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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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Wang WQ, Li J, Lv X, Wang JL, Zhang EL, Zhang BH, Xiao ZY, Liang BY, Huang ZY. Anatomical sectionectomy based on Takasaki's segmentation for solitary intrahepatic cholangiocarcinoma: a propensity-matched analysis. HPB (Oxford) 2024; 26:753-763. [PMID: 38485565 DOI: 10.1016/j.hpb.2024.01.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 12/27/2023] [Accepted: 01/26/2024] [Indexed: 06/02/2024]
Abstract
BACKGROUND Anatomical sectionectomy based on Takasaki's segmentation has shown advantages in hepatocellular carcinoma. However, whether this approach improves the survival of intrahepatic cholangiocarcinoma (ICC) remains unknown. METHODS A series of 248 consecutive patients with solitary ICCs who underwent hepatectomy were studied retrospectively. The patients were classified into the groups of anatomical sectionectomy based on Takasaki's segmentation (TS group) and non-Takasaki's hepatectomy (NTH group). The bias between the two groups was minimized using propensity score matching (PSM). Recurrence-free survival (RFS) and overall survival (OS) were evaluated with Kaplan-Meier analysis. The Cox proportional hazards model was performed to determine the adverse risk factors associated with survival. RESULTS After PSM, 67 pairs of patients were compared. Both the RFS and OS rates in the TS group were significantly better than those in the NTH group (23.2 % vs. 16.5 %, and 40.4 % vs. 27.3 %, P = 0.035 and 0.032, respectively). Multivariate analysis showed that NTH was independently associated with worse RFS and OS than TS. The stratified analysis demonstrated that the RFS and OS rates in the TS group with tumor stage I and tumor size ≥3 cm were significantly better than those in the NTH group, while the survival rates for ICC with stage I and tumor size <3 cm or stage II-III showed no significant difference. CONCLUSION TS was associated with improved RFS and OS in patients with solitary ICC even after PSM. TS may be preferred particularly in patients with tumor stage I and tumor size ≥3 cm.
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Affiliation(s)
- Wen-Qiang Wang
- Center for Liver Transplantation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 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.; Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Xing Lv
- 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
| | - Er-Lei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bin-Hao Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhen-Yu Xiao
- 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..
| | - Zhi-Yong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China..
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Fu J, Zheng L, Tang S, Lin K, Zheng S, Bi X, Wang J, Guo W, Li F, Wang J, Wang K, Li H, Zeng Y. Tumor burden score and carcinoembryonic antigen predict outcomes in patients with intrahepatic cholangiocarcinoma following liver resection: a multi‑institutional analysis. BMC Cancer 2024; 24:358. [PMID: 38509498 PMCID: PMC10953220 DOI: 10.1186/s12885-024-12091-2] [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: 12/15/2023] [Accepted: 03/07/2024] [Indexed: 03/22/2024] Open
Abstract
BACKGROUND The prognostic significance of tumor burden score (TBS) in relation to carcinoembryonic antigen (CEA) has not been investigated among patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC). This study aimed to develop and validate a simplified model, a combination of TBS and CEA (CTC grade), for predicting the long-term outcomes of postoperative ICC patients. METHODS Patients who underwent curative - intent resection of ICC between 2011 and 2019 were identified from a large multi - institutional database. The impact of TBS, CEA, and the CTC grade on overall survival (OS) and recurrence - free survival (RFS) was evaluated in both the derivation and validation cohorts. The receiver operating characteristic curve was utilized for assessing the predictive accuracy of the model. Subgroup analyses were performed across 8th TNM stage system stratified by CTC grade to assess the discriminatory capacity within the same TNM stage. RESULTS A total of 812 patients were included in the derivation cohort and 266 patients in the validation cohort. Survival varied based on CEA (low: 36.7% vs. high: 9.0%) and TBS (low: 40.3% vs. high: 17.6%) in relation to 5 - year survival (both p < 0.001). As expected, patients with low CTC grade (i.e., low TBS/low CEA) were associated with the best OS as well as RFS, while high CTC grade (i.e., high TBS/high CEA) correlated to the worst outcomes. The model exhibited well performance in both the derivation cohort (area under the curve of 0.694) and the validation cohort (0.664). The predictive efficacy of the CTC grade system remains consistently stable across TNM stages I and III/IV. CONCLUSION The CTC grade, a composite parameter derived from the combination of TBS and CEA levels, served as an easy - to - use tool and performed well in stratifying patients with ICC relative to OS and RFS.
