk model, and overall survival analyses to identify the key DETF. Combined with the regulatory networks and binding site analysis, the target mRNA of key DETF was determined, and its prognostic value in HCC was evaluated by survival, clinical characteristics analyses, and experiments. Finally, the expressions and functions of the key DETF on the DEmRNAs were investigated in HCC cells. Results Through multiple bioinformatics analyses, ASCL1 was identified as the key DETF, and SLC6A13 was predicted to be its target mRNA with the common binding site of CCAGCAACTGGCC, both downregulated in HCC. In survival analysis, high SLC6A13 was related to better HCC prognosis, and SLC6A13 was differentially expressed in HCC patients with clinical characteristics. Furthermore, cell experiments showed the mRNA expressions of ASCL1 and SLC6A13 were both reduced in HCC, and their overexpressions suppressed the growth, invasion, and migration of HCC cells. Besides, over-ASCL1 could upregulate SLC6A13 expression in HCC cells. Conclusion This study identifies two suppressor genes in HCC progression, ASCL1 and SLC6A13, and the key transcription factor ASCL1 suppresses HCC progression by targeting SLC6A13 mRNA. They are both potential treatment targets and prognostic biomarkers for HCC patients, which provides new clues for HCC research.
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Affiliation(s)
- Hong-yan Zhang
- Department of Intensive Care Medicine, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Rui-qing Zong
- Department of Intensive Care Medicine, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Fei-xiang Wu
- Department of Intensive Care Medicine, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Yi-ran Li
- Department of Intensive Care Medicine, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Medical University, Shanghai, China
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Surgical Strategies for Combined Hepatocellular-Cholangiocarcinoma (cHCC-CC). Cancers (Basel) 2023; 15:cancers15030774. [PMID: 36765731 PMCID: PMC9913263 DOI: 10.3390/cancers15030774] [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: 12/31/2022] [Revised: 01/17/2023] [Accepted: 01/19/2023] [Indexed: 01/28/2023] Open
Abstract
Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a tumor entity presenting features of hepatocellular and cholangiocellular epithelial differentiation. Due to the likeness between cHCC-CC, HCC and CC, accurate pretherapeutical diagnosis is challenging and advanced stages are prevalent. Radical oncological surgery is the only curative therapeutical option in patients with cHCC-CC. To reach this goal a profound understanding of this rare liver tumor is crucial. Factors such as clinicopathological characteristics, growth patterns and biological behavior are of central importance. To explore onco-surgical strategies and aspects for complete resection of cHCC-CC and to answer important key questions, an extensive review of the literature was conducted to answer the following questions: What are the best surgical options? Is there a significance for nonanatomical resections? Is there a prognostic value of concomitant lymphadenectomy? What about multimodal concepts in local advanced cHCC-CC? The role of minimally invasive liver surgery (MILS) including the role of robotic liver surgery for cHCC-CC will be discussed. While liver transplantation (LT) is standard for patients with unresectable HCC, the role of LT in cHCC-CC patients is still controversial. How can patients with high risk for early tumor recurrence be identified to avoid aggressive surgical treatment without clinical benefit? The comprehensive understanding of this challenging liver tumor will help to improve future treatment options for these patients.
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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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21
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Xu RC, Wang F, Sun JL, Abuduwaili W, Zhang GC, Liu ZY, Liu TT, Dong L, Shen XZ, Zhu JM. A novel murine model of combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Transl Med 2022; 20:579. [PMID: 36494846 PMCID: PMC9733131 DOI: 10.1186/s12967-022-03791-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 11/24/2022] [Indexed: 12/13/2022] Open
Abstract
Primary liver cancer (PLC) is a common gastrointestinal malignancy worldwide. While hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are two major pathologic types of PLC, combined HCC and ICC (cHCC-ICC) is a relatively rare subtype that shares both hepatocyte and cholangiocyte differentiation. However, the molecular feature of this unique tumor remains elusive because of its low incidence and lack of a suitable animal model. Herein, we generated a novel spontaneous cHCC-ICC model using a Sleeping Beauty-dependent transposon plasmid co-expressing oncogenic Myc and AKT1 and a CRISPR-Cas9 plasmid expressing single-guide RNA targeting p53 into mouse hepatocytes via in situ electroporation. The histological and transcriptional analysis confirmed that this model exhibits cHCC-ICC features and activates pathways committing cHCC-ICC formation, such as TGF-β, WNT, and NF-κB. Using this model, we further screened and identified LAMB1, a protein involved in cell adhesion and migration, as a potential therapeutic target for cHCC-ICC. In conclusion, our work presents a novel genetic cHCC-ICC model and provides new insights into cHCC-ICC.
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Affiliation(s)
- Ru-Chen Xu
- grid.413087.90000 0004 1755 3939Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032 China ,grid.413087.90000 0004 1755 3939Shanghai Institute of Liver Diseases, Shanghai, China
| | - Fu Wang
- grid.413087.90000 0004 1755 3939Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032 China ,grid.413087.90000 0004 1755 3939Shanghai Institute of Liver Diseases, Shanghai, China
| | - Jia-Lei Sun
- grid.413087.90000 0004 1755 3939Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032 China ,grid.413087.90000 0004 1755 3939Shanghai Institute of Liver Diseases, Shanghai, China
| | - Weinire Abuduwaili
- grid.413087.90000 0004 1755 3939Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032 China ,grid.413087.90000 0004 1755 3939Shanghai Institute of Liver Diseases, Shanghai, China
| | - Guang-Cong Zhang
- grid.413087.90000 0004 1755 3939Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032 China ,grid.413087.90000 0004 1755 3939Shanghai Institute of Liver Diseases, Shanghai, China
| | - Zhi-Yong Liu
- grid.413087.90000 0004 1755 3939Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032 China ,grid.413087.90000 0004 1755 3939Shanghai Institute of Liver Diseases, Shanghai, China
| | - Tao-Tao Liu
- grid.413087.90000 0004 1755 3939Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032 China ,grid.413087.90000 0004 1755 3939Shanghai Institute of Liver Diseases, Shanghai, China
| | - Ling Dong
- grid.413087.90000 0004 1755 3939Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032 China ,grid.413087.90000 0004 1755 3939Shanghai Institute of Liver Diseases, Shanghai, China
| | - Xi-Zhong Shen
- grid.413087.90000 0004 1755 3939Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032 China ,grid.413087.90000 0004 1755 3939Shanghai Institute of Liver Diseases, Shanghai, China ,grid.11841.3d0000 0004 0619 8943Key Laboratory of Medical Molecular Virology, Shanghai Medical College of Fudan University, Shanghai, China
| | - Ji-Min Zhu
- grid.413087.90000 0004 1755 3939Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, 200032 China ,grid.413087.90000 0004 1755 3939Shanghai Institute of Liver Diseases, Shanghai, China
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22
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Wang WQ, Li J, Liang BY, Lv X, Zhu RH, Wang JL, Huang ZY, Yang SH, Zhang EL. Anatomical liver resection improves surgical outcomes for combined hepatocellular-cholangiocarcinoma: A propensity score matched study. Front Oncol 2022; 12:980736. [PMID: 36059669 PMCID: PMC9433922 DOI: 10.3389/fonc.2022.980736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 07/29/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundThe efficacies of anatomical resection (AR) and non-anatomical resection (NAR) in the treatment of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) remain unclear. This study aimed to compare the prognostic outcomes of AR with those of NAR for cHCC-CCA.MethodPatients diagnosed with pathology-confirmed cHCC-CCA, and who underwent curative resection at Tongji hospital between January 2010 and December 2019 were included in this retrospective study. A one-to-one propensity score matching (PSM) analysis was used to compare the long-term outcomes of AR to those of NAR.ResultsA total of 105 patients were analyzed, of whom 48 (45.7%) and 57 (54.3%) underwent AR and NAR, respectively. There were no significant differences in short-term outcomes between the two groups, including duration of postoperative hospital stay, the incidence of perioperative complications, and incidence of 30-day mortality. However, both, the 5-year overall survival (OS) and recurrence-free survival (RFS) rates of AR were significantly better than those of NAR (40.5% vs. 22.4%, P=0.002; and 37.3% vs. 14.4%, P=0.002, respectively). Multivariate analysis showed that NAR, multiple tumors, larger-sized tumors (>5 cm), cirrhosis, lymph node metastasis, and vascular invasion were independent risk factors for poor prognoses. Stratified analysis demonstrated similar outcomes following AR versus NAR for patients with tumors > 5cm in diameter, while AR had better survival than NAR in patients with tumors ≤5 cm in diameter. After PSM, when 34 patients from each group were matched, the 5-year OS and RFS rates of AR were still better than those of NAR.ConclusionPatients with cHCC-CCA who underwent AR had better long-term surgical outcomes than those who underwent NAR, especially for those with tumors ≤5 cm in diameter. However, no differences in the risk of surgical complications were detected between the two groups.
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Affiliation(s)
- Wen-qiang Wang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jian Li
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bin-yong Liang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xing Lv
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Rong-hua Zhu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jin-lin Wang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhi-yong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shu-hong Yang
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- *Correspondence: Er-lei Zhang, ; Shu-hong Yang,
| | - Er-lei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- *Correspondence: Er-lei Zhang, ; Shu-hong Yang,
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Guo HL, Lu XZ, Hu HT, Ruan SM, Zheng X, Xie XY, Lu MD, Kuang M, Shen SL, Chen LD, Wang W. Contrast-Enhanced Ultrasound-Based Nomogram: A Potential Predictor of Individually Postoperative Early Recurrence for Patients With Combined Hepatocellular-Cholangiocarcinoma. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2022; 41:1925-1938. [PMID: 34751450 DOI: 10.1002/jum.15869] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 10/17/2021] [Accepted: 10/22/2021] [Indexed: 12/17/2022]
Abstract
PURPOSES To evaluate the postsurgical prognostic implication of contrast-enhanced ultrasound (CEUS) for combined hepatocellular-cholangiocarcinoma (CHC). To build a CEUS-based early recurrence prediction classifier for CHC, in comparison with tumor-node-metastasis (TNM) staging. METHODS The CEUS features and clinicopathological findings of each case were analyzed, and the Liver Imaging Reporting and Data System categories were assigned. The recurrence-free survival associated factors were evaluated by Cox proportional hazard model. Incorporating the independent factors, nomograms were built to estimate the possibilities of 3-month, 6-month, and 1-year recurrence and whose prognostic value was determined by time-dependent receiver operating characteristics, calibration curves, and hazard layering efficiency validation, comparing with TNM staging system. RESULTS In the multivariable analysis, the levels of carbohydrate antigen 19-9, prothrombin time and total bilirubin, and tumor shape, the Liver Imaging Reporting and Data System category were independent factors for recurrence-free survival. The LR-M category showed longer recurrence-free survival than did the LR-4/5 category. The 3-month, 6-month, and 1-year area under the curves of the CEUS-clinical nomogram, clinical nomogram, and TNM staging system were 0.518, 0.552, and 0.843 versus 0.354, 0.240, and 0.624 (P = .048, .049, and .471) vs. 0.562, 0.545, and 0.843 (P = .630, .564, and .007), respectively. The calibration curves of the CEUS-clinical model at different prediction time pionts were all close to the ideal line. The CEUS-clinical model effectively stratified patients into groups of high and low risk of recurrence in both training and validation set, while the TNM staging system only works on the training set. CONCLUSIONS Our CEUS-clinical nomogram is a reliable early recurrence prediction tool for hepatocellular-cholangiocarcinoma and helps postoperative risk stratification.
