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1
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Lederer AK, Görrissen N, Nguyen TT, Kreutz C, Rasel H, Bartsch F, Lang H, Endres K. Exploring the effects of gut microbiota on cholangiocarcinoma progression by patient-derived organoids. J Transl Med 2025; 23:34. [PMID: 39789543 PMCID: PMC11716211 DOI: 10.1186/s12967-024-06012-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 12/19/2024] [Indexed: 01/12/2025] Open
Abstract
BACKGROUND Recent research indicates a role of gut microbiota in development and progression of life-threatening diseases such as cancer. Carcinomas of the biliary ducts, the so-called cholangiocarcinomas, are known for their aggressive tumor biology, implying poor prognosis of affected patients. An impact of the gut microbiota on cholangiocarcinoma development and progression is plausible due to the enterohepatic circulation and is therefore the subject of scientific debate, however evidence is still lacking. This review aimed to discuss the suitability of complex cell culture models to investigate the role of gut microbiota in cholangiocarcinoma progression. MAIN BODY Clinical research in this area is challenging due to poor comparability of patients and feasibility reasons, which is why translational models are needed to understand the basis of tumor progression in cholangiocarcinoma. A promising approach to investigate the influence of gut microbiota could be an organoid model. Organoids are 3D cell models cultivated in a modifiable and controlled condition, which can be grown from tumor tissue. 3D cell models are able to imitate physiological and pathological processes in the human body and thus contribute to a better understanding of health and disease. CONCLUSION The use of complex cell cultures such as organoids and organoid co-cultures might be powerful and valuable tools to study not only the growth behavior and growth of cholangiocarcinoma cells, but also the interaction with the tumor microenvironment and with components of the gut microbiota.
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Affiliation(s)
- Ann-Kathrin Lederer
- Department of General, Visceral and Transplantation Surgery, University Medical Center Mainz, 55131, Mainz, Germany.
- Center for Complementary Medicine, Department of Medicine II, Faculty of Medicine, Medical Center-University of Freiburg, University of Freiburg, 79106, Freiburg, Germany.
| | - Nele Görrissen
- Department of General, Visceral and Transplantation Surgery, University Medical Center Mainz, 55131, Mainz, Germany
| | - Tinh Thi Nguyen
- Department of Psychiatry and Psychotherapy, University Medical Center Mainz, 55131, Mainz, Germany
- Institute of Molecular Biology (IMB), 55128, Mainz, Germany
| | - Clemens Kreutz
- Institute of Medical Biometry and Statistics (IMBI), Faculty of Medicine and Medical Center, 79106, Freiburg, Germany
| | - Hannah Rasel
- Department of General, Visceral and Transplantation Surgery, University Medical Center Mainz, 55131, Mainz, Germany
| | - Fabian Bartsch
- Department of General, Visceral and Transplantation Surgery, University Medical Center Mainz, 55131, Mainz, Germany
| | - Hauke Lang
- Department of General, Visceral and Transplantation Surgery, University Medical Center Mainz, 55131, Mainz, Germany
| | - Kristina Endres
- Department of Psychiatry and Psychotherapy, University Medical Center Mainz, 55131, Mainz, Germany
- Faculty of Computer Sciences and Microsystems Technology, University of Applied Sciences Kaiserslautern, 66482, Zweibrücken, Germany
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Akita M, Yanagimoto H, Tsugawa D, Zen Y, Fukumoto T. Surgical interpretation of the WHO subclassification of intrahepatic cholangiocarcinoma: a narrative review. Surg Today 2025; 55:1-9. [PMID: 38563999 DOI: 10.1007/s00595-024-02825-x] [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: 10/02/2023] [Accepted: 02/14/2024] [Indexed: 04/04/2024]
Abstract
Intrahepatic cholangiocarcinoma (iCCA) has been subclassified by its gross morphology into the mass-forming (MF), periductal-infiltrating (PI), and intraductal growth (IG) types and their combinations. This classification correlates well with clinical features; for example, MF-iCCA has less lymph-node metastasis and a better prognosis than PI-iCCA. According to the recently accumulated evidence from histological investigations, the WHO classification endorsed a subclassification scheme in which iCCA cases are classified into small- and large-duct types. Small-duct iCCA is considered to originate from septal or smaller bile ducts and is characterized by less frequent lymph-node metastasis, a favorable prognosis, and an MF appearance. Large-duct iCCA arises around the second branch of the biliary tree and has more aggressive biology and distinct genetic abnormalities. According to the practice guidelines for iCCA from the Liver Cancer Study Group of Japan and the National Comprehensive Cancer Network, upfront surgery is recommended for iCCA without distant metastasis regardless of the morphological subtype, based on clinical experience. In consideration of the biological heterogeneity of iCCA, the treatment strategy for iCCA needs to be reconsidered based on the WHO subtypes.
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Affiliation(s)
- Masayuki Akita
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan
| | - Hiroaki Yanagimoto
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan.