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Affiliation(s)
- Jun Fu
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, 312 Xihong Road, Fuzhou, China
- Department of Hepatopancreatobiliary Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Lifang Zheng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, 312 Xihong Road, Fuzhou, China
| | - Shicuan Tang
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, 312 Xihong Road, Fuzhou, China
| | - Kongying Lin
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, 312 Xihong Road, Fuzhou, China
| | - Shuguo Zheng
- Department of Hepatobiliary Surgery, The Southwest Hospital Affiliated to the Army Medical University, Chongqing, China
| | - Xinyu Bi
- Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Jianming Wang
- Department of Hepatobiliary Surgery, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science Technology, Wuhan, China
| | - Wei Guo
- Department of Hepatobiliary Surgery, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing, China
| | - Fuyu Li
- Department of Hepatobiliary Surgery, The West China Hospital of Sichuan University, Chengdu, China
| | - Jian Wang
- Department of Hepatobiliary Surgery, Renji Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Kui Wang
- Department of Hepatic Surgery (II), Eastern Hepatobiliary Surgery Hospital, Navy edical University, Shanghai, China
| | - Haitao Li
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, 312 Xihong Road, Fuzhou, China.
| | - Yongyi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, 312 Xihong Road, Fuzhou, China.
- Department of Hepatopancreatobiliary Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
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Nash S, Weeks K, Kahl AR, Del Vecchio NJ, Gao X, Guyton K, Charlton M. Diagnosing Provider, Referral Patterns, Facility Type, and Patient Satisfaction Among Iowa Rectal Cancer Patients. J Gastrointest Cancer 2024; 55:355-364. [PMID: 37646879 PMCID: PMC11611274 DOI: 10.1007/s12029-023-00963-y] [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] [Accepted: 08/09/2023] [Indexed: 09/01/2023]
Abstract
PURPOSE Rectal cancer treatment at high-volume centers is associated with higher likelihood of guideline-concordant care and improved outcomes. Whether rectal cancer patients are referred for treatment at high-volume hospitals may depend on diagnosing provider specialty. We aimed to determine associations of diagnosing provider specialty with treating provider specialty and characteristics of the treating facility for rectal cancer patients in Iowa. METHODS Rectal cancer patients identified using the Iowa Cancer Registry completed a mailed survey on their treatment experience and decision-making process. Provider type was defined by provider specialty and whether the provider referred patients elsewhere for surgery. Multivariable-adjusted logistic regression models were used to examine predictors of being diagnosed by a general surgeon who also performed the subsequent surgery. RESULTS Of 417 patients contacted, 381 (76%) completed the survey; our final analytical sample size was 267. Half of respondents were diagnosed by a gastroenterologist who referred them elsewhere; 30% were diagnosed by a general surgeon who referred them elsewhere, and 20% were diagnosed by a general surgeon who performed the surgery. Respondents who were ≥ 65 years old, had less than a college education, and who made < $50,000 per year were more likely to be diagnosed by a general surgeon who performed surgery. In multivariable-adjusted models, respondents diagnosed and treated by the same general surgeon were more likely to have surgery at hospitals with low annual colorectal cancer surgery volume and less likely to be satisfied with their care. CONCLUSIONS Among rectal cancer patients in Iowa, respondents who were diagnosed and treated by the same provider were less likely to get treatment at a high-volume facility. This study informs the importance of provider referral in centralization of rectal cancer care.