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Affiliation(s)
- Huan-Ling Guo
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xiao-Zhou Lu
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Hang-Tong Hu
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Si-Min Ruan
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xin Zheng
- Department of Medical Ultrasonics, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Xiao-Yan Xie
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Ming-De Lu
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Ming Kuang
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Shun-Li Shen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Li-Da Chen
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Wei Wang
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
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24
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Saito N, Hatanaka T, Nakano S, Hazama Y, Yoshida S, Hachisu Y, Tanaka Y, Yoshinaga T, Kashiwabara K, Kubo N, Hosouchi Y, Tojima H, Kakizaki S, Uraoka T. A case of unresectable combined hepatocellular and cholangiocarcinoma treated with atezolizumab plus bevacizumab. Clin Case Rep 2022; 10:e6129. [PMID: 35898742 PMCID: PMC9309740 DOI: 10.1002/ccr3.6129] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 06/23/2022] [Accepted: 06/29/2022] [Indexed: 11/24/2022] Open
Abstract
An 81-year-old man initially underwent right hepatic lobectomy for liver cancer and was pathologically diagnosed with combined hepatocellular and cholangiocarcinoma (CHC). At 13 months after resection, multiple lymph node metastases were observed. We started atezolizumab plus bevacizumab (Atez/Bev), achieving a 7.5-month progression-free survival. Atez/Bev might exhibit efficacy for CHC patients.
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Affiliation(s)
- Naoto Saito
- Department of GastroenterologyGunma Saiseikai Maebashi HospitalMaebashiJapan
| | - Takeshi Hatanaka
- Department of GastroenterologyGunma Saiseikai Maebashi HospitalMaebashiJapan
| | - Sachi Nakano
- Department of GastroenterologyGunma Saiseikai Maebashi HospitalMaebashiJapan
| | - Yoichi Hazama
- Department of GastroenterologyGunma Saiseikai Maebashi HospitalMaebashiJapan
| | - Sachiko Yoshida
- Department of GastroenterologyGunma Saiseikai Maebashi HospitalMaebashiJapan
| | - Yoko Hachisu
- Department of GastroenterologyGunma Saiseikai Maebashi HospitalMaebashiJapan
| | - Yoshiki Tanaka
- Department of GastroenterologyGunma Saiseikai Maebashi HospitalMaebashiJapan
| | - Teruo Yoshinaga
- Department of GastroenterologyGunma Saiseikai Maebashi HospitalMaebashiJapan
| | - Kenji Kashiwabara
- Department of PathologyGunma Saiseikai Maebashi HospitalMaebashiJapan
| | - Norio Kubo
- Department of SurgeryGunma Saiseikai Maebashi HospitalMaebashiJapan
| | - Yasuo Hosouchi
- Department of SurgeryGunma Saiseikai Maebashi HospitalMaebashiJapan
| | - Hiroki Tojima
- Department of Gastroenterology and HepatologyGunma University Graduate School of MedicineMaebashiJapan
| | - Satoru Kakizaki
- Department of Gastroenterology and HepatologyGunma University Graduate School of MedicineMaebashiJapan
- Department of Clinical ResearchNational Hospital Organization Takasaki General Medical CenterTakasakiJapan
| | - Toshio Uraoka
- Department of Gastroenterology and HepatologyGunma University Graduate School of MedicineMaebashiJapan
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25
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Lee SJ, Kang SH, Choi Y, Lee B, Hong S, Cho JY, Yi N, Lee K, Suh K, Han H. Long-term outcomes of laparoscopic versus open liver resection for intrahepatic combined hepatocellular-cholangiocarcinoma with propensity score matching. Ann Gastroenterol Surg 2022; 6:562-568. [PMID: 35847442 PMCID: PMC9271021 DOI: 10.1002/ags3.12555] [Citation(s) in RCA: 3] [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: 11/02/2021] [Revised: 01/04/2022] [Accepted: 02/01/2022] [Indexed: 11/23/2022] Open
Abstract
Background Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary hepatic neoplasm. Currently, there are no well-structured studies that analyze the feasibility of laparoscopic liver resection in cHCC-CCA alone. This retrospective cohort study aimed to compare the long-term survival of laparoscopic liver resection with open liver resection in cHCC-CCA. Methods Patients with a postoperative pathologic report of cHCC-CCA who underwent liver resection from August 2004 to December 2017 were included in this study. Kaplan-Meier survival analysis was performed to analyze the 3-y disease-free survival and 3-y overall survival. Propensity score matching was done to reduce the influence of confounding variables. Results A total of 145 patients were pathologically confirmed to have cHCC-CCA, of which 10 patients were excluded due to having received palliative surgery. Of the remaining 135 patients, 43 underwent laparoscopic and 92 underwent open liver resection; propensity score matching yielded 30 patients for each group. The 3-y overall survival was 38 (88.4%) in the laparoscopic group and 84 (91.3%) in the open group before propensity score matching (P = .678), and 25 (83.3%) and 28 (93.3%), respectively, after matching (P = .257). The 3-y disease-free survival was 24 (55.8%) in the laparoscopic group and 32 (34.8%) in the open group before matching (P = .040), and 17 (56.7%) and 16 (53.3%), respectively, after matching (P = .958). The hospital stay was shorter in the laparoscopic group before and after matching, while other operative outcomes were similar in both groups. Conclusion Laparoscopic liver resection for cHCC-CCA is technically feasible and safe, having a shorter hospital stay without compromising oncological outcomes.
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Affiliation(s)
- Seung Jae Lee
- Department of SurgerySeoul National University College of MedicineSeoul National University HospitalSeoulKorea
| | - So Hyun Kang
- Department of SurgerySeoul National University College of MedicineSeoul National University Bundang HospitalSeongnamKorea
| | - YoungRok Choi
- Department of SurgerySeoul National University College of MedicineSeoul National University HospitalSeoulKorea
- Department of SurgerySeoul National University College of MedicineSeoul National University Bundang HospitalSeongnamKorea
| | - Boram Lee
- Department of SurgerySeoul National University College of MedicineSeoul National University Bundang HospitalSeongnamKorea
| | - Suk Kyun Hong
- Department of SurgerySeoul National University College of MedicineSeoul National University HospitalSeoulKorea
| | - Jai Young Cho
- Department of SurgerySeoul National University College of MedicineSeoul National University Bundang HospitalSeongnamKorea
| | - Nam‐Joon Yi
- Department of SurgerySeoul National University College of MedicineSeoul National University HospitalSeoulKorea
| | - Kwang‐Woong Lee
- Department of SurgerySeoul National University College of MedicineSeoul National University HospitalSeoulKorea
| | - Kyung‐Suk Suh
- Department of SurgerySeoul National University College of MedicineSeoul National University HospitalSeoulKorea
| | - Ho‐Seong Han
- Department of SurgerySeoul National University College of MedicineSeoul National University Bundang HospitalSeongnamKorea
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Combined Hepatocellular-Cholangiocarcinoma: What the Multidisciplinary Team Should Know. Diagnostics (Basel) 2022; 12:diagnostics12040890. [PMID: 35453938 PMCID: PMC9026907 DOI: 10.3390/diagnostics12040890] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 04/01/2022] [Accepted: 04/01/2022] [Indexed: 12/10/2022] Open
Abstract
Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare type of primary liver malignancy. Among the risk factors, hepatitis B and hepatitis C virus infections, cirrhosis, and male gender are widely reported. The clinical appearance of cHCC-CCA is similar to that of HCC and iCCA and it is usually silent until advanced states, causing a delay of diagnosis. Diagnosis is mainly based on histology from biopsies or surgical specimens. Correct pre-surgical diagnosis during imaging studies is very problematic and is due to the heterogeneous characteristics of the lesion in imaging, with overlapping features of HCC and CCA. The predominant histological subtype within the lesion establishes the predominant imaging findings. Therefore, in this scenario, the radiological findings characteristic of HCC show an overlap with those of CCA. Since cHCC-CCAs are prevalent in patients at high risk of HCC and there is a risk that these may mimic HCC, it is currently difficult to see a non-invasive diagnosis of HCC. Surgery is the only curative treatment of HCC-CCA. The role of liver transplantation (LT) in the treatment of cHCC-CCA remains controversial, as is the role of ablative or systemic therapies in the treatment of this tumour. These lesions still remain challenging, both in diagnosis and in the treatment phase. Therefore, a pre-treatment imaging diagnosis is essential, as well as the identification of prognostic factors that could stratify the risk of recurrence and the most adequate therapy according to patient characteristics.