| | - Daisuke Tsugawa
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan
| | - Yoh Zen
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Takumi Fukumoto
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan
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Chiablaem K, Jinawath A, Nuanpirom J, Arora JK, Nasaree S, Thanomchard T, Singhto N, Chittavanich P, Suktitipat B, Charoensawan V, Chairoungdua A, Jinn-Chyuan Sheu J, Kiyotani K, Svasti J, Nakamura Y, Jinawath N. Identification of RNF213 as a Potential Suppressor of Local Invasion in Intrahepatic Cholangiocarcinoma. J Transl Med 2024; 104:102074. [PMID: 38723854 DOI: 10.1016/j.labinv.2024.102074] [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: 10/16/2023] [Revised: 04/08/2024] [Accepted: 04/30/2024] [Indexed: 06/14/2024] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is a lethal cancer with poor survival especially when it spreads. The histopathology of its rare intraductal papillary neoplasm of the bile duct type (IPNB) characteristically shows cancer cells originating within the confined bile duct space. These cells eventually invade and infiltrate the nearby liver tissues, making it a good model to study the mechanism of local invasion, which is the earliest step of metastasis. To discover potential suppressor genes of local invasion in ICC, we analyzed the somatic mutation profiles and performed clonal evolution analyses of the 11 pairs of macrodissected locally invasive IPNB tissues (LI-IPNB) and IPNB tissues without local invasion from the same patients. We identified a protein-truncating variant in an E3 ubiquitin ligase, RNF213 (c.6967C>T; p.Gln2323X; chr17: 78,319,102 [hg19], exon 29), as the most common protein-truncating variant event in LI-IPNB samples (4/11 patients). Knockdown of RNF213 in HuCCT1 and YSCCC cells showed increased migration and invasion, and reduced vasculogenic mimicry but maintained normal proliferation. Transcriptomic analysis of the RNF213-knockdown vs control cells was then performed in the HuCCT1, YSCCC, and KKU-100 cells. Gene ontology enrichment analysis of the common differentially expressed genes revealed significantly altered cytokine and oxidoreductase-oxidizing metal ion activities, as confirmed by Western blotting. Gene Set Enrichment Analysis identified the most enriched pathways being oxidative phosphorylation, fatty acid metabolism, reactive oxygen species, adipogenesis, and angiogenesis. In sum, loss-of-function mutation of RNF213 is a common genetic alteration in LI-IPNB tissues. RNF213 knockdown leads to increased migration and invasion of ICC cells, potentially through malfunctions of the pathways related to inflammation and energy metabolisms.
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Affiliation(s)
- Khajeelak Chiablaem
- Program in Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, Thailand
| | - Artit Jinawath
- Molecular Histopathology Laboratory, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Jiratchaya Nuanpirom
- Integrative Computational Bioscience (ICBS) Center, Mahidol University, Nakhon Pathom, Thailand
| | - Jantarika Kumar Arora
- Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand
| | - Sirawit Nasaree
- Program in Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Thanastha Thanomchard
- Ramathibodi Comprehensive Cancer Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Nilubon Singhto
- Ramathibodi Comprehensive Cancer Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Pamorn Chittavanich
- Program in Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Bhoom Suktitipat
- Integrative Computational Bioscience (ICBS) Center, Mahidol University, Nakhon Pathom, Thailand; Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Varodom Charoensawan
- Integrative Computational Bioscience (ICBS) Center, Mahidol University, Nakhon Pathom, Thailand; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand; Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Siriraj Genomics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Arthit Chairoungdua
- Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand
| | - Jim Jinn-Chyuan Sheu
- Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan; School of Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Kazuma Kiyotani
- Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Jisnuson Svasti
- Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, Thailand
| | - Yusuke Nakamura
- Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan; National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan
| | - Natini Jinawath
- Program in Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Integrative Computational Bioscience (ICBS) Center, Mahidol University, Nakhon Pathom, Thailand; Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bang Phli, Samut Prakan, Thailand.
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Liu H, Lan T, Cai YS, Lyu YH, Zhu J, Xie SN, Hu FJ, Liu C, Wu H. Predicting prognosis in intrahepatic cholangiocarcinoma by the histopathological features. Asian J Surg 2024; 47:2589-2597. [PMID: 38604849 DOI: 10.1016/j.asjsur.2024.03.085] [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: 09/12/2023] [Revised: 12/23/2023] [Accepted: 03/06/2024] [Indexed: 04/13/2024] Open
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (ICC) is a highly heterogeneous liver tumor. The associations between histopathological feature and prognosis of ICC are limited. The present study aimed to investigate the prognostic significance of glandular structure and tumor budding in ICC. METHODS Patients received radical hepatectomy for ICC were included. Glandular structure and tumor budding were detected by Hematoxylin-eosin staining. The Kaplan-Meier method and the Cox proportional hazards regression model were used to calculate the survival and hazard ratio. Based on the results of multivariate analysis, nomograms of OS and DFS were constructed. C-index and Akaike information criterion (AIC) were used to assess accuracy of models. RESULTS A total of 323 ICC patients who underwent surgery were included in our study. Glandular structure was associated with worse overall survival (OS) [hazard ratio (HR): 2.033, 95% confidence interval (CI): 1.047 to 3.945] and disease-free survival (DFS) [HR: 1.854, 95% CI: 1.082 to 3.176]. High tumor budding was associated with worse DFS [HR: 1.636, 95%CI: 1.060 to 2.525]. Multivariate analysis suggested that glandular structure, tumor number, lymph node metastasis, and CA19-9 were independent risk factors for OS. Independent predictor factors for DFS were tumor budding, glandular structure, tumor number, and lymph node metastasis. The c-index (0.641 and 0.642) and AIC (957.69 and 1188.52) showed that nomograms of OS and DFS have good accuracy. CONCLUSION High tumor budding and glandular structure are two important histopathological features that serve as prognostic factors for ICC patients undergoing hepatectomy.
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Affiliation(s)
- Hu Liu
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China; Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Tian Lan
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China; Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yun-Shi Cai
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China; Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Ying-Hao Lyu
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China; Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jiang Zhu
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China; Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Si-Nan Xie
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China; Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Feng-Juan Hu
- The Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Chang Liu
- Division of Liver, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China; Department of Minimal Invasive Surgery, Shangjin Nanfu Hospital, Chengdu, 610037, China.
| | - Hong Wu
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China; Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
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Dixon ME, Williams M, Pappas SG. Cholangiocarcinoma. Cancer Treat Res 2024; 192:165-184. [PMID: 39212921 DOI: 10.1007/978-3-031-61238-1_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Cholangiocarcinoma (CC) is a heterogeneous group of malignancies that originates at any point along the biliary tree. CC is an uncommon malignancy as it represents approximately 3% of all gastrointestinal malignancies, though its global incidence is rising. CC can often be asymptomatic in its early stages and as a result, it is frequently diagnosed in later stages, leading to challenges in clinical management.