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Affiliation(s)
- Sarah Nash
- Department of Epidemiology, College of Public Health, University of Iowa, 145 N Riverside Dr., IA, 52242, Iowa City, USA
- State Health Registry of Iowa, College of Public Health, University of Iowa, 145 N Riverside Dr., IA, 52242, Iowa City, USA
| | - Kristin Weeks
- Department of Internal Medicine, The Ohio State University Medical Center, 410 W Tenth Ave, Columbus, OH, 43210, USA
| | - Amanda R Kahl
- State Health Registry of Iowa, College of Public Health, University of Iowa, 145 N Riverside Dr., IA, 52242, Iowa City, USA
| | - Natalie J Del Vecchio
- Division of Public Health Science, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA
| | - Xiang Gao
- Department of Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Dr., IA, 52242, Iowa City, USA
| | - Kristina Guyton
- Department of Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Dr., IA, 52242, Iowa City, USA
| | - Mary Charlton
- Department of Epidemiology, College of Public Health, University of Iowa, 145 N Riverside Dr., IA, 52242, Iowa City, USA.
- State Health Registry of Iowa, College of Public Health, University of Iowa, 145 N Riverside Dr., IA, 52242, Iowa City, USA.
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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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Ferrell LD, Kakar S, Terracciano LM, Wee A. Tumours and Tumour-Like Lesions. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:842-946. [DOI: 10.1016/b978-0-7020-8228-3.00013-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Moris D, Palta M, Kim C, Allen PJ, Morse MA, Lidsky ME. Advances in the treatment of intrahepatic cholangiocarcinoma: An overview of the current and future therapeutic landscape for clinicians. CA Cancer J Clin 2023; 73:198-222. [PMID: 36260350 DOI: 10.3322/caac.21759] [Citation(s) in RCA: 201] [Impact Index Per Article: 100.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 08/25/2022] [Accepted: 08/29/2022] [Indexed: 01/27/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor and remains a fatal malignancy in the majority of patients. Approximately 20%-30% of patients are eligible for resection, which is considered the only potentially curative treatment; and, after resection, a median survival of 53 months has been reported when sequenced with adjuvant capecitabine. For the 70%-80% of patients who present with locally unresectable or distant metastatic disease, systemic therapy may delay progression, but survival remains limited to approximately 1 year. For the past decade, doublet chemotherapy with gemcitabine and cisplatin has been considered the most effective first-line regimen, but results from the recent use of triplet regimens and even immunotherapy may shift the paradigm. More effective treatment strategies, including those that combine systemic therapy with locoregional therapies like radioembolization or hepatic artery infusion, have also been developed. Molecular therapies, including those that target fibroblast growth factor receptor and isocitrate dehydrogenase, have recently received US Food and Drug Administration approval for a defined role as second-line treatment for up to 40% of patients harboring these actionable genomic alterations, and whether they should be considered in the first-line setting is under investigation. Furthermore, as the oncology field seeks to expand indications for immunotherapy, recent data demonstrated that combining durvalumab with standard cytotoxic therapy improved survival in patients with ICC. This review focuses on the current and future strategies for ICC treatment, including a summary of the primary literature for each treatment modality and an algorithm that can be used to drive a personalized and multidisciplinary approach for patients with this challenging malignancy.