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27
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Nguyen CT, Caruso S, Maille P, Beaufrère A, Augustin J, Favre L, Pujals A, Boulagnon-Rombi C, Rhaiem R, Amaddeo G, di Tommaso L, Luciani A, Regnault H, Brustia R, Scatton O, Charlotte F, Brochériou I, Sommacale D, Soussan P, Leroy V, Laurent A, Le VK, Ta VT, Trinh HS, Tran TL, Gentien D, Rapinat A, Nault JC, Allaire M, Mulé S, Zucman-Rossi J, Pawlotsky JM, Tournigand C, Lafdil F, Paradis V, Calderaro J. Immune profiling of combined hepatocellular-cholangiocarcinoma reveals distinct subtypes and activation of gene signatures predictive of response to immunotherapy. Clin Cancer Res 2021; 28:540-551. [PMID: 34785581 DOI: 10.1158/1078-0432.ccr-21-1219] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 06/18/2021] [Accepted: 11/09/2021] [Indexed: 11/16/2022]
Abstract
Purpose: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare malignancy associated with an overall poor prognosis. We aimed to investigate the immune profile of cHCC-CCA and determine its impact on disease outcome. Experimental Design: We performed a multicenter study of 96 patients with cHCC-CCA. Gene expression profile was analyzed using nCounter PanCancer IO 360 Panel. Densities of main immune cells subsets were quantified from digital slides of immunohistochemical stainings. Genetic alterations were investigated using targeted next generation sequencing. Results: Two main immune subtypes of cHCC-CCA were identified by clustering analysis: an "Immune High" (IH) subtype (57% of the cases) and an "Immune Low" (IL) subtype (43% of the cases). Tumors classified as IH showed overexpression of genes related to immune cells recruitment, adaptive and innate immunity, antigen presentation, cytotoxicity, immune suppression, and inflammation (p<0.0001). IH cHCC-CCAs also displayed activation of gene signatures recently shown to be associated with response to immunotherapy in patients with HCC. Immunostainings confirmed that IH tumors were also characterized by higher densities of immune cells. Immune subtypes were not associated with any genetic alterations. Finally, multivariate analysis showed that the IH subtype was an independent predictor of improved overall survival. Conclusions: We have identified a subgroup of cHCC-CCA that displays features of an ongoing intra-tumor immune response, along with an activation of gene signatures predictive of response to immunotherapy in HCC. This tumor subclass is associated with an improved clinical outcome. These findings suggest that a subset of patients with cHCC-CCA may benefit from immunomodulating therapeutic approaches.
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Affiliation(s)
- Cong Trung Nguyen
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
| | - Stefano Caruso
- INSERM UMR-1162, Génomique Fonctionnelle des Tumeurs Solides, Paris, France
| | - Pascale Maille
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Département de Pathologie, Créteil, France
| | - Aurélie Beaufrère
- Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, Service d'Anatomo-Pathologie, Clichy, France
| | - Jérémy Augustin
- Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service d'Anatomie et de Cytologie Pathologiques, Sorbonne Université, Paris, France
| | - Loetitia Favre
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Département de Pathologie, Créteil, France
| | - Anaïs Pujals
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Département de Pathologie, Créteil, France
| | - Camille Boulagnon-Rombi
- Centre Hospitalier Universitaire de Reims, Service d'Anatomie et de Cytologie Pathologiques, Reims, France
| | - Rami Rhaiem
- Hôpital Robert Debré, Service de Chirurgie Digestive et Hépatobiliaire, Reims, France
| | - Giuliana Amaddeo
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service d'Hépatologie, Créteil, France
| | - Luca di Tommaso
- Department of Pathology, Humanitas University, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy
| | - Alain Luciani
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service d'Imagerie Médicale, Créteil, France
| | - Hélène Regnault
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service d'Hépatologie, Créteil, France
| | - Raffaele Brustia
- Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service de Chirurgie Digestive, Hépato-Bilio-Pancréatique et Transplantation Hépatique, Paris, France
| | - Olivier Scatton
- Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service de Chirurgie Digestive, Hépato-Bilio-Pancréatique et Transplantation Hépatique, Paris, France
| | - Frédéric Charlotte
- Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service d'Anatomie et de Cytologie Pathologiques, Sorbonne Université, Paris, France
| | - Isabelle Brochériou
- Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service d'Anatomie et de Cytologie Pathologiques, Sorbonne Université, Paris, France
| | - Daniele Sommacale
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service de Chirurgie Digestive et Hépato-bilio-pancréatique, Créteil, France
| | - Patrick Soussan
- Centre National de la Recherche Scientifique (CNRS, ERL8255), Institut National de la Santé et de la Recherche Médicale (Inserm, UMR1135), Sorbonne Universités, Paris, France
| | - Vincent Leroy
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service d'Hépatologie, Créteil, France
| | - Alexis Laurent
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service de Chirurgie Digestive et Hépato-bilio-pancréatique, Créteil, France
| | - Van Ky Le
- Department of Pathology, National Cancer Hospital, Hanoi, Vietnam
| | - Van To Ta
- Department of Pathology, National Cancer Hospital, Hanoi, Vietnam
| | - Hong Son Trinh
- Department of Surgical Oncology, Vietduc Hospital, Hanoi, Vietnam
| | - Thi Lan Tran
- Department of Pathology, Hanoi Medical University, Hanoi, Vietnam
| | - David Gentien
- Institut Curie, PSL Research University, Translational Research Department, Genomics platform, Paris, France
| | - Audrey Rapinat
- Institut Curie, PSL Research University, Translational Research Department, Genomics platform, Paris, France
| | - Jean Charles Nault
- INSERM UMR-1162, Génomique Fonctionnelle des Tumeurs Solides, Paris, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Jean Verdier, Service d'Hépatologie, Bondy, France
| | - Manon Allaire
- Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service d'Hépatologie, Paris, France
| | - Sebastien Mulé
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service d'Imagerie Médicale, Créteil, France
| | - Jessica Zucman-Rossi
- INSERM UMR-1162, Génomique Fonctionnelle des Tumeurs Solides, Paris, France
- Assistance Publique-Hôpitaux de Paris, Service d'Oncologie Médicale, Hôpital Européen Georges Pompidou, Paris, France
- Université Paris Descartes, Université Paris Diderot, Université Paris 13, France
| | - Jean-Michel Pawlotsky
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
| | - Christophe Tournigand
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Service d'Oncologie Médicale, Créteil, France
| | - Fouad Lafdil
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
- Institut Universitaire de France (IUF), Paris, France
| | - Valérie Paradis
- Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, Service d'Anatomo-Pathologie, Clichy, France
- Université de Paris, Centre de recherche sur l'inflammation, Inserm, U1149, CNRS, ERL8252, Paris, France
| | - Julien Calderaro
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France.
- INSERM, U955, Equipe 18 "Physiopathologie et Thérapeutiques des Hépatites Virales Chroniques et des cancers liés", Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Département de Pathologie, Créteil, France
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Tang YY, Zhao YN, Zhang T, Chen ZY, Ma XL. Comprehensive radiomics nomogram for predicting survival of patients with combined hepatocellular carcinoma and cholangiocarcinoma. World J Gastroenterol 2021; 27:7173-7189. [PMID: 34887636 PMCID: PMC8613648 DOI: 10.3748/wjg.v27.i41.7173] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 06/26/2021] [Accepted: 09/03/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (cHCC-CCA) is defined as a single nodule showing differentiation into HCC and intrahepatic cholangiocarcinoma and has a poor prognosis. AIM To develop a radiomics nomogram for predicting post-resection survival of patients with cHCC-CCA. METHODS Patients with pathologically diagnosed cHCC-CCA were randomly divided into training and validation sets. Radiomics features were extracted from portal venous phase computed tomography (CT) images using the least absolute shrinkage and selection operator Cox regression and random forest analysis. A nomogram integrating the radiomics score and clinical factors was developed using univariate analysis and multivariate Cox regression. Nomogram performance was assessed in terms of the C-index as well as calibration, decision, and survival curves. RESULTS CT and clinical data of 118 patients were included in the study. The radiomics score, vascular invasion, anatomical resection, total bilirubin level, and satellite lesions were found to be independent predictors of overall survival (OS) and were therefore included in an integrative nomogram. The nomogram was more strongly associated with OS (hazard ratio: 8.155, 95% confidence interval: 4.498-14.785, P < 0.001) than a model based on the radiomics score or only clinical factors. The area under the curve values for 1-year and 3-year OS in the training set were 0.878 and 0.875, respectively. Patients stratified as being at high risk of poor prognosis showed a significantly shorter median OS than those stratified as being at low risk (6.1 vs 81.6 mo, P < 0.001). CONCLUSION This nomogram may predict survival of cHCC-CCA patients after hepatectomy and therefore help identify those more likely to benefit from surgery.
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Affiliation(s)
- You-Yin Tang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yu-Nuo Zhao
- Department of Biotherapy, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, West China Hospital, Chengdu 610041, Sichuan Province, China
| | - Tao Zhang
- West China School of Medicine of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Zhe-Yu Chen
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xue-Lei Ma
- Department of Biotherapy, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, West China Hospital, Chengdu 610041, Sichuan Province, China
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29
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Yang J, Huang JY, Chen X, Ling WW, Luo Y, Shi YJ, Liu JB, Lu Q, Lyshchik A. Combined hepatocellular-cholangiocarcinoma: can we use contrast-enhanced ultrasound Liver Imaging Reporting and Data System (LI-RADS) to predict the patient's survival? Eur Radiol 2021; 31:6397-6405. [PMID: 33492470 DOI: 10.1007/s00330-020-07656-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 11/26/2020] [Accepted: 12/18/2020] [Indexed: 02/08/2023]
Abstract
OBJECTIVES To evaluate the relationship between contrast-enhanced (CE) ultrasound Liver Reporting and Data System (LI-RADS) classification of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and their histopathological component predominance, and to determine if the CEUS LI-RADS category can be used to predict the patient's survival after surgical resection. METHODS Between January 2011 and December 2018, medical records and CEUS of patients with pathologically proven cHCC-CCA were studied. The predominance of hepatocellular carcinoma (HCC)/intrahepatic cholangiocarcinoma (ICC) component of cHCC-CCA was analyzed by histopathology. The proportion of HCC-predominant cHCC-CCA in different LI-RADS category was compared by using Fisher's exact test. Factors affecting tumor recurrence were analyzed by Cox proportional hazard model. Disease-free survival (DFS) was estimated by using Kaplan-Meier survival curve and compared by log-rank test. RESULTS The study included 37 cHCC-CCA patients (33 men, 4 women; average age, 50.4 ± 11.0 years) and 37 nodules (mean diameter, 6.1 ± 3.9 cm). According to CEUS LI-RADS, 62.2% (23/37), 18.9% (7/37), and 18.9% (7/37) of cHCC-CCA were classified as LR-M, LR-5, and LR-TIV, respectively. The ratio of HCC predominance in LR-5 was 100% (10/10) vs 81.5% (22/27) in the LR-M group (p = 0.591). In our population, LR-5 patients had longer DFS than LR-M and LR-TIV patients combined (median DFS: 18.0 vs 6.4 months, p = 0.016). Multiple lesions (hazard ratio, 3.1; p = 0.007), tumor size (≥ 5 cm, hazard ratio, 4.1; p = 0.003), and CEUS LI-RADS category (LR-M and LR-TIV, hazard ratio, 4.7; p = 0.011) showed independent association with shorter DFS. CONCLUSION cHCC-CCA characterized as LR-5 on CEUS tend to represent HCC-predominant tumors with significantly longer disease-free survival compared to cHCC-CCA categorized as LR-M and LR-TIV. KEY POINTS • By using the American College of Radiology contrast-enhanced ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS), majority (30/37, 81.1%) of cHCC-CCA tumors were classified as LR-M or LR-TIV and only 18.9% (7/30) of cHCC-CCA were categorized as LR-5. • Patients with CEUS LR-5 cHCC-CCA had statistically significant longer disease-free time than those with LR-M and TIV cHCC-CCA (median DFS: 18.0 vs 6.4 months, p = 0.016). • Multiple lesions (hazard ratio, 3.1; p = 0.007), tumor size (≥ 5 cm, hazard ratio, 4.1; p = 0.003), and CEUS LI-RADS category (LR-M and LR-TIV, hazard ratio, 4.7; p = 0.011) showed independent association with shorter DFS.