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Affiliation(s)
- Matthew E Dixon
- Division of Surgical Oncology, Department of Surgery, Rush University Medical Center, Chicago, IL, USA
| | - Michael Williams
- Division of Surgical Oncology, Department of Surgery, Rush University Medical Center, Chicago, IL, USA
| | - Sam G Pappas
- Division of Surgical Oncology, Department of Surgery, Rush University Medical Center, Chicago, IL, USA.
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6
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Kubota H, Hashimoto Y, Toyota K, Yano R, Kobayashi H, Yokoyama Y, Sakashita Y, Taniyama K, Miyamoto K, Murakami Y. Intrahepatic cholangiocarcinoma with extensive intraductal extension of high-grade biliary intraepithelial neoplasia: a case report. Surg Case Rep 2023; 9:164. [PMID: 37721561 PMCID: PMC10506985 DOI: 10.1186/s40792-023-01748-y] [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: 08/01/2023] [Accepted: 09/04/2023] [Indexed: 09/19/2023] Open
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (ICC) is frequently associated with precursor lesions, and biliary intraepithelial neoplasia (BilIN) may play a significant role in the development of ICC. However, the exact sequence and progression of these lesions remain to be elucidated. We report a rare case of ICC that exhibited extensive longitudinal intraductal extension of high-grade BilIN in the posterior bile ducts and involved the hepatic hilum and the peripheral hepatic parenchyma. CASE PRESENTATION A 70-year-old female presented with anorexia. Computed tomography (CT) revealed a 15 mm enhancing intrahepatic tumor extending to the right intrahepatic secondary confluence. This was associated with a 7 mm diameter cystic dilatation of the segment 6 bile duct (B6). Endoscopic retrograde cholangiopancreatography (ERCP) revealed stenosis at the bifurcation of the posterior bile duct branch. Bile cytology confirmed the diagnosis of adenocarcinoma cells. Therefore, the patient was diagnosed with an ICC involving the right glissonean pedicle and underwent a right hepatectomy and lymph node dissection. Histologic examination revealed the tumor consisted of moderately differentiated adenocarcinoma. In connection with this lesion, diffuse intraductal atypical epithelial cells, which were diagnosed as high-grade BilIN, was observed not only in the dilated B6 but in the entire posterior bile ducts, which measured approximately 120 mm in diameter. Furthermore, two distinct foci of adenocarcinomas were identified in the peripheral hepatic parenchyma. A lymph node metastasis was also present. The pathological diagnosis was ICC pT4N1M0 stage IVA. The patient underwent adjuvant chemotherapy and has shown no recurrence 5 years after surgery. Imaging modalities were unable to accurately assess the extent of the intraductal neoplastic lesions due to their low papillary or sessile intraductal tubular growth. No risk factors for BilIN development, which has the potential to predispose to cholangiocarcinoma, were identified in the present case. CONCLUSIONS We present a case of ICC involving the right hepatic hilum, accompanied by extensive longitudinal extensions of high-grade BilIN and multifocal microscopic invasions in peripheral hepatic parenchyma. Notably, the intraductal lesions involved the entire posterior intrahepatic bile ducts. The presence of biliary neoplasia with extensive intraductal extension, in conjunction with ICC, should be considered as a variant of BilIN.
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Affiliation(s)
- Haruna Kubota
- Department of Surgery, Hiroshima Memorial Hospital, Honkawa-cho1-4-3, Naka-ku, Hiroshima, 730-0802, Japan.
| | - Yasushi Hashimoto
- Department of Surgery, Hiroshima Memorial Hospital, Honkawa-cho1-4-3, Naka-ku, Hiroshima, 730-0802, Japan
| | - Kazuhiro Toyota
- Department of Surgery, Hiroshima Memorial Hospital, Honkawa-cho1-4-3, Naka-ku, Hiroshima, 730-0802, Japan
| | - Raita Yano
- Department of Surgery, Hiroshima Memorial Hospital, Honkawa-cho1-4-3, Naka-ku, Hiroshima, 730-0802, Japan
| | - Hironori Kobayashi
- Department of Surgery, Hiroshima Memorial Hospital, Honkawa-cho1-4-3, Naka-ku, Hiroshima, 730-0802, Japan
| | - Yujiro Yokoyama
- Department of Surgery, Hiroshima Memorial Hospital, Honkawa-cho1-4-3, Naka-ku, Hiroshima, 730-0802, Japan
| | - Yoshihiro Sakashita
- Department of Surgery, Hiroshima Memorial Hospital, Honkawa-cho1-4-3, Naka-ku, Hiroshima, 730-0802, Japan
| | - Kiyomi Taniyama
- Department of Pathology, Hiroshima Memorial Hospital, Hiroshima, Japan
| | - Katsunari Miyamoto
- Department of Surgery, Hiroshima Memorial Hospital, Honkawa-cho1-4-3, Naka-ku, Hiroshima, 730-0802, Japan
| | - Yoshiaki Murakami
- Department of Surgery, Hiroshima Memorial Hospital, Honkawa-cho1-4-3, Naka-ku, Hiroshima, 730-0802, Japan
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Jongkatkorn C, Luvira V, Suwanprinya C, Piampatipan K, Leeratanakachorn N, Tipwaratorn T, Titapun A, Srisuk T, Theeragul S, Jarearnrat A, Thanasukarn V, Pugkhem A, Khuntikeo N, Pairojkul C, Kamsa-Ard S, Bhudhisawasdi V. Compliance with enhanced recovery after surgery predicts long-term outcome after hepatectomy for cholangiocarcinoma. World J Gastrointest Surg 2023; 15:362-373. [PMID: 37032797 PMCID: PMC10080603 DOI: 10.4240/wjgs.v15.i3.362] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 12/09/2022] [Accepted: 02/28/2023] [Indexed: 03/27/2023] Open
Abstract
BACKGROUND Enhanced recovery after surgery (ERAS) program has been proved to improve postoperative outcome for many surgical procedures, including liver resection. There was limited evidence regarding the feasibility and benefit of ERAS in patients who underwent liver resection for cholangiocarcinoma.