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Affiliation(s)
- Dimitrios Moris
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Manisha Palta
- Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA
| | - Charles Kim
- Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA
| | - Peter J Allen
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Michael A Morse
- Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
| | - Michael E Lidsky
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
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Newest Therapies for Cholangiocarcinoma: An Updated Overview of Approved Treatments with Transplant Oncology Vision. Cancers (Basel) 2022; 14:cancers14205074. [PMID: 36291857 PMCID: PMC9600404 DOI: 10.3390/cancers14205074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 10/09/2022] [Accepted: 10/12/2022] [Indexed: 11/30/2022] Open
Abstract
Simple Summary Cholangiocarcinoma is a relatively rare but deadly disease with traditionally limited treatment options. The disease can be categorized by anatomic location within the biliary tree, with different associated risk factors and molecular profiles. Recent years have seen a burgeoning of targeted therapies that have enhanced survival in subsets of patients with certain mutations. We herein discuss these more recent advances as well as providing an overview of more well-known treatment modalities, with the goal of providing an accessible source for practicing clinicians. Abstract A minority of cholangiocarcinoma (CCA) can be cured by surgical intervention (i.e., liver resection (LR) and liver transplantation (LT)). When modern criteria for LT are met, this intervention along with neoadjuvant treatments may achieve unprecedented survival in selected patients. Liver resection is associated with a median overall survival (OS) of 40 months, this number drastically decreases for unresectable advanced cholangiocarcinoma (CCA), which is treated with systemic therapy. The first-line chemotherapy regimen of gemcitabine and cisplatin is associated with a median overall survival of only 11.7 months. Since the Food and Drug Administration (FDA)’s approval of the isocitrate dehydrogenase (IDH) 1 inhibitor ivosidenib in August 2021, there has been increasing interest in targeted therapy for CCA patients harboring mutations in fibroblast growth factor receptor (FGFR) 2, neurotrophic receptor tyrosine kinase (NTRK), B-raf kinase (BRAF), and HER2. At the same time, immunotherapy with immune checkpoint inhibitors isalso being used in relapsed CCA. This review looks into the most recently completed and ongoing studies of targeted therapy as monotherapy or in combination with chemo- and/or immunotherapy. Whether it is resection, liver transplant, radiotherapy, chemotherapy, immunotherapy, targeted therapy, or any combination of these treatment modalities, great strides are being made to improve outcomes for this challenging disease.
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Zhu Q, Zhai S, Ge E, Li L, Jiao X, Xiong J, Zhu G, Xu Y, Qu J, Wang Z. Intrahepatic cholangiocarcinoma with gastric metastasis misdiagnosed as primary gastric cancer: A case report and literature review. Front Oncol 2022; 12:997735. [PMID: 36132146 PMCID: PMC9483163 DOI: 10.3389/fonc.2022.997735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 08/19/2022] [Indexed: 11/13/2022] Open
Abstract
We describe a case of intrahepatic cholangiocarcinoma with gastric metastasis misdiagnosed as primary gastric cancer. In addition, combined with the literature, we summarized the clinical and imaging features of gastric metastasis of intrahepatic cholangiocarcinoma in order to improve the understanding of the preoperative diagnosis. Positron emission tomography/computed tomography (PET/CT) is accurate in evaluating the primary tumor, lymph node metastasis, and distant metastasis of patients. In addition, immunohistochemical staining can determine the primary site of metastatic adenocarcinoma. For patients who can not determine the location of the primary tumor, the rigorous preoperative examination is necessary, it can improve the accuracy of diagnosis and avoid excessive treatment of patients.
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Affiliation(s)
- Qingshun Zhu
- Department of Clinical Medical College, Weifang Medical University, Weifang, China
| | - Shengyong Zhai
- Department of General Surgery, The first affiliated Hospital of Weifang Medical University (Weifang People’s Hospital), Weifang, China
| | - Enkang Ge
- Department of Clinical Medical College, Weifang Medical University, Weifang, China
| | - Lei Li
- Department of Clinical Medical College, Weifang Medical University, Weifang, China
| | - Xuguang Jiao
- Department of General Surgery, The first affiliated Hospital of Weifang Medical University (Weifang People’s Hospital), Weifang, China
| | - Jinqiu Xiong
- Department of General Surgery, The first affiliated Hospital of Weifang Medical University (Weifang People’s Hospital), Weifang, China
| | - Guangxu Zhu
- Department of General Surgery, The first affiliated Hospital of Weifang Medical University (Weifang People’s Hospital), Weifang, China
| | - Yuanyuan Xu