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Affiliation(s)
- Jie Yang
- Department of Ultrasound, West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan Province, China
| | - Jia-Yan Huang
- Department of Ultrasound, West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan Province, China
| | - Xing Chen
- Department of General Surgery, West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan Province, China
| | - Wen-Wu Ling
- Department of Ultrasound, West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan Province, China
| | - Yan Luo
- Department of Ultrasound, West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan Province, China
| | - Yu-Jun Shi
- Department of Pathology, West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan Province, China
| | - Ji-Bin Liu
- Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Qiang Lu
- Department of Ultrasound, West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan Province, China.
| | - Andrej Lyshchik
- Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
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Yang G, Hwang S, Ahn CS, Kim KH, Moon DB, Ha TY, Song GW, Jung DH, Park GC, Hong SM. Clinicopathological correlation and post-resection outcomes of hepatic angiomyolipoma. Ann Hepatobiliary Pancreat Surg 2021; 25:215-220. [PMID: 34053924 PMCID: PMC8180398 DOI: 10.14701/ahbps.2021.25.2.215] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 09/29/2020] [Accepted: 10/01/2020] [Indexed: 01/12/2023] Open
Abstract
Backgrounds/Aims Angiomyolipoma is a rare neoplasm of mesenchymal origin derived from perivascular epithelioid cells. Due to rarity, hepatic angiomyolipoma (HAML) has been often misdiagnosed as hepatocellular carcinoma (HCC) or other hypervascular liver tumors based on imaging studies. This study investigated the clinicopathological correlation and post-resection outcomes of HAML. Methods This retrospective observational study included 40 patients who underwent hepatic resection (HR) for HAML between 2008 and 2018. Results Mean age of the patients was 42.6±11.4 years and there were 30 (75.0%) females. Hepatitis B and C virus infection was present in 8 patients (20.0%) and 1 patient (2.5%), respectively. Preoperative diagnoses on imaging studies were HCC in 23 (57.5%) patients, HAML in 14 (35.0%) patients, focal nodular hyperplasia in 2 (5.0%) patients, and hepatic adenoma in 1 (2.5%) patient. Percutaneous liver biopsy was performed in 10 (25.0%) patients and HAML was diagnosed in all patients. Only 3 patients (7.5%) showed a slight elevation in the level of liver tumor markers. Major HR was performed in 10 (25.0%). Laparoscopic HR was performed in 9 (22.5%). The mean tumor size was 4.8±3.9 cm and single tumor was present in 38 (95.0%) patients. Currently, all the patients are alive without tumor recurrence during the follow-up observation period of 75.7±37.3 months. Conclusions HAML is a rare form of primary liver tumor and is often misdiagnosed as HCC or other hypervascular tumors. Although HAML is benign in nature, it has malignant potential, thus resection is indicated if the tumor grows or malignancy cannot be excluded.
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Affiliation(s)
- Geunhyeok Yang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chul-Soo Ahn
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ki-Hun Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Deok-Bog Moon
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae-Yong Ha
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gi-Won Song
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Hwan Jung
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gil-Chun Park
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Beaufrère A, Calderaro J, Paradis V. Combined hepatocellular-cholangiocarcinoma: An update. J Hepatol 2021; 74:1212-1224. [PMID: 33545267 DOI: 10.1016/j.jhep.2021.01.035] [Citation(s) in RCA: 124] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 01/08/2021] [Accepted: 01/18/2021] [Indexed: 12/13/2022]
Abstract
Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a tumour that exhibits both hepatocytic and biliary differentiation. Classical risk factors for hepatocellular carcinoma (HCC) seem to also predispose patients to the development of cHCC-CCA. The pathological definition of cHCC-CCA has significantly evolved over time. The last 2019 WHO classification highlighted that the diagnosis of cHCC-CCA should be primarily based on morphology using routine stainings, with additional immunostaining used to refine the identification of subtypes. Among them, "intermediate cell carcinoma" is recognised as a specific subtype, while "cholangiolocellular carcinoma" is now considered a subtype of iCCA. Increasing molecular evidence supports the clonal nature of cHCC-CCA and parallels its biphenotypic histological appearance, with genetic alterations that are classically observed in HCC and/or iCCA. That said, the morphological diagnosis of cHCC-CCA is still challenging for radiologists and pathologists, especially on biopsy specimens. Identification of cHCC-CCA's cell of origin remains an area of active research. Its prognosis is generally worse than that of HCC, and similar to that of iCCA. Resection with lymph node dissection is unfortunately the only curative option for patients with cHCC-CCA. Thus, there remains an urgent need to develop specific therapeutic strategies for this unique clinical entity.
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Affiliation(s)
- Aurélie Beaufrère
- Université de Paris, INSERM U1149, Hôpital Beaujon, Clichy, France; Pathology Department, Hôpital Beaujon, AP-HP, Clichy, France
| | | | - Valérie Paradis
- Université de Paris, INSERM U1149, Hôpital Beaujon, Clichy, France; Pathology Department, Hôpital Beaujon, AP-HP, Clichy, France.
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32
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Yen CC, Yen CJ, Shan YS, Lin YJ, Liu IT, Huang HY, Yeh MM, Chan SH, Tsai HW. Comparing the clinicopathological characteristics of combined hepatocellular-cholangiocarcinoma with those of other primary liver cancers by use of the updated World Health Organization classification. Histopathology 2021; 79:556-572. [PMID: 33837585 DOI: 10.1111/his.14384] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 03/26/2021] [Accepted: 04/08/2021] [Indexed: 11/29/2022]
Abstract
AIMS Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is an uncommon hepatic malignancy with a poor outcome. The 2019 World Health Organization (WHO) classification modified the definition and discarded the subtypes with stem cell features. However, the differences among cHCC-CCA, hepatocellular carcinoma (HCC), HCC with stem cell/progenitor features (HCCscf) and intrahepatic cholangiocarcinoma (iCCA) remain undetermined. The aim of this study was to investigate the characteristics of cHCC-CCA in comparison with those of other primary liver cancers by utilising the updated WHO classification. METHODS AND RESULTS We retrospectively analysed 64 cHCC-CCA patients and 55 HCCscf patients from December 2007 to May 2018. Propensity score matching was conducted to compare these with HCC and iCCA patients. Clinicopathological characteristics, event-free survival and overall survival were evaluated with multivariate Cox proportional hazard regression. During a median follow-up of 55.9 months, cHCC-CCA patients had significantly poorer survival than HCCscf patients, and survival intermediate between that of HCC patients and that of iCCA patients. Hepatitis B virus (HBV) infection and high levels of tumour-infiltrating lymphocytes (TILs) were associated with favourable survival in cHCC-CCA patients. In the multivariate analysis, poor hepatic reserve, absence of HBV infection, stage IV disease and low levels of TILs were significant negative prognostic factors in cHCC-CCA patients. After being pooled with other primary liver cancers, cHCC-CCA and iCCA resulted in the worse survival. CONCLUSIONS cHCC-CCA patients have survival intermediate between that of HCC patients and iCCA patients, and HBV infection and high levels of TILs predict favourable survival. Our study provides clinical correlations for the new 2019 WHO classification.
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Affiliation(s)
- Chih-Chieh Yen
- Division of Haematology/Oncology, Department of Internal Medicine, National Cheng Kung University Hospital DouLiuo Branch, Yunlin, Taiwan.,Institute of Clinical Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Chia-Jui Yen
- Department of Oncology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Yan-Shen Shan
- Department of Surgery, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Yih-Jyh Lin
- Department of Surgery, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - I-Ting Liu
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan.,Department of Oncology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Hsuan-Yi Huang
- Division of Colorectal Surgery, Department of Surgery, Chi Mei Medical Centre, Tainan, Taiwan
| | - Matthew M Yeh
- Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA.,Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA
| | - Shih-Huang Chan
- Department of Statistics, College of Management, National Cheng Kung University, Tainan, Taiwan
| | - Hung-Wen Tsai
- Department of Pathology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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Na BG, Hwang S, Ahn CS, Kim KH, Moon DB, Ha TY, Song GW, Jung DH, Park GC, Yoon YI, Kang WH, Cho HD, Kim SH, Hong SM, Lee SG. Prognosis of hepatic epithelioid hemangioendothelioma after living donor liver transplantation. KOREAN JOURNAL OF TRANSPLANTATION 2021; 35:15-23. [PMID: 35769618 PMCID: PMC9235330 DOI: 10.4285/kjt.20.0049] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 11/05/2020] [Accepted: 11/06/2020] [Indexed: 12/24/2022] Open
Abstract
Background Epithelioid hemangioendothelioma (EHE) is a rare borderline vascular tumor. Due to its rarity and protean behavior, the optimal treatment of hepatic EHE has not yet been standardized. This single-center study describes outcomes in patients with hepatic EHE who underwent living donor liver transplantation (LDLT). Methods The medical records of patients who underwent LDLT for hepatic EHE from 2007 to 2016 were reviewed. Results During 10-year period, four patients, one man and three women, of mean age 41.3±11.1 years, underwent LDLT for hepatic EHE. Based on imaging modalities, these patients were preoperatively diagnosed with EHE or hepatocellular carcinoma, with percutaneous liver biopsy confirming that all four had hepatic EHE. The tumors were multiple and scattered over entire liver, precluding liver resection. Blood tumor markers were not elevated, except that CA19-9 and des-γ-carboxy prothrombin was slightly elevated in one patient. Mean model for end-stage liver disease score was 10.8±5.7. All patients underwent LDLT using modified right liver grafts, with graft-recipient weight ratio of 1.11±0.19, and all recovered uneventfully after LDLT. One patient died due to tumor recurrence at 9 months, whereas the other three have done well without tumor recurrence, resulting in 5-year disease-free and overall patient survival rates of 75% each. The patient with tumor recurrence was classified as a high-risk patient based on the original and modified hepatic EHE-LT scoring systems. Conclusions LDLT can be an effective treatment for patients with unresectable hepatic EHEs that are confined within the liver and absence of macrovascular invasion and lymph node metastasis.