AIM To evaluate the feasibility of ERAS in patients who underwent liver resection for cholangiocarcinoma and its association with patient outcomes.
METHODS We retrospectively analyzed 116 cholangiocarcinoma patients who underwent hepatectomy at Srinagarind Hospital, Khon Kaen University between January 2015 and December 2016. The primary outcome was the compliance with ERAS. To determine the association between ERAS compliance and patient outcomes. the patients were categorized into those adhering more than and equal to 50% (ERAS ≥ 50), and below 50% (ERAS < 50) of all components. Details on type of surgical procedure, preoperative and postoperative care, tumor location, postoperative laboratory results, and survival time were evaluated. The compliance with ERAS was measured by the percentage of ERAS items achieved. The Kaplan-Meier curve was used for survival analysis.
RESULTS The median percentage of ERAS goals achieved was 40% (± 12%). Fourteen patients (12.1%) were categorized into the ERAS ≥ 50 group, and 102 patients were in the ERAS < 50 group. Postoperative hospital stay was significantly shorter in the ERAS ≥ 50 group [8.9 d, 95% confidence interval (CI): 7.3-10.4 d] than in the ERAS < 50 group (13.7 d, 95%CI: 12.2-15.2 d) (P = 0.0217). No hepatobiliary-related complications or in-hospital mortality occurred in the ERAS ≥ 50 group. Overall survival was significantly higher in the ERAS ≥ 50 group. The median survival of the patients in the ERAS < 50 group was 1257 d (95%CI: 853.2-1660.8 d), whereas that of the patients in the ERAS ≥ 50 group was not reached.
CONCLUSION Overall ERAS compliance for patients who underwent liver resection for cholangiocarcinoma is poor. Greater ERAS compliance could predict in-hospital, short-term, and long-term outcomes of the patients.
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Affiliation(s)
| | - Vor Luvira
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Chalisa Suwanprinya
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | | | | | - Theerawee Tipwaratorn
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Attapol Titapun
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Tharatip Srisuk
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Suapa Theeragul
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Apiwat Jarearnrat
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Vasin Thanasukarn
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Ake Pugkhem
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Narong Khuntikeo
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Chawalit Pairojkul
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Supot Kamsa-Ard
- Department of Epidemiology and Biostatistics, Faculty of Public Health, Khon Kaen University, Khon Kaen 40002, Thailand
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Chen X, Du J, Huang J, Zeng Y, Yuan K. Neoadjuvant and Adjuvant Therapy in Intrahepatic Cholangiocarcinoma. J Clin Transl Hepatol 2022; 10:553-563. [PMID: 35836758 PMCID: PMC9240234 DOI: 10.14218/jcth.2021.00250] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 09/07/2021] [Accepted: 10/14/2021] [Indexed: 12/04/2022] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and causes major economic and health burdens throughout the world. Although the incidence of ICC is relatively low, an upward trend has been seen over the past few decades. Owing to the lack of specific manifestations and tools for early diagnosis, most ICC patients have relatively advanced disease at diagnosis. Thus, neoadjuvant therapy is necessary to evaluate tumor biology and downstage these patients so that appropriate candidates can be selected for radical liver resection. However, even after radical resection, the recurrence rate is relatively high and is a main cause leading to death after surgery, which makes adjuvant therapy necessary. Because of its low incidence, studies in both neoadjuvant and adjuvant settings of ICC are lagging compared with other types of malignancy. While standard neoadjuvant and adjuvant regimens are not available in the current guidelines due to a lack of high-level evidence, some progress has been achieved in recent years. In this review, the available literature on advances in neoadjuvant and adjuvant strategies in ICC are evaluated, and possible challenges and opportunities for clinical and translational investigations in the near future are discussed.
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Affiliation(s)
| | | | | | - Yong Zeng
- Correspondence to: Kefei Yuan and Yong Zeng, Department of Liver Surgery and Liver Transplantation, Laboratory of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, No. 37 Guoxue Road, Wuhou District, Chengdu, Sichuan 610041, China. ORCID: https://orcid.org/0000-0003-4308-7743 (KY), https://orcid.org/0000-0002-3347-9690 (YZ). Tel: +86-17340135791 (KY), +86-18680601472 (YZ), Fax: +86-28-8558-2944, E-mail: (KY), (YZ)
| | - Kefei Yuan
- Correspondence to: Kefei Yuan and Yong Zeng, Department of Liver Surgery and Liver Transplantation, Laboratory of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, No. 37 Guoxue Road, Wuhou District, Chengdu, Sichuan 610041, China. ORCID: https://orcid.org/0000-0003-4308-7743 (KY), https://orcid.org/0000-0002-3347-9690 (YZ). Tel: +86-17340135791 (KY), +86-18680601472 (YZ), Fax: +86-28-8558-2944, E-mail: (KY), (YZ)
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Feng J, Liang B, Zhang HY, Liu Z, Jiang K, Zhao XQ. Prognostic factors for patients with mass-forming intrahepatic cholangiocarcinoma: A case series of 68 patients. World J Gastrointest Surg 2022; 14:442-451. [PMID: 35734620 PMCID: PMC9160678 DOI: 10.4240/wjgs.v14.i5.442] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 11/30/2021] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer in humans after hepatocellular carcinoma and a rare epithelial malignancy that results in a poor prognosis. According to the Liver Cancer Study Group of Japan classification, ICC can be divided into three types: Mass-forming (MF) type, periductal-infiltrating (PI) type, and intraductal-growth type. The MF type is the most common, accounting for 57.1-83.6% of ICCs. Nevertheless, little is known about the epidemiology and treatment of MF ICC.