- Department of General Surgery, The first affiliated Hospital of Weifang Medical University (Weifang People’s Hospital), Weifang, China
| | - Jianjun Qu
- Department of General Surgery, The first affiliated Hospital of Weifang Medical University (Weifang People’s Hospital), Weifang, China
- *Correspondence: Jianjun Qu, ; Zhengjiang Wang,
| | - Zhengjiang Wang
- Department of General Surgery, The first affiliated Hospital of Weifang Medical University (Weifang People’s Hospital), Weifang, China
- *Correspondence: Jianjun Qu, ; Zhengjiang Wang,
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Li J, Chen Q, Guo L, Li J, Jin B, Wu X, Shi Y, Xu H, Zheng Y, Wang Y, Du S, Li Z, Lu X, Sang X, Mao Y. In situ Detecting Lipids as Potential Biomarkers for the Diagnosis and Prognosis of Intrahepatic Cholangiocarcinoma. Cancer Manag Res 2022; 14:2903-2912. [PMID: 36187448 PMCID: PMC9524278 DOI: 10.2147/cmar.s357000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 08/20/2022] [Indexed: 11/23/2022] Open
Abstract
Purpose To quantitatively analyze lipid molecules in tumors and adjacent tissues of intrahepatic cholangiocarcinoma (ICC), to establish diagnostic model and to examine lipid changes with clinical classification. Patients and Methods We measured the quantity of 202 lipid molecules in 100 tumor observation points and 100 adjacent observation points of patients who were diagnosed with ICC. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were handles, along with Student’s t-test to identify specific metabolites. Prediction accuracy was validated in the validation set. Another logistic regression model was also established on the training set and validated on the validation set. Results Distinct separation was obtained from PCA and OPLS-DA model. Ten differentiating metabolites were identified using PCA, OPLA-DA and Lasso regression: [m/z 722.5130], [m/z 863.5655], [m/z 436.2834], [m/z 474.2626], [m/z 661.4813], [m/z 750.5443], [m/z 571.2889], [m/z 836.5420], [m/z 772.5862] and [m/z 478.2939]. Using logical regression, a diagnostic equation: y = 3.4*[m/z 436.2834] - 3.773*[m/z 474.2626] + 3.82*[m/z 661.4813] - 4.394*[m/z 863.5655] + 10.165 based on four metabolites successfully differentiated cancerous areas from adjacent normal areas. The AUROC of the model reached 0.993 (95% CI: 0.985–0.999) in the validation group. Compared with the adjacent non-tumor area, three characteristic metabolites FA (22:4), PA (P-18:0/0:0) and Glucosylceramide (d18:1/12:0) showed an increasing trend from stage I to stage II, while seven other metabolites LPA(16:0), PE(34:2), PE(36:4), PE(38:3), PE(40:6), PE(40:5) and LPE(16:0) showed a decreasing trend from stage I to stage II. Conclusion We successfully identified lipid molecules in differentiating tumor tissue and adjacent tissue of ICC, established a discrimination logistic model which could be used as a classifier to classify tumor and non-tumor regions based on analysis in tumor margins and provided information for biomarker changes in ICC, and proposed to related lipid changes with clinical classification.
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Affiliation(s)
- Jiayi Li
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China
- Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China
| | - Qiao Chen
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China
- Department of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China
| | - Lei Guo
- Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, People’s Republic of China
| | - Ji Li
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China
| | - Bao Jin
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China
| | - Xiangan Wu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China
| | - Yue Shi
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China
| | - Haifeng Xu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China
| | - Yongchang Zheng
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China
| | - Yingyi Wang
- Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China
| | - Shunda Du
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China
- Correspondence: Shunda Du; Zhili Li, Email ;
| | - Zhili Li
- Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, People’s Republic of China
| | - Xin Lu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China
| | - Xinting Sang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China
| | - Yilei Mao
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China
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Chen W, Hu Z, Song J, Wu Y, Zhang B, Zhang L. The state of therapy modalities in clinic for biliary tract cancer. FRONT BIOSCI-LANDMRK 2022; 27:185. [PMID: 35748261 DOI: 10.31083/j.fbl2706185] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2021] [Revised: 01/26/2022] [Accepted: 01/27/2022] [Indexed: 11/06/2022]
Abstract