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Affiliation(s)
- Byeong-Gon Na
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chul-Soo Ahn
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ki-Hun Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Deok-Bog Moon
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae-Yong Ha
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gi-Won Song
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Hwan Jung
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gil-Chun Park
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-In Yoon
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Woo-Hyoung Kang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hwui-Dong Cho
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang Hoon Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Gyu Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Bello HR, Mahdi ZK, Lui SK, Nandwana SB, Harri PA, Davarpanah AH. Hepatocellular Carcinoma With Atypical Imaging Features: Review of the Morphologic Hepatocellular Carcinoma Subtypes With Radiology-Pathology Correlation. J Magn Reson Imaging 2021; 55:681-697. [PMID: 33682266 DOI: 10.1002/jmri.27553] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 01/25/2021] [Accepted: 01/26/2021] [Indexed: 12/17/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer death in the United States with the incidence rate more than doubling in 20 years. HCC is unique since a noninvasive diagnosis can be achieved with imaging alone when specific clinical criteria and imaging characteristics are met, obviating the need for tissue sampling. However, HCC is a highly heterogeneous neoplasm. Atypical HCC subtypes vary significantly in their morphology, which can be attributed to specific histologic and molecular features, and can cause deviations from the classic imaging characteristics. The different morphologic subtypes of HCC frequently present a diagnostic challenge for radiologists and pathologists since their imaging and pathologic features can overlap with those of non-HCC malignancies. Identifying an atypical subtype can have important clinical implications. Liver transplant, albeit a scarce and limited resource, is the optimal treatment for conventional HCC, potentially curing both the tumor and the underlying pre-malignant condition. Some HCC subtypes as well as mimickers are associated with unacceptably high recurrence and poor outcome after transplant, and there remains limited data on the role and prognosis of liver transplantation for treatment of rare HCC subtypes. Other subtypes tend to recur later than classic HCC, potentially requiring a different follow-up scheme. This review will discuss the appearance of different HCC subtypes in relation to their histopathologic features. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3.
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Affiliation(s)
- Hernan R Bello
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Zaid K Mahdi
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Shu K Lui
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Sadhna B Nandwana
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Peter A Harri
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Amir H Davarpanah
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia, USA
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Huang C, Xu X, Wang M, Xiao X, Cheng C, Ji J, Fang M, Gao C. Serum N-glycan fingerprint helps to discriminate intrahepatic cholangiocarcinoma from hepatocellular carcinoma. Electrophoresis 2021; 42:1187-1195. [PMID: 33570803 DOI: 10.1002/elps.202000392] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 01/26/2021] [Accepted: 02/03/2021] [Indexed: 12/13/2022]
Abstract
Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are two main types of primary liver cancer, and reliable discrimination is important for optimal treatment. Aberrant glycosylation was detected in HCC and ICC. Both cross-sectional and follow-up studies were performed to establish a differential diagnosis model using N-glycans. A total of 420 participants were enrolled, with 310 patients in training cohort and 110 patients in validation cohort. The follow-up cohort was used to assess the prognosis of ICC. As the results, the diagnostic efficacy of the model was superior to alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) when identifying ICC from HCC (AUC of the nomogram: 0.845, 95%CI: 0.788-0.902; AFP: 0.793, 95%CI: 0.732-0.854; CEA: 0.592, 95%CI: 0.496-0.687; CA 19-9: 0.674, 95%CI: 0.582-0.767) in training cohort. In validation cohort, this model (AUC: 0.810, 95% CI: 0.728-0.891) also demonstrated high efficacy in distinguishing ICC from HCC. Furthermore, the nomogram helps to stratify ICC into two subgroups with high or low risk of survival and recurrence. Therefore, a nomogram integrating six N-glycans [NGA2FB(Peak2), NG1A2F (Peak3), NA2 (Peak5), NA2F (Peak6), NA3 (Peak8) and NA4 (Peak11)] was established for ICC and HCC differentiation, and for prognosis assessment in ICC patients.
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Affiliation(s)
- Chenjun Huang
- Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, P. R. China
| | - Xuewen Xu
- Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, P. R. China
| | - Mengmeng Wang
- Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, P. R. China
| | - Xiao Xiao
- Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, P. R. China
| | - Cheng Cheng
- Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, P. R. China
| | - Jun Ji
- Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, P. R. China
| | - Meng Fang
- Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, P. R. China
| | - Chunfang Gao
- Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, P. R. China
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Na BG, Hwang S, Ahn CS, Kim KH, Moon DB, Ha TY, Song GW, Jung DH, Hong SM, Lee SG. Post-resection prognosis of patients with hepatic epithelioid hemangioendothelioma. Ann Surg Treat Res 2021; 100:137-143. [PMID: 33748027 PMCID: PMC7943284 DOI: 10.4174/astr.2021.100.3.137] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 12/10/2020] [Accepted: 01/05/2021] [Indexed: 12/03/2022] Open
Abstract
Purpose Epithelioid hemangioendothelioma (EHE) is a rare borderline vascular tumor. This retrospective, single-center study evaluated the outcomes of hepatic resection (HR) in patients with hepatic EHE. Methods Over the 10-year period from 2009 to 2018, 11 patients with hepatic EHE underwent HR, accounting for 0.1% of the 11,979 adults who underwent HR at our center. Diagnosis of hepatic EHE was confirmed by immunohistochemical staining for CD34, CD31, and factor VIII-related antigen. Results The 11 patients included 9 females (81.8%) and 2 males (18.2%) with mean age of 43.5 ± 13.6 years. Preoperative imaging resulted in a preliminary diagnosis of suspected liver metastasis or EHE, with 9 patients (81.8%) undergoing liver biopsy. No patient presented with abnormally elevated concentrations of liver tumor markers. The extents of HR were determined by tumor size and location from trisectionectomy to partial hepatectomy. All patients recovered uneventfully from HR. Five patients showed tumor recurrence, with 4 receiving locoregional treatments for recurrent lesions. The 1-, 3- and 5-year disease-free survival rates were 90.9%, 54.5%, and 54.5%, respectively. Currently, all patients remain alive and are doing well. Univariate analysis on tumor recurrence showed that tumor size ≥ 4 cm was significantly associated with tumor recurrence (P = 0.032), but tumor number ≥ 4 was not related to (P = 0.24). Conclusion Hepatic EHE is a rare form of primary liver tumor often misdiagnosed as a metastatic tumor. Because of its malignant potential, HR is indicated if possible. HR plus, when necessary, treatment of recurrence yields favorable overall survival rates in patients with hepatic EHE.
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Affiliation(s)
- Byeong-Gon Na
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chul-Soo Ahn
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ki-Hun Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Deok-Bog Moon
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae-Yong Ha
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gi-Won Song
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Hwan Jung
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Gyu Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Kim DH, Choi SH, Kim DW, Lee SS, Lim YS, Kim SY, Kim HJ, Kim JH, Byun JH. Combined Hepatocellular-Cholangiocarcinoma: Magnetic Resonance Imaging Features and Prognosis According to Risk Factors for Hepatocellular Carcinoma. J Magn Reson Imaging 2021; 53:1803-1812. [PMID: 33565208 DOI: 10.1002/jmri.27528] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 12/26/2020] [Accepted: 12/28/2020] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) can develop in patients with and without risk factors for hepatocellular carcinoma (HCC). PURPOSE To compare the clinical and magnetic resonance imaging (MRI) characteristics of cHCC-CCA in patients with and without risk factors for HCC, and to assess the influence of risk factors on patient prognosis. STUDY TYPE Retrospective. POPULATION A total of 152 patients with surgically confirmed cHCC-CCA. FIELD STRENGTH/SEQUENCE 1.5-T and 3-T/T1-weighted dual gradient-echo in- and opposed-phase, T2-weighted turbo-spin-echo, diffusion-weighted single-shot spin-echo echo-planar, and T1-weighted three-dimensional gradient-echo contrast-enhanced sequences. ASSESSMENT MRI features according to the Liver Imaging Reporting and Data System (LI-RADS) and pathologic findings based on revised classification were compared between patients with and without risk factors for HCC. Overall survival (OS) and recurrence-free survival (RFS) were also compared between the two groups, and factors associated with survival were evaluated. STATISTICAL TESTS The clinico-pathologic and MRI features of the two groups were compared using Student's t-tests, Mann-Whitney U-tests, and chi-square tests. OS and RFS were evaluated by the Kaplan-Meier method, and factors associated with survival were evaluated by Cox proportional hazard model. RESULTS cHCC-CCA in patients with risk factors were more frequently classified as LI-RADS category 4 or 5 (LR-4/5; probably or definitely HCC) (48.7%), whereas those without risk factors were more frequently classified as category M (LR-M; probably malignant, not specific for HCC) (63.6%). RFS and OS did not differ significantly according to risk factors (P = 0.63 and 0.83). Multivariable analysis showed that pathologic tumor type (hazard ratio 2.02; P < 0.05) and LI-RADS category (hazard ratio 2.19; P < 0.05) were significantly associated with RFS and OS, respectively. DATA CONCLUSION Although MRI features of cHCC-CCA differed significantly between patients with and without risk factors for HCC, postsurgical prognosis did not. LI-RADS category and pathologic tumor type were independently correlated with postsurgical prognosis in patients with cHCC-CCA. LEVEL OF EVIDENCE 3 TECHNICAL EFFICACY STAGE: 2.
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Affiliation(s)
- Dong Hwan Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.,Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Dong Wook Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Seung Soo Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Young-Suk Lim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Hyoung Jung Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jin Hee Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
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Gigante E, Paradis V, Ronot M, Cauchy F, Soubrane O, Ganne-Carrié N, Nault JC. New insights into the pathophysiology and clinical care of rare primary liver cancers. JHEP Rep 2021; 3:100174. [PMID: 33205035 PMCID: PMC7653076 DOI: 10.1016/j.jhepr.2020.100174] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 08/06/2020] [Accepted: 08/10/2020] [Indexed: 02/07/2023] Open
Abstract
Hepatocholangiocarcinoma, fibrolamellar carcinoma, hepatic haemangioendothelioma and hepatic angiosarcoma represent less than 5% of primary liver cancers. Fibrolamellar carcinoma and hepatic haemangioendothelioma are driven by unique somatic genetic alterations (DNAJB1-PRKCA and CAMTA1-WWTR1 fusions, respectively), while the pathogenesis of hepatocholangiocarcinoma remains more complex, as suggested by its histological diversity. Histology is the gold standard for diagnosis, which remains challenging even in an expert centre because of the low incidences of these liver cancers. Resection, when feasible, is the cornerstone of treatment, together with liver transplantation for hepatic haemangioendothelioma. The role of locoregional therapies and systemic treatments remains poorly studied. In this review, we aim to describe the recent advances in terms of diagnosis and clinical management of these rare primary liver cancers.