AIM To examine the prognostic factors for patients with MF ICC.
METHODS We carried out a retrospective analysis of consecutive patients with MF ICC treated at the Faculty of Hepato-Pancreato-Biliary Surgery of Chinese PLA General Hospital between January 2008 and December 2018. According to the treatment received, the patients were divided into either a resection group or an exploration group.
RESULTS The pooled 1-, 3-, and 5-year survival rates in the 68 patients with MF ICC were 66.5%, 36.3%, and 9.3%, respectively. Univariate analysis revealed that surgical resection (P < 0.001), nodal metastasis (P < 0.001), tumor location (P = 0.039), vascular invasion (P < 0.001), ascites (P < 0.001), and differentiation (P = 0.009) were significantly associated with the prognosis and survival of MF ICC. Multivariate analysis revealed that ascites (hazard ratio [HR] = 5.6, 95% confidence interval [CI]: 1.6-18.9, P = 0.006) and vascular invasion (HR = 2.5, 95%CI: 1.0-6.1, P = 0.045) were independent risk factors for MF ICC. The pooled 1-, 3-, and 5-year survival rates in the 19 patients of the exploration group were 5.3%, 5.3%, and 0, respectively. Among the 49 patients who underwent surgical resection, the pooled 1-, 3-, and 5-year survival rates were 93.5%, 49.7%, and 14.4%, respectively. Univariate and multivariate analyses revealed that vascular invasion (HR = 3.1, 95%CI: 1.2-8.5, P = 0.024) and nodal metastasis (HR = 3.2, 95%CI: 1.4-7.6, P = 0.008) were independent prognostic risk factors for surgical resection patients.
CONCLUSION The prognosis of MF ICC patients is dismal, especially those with ascites or vascular invasion. Surgical resection is a key factor in improving overall survival in patients with MF ICC, and vascular invasion and lymph node metastasis affect the efficacy of surgical resection.
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Affiliation(s)
- Jian Feng
- Department of Hepatopancreatobiliary Surgery, Peking University Shougang Hospital, Beijing 100144, China
- Faculty of Hepato-Pancreato-Biliary Surgery, Institute of Hepatobiliary Surgery of Chinese PLA, Key Laboratory of Digital Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Bin Liang
- Faculty of Hepato-Pancreato-Biliary Surgery, Institute of Hepatobiliary Surgery of Chinese PLA, Key Laboratory of Digital Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Hang-Yu Zhang
- Faculty of Hepato-Pancreato-Biliary Surgery, Institute of Hepatobiliary Surgery of Chinese PLA, Key Laboratory of Digital Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Zhe Liu
- Faculty of Hepato-Pancreato-Biliary Surgery, Institute of Hepatobiliary Surgery of Chinese PLA, Key Laboratory of Digital Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Kai Jiang
- Faculty of Hepato-Pancreato-Biliary Surgery, Institute of Hepatobiliary Surgery of Chinese PLA, Key Laboratory of Digital Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
| | - Xiang-Qian Zhao
- Faculty of Hepato-Pancreato-Biliary Surgery, Institute of Hepatobiliary Surgery of Chinese PLA, Key Laboratory of Digital Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
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Luvira V, Sirichantakul N, Theeragul S, Pairojkul C. Ruptured Intraductal Papillary Neoplasm of the Bile Duct: a Rare Cause of Peritoneal Carcinomatosis. Indian J Surg 2022. [DOI: 10.1007/s12262-021-03254-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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11
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Progression of intraductal papillary neoplasm of the bile duct (IPNB): A proposed model through the observation of patients with non-resected tumors. Ann Hepatol 2022; 23:100299. [PMID: 33378705 DOI: 10.1016/j.aohep.2020.100299] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 11/11/2020] [Accepted: 11/23/2020] [Indexed: 02/04/2023]
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Tan J, Sun X, Wang S, Ma B, Chen Z, Shi Y, Zhang L, Shah MA. Evaluation of Angiogenesis and Pathological Classification of Extrahepatic Cholangiocarcinoma by Dynamic MR Imaging for E-Healthcare. JOURNAL OF HEALTHCARE ENGINEERING 2021; 2021:8666498. [PMID: 34671450 PMCID: PMC8523230 DOI: 10.1155/2021/8666498] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Revised: 08/07/2021] [Accepted: 09/01/2021] [Indexed: 12/16/2022]
Abstract
For staging cholangiocarcinoma and determining respectability, MR is an accurate noninvasive method which provides size of tumor and vascular patency information. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive inspection method for evaluating the vascular structure and functional characteristics of tumor tissue. However, some limitations should be noted about the technology. At present, the technology cannot be used alone, which is just an assisted method during the conventional MRI examination. 50 ECC patients, admitted to Indira Gandhi Medical College and Hospital between 2016 and 2019, were selected as research subjects. They were classified pathologically according to the Steiner classification system. After image processing, regions of interest (ROIs) were selected from the image to measure the rate constant (Kep), extravascular space volume fraction (Ve), and tissue volume transfer constant (Ktrans). There were 15 cases with highly differentiated carcinoma, 23 cases with moderately differentiated carcinoma, and 12 cases with lowly differentiated carcinoma. Non-VEGF expression was noted in 21 cases, with low expression noted in 15 cases, moderate expression noted in 14 cases, and no high expression case noted. The relevant parameters in the dynamic MRI image can quantitatively reflect the angiogenesis and pathological classification of ECC, which is suggested in the clinical treatment of ECC. The Ktrans, Kep, and Ve values of the ECC patients were all not associated with the pathological classification, with no significant difference (P < 0.05). Besides, due to the fact that the patient cannot completely hold his breath, the air leak reduces the image quality.