Biliary tract cancers (BTCs) include intrahepatic cholangiocarcinoma (iCCA), perihilar and distal cholangiocarcinoma (pCCA and dCCA), and gallbladder carcinoma based on the epithelial site of origin. BTCs are highly aggressive tumors associated with poor prognosis due to widespread metastasis and high recurrence. Surgery is the typical curative-intent treatment, yet the cornerstone of cure depends on the anatomical site of the primary tumor, and only a minority of patients (approximately 30%) has an indication necessitating surgery. Similarly, only a small subset of carefully selected patients with early iCCA who are not candidates for liver resection can opt for liver transplantation. Chemotherapy, target therapy, and immunotherapy are the main treatment options for patients who have advanced stage or unresectable disease. The genetic background of each cholangiocarcinoma subtype has been accurately described based on whole gene exome and transcriptome sequencing. Accordingly, precision medicine in targeted therapies has been identified to be aimed at distinct patient subgroups harboring unique molecular alterations. Immunotherapy such as immune checkpoint inhibitors (ICIs) was identified as antitumor responses in a minority of select patients. Current studies indicate that immunotherapy of adoptive cell therapy represents a promising approach in hematological and solid tumor malignancies, yet clinical trials are needed to validate its effectiveness in BTC. Herein, we review the progress of BTC treatment, stratified patients according to the anatomic subtypes of cholangiocarcinoma and the gene drivers of cholangiocarcinoma progression, and compare the efficacy and safety of chemotherapy, targeted therapy, and immunotherapy, which will be conducive to the design of individualized therapies.
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Affiliation(s)
- Weixun Chen
- Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, Hubei, China
| | - Zhengnan Hu
- Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, Hubei, China
| | - Jia Song
- Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, Hubei, China
| | - Yu Wu
- Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, Hubei, China
| | - Bixiang Zhang
- Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, Hubei, China
| | - Lei Zhang
- Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, Hubei, China
- Department of Hepatobiliary Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Shanxi Medical University; Shanxi Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 030032 Taiyuan, Shanxi, China
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Brustia R, Laurent A, Goumard C, Langella S, Cherqui D, Kawai T, Soubrane O, Cauchy F, Farges O, Menahem B, Hobeika C, Rhaiem R, Sommacale D, Okumura S, Hofmeyr S, Ferrero A, Pruvot FR, Regimbeau JM, Fuks D, Vibert E, Scatton O. Laparoscopic versus open liver resection for intrahepatic cholangiocarcinoma: Report of an international multicenter cohort study with propensity score matching. Surgery 2022; 171:1290-1302. [PMID: 34535270 DOI: 10.1016/j.surg.2021.08.015] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 08/09/2021] [Accepted: 08/12/2021] [Indexed: 11/09/2022]
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma is a rare disease with a poor prognosis. In patients where surgical resection is possible, outcome is influenced by perioperative morbidity and lymph node status. Laparoscopic liver resection is associated with improved clinical and oncological outcomes in primary and metastatic liver cancer compared with open liver resection, but evidence on intrahepatic cholangiocarcinoma is still insufficient. The primary aim of this study was to compare overall survival for a large series of patients treated for intrahepatic cholangiocarcinoma by open or laparoscopic approach. Secondary objectives were to compare disease-free survival, predictors of death, and recurrence. METHODS Patients treated with laparoscopic or open liver resection for intrahepatic cholangiocarcinoma from 2000 to 2018 from 3 large international databases were analyzed retrospectively. Each patient in the laparoscopic resection group (case) was matched with 1 open resection control (1:1 ratio), through a propensity score calculated on clinically relevant preoperative covariates. Overall and disease-free survival were compared between the matched groups. Predictors of mortality and recurrence were analyzed with Cox regression, and the Textbook Outcomes were described. RESULTS During the study period, 855 patients met the inclusion criteria (open liver resection = 709, 82.9%; laparoscopic liver resection = 146, 17.1%). Two groups of 89 patients each were analyzed after propensity score matching, with no significant difference regarding pre- and postoperative variables. Overall survival at 1, 3, and 5 years was 92%, 75%, and 63% in the laparoscopic liver resection group versus 92%, 58%, and 49% in the open liver resection group (P = .0043). Adjusted Cox regression revealed severe postoperative complications (hazard ratio: 10.5, 95% confidence interval [1.01-109] P = .049) and steatosis (hazard ratio: 13.8, 95% confidence interval [1.23-154] P = .033) as predictors of death, and transfusion (hazard ratio: 19.2, 95% confidence interval [4.04-91.4] P < .001) and severe postoperative complications (hazard ratio: 4.07, 95% confidence interval [1.15-14.4] P = .030) as predictors of recurrence. CONCLUSION The survival advantage of laparoscopic liver resection over open liver resection for intrahepatic cholangiocarcinoma is equivocal, given historical bias and missing data.