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Key Words
- 5-FU, 5-Fluorouracil
- AFP, alpha-fetoprotein
- APHE, arterial phase hyperenhancement
- CA19-9, carbohydrate antigen 19-9
- CCA, cholangiocarcinoma
- CEUS, contrast-enhanced ultrasound
- CK, cytokeratin
- CLC, cholangiolocellular carcinoma
- EpCAM, epithelial cell adhesion molecule
- FISH, fluorescence in situ hybridisation
- FLC, fibrolamellar carcinoma
- Fibrolamellar carcinoma
- HAS, hepatic angiosarcoma
- HCC, hepatocellular carcinoma
- HEH, hepatic epithelioid haemangioendothelioma
- HepPar1, hepatocyte specific antigen antibody
- Hepatic angiosarcoma
- Hepatic hemangioendothelioma
- Hepatocellular carcinoma
- Hepatocholangiocarcinoma
- IHC, immunohistochemistry
- LI-RADS, liver imaging reporting and data system
- LT, liver transplantation
- Mixed tumor
- RT-PCR, reverse transcription PCR
- SIRT, selective internal radiation therapy
- TACE, transarterial chemoembolisation
- WHO, World Health Organization
- cHCC-CCA, combined hepatocholangiocarcinoma
- iCCA, intrahepatic cholangiocarcinoma
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Affiliation(s)
- Elia Gigante
- Service d’hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France
- Centre de recherche sur l’inflammation, Inserm, Université de Paris, INSERM UMR 1149 « De l'inflammation au cancer », Paris, France
- Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Paris, France
| | - Valérie Paradis
- Centre de recherche sur l’inflammation, Inserm, Université de Paris, INSERM UMR 1149 « De l'inflammation au cancer », Paris, France
- Service d'anatomie pathologique, Hôpitaux Universitaires Paris-Nord-Val-de-Seine, Assistance-Publique Hôpitaux de Paris, Clichy, France
- Université de Paris, Paris, France
| | - Maxime Ronot
- Centre de recherche sur l’inflammation, Inserm, Université de Paris, INSERM UMR 1149 « De l'inflammation au cancer », Paris, France
- Service de radiologie, Hôpital Beaujon, Hôpitaux Universitaires Paris-Nord-Val-de-Seine, Assistance-Publique Hôpitaux de Paris, Clichy, France
- Université de Paris, Paris, France
| | - François Cauchy
- Centre de recherche sur l’inflammation, Inserm, Université de Paris, INSERM UMR 1149 « De l'inflammation au cancer », Paris, France
- Service de chirurgie hépato-bilio-pancréatique et transplantation hépatique, Hôpitaux Universitaires Paris-Nord-Val-de-Seine, Assistance-Publique Hôpitaux de Paris, Clichy, France
- Université de Paris, Paris, France
| | - Olivier Soubrane
- Centre de recherche sur l’inflammation, Inserm, Université de Paris, INSERM UMR 1149 « De l'inflammation au cancer », Paris, France
- Service de chirurgie hépato-bilio-pancréatique et transplantation hépatique, Hôpitaux Universitaires Paris-Nord-Val-de-Seine, Assistance-Publique Hôpitaux de Paris, Clichy, France
- Université de Paris, Paris, France
| | - Nathalie Ganne-Carrié
- Service d’hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France
- Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Paris, France
- Centre de Recherche des Cordeliers, Inserm, Sorbonne Université, Université Paris, INSERM UMR 1138, Functional Genomics of Solid Tumors, F-75006, Paris, France
| | - Jean-Charles Nault
- Service d’hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France
- Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Paris, France
- Centre de Recherche des Cordeliers, Inserm, Sorbonne Université, Université Paris, INSERM UMR 1138, Functional Genomics of Solid Tumors, F-75006, Paris, France
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Zhou Q, Cai H, Xu MH, Ye Y, Li XL, Shi GM, Huang C, Zhu XD, Cai JB, Zhou J, Fan J, Ji Y, Sun HC, Shen YH. Do the existing staging systems for primary liver cancer apply to combined hepatocellular carcinoma-intrahepatic cholangiocarcinoma? Hepatobiliary Pancreat Dis Int 2021; 20:13-20. [PMID: 33160852 DOI: 10.1016/j.hbpd.2020.10.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Accepted: 10/15/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND The incidence of combined hepatocellular carcinoma-intrahepatic cholangiocarcinoma (cHCC-ICC) is relatively low, and the knowledge about the prognosis of cHCC-ICC remains obscure. In the study, we aimed to screen existing primary liver cancer staging systems and shed light on the prognosis and risk factors for cHCC-ICC. METHODS We retrospectively reviewed 206 cHCC-ICC patients who received curative surgical resection from April 1999 to March 2017. The correlation of survival measures with the histological types or with tumor staging systems was determined and predictive values of tumor staging systems with cHCC-ICC prognosis were compared. RESULTS The histological type was not associated with overall survival (OS) (P = 0.338) or disease-free survival (DFS) (P = 0.843) of patients after curative surgical resection. BCLC, TNM for HCC, and TNM for ICC stages correlated with both OS and DFS in cHCC-ICC (all P < 0.05). The predictive values of TNM for HCC and TNM for ICC stages were similar in terms of predicting postoperative OS (P = 0.798) and DFS (P = 0.191) in cHCC-ICC. TNM for HCC was superior to BCLC for predicting postoperative OS (P = 0.022) in cHCC-ICC. CONCLUSION The TNM for HCC staging system should be prioritized for clinical applications in predicting cHCC-ICC prognosis.
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Affiliation(s)
- Qiang Zhou
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, China
| | - Hao Cai
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, China
| | - Ming-Hao Xu
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, China
| | - Yao Ye
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Xiao-Long Li
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, China
| | - Guo-Ming Shi
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, China
| | - Cheng Huang
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, China
| | - Xiao-Dong Zhu
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, China
| | - Jia-Bin Cai
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, China
| | - Jian Zhou
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, China
| | - Jia Fan
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, China
| | - Yuan Ji
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Hui-Chuan Sun
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, China
| | - Ying-Hao Shen
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, China.
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Clinical features and outcomes of combined hepatocellular carcinoma and cholangiocarcinoma versus hepatocellular carcinoma versus cholangiocarcinoma after surgical resection: a propensity score matching analysis. BMC Gastroenterol 2021; 21:20. [PMID: 33413162 PMCID: PMC7788698 DOI: 10.1186/s12876-020-01586-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 12/16/2020] [Indexed: 02/06/2023] Open
Abstract
Background Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an infrequent type of primary liver cancer that comprises hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). This study investigated the clinicopathological features and prognosis among cHCC-CC, HCC, and CC groups. Methods We prospectively collected the data of 608 patients who underwent surgical resection for liver cancer between 2011 and 2018 at E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. Overall, 505 patients with cHCC-CC, HCC, and CC were included, and their clinicopathological features, overall survival (OS), and recurrence were recorded. OS and recurrence rates were analyzed using the Kaplan–Meier analysis. Results In the entire cohort, the median age was 61 years and 80% were men. Thirty-five (7.0%) had cHCC-CC, 419 (82.9%) had HCC, and 51 (10.1%) had CC. The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. OS was significantly lower in the cHCC-CC group than in the HCC group but was not significantly higher in the cHCC-CC group than in the CC group. The median OS of cHCC-CC, HCC, and CC groups was 50.1 months [95% confidence interval (CI): 38.7–61.2], 62.3 months (CI: 42.1–72.9), and 36.2 months (CI: 15.4–56.5), respectively. Cumulative OS rates at 1, 3, and 5 years in cHCC-CC, HCC, and CC groups were 88.5%, 62.2%, and 44.0%; 91.2%, 76.1%, and 68.0%; and 72.0%, 48.1%, and 34.5%, respectively. After propensity score matching (PSM), OS in the cHCC-CC group was not significantly different from that in the HCC or CC group. However, OS was significantly higher in the HCC group than in the CC group before and after PSM. Furthermore, the disease-free survival was not significantly different among cHCC-CC, HCC, and CC groups before and after PSM. Conclusion The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. The OS rate was significantly lower in the cHCC-CC group than the HCC group. However, after PSM, OS and disease-free survival in the cHCC-CC group were not significantly different from those in the HCC or CC group.
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Tang Y, Wang L, Teng F, Zhang T, Zhao Y, Chen Z. The clinical characteristics and prognostic factors of combined Hepatocellular Carcinoma and Cholangiocarcinoma, Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma after Surgical Resection: A propensity score matching analysis. Int J Med Sci 2021; 18:187-198. [PMID: 33390787 PMCID: PMC7738961 DOI: 10.7150/ijms.50883] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 10/13/2020] [Indexed: 02/05/2023] Open
Abstract
Background: Clinical characteristics and prognosis among combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (cHCC-CC) with HCC and intrahepatic cholangiocarcinoma (ICC) were inconsistent in previous studies. The aim of this study was to compare postoperative prognosis among cHCC-CC, HCC and ICC, and investigated the prognostic risk factor of cHCC-CC after surgical resection. Methods: A total of 1041 eligible patients with pathological diagnosis of cHCC-CC (n=135), HCC (n=698) and ICC (n=208) were enrolled in this study. Univariate and multivariate Cox analysis were applied for assessing important risk factors. cHCC-CC were further 1:1 matched with HCC and ICC on important clinical risk factors. Survival curves of matched and unmatched cohorts were depicted by Kaplan-Meier method with log-rank test. Results: Patients with cHCC-CC had similar rate of sex, age and cirrhosis with HCC (p<0.05) and comparable incidence of hepatitis B or C with ICC (p=0.197). Patients of cHCC-CC had intermediate prognosis between HCC and ICC, with median overall survival (OS) time of cHCC-CC, HCC and ICC of 20.5 months, 35.7 months and 11.6 months (p<0.001). In matched cohorts, the OS of cHCC-CC were worse than HCC (p<0.001) but comparable with ICC (p=0.06), while the disease-free survival (DFS) of cHCC-CC was worse than HCC but better than ICC (p<0.05). And lymph node infiltration and postoperative transarterial chemoembolization (TACE) were independent risk factors of cHCC-CC associated with prognosis. Conclusion: The long term survival of cHCC-CC was worse than HCC but comparable with ICC when matched on albumin level, tumor size, lymph node infiltration, tumor stage and margin. Presence of lymph node infiltration and no postoperative TACE were associated with poor prognosis of cHCC-CC.