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Affiliation(s)
- Jinyun Tan
- Department of Hepatobiliary and Pancreatic Surgery, Lanzhou Second People's Hospital, Lanzhou, Gansu Province, China
| | - Xijun Sun
- Department of Medical Imaging, The Second People's Hospital of Lanzhou, Lanzhou, Gansu Province, China
| | - Shaoyu Wang
- MR Scientific Marketing,Siemens Healthineers, Shanghai, China
| | - Baoqin Ma
- Department of Medical Imaging, The Second People's Hospital of Lanzhou, Lanzhou, Gansu Province, China
| | - Zhaohui Chen
- Department of Medical Imaging, The Second People's Hospital of Lanzhou, Lanzhou, Gansu Province, China
| | - Yaowei Shi
- Department of Hepatobiliary and Pancreatic Surgery, Lanzhou Second People's Hospital, Lanzhou, Gansu Province, China
| | - Li Zhang
- Department of Medical Imaging, The Second People's Hospital of Lanzhou, Lanzhou, Gansu Province, China
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Tang Y, Zhang T, Zhou X, Zhao Y, Xu H, Liu Y, Wang H, Chen Z, Ma X. The preoperative prognostic value of the radiomics nomogram based on CT combined with machine learning in patients with intrahepatic cholangiocarcinoma. World J Surg Oncol 2021; 19:45. [PMID: 34334138 PMCID: PMC8327418 DOI: 10.1186/s12957-021-02162-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 02/02/2021] [Indexed: 02/08/2023] Open
Abstract
Background Intrahepatic cholangiocarcinoma is an aggressive liver carcinoma with increasing incidence and mortality. A good auxiliary prognostic prediction tool is desperately needed for the development of treatment strategies. The purpose of this study was to explore the prognostic value of the radiomics nomogram based on enhanced CT in intrahepatic cholangiocarcinoma. Methods In this retrospective study, 101 patients with pathological confirmation of intrahepatic cholangiocarcinoma were recruited. A radiomics nomogram was developed by radiomics score and independent clinical risk factors selecting from multivariate Cox regression. All patients were stratified as high risk and low risk by a nomogram. Model performance and clinical usefulness were assessed by calibration curve, ROC curve, and survival curve. Results A total of 101patients (mean age, 58.2 years old; range 36–79 years old) were included in the study. The 1-year, 3-year, and 5-year overall survival rates were 49.5%, 26.6%, and 14.4%, respectively, with a median survival time of 12.2 months in the whole set. The least absolute shrinkage and selection operator (LASSO) method selected 3 features. Multivariate Cox analysis found three independent prognostic factors. The radiomics nomogram showed a significant prognosis value with overall survival. There was a significant difference in the 1-year and 3-year survival rates of stratified high-risk and low-risk patients in the whole set (30.4% vs. 56.4% and 13.0% vs. 30.6%, respectively, p = 0.018). Conclusions This radiomics nomogram has potential application value in the preoperative prognostic prediction of intrahepatic cholangiocarcinoma and may facilitate in clinical decision-making. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-021-02162-0.
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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, People's Republic of China
| | - Tao Zhang
- West China School of Medicine, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu, 610041, People's Republic of China
| | - Xianghong Zhou
- Department of Biotherapy, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu, 610041, People's Republic of China
| | - Yunuo Zhao
- West China School of Medicine, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu, 610041, People's Republic of China
| | - Hanyue Xu
- West China School of Medicine, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu, 610041, People's Republic of China
| | - Yichun Liu
- West China School of Public Health, NO.4 West China Teaching Hospital, Sichuan University, No. 18, three section of people south road, Chengdu, 610041, People's Republic of China
| | - Hang Wang
- West China School of Medicine, West China Hospital, Sichuan University, No.14, 3Rd Section Of Ren Min Nan Rd., Chengdu, Sichuan, 610041, People's Republic of China
| | - Zheyu Chen
- Department of Liver Surgery, Division of Liver Transplantation Center, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu, 610041, People's Republic of China.
| | - Xuelei Ma
- Department of Biotherapy, West China Hospital and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu, 610041, People's Republic of China.
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Kim KM, Na JE, Shim SG, Sinn DH. Comparison of ICC patients with hepatitis B infection to those with no major risk factors for HCC. HPB (Oxford) 2021; 23:945-953. [PMID: 33132045 DOI: 10.1016/j.hpb.2020.10.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 09/10/2020] [Accepted: 10/14/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND There has been renewed interest in HBV-associated ICC, because it could share a common carcinogenesis disease process with HCC. We investigated whether there is a difference in clinical outcome between ICC patients with HBV infection and those without any major risk factors for HCC. METHODS A total of 253 curatively resected, surgically diagnosed ICC patients were analyzed and divided into two groups according to the presence or absence of major risk factors for HCC: an HBV group (n = 45) and a non-HCC-risk (NHR) group (n = 208). RESULTS Lymph node metastasis was more frequently observed in the NHR group (HBV vs. NHR: 8.89% vs. 24.52%, P = 0.027). Patients in the HBV group demonstrated more favorable survival than those in the NHR group. However, this difference was not statistically significant (5-year survival rate, 54.7% vs. 42.3%, P = 0.128). Cumulative recurrence rate in the HBV group was 62.2%, which was not significantly different from 63.0% in the NHR group (P = 1.000). CONCLUSION This study found that while ICC patients with HBV infection showed some favorable tumor characteristics, patients' stage-specific survival and recurrence rates were not significantly different compared to those without any major risk factors for HCC.