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Affiliation(s)
- 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. https://twitter.com/raffaele.brustia
| | - Alexis Laurent
- Univ Paris Est Creteil, Faculté de Santé, Créteil, France and Department of Digestive and Hepato-Pancreatic-Biliary Surgery, DMU CARE, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, Créteil, France
| | - Claire Goumard
- Department of Hepatobiliary and Liver Transplantation Surgery, AP-HP, Hôpital Pitié Salpêtrière, CRSA, Sorbonne Université, Paris, France
| | - Serena Langella
- Department of General and Oncological Surgery, Ospedale Mauriziano, Torino, Italy
| | - Daniel Cherqui
- Centre Hepato-Biliaire, AP-HP Paul Brousse Hospital, Paris-Saclay University, Villejuif, France
| | - Takayuki Kawai
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Olivier Soubrane
- Department of Hepatobiliary Surgery, APHP, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, France
| | - Francois Cauchy
- Department of Hepatobiliary Surgery, APHP, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, France
| | - Olivier Farges
- Department of Hepatobiliary Surgery, APHP, University Hospitals Paris Nord Val de Seine, Beaujon, Clichy, France
| | - Benjamin Menahem
- Department of Digestive Surgery, University Hospital of Caen, France
| | - Christian Hobeika
- Department of Hepatobiliary and Liver Transplantation Surgery, AP-HP, Hôpital Pitié Salpêtrière, CRSA, Sorbonne Université, Paris, France
| | - Rami Rhaiem
- Department of Hepatobiliary, Pancreatic, and Digestive Surgery, Robert Debré University Hospital, Reims, France University Reims Champagne-Ardenne, France
| | - Daniele Sommacale
- Univ Paris Est Creteil, Faculté de Santé, Créteil, France and Department of Digestive and Hepato-Pancreatic-Biliary Surgery, DMU CARE, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, Créteil, France
| | - Shinya Okumura
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - 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
| | - François-René Pruvot
- Department of Digestive Surgery and Transplantation, Univ Lille, CHRU Lille, Lille, France
| | - Jean-Marc Regimbeau
- SSPC (Simplification of Surgical Patients Care), Clinical Research Unit, University of Picardie Jules Verne, Amiens, France and Department of Digestive Surgery, Amiens University Medical Center, Amiens, France
| | - David Fuks
- Department of Digestive, Oncologic, and Metabolic Surgery, Institut Mutualiste Montsouris, Université Paris Descartes, Paris, France
| | - Eric Vibert
- Centre Hepato-Biliaire, AP-HP Paul Brousse Hospital, Paris-Saclay University, Villejuif, France
| | - Olivier Scatton
- Department of Hepatobiliary and Liver Transplantation Surgery, AP-HP, Hôpital Pitié Salpêtrière, CRSA, Sorbonne Université, Paris, France.