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Affiliation(s)
- Youyin Tang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, P.R. China
| | - Lingyan Wang
- Department of Obstetrics and Gynecology Nursing, Key Laboratory of Birth Defects and Related Disease of Women and Children, West China Second University Hospital, Sichuan University, No. 20 South Renmin Road, Chengdu 610041, P.R. China
| | - Fei Teng
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, P.R. China
| | - Tao Zhang
- Department of Biotherapy, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, P.R. China
| | - Yunuo Zhao
- Department of Biotherapy, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, P.R. China
| | - Zheyu Chen
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, No. 37 GuoXue Alley, Chengdu 610041, P.R. China
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Kang X, Bai L, QI X, Wang J. Screening and identification of key genes between liver hepatocellular carcinoma (LIHC) and cholangiocarcinoma (CHOL) by bioinformatic analysis. Medicine (Baltimore) 2020; 99:e23563. [PMID: 33327311 PMCID: PMC7738106 DOI: 10.1097/md.0000000000023563] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 10/27/2020] [Accepted: 11/05/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Liver hepatocellular carcinoma (LIHC) and cholangiocarcinoma (CHOL) are common primary liver cancers worldwide. Liver stem cells have biopotential to differentiate into either hepatocytes and cholangiocytes, the phenotypic overlap between LIHC and CHOL has been acceptable as a continuous liver cancer spectrum. However, few studies directly investigated the underlying molecular mechanisms between LIHC and CHOL. METHOD To identify the candidate genes between LIHC and CHOL, three data series including GSE31370, GSE15765 and GSE40367 were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified, and function enrichment analyses were performed. The protein-protein interaction network (PPI) was constructed and the module analysis was performed using STRING and Cytoscape. RESULTS A total of 171 DEGs were identified, consisting of 49 downregulated genes and 122 upregulated genes. Compared with CHOL, the enriched functions of the DEGs mainly included steroid metabolic process, acute inflammatory response, coagulation. Meanwhile, the pathway of KEGG enrichment analyses showed that the upregulated gene(s) were mainly enriched complement and coagulation cascades, cholesterol metabolism and PPAR signaling pathway, while the downregulated gene(s) were mainly enriched in ECM-receptor interaction, focal adhesion, bile secretion. Similarly, the most significant module was identified and biological process analysis revealed that these genes were mainly enriched in regulation of blood coagulation, acute inflammatory response, complement and coagulation cascades. Finally, two (ITIH2 and APOA2) of 10 hub genes had been screened out to help differential diagnosis. CONCLUSION 171 DEGs and two (ITIH2 and APOA2) of 10 hub genes identified in the present study help us understand the different molecular mechanisms between LIHC and CHOL, and provide candidate targets for differential diagnosis.
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Affiliation(s)
- Xindan Kang
- Department of Oncology, The First Medical Center of Chinese People's Liberation Army General Hospital
- Department of Graduate Administration, Chinese PLA General Hospital/Medical School of Chinese PLA, Beijing, China
| | - Li Bai
- Department of Oncology, The First Medical Center of Chinese People's Liberation Army General Hospital
| | - Xiaoguang QI
- Department of Oncology, The First Medical Center of Chinese People's Liberation Army General Hospital
| | - Jing Wang
- Department of Graduate Administration, Chinese PLA General Hospital/Medical School of Chinese PLA, Beijing, China
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Raevskaya O, Appelman H, Razumilava N. A Contemporary Approach to Diagnosis and Treatment of Combined Hepatocellular-Cholangiocarcinoma. ACTA ACUST UNITED AC 2020; 19:478-485. [PMID: 33415066 DOI: 10.1007/s11901-020-00556-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Purpose of review To provide updates on terminology, epidemiology, diagnosis, and treatment of combined hepatocellular-cholangiocarcinoma (cHCC-CCA). Recent findings cHCC-CCAs are tumors that in the same nodule contain a variable degree of HCC and CCA components with a transition zone. cHCC-CCAs develop in cirrhotic and non-cirrhotic livers like and is associated with poor outcomes. Mutations in TP53, TERT promoter, and ARID1A are the most common genetic aberrations in cHCC-CCA. Fusion gene PTMS-AP1G1 is unique for cHCC-CCA. A biopsy is required for diagnosis. Surgical resection remains treatment of choice, while liver transplantation for early cHCC-CCA is associated with favorable outcomes. Gemcitabine-based therapy shows benefits for advanced cHCC-CCA. Summary cHCC-CCAs are a heterogeneous group of primary liver cancers with unique biological behavior. Multicenter studies are required for a molecular analysis to inform novel therapeutic approaches, and understand epidemiology and benefits of liver transplantation, liver-directed and targeted therapies for this rare aggressive cancer.
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Affiliation(s)
- Olga Raevskaya
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Henry Appelman
- Department of Pathology, University of Michigan, Ann Arbor, MI, USA
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Azizi AA, Hadjinicolaou AV, Goncalves C, Duckworth A, Basu B. Update on the Genetics of and Systemic Therapy Options for Combined Hepatocellular Cholangiocarcinoma. Front Oncol 2020; 10:570958. [PMID: 33102226 PMCID: PMC7545907 DOI: 10.3389/fonc.2020.570958] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 08/26/2020] [Indexed: 12/14/2022] Open
Abstract
Combined hepatocellular-cholangiocarcinoma (cHCC-ICC) is an uncommon and aggressive form of primary liver cancer. Currently, there are no international guidelines for optimal management. For localized tumors, radical resection represents the preferred treatment option, whereas for advanced tumors, systemic therapies recommended for intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are often selected. Emerging information from comparative cohort studies, genomic and transcriptomic data sets are starting to build a case for rationalized approaches to systemic treatment in the advanced setting specific to cHCC-ICC.
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Affiliation(s)
- Alexander A Azizi
- Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Andreas V Hadjinicolaou
- Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Carla Goncalves
- Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Adam Duckworth
- Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Bristi Basu
- Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.,Department of Oncology, University of Cambridge, Cambridge, United Kingdom
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Gentile D, Donadon M, Di Tommaso L, Samà L, Franchi E, Costa G, Lleo A, Torzilli G. Is the outcome after hepatectomy for transitional hepatocholangiocarcinoma different from that of hepatocellular carcinoma and mass-forming cholangiocarcinoma? A case-matched analysis. Updates Surg 2020; 72:671-679. [PMID: 32445033 DOI: 10.1007/s13304-020-00802-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 05/13/2020] [Indexed: 02/06/2023]
Abstract
Hepatocholangiocarcinoma (HCC-CC) is a rare malignancy containing features of both hepatocellular carcinoma (HCC) and mass-forming cholangiocarcinoma (MFCCC), of which the outcome after hepatectomy remains to be clarified. The aim of this study was to analyze the characteristics and outcomes of patients with transitional HCC-CC and compare them with those of patients with HCC and MFCCC. Our prospectively maintained database was queried, and 14 transitional HCC-CC patients were identified over a total of 406 consecutive hepatic resections. A 1:1:1 match was performed with HCC and MFCCC patients operated in the same period. A total of 42 patients were matched according to tumor stage (T1-2-3, N0, M0), number of tumors, R0 resection, no 90-day mortality, and follow-up. Primary endpoints were disease-free survival (DFS) and overall survival (OS). Disease-free survival rates at 1-, 3-, and 5-year were 71.4%, 57.1%, 35.7% for transitional HCC-CC patients; 85.7%, 40.4%, 10.1% for HCC patients; 85.1%, 34.0%, 22.7% for MFCCC patients (5-year DFS: HCC-CC vs. HCC, p = 0.575; HCC-CC vs. MFCCC, p = 0.766, respectively). Similarly, OS rates at 1-, 3-, and 5-year were 92.9%, 71.4%, 64.3% for transitional HCC-CC patients; 100%, 64.3%, 41.7% for HCC patients; 100%, 54.5%, 43.6% for MFCCC patients (5-year OS: HCC-CC vs. HCC, p = 0.891; HCC-CC vs. MFCCC, p = 0.673, respectively). When accurately matched with respect to tumor burden, transitional HCC-CC patients show similar outcomes to those of HCC and MFCCC patients. Further evaluations of differences in tumor biology are necessary to better characterize the prognosis of transitional HCC-CC patients.
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Affiliation(s)
- Damiano Gentile
- Department of Hepatobiliary and General Surgery, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy
| | - Matteo Donadon
- Department of Hepatobiliary and General Surgery, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy
- Department of Biomedical Science, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Luca Di Tommaso
- Department of Biomedical Science, Humanitas University, Pieve Emanuele, Milan, Italy
- Department of Pathology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy
| | - Laura Samà
- Department of Hepatobiliary and General Surgery, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy
| | - Eloisa Franchi
- Department of Hepatobiliary and General Surgery, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy
| | - Guido Costa
- Department of Hepatobiliary and General Surgery, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy
| | - Ana Lleo
- Department of Biomedical Science, Humanitas University, Pieve Emanuele, Milan, Italy
- Department of Internal Medicine, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy
| | - Guido Torzilli
- Department of Hepatobiliary and General Surgery, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy.
- Department of Biomedical Science, Humanitas University, Pieve Emanuele, Milan, Italy.
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University, Humanitas Clinical and Research Center-IRCCS, Via Manzoni, 56, 20089, Rozzano, Milano, Italy.
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Holzner ML, Tabrizian P, Parvin-Nejad FP, Fei K, Gunasekaran G, Rocha C, Facciuto ME, Florman S, Schwartz ME. Resection of Mixed Hepatocellular-Cholangiocarcinoma, Hepatocellular Carcinoma, and Intrahepatic Cholangiocarcinoma. Liver Transpl 2020; 26:888-898. [PMID: 32352208 DOI: 10.1002/lt.25786] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2019] [Revised: 02/16/2020] [Accepted: 03/11/2020] [Indexed: 12/13/2022]
Abstract
Mixed hepatocellular-cholangiocarcinoma (HCC-CC) is a biphenotypic liver cancer thought to have unfavorable tumor biology and a poor prognosis. Surgical outcomes of HCC-CC remain unclear. We aimed to evaluate the clinical characteristics and surgical outcomes of HCC-CC. We analyzed a series of patients undergoing resection for HCC-CC (n = 47), hepatocellular carcinoma (HCC; n = 468), and intrahepatic cholangiocarcinoma (ICC; n = 108) at a single Western center between 2001 and 2015. Patients with HCC-CC were matched to patients with HCC and ICC on important clinical factors including tumor characteristics (size, vascular invasion, and differentiation) and underlying cirrhosis. Patients with HCC-CC had rates of viral hepatitis comparable to patients with HCC (78.7% versus 80.0%), and 42.5% had underlying cirrhosis. When matched on tumor size, HCC-CC was more poorly differentiated than HCC (68.3% versus 27.3%; P < 0.001) and ICC (68.3% versus 34.8%; P = 0.01) but had similar postresection survival (5-year survival: HCC-CC 49.7%, HCC 54.8%, ICC 68.7%; P = 0.61) and recurrence (3-year recurrence: HCC-CC 57.9%, HCC 61.5%, and ICC 56%; P = 0.58). Outcomes were similar between HCC-CC and HCC when matched on underlying cirrhosis and tumor size. Cancer type was not predictive of survival or tumor recurrence. Survival after resection of HCC-CC is similar to HCC when matched for tumor size, despite HCC-CC tumors being more poorly differentiated. Exclusion of HCC-CC from management strategies recommended for HCC, including consideration for liver transplantation, may not be warranted.