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Affiliation(s)
- Kwang Min Kim
- Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea
| | - Ji Eun Na
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sang Goon Shim
- Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
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Sirica AE, Strazzabosco M, Cadamuro M. Intrahepatic cholangiocarcinoma: Morpho-molecular pathology, tumor reactive microenvironment, and malignant progression. Adv Cancer Res 2020; 149:321-387. [PMID: 33579427 PMCID: PMC8800451 DOI: 10.1016/bs.acr.2020.10.005] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is a relatively rare, but highly lethal and biologically complex primary biliary epithelial cancer arising within liver. After hepatocellular carcinoma, iCCA is the second most common primary liver cancer, accounting for approximately 10-20% of all primary hepatic malignancies. Over the last 10-20 years, iCCA has become the focus of increasing concern largely due to its rising incidence and high mortality rates in various parts of the world, including the United States. The challenges posed by iCCA are daunting and despite recent progress in the standard of care and management options for iCCA, the prognosis for this cancer continues to be dismal. In an effort to provide a framework for advancing our understanding of iCCA malignant aggressiveness and therapy resistance, this review will highlight key etiological, biological, molecular, and microenvironmental factors hindering more effective management of this hepatobiliary cancer. Particular focus will be on critically reviewing the cell origins and morpho-molecular heterogeneity of iCCAs, providing mechanistic insights into high risk fibroinflammatory cholangiopathies associated with iCCA development, and notably discussing the deleterious role played by the tumor reactive desmoplastic stroma in regulating iCCA malignant progression, lymphangiogenesis, and tumor immunobiology.
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Affiliation(s)
- Alphonse E Sirica
- Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, VA, United States.
| | - Mario Strazzabosco
- Liver Center and Section of Digestive Diseases, Department of Internal Medicine, Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, United States
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Effect of liver fibrosis on survival in patients with intrahepatic cholangiocarcinoma: a SEER population-based study. Oncotarget 2020; 11:4438-4447. [PMID: 33315979 PMCID: PMC7720776 DOI: 10.18632/oncotarget.27820] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Accepted: 11/03/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (iCCA) is a biliary tract malignancy with rising incidence in recent decades. While the causative role of cirrhosis in the development of iCCA is well established, the role of cirrhosis as a prognostic factor in iCCA is debatable. MATERIALS AND METHODS The study population consisted of 512 patients diagnosed with iCCA between 2004-2016 collected from the Surveillance, Epidemiology and End Results (SEER) database. The impact of fibrosis on overall and cancer-specific survival 12, 36 and 60 months following diagnosis, was evaluated in the entire cohort and in sub-groups stratified according to treatment approach and the American Joint Committee on Cancer (AJCC) tumor stage using a Cox proportional-hazards model. RESULTS After adjusting for age, sex, race, year of diagnosis, AJCC stage, and surgical treatment strategy, advanced fibrosis was associated with worse cancer-specific survival across follow up periods (HR 1.49 (1.13-1.96, p = 0.005); HR 1.44 (1.14-1.83, p = 0.002) and HR 1.45 (1.15-1.83, p = 0.002) for 12, 36 and 60 months, respectively). Similar effects were observed for overall survival. Among patients that underwent surgical resection, advanced fibrosis was associated with worse overall survival and cancer-specific survival across follow up periods. Fibrosis was associated with worse overall and cancer-specific survival in patients with a later stage (III-IV) at diagnosis but this effect was not demonstrated in early stages. CONCLUSIONS Patients with iCCA and advanced liver fibrosis have an increased risk of both overall and cancer-specific mortality compared to patients with earlier stages of fibrosis.
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Abstract
Intrahepatic cholangiocarcinoma (ICC) arises from the epithelial cells of the intrahepatic and extrahepatic bile ducts and occurs proximal to the segmental biliary ducts. Risk factors include chronic hepatitis and cirrhosis, biliary inflammatory diseases, and hepatobiliary flukes, although in most cases, no known risk factor is identified. ICC is highly aggressive, with long-term survival only observed in patients with a complete R0 surgical resection. Technical and physiologic resectability should be considered when performing an operative plan. Nodal involvement is among the most important prognostic factors associated with survival and a porta hepatis lymphadenectomy should be performed at the time of resection. Adjuvant chemotherapy can provide a significant survival benefit for patients with more advanced or aggressive tumors. Systemic, locoregional, and targeted therapies exist for patients with unresectable or metastatic disease.
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Affiliation(s)
- Ramy El-Diwany
- Department of Surgery, Johns Hopkins University, 600 N. Wolfe St, Tower 110 Baltimore, MD 21287, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University, 320 W. 10th Avenue, M-260 Starling Loving Hall, Columbus, OH 43210, USA
| | - Aslam Ejaz
- Department of Surgery, Johns Hopkins University, 600 N. Wolfe St, Tower 110 Baltimore, MD 21287, USA.