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Affiliation(s)
- Matthew L Holzner
- Liver Cancer Program, Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Parissa Tabrizian
- Liver Cancer Program, Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY
| | | | - Kezhen Fei
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Ganesh Gunasekaran
- Liver Cancer Program, Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Chiara Rocha
- Liver Cancer Program, Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Marcelo E Facciuto
- Liver Cancer Program, Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Sander Florman
- Liver Cancer Program, Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Myron E Schwartz
- Liver Cancer Program, Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY
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Major and ancillary features according to LI-RADS in the assessment of combined hepatocellular-cholangiocarcinoma. Radiol Oncol 2020; 54:149-158. [PMID: 32463393 PMCID: PMC7276649 DOI: 10.2478/raon-2020-0029] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Accepted: 04/22/2020] [Indexed: 12/11/2022] Open
Abstract
Background The aim of the study was to investigate the performance of the Liver Imaging Reporting and Data System (LI-RADS) v2018 for combined hepatocellular-cholangiocarcinoma (cHCC-CCA) identifying the features that allow an accurate characterization. Patients and methods Sixty-two patients (median age, 63 years; range, 38–80 years), with pre-surgical biopsy diagnosis of hepatocellular carcinoma (HCC) that underwent hepatic resection, comprised our retrospective study. All patients were subject to multidetector computed tomography (MDCT); 23 patients underwent to magnetic resonance (MR) study. The radiologist reported the presence of the HCC by using LIRADS v2018 assessing major and ancillary features. Results Final histological diagnosis was HCC for 51 patients and cHCC-CCA for 11 patients. The median nodule size was 46.0 mm (range 10–190 mm). For cHCC-CCA the median size was 33.5 mm (range 20–80 mm), for true HCC the median size was 47.5 mm (range 10–190 mm). According to LIRADS categories: 54 (87.1%) nodules as defined as LR-5, 1 (1.6%) as LR-3, and 7 (11.3%) as LR-M. Thirty-nine nodules (63%) showed hyper-enhancement in arterial phase; among them 4 were cHCC-CCA (36.4% of cHCC-CCA) and 35 (68.6%) true HCC. Forty-three nodules (69.3%) showed washout appearance; 6 cHCC-CCAs (54.5% of cHCC-CCA) and 37 true HCC (72.5%) had this feature. Only two cHCC-CCA patients (18.2% of cHCC-CCA) showed capsule appearance. Five cHCC-CCA (71.4% of cHCC-CCA) showed hyperintensity on T2-W sequences while two (28.6%) showed inhomogeneous signal in T2-W. All cHCC-CCA showed restricted diffusion. Seven cHCC-CCA patients showed a progressive contrast enhancement and satellite nodules. Conclusions The presence of satellite nodules, hyperintense signal on T2-W, restricted diffusion, the absence of capsule appearance in nodule that shows peripheral and progressive contrast enhancement are suggestive features of cHCC-CCA.
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Akiba J, Fujita N, Yano H. Recent Topics Concerning Combined Hepatocellular Cholangiocarcinoma. Kurume Med J 2020; 66:29-36. [PMID: 32378534 DOI: 10.2739/kurumemedj.ms661014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Combined hepatocellular-cholangiocarcinoma (CHC) is a relatively rare tumor with an incidence range of 1.0-4.7%. CHC is defined as a tumor containing unequivocal, intimately mixed components of both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. The recent development of biochemical methodologies and cancer stem cell theory have paved the way for a clearer understanding of the histogenesis of CHC. The latest edited WHO classification published in 2010 adopted the concept of stem cell/hepatic progenitor cells in the pathological classification of CHC. Although this classification includes novel and unique concepts of histogenesis and facilitates the recognition of CHC, there are several problems with it in practice. To reduce confusion, an international group of hepatic pathologists, radiologists, surgeons, and clinicians formulated a nomenclature for CHC and issued a consensus article in 2018. In this review article, we discuss the problems with the latest WHO classification and introduce recent topics concerning CHC from pathologic and genetic points of view.
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Affiliation(s)
- Jun Akiba
- Department of Diagnostic Pathology, Kurume University Hospital
| | - Naoya Fujita
- Discovery and Preclinical Research Division, Taiho Pharmaceutical Co., Ltd
| | - Hirohisa Yano
- Department of Pathology, Kurume University School of Medicine
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Leoni S, Sansone V, De Lorenzo S, Ielasi L, Tovoli F, Renzulli M, Golfieri R, Spinelli D, Piscaglia F. Treatment of Combined Hepatocellular and Cholangiocarcinoma. Cancers (Basel) 2020; 12:794. [PMID: 32224916 PMCID: PMC7226028 DOI: 10.3390/cancers12040794] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 03/15/2020] [Accepted: 03/23/2020] [Indexed: 02/07/2023] Open
Abstract
Combined hepatocellular and cholangiocarcinoma (HCC-CC) is a rare primary liver cancer. It is constituted by neoplastic cells of both hepatocellular and cholangiocellular derivation. Different histology types of HCC-CC have been reported, hinting at heterogeneous carcinogenic pathways leading to the development of this cancer. Due to its rarity and complexity, mixed HCC-CC is a scantly investigated condition with unmet needs and unsatisfactory outcomes. Surgery remains the preferred treatment in resectable patients. The risk of recurrence, however, is high, especially in comparison with other primary liver cancers such as hepatocellular carcinoma. In unresectable or recurring patients, the therapeutic options are challenging due to the dual nature of the neoplastic cells. Consequently, the odds of survival of patients with HCC-CC remains poor. We analysed the literature systematically about the treatment of mixed HCC-CC, reviewing the main therapeutic options and their outcomes and analysing the most interesting developments in this topic with a focus on new potential therapeutic avenues.
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Affiliation(s)
- Simona Leoni
- Internal Medicine Unit, Department of Digestive Diseases, Bologna Authority Hospital S.Orsola-Malpighi, 40136 Bologna, Italy
| | - Vito Sansone
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40136 Bologna, Italy; (V.S.); (L.I.); (F.T.); (F.P.)
| | - Stefania De Lorenzo
- Oncology Unit, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40136 Bologna, Italy;
| | - Luca Ielasi
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40136 Bologna, Italy; (V.S.); (L.I.); (F.T.); (F.P.)
| | - Francesco Tovoli
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40136 Bologna, Italy; (V.S.); (L.I.); (F.T.); (F.P.)
| | - Matteo Renzulli
- Radiology Unit, Department of Experimental, Diagnostic and Specialty Medicine, Sant’Orsola Hospital, University of Bologna, 40136 Bologna, Italy; (M.R.); (R.G.); (D.S.)
| | - Rita Golfieri
- Radiology Unit, Department of Experimental, Diagnostic and Specialty Medicine, Sant’Orsola Hospital, University of Bologna, 40136 Bologna, Italy; (M.R.); (R.G.); (D.S.)
| | - Daniele Spinelli
- Radiology Unit, Department of Experimental, Diagnostic and Specialty Medicine, Sant’Orsola Hospital, University of Bologna, 40136 Bologna, Italy; (M.R.); (R.G.); (D.S.)
| | - Fabio Piscaglia
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40136 Bologna, Italy; (V.S.); (L.I.); (F.T.); (F.P.)
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Wakizaka K, Yokoo H, Kamiyama T, Kakisaka T, Ohira M, Tani M, Kato K, Fujii Y, Sugiyama K, Nagatsu A, Shimada S, Orimo T, Kamachi H, Matsuoka R, Taketomi A. CD133 and epithelial cell adhesion molecule expressions in the cholangiocarcinoma component are prognostic factors for combined hepatocellular cholangiocarcinoma. Hepatol Res 2020; 50:258-267. [PMID: 31661725 DOI: 10.1111/hepr.13443] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Revised: 09/25/2019] [Accepted: 10/11/2019] [Indexed: 02/05/2023]
Abstract
AIM A new classification of combined hepatocellular cholangiocarcinoma (CHC) was recently reported. Cancer stem cells have been associated with CHC carcinogenesis. This study examined the association of cancer stem cell marker expression and prognosis in CHC classified using the new classification. METHODS We enrolled 26 CHC patients and classified them according to the new classification. We evaluated the expression of cancer stem cell markers (CD56, CD133, and epithelial cell adhesion molecule [EpCAM]) by immunohistochemical staining in each component. We analyzed the association between expressions and prognosis. RESULTS Seven cases were hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) (cHCC-CCA), 12 were HCC and intermediate cell carcinoma (HCC-INT), and seven were intermediate cell carcinoma (INT). The CD133-positive rate tended to be higher in the CCA (42.9%) and INT component (50.0%) than the HCC component (14.3%) in cHCC-CCA. In HCC-INT, the CD133-positive rate in the INT component (83.3%) was significantly higher than the HCC component (8.3%; P = 0.001). For EpCAM, the positive rate in the CCA component (71.4%) and INT component (50.0%) tended to be higher than the HCC component (14.3%) in cHCC-CCA. Overall survival and disease-free survival were significantly worse in cases with CD133-positive (P = 0.048 and P = 0.048, respectively) or EpCAM-positive (P = 0.041 and P = 0.041, respectively) CCA component in cHCC-CCA. CONCLUSIONS INT and CCA components showed higher expression rates of cancer stem cell markers than the HCC component. CD133 or EpCAM expression in the CCA component was associated with poor prognosis in cHCC-CCA.
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Affiliation(s)
- Kazuki Wakizaka
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Hideki Yokoo
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Toshiya Kamiyama
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Tatsuhiko Kakisaka
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Masafumi Ohira
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Michio Tani
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Koichi Kato
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Yuki Fujii
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Ko Sugiyama
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Akihisa Nagatsu
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Shingo Shimada
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Tatsuya Orimo
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Hirofumi Kamachi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Ryosuke Matsuoka
- Department of Pathology, International University of Health and Welfare, Mita Hospital, Tokyo, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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