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Merath K, Mehta R, Hyer JM, Bagante F, Sahara K, Alexandrescu S, Marques HP, Aldrighetti L, Maithel SK, Pulitano C, Weiss MJ, Bauer TW, Shen F, Poultsides GA, Soubrane O, Martel G, Koerkamp BG, Guglielmi A, Itaru E, Ejaz A, Pawlik TM. Impact of body mass index on tumor recurrence among patients undergoing curative-intent resection of intrahepatic cholangiocarcinoma- a multi-institutional international analysis. Eur J Surg Oncol 2019; 45:1084-1091. [PMID: 30871884 DOI: 10.1016/j.ejso.2019.03.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 02/27/2019] [Accepted: 03/01/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The association between body mass index (BMI) and long-term outcomes of patients with ICC has not been well defined. We sought to define the presentation and oncologic outcomes of patients with ICC undergoing curative-intent resection, according to their BMI category. METHODS Patients who underwent resection of ICC were identified in a multi-institutional database. Patients were categorized as normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2) and obese (BMI≥30 kg/m2) according to the World Health Organization (WHO) definition. Impact of clinico-pathological factors on recurrence-free survival (RFS) was assessed using Cox proportional hazards model among patients in the three BMI categories. RESULTS Among a total of 790 patients undergoing curative-intent resection of ICC in the analytic cohort, 399 (50.5%) had normal weight, 274 (34.7%) were overweight and 117 (14.8%) were obese. Caucasian patients were more likely to be obese (66.7%, n = 78) and overweight (47.1%, n = 129) compared with Asian (obese: 18.8%, n = 22; overweight: 46%, n = 126) and other races (obese: 14.5%, n = 17; overweight: 6.9%, n = 19)(p < 0.001). There were no differences in the presence of cirrhosis (10.9%, vs. 12.8%, vs. 12.9%), preoperative jaundice (8.6% vs. 9.5% vs. 12.0%), or levels of CA 19-9 (75, IQR 24.6-280 vs. 50.9, IQR 17.9-232 vs. 43, IQR 16.9-192.7) among the BMI groups (all p > 0.05). On multivariable analysis, increased BMI was an independent risk factor for tumor recurrence (OR 1.16, 95% CI 1.02-1.32, for every 5 unit increase). CONCLUSION Increasing BMI was associated with incremental increases in the risk of recurrence following curative-intent resection of ICC. Future studies should aim to achieve a better understanding of BMI-related factors relative to prognosis of patients with ICC.
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Affiliation(s)
- Katiuscha Merath
- The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Rittal Mehta
- The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - J Madison Hyer
- The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Fabio Bagante
- The Ohio State University Wexner Medical Center, Columbus, OH, USA; University of Verona, Verona, Italy
| | - Kota Sahara
- The Ohio State University Wexner Medical Center, Columbus, OH, USA; Yokohama City University, Yokohama, Japan
| | | | | | | | | | | | | | - Todd W Bauer
- University of Virginia, Charlottesville, VA, USA
| | - Feng Shen
- Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | | | | | | | | | | | - Endo Itaru
- Yokohama City University, Yokohama, Japan
| | - Aslam Ejaz
- The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Timothy M Pawlik
- The Ohio State University Wexner Medical Center, Columbus, OH, USA.
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Abstract
Cholangiocarcinoma is a rare malignancy and accounts for 2% of all malignancies. Incidence is on the increase in the Western world. Cholangiocarcinoma arises from the malignant growth of the epithelial lining of the bile ducts and can be found all along the biliary tree. It can be classified into subtypes based on location: intrahepatic (arising from the intrahepatic biliary tract in the hepatic parenchyma), perihilar (at the hilum of the liver involving the biliary confluence) and distal (extrahepatic, often in the head of the pancreas). Margin status and locoregional lymph node metastases are the most important determinants of postsurgical outcomes.
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Affiliation(s)
- Adeel S Khan
- Section of Abdominal Transplant Surgery, Washington University St Louis, One Barnes-Jewish Hospital Plaza, Suite 6107 Queeny Tower, St Louis, MO 63110, USA.
| | - Leigh Anne Dageforde
- Division of Transplant Surgery, Massachusetts General Hospital, 55 Fruit Street, White 511, Boston, MA 02114, USA
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Waisberg DR, Pinheiro RS, Nacif LS, Rocha-Santos V, Martino RB, Arantes RM, Ducatti L, Lai Q, Andraus W, D'Albuquerque LC. Resection for intrahepatic cholangiocellular cancer: new advances. Transl Gastroenterol Hepatol 2018; 3:60. [PMID: 30363713 DOI: 10.21037/tgh.2018.08.03] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Accepted: 08/22/2018] [Indexed: 12/14/2022] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second most prevalent primary liver neoplasm after hepatocellular carcinoma (HCC), corresponding to 10% to 15% of cases. Pathologies that cause chronic biliary inflammation and bile stasis are known predisposing factors for development of ICC. The incidence and cancer-related mortality of ICC is increasing worldwide. Most patients remain asymptomatic until advance stage, commonly presenting with a liver mass incidentally diagnosed. The only potentially curative treatment available for ICC is surgical resection. The prognosis is dismal for unresectable cases. The principle of the surgical approach is a margin negative hepatic resection with preservation of adequate liver remnant. Regional lymphadenectomy is recommended at time of hepatectomy due to the massive impact on outcomes caused by lymph node (LN) metastasis. Multicentric disease, tumor size, margin status and tumor differentiation are also important prognostic factors. Staging laparoscopy is warranted in high-risk patients to avoid unnecessary laparotomy. Exceedingly complex surgical procedures, such as major vascular, extrahepatic bile ducts and visceral resections, ex vivo hepatectomy and autotransplantation, should be implemented in properly selected patients to achieve negative margins. Neoadjuvant therapy may be used in initially unresectable lesions in order to downstage and allow resection. Despite optimal surgical management, recurrence is frustratingly high. Adjuvant chemotherapy with radiation associated with locoregional treatments should be considered in cases with unfavorable prognostic factors. Selected patients may undergo re-resection of tumor recurrence. Despite the historically poor outcomes of liver transplantation for ICC, highly selected patients with unresectable disease, especially those with adequate response to neoadjuvant therapy, may be offered transplant. In this article, we reviewed the current literature in order to highlight the most recent advances and recommendations for the surgical treatment of this aggressive malignancy.
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Affiliation(s)
- Daniel R Waisberg
- Disciplina de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Rafael S Pinheiro
- Disciplina de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Lucas S Nacif
- Disciplina de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Vinicius Rocha-Santos
- Disciplina de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Rodrigo B Martino
- Disciplina de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Rubens M Arantes
- Disciplina de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Liliana Ducatti
- Disciplina de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Quirino Lai
- Transplant Unit, Department of Surgery, University of L'Aquila, San Salvatore Hospital, L'Aquila, Italy
| | - Wellington Andraus
- Disciplina de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Luiz C D'Albuquerque
- Disciplina de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
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