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Yan X, Wang L, Meng Z. Conditional cancer-specific survival after radical hepatectomy in patients with nonmetastatic intrahepatic cholangiocarcinoma. Scand J Gastroenterol 2022; 57:481-485. [PMID: 35007461 DOI: 10.1080/00365521.2021.2022192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES To examine conditional survival (CS) in patients with non-metastatic intrahepatic cholangiocarcinoma (nmICC) after surgical treatment according to pT and pN stages. METHODS A total of 608 patients were included. Conditional three-year cancer-specific mortality estimates were obtained according to pT and pN stages. Multivariable Cox regression analysis was applied to predict factors affecting cancer-specific mortality (CSM). RESULTS According to substages based on pT and pN status, 109 patients (17.9%) with pT1aN0, 96 (15.8%) with pT1bN0, 205 (33.7%) with pT2N0, 82(13.5%) with pT3-5N0, and 116 (19.1%) with pTanyN1 were identified. Conditional CSM-free estimates increased from 75% to 87%, 66% to 70%, 53% to 86%, and 36 to 54% after three years of event-free follow-up in pT1b, pT2, pT3-4N0, and pTanyN1 patients, respectively, whereas it decreased from 87% to 79% in pT1aN0 patients. Based on multivariable analysis, patients with pT2N0 (hazard ratio [HR] 2.0 p < .01), pT3-4N0 (HR 2,7 p < .01), and pTanyN1-3 (HR 4.8 p < .01) had higher CSM than patients with pT1aN0 at baseline. CONCLUSIONS CS varied across stage categories in nmICC patients after surgery, and it was important in individualized clinical counseling and decision-making for nmICC.
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Affiliation(s)
- Xia Yan
- Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Lai Wang
- Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Zhiqiang Meng
- Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
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Xu L, Wang P, Zhang W, Li W, Liu T, Che X. Dual-Specificity Phosphatase 11 Is a Prognostic Biomarker of Intrahepatic Cholangiocarcinoma. Front Oncol 2021; 11:757498. [PMID: 34660327 PMCID: PMC8513537 DOI: 10.3389/fonc.2021.757498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 08/31/2021] [Indexed: 11/23/2022] Open
Abstract
Background Cholangiocarcinoma (CCA), including intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA) CCA, is a highly aggressive malignancy originating from bile duct. The prognosis of CCA is very poor, and the biomarker study is unsatisfactory compared with other common cancers. Materials and methods In our study, we investigated the expression of dual-specificity phosphatase 11(DUSP11) in eight pairs of iCCAs, pCCAs, and dCCAs, and their corresponding tumor-adjacent tissues, as well as their tumor-adjacent tissues with qPCR. Moreover, we investigated the expression of DUSP11 in 174 cases of CCAs with immunohistochemistry, including 74 iCCAs, 64 pCCAs, and 36 dCCAs. We classified these patients into subsets with low and high expressions of DUSP11, and evaluated the correlations between the DUSP11 subsets and clinicopathological factors. With univariate and multivariate analyses, we assessed the correlation between DUSP11 and the overall survival (OS) rates in these CCA patients. Results In all the CCA subtypes, DUSP11 was elevated in CCAs compared with their paired adjacent tissues. In iCCA, pCCA, and dCCA, the percentages of DUSP11 high expression were 44.59%, 53.85%, and 55.56%, respectively. In iCCA, high DUSP11 expression was significantly associated with an advanced T stage and a poor prognosis. However, the prognostic value of DUSP11 in pCCA and dCCA was not significant. To decrease the statistical error caused by the small sample size of the dCCA cohort, we merged pCCA and dCCA into extracellular CCA (eCCA). In the 101 cases of eCCA, DUSP11 expression was also not significantly associated with the prognosis. Conclusions DUSP11 expression was associated with tumor infiltration and the OS rate in iCCA, but not in pCCA and dCCA. DUSP11 was an independent biomarker of iCCA indicating a poor prognosis. Our results suggested that a high expression of DUSP11 was a post-operational risk factor, and detecting DUSP11 could guide the individual treatment for patients with CCA.
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Affiliation(s)
- Lin Xu
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Peng Wang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wei Zhang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weiran Li
- Department of Oncology Rehabilitation, Shenzhen Luohu People's Hospital, Shenzhen, China
| | - Tao Liu
- Department of Oncology Rehabilitation, Shenzhen Luohu People's Hospital, Shenzhen, China
| | - Xu Che
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China.,Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Kim YY, Yeom SK, Shin H, Choi SH, Rhee H, Park JH, Cho ES, Park S, Lee SS, Park MS. Clinical Staging of Mass-Forming Intrahepatic Cholangiocarcinoma: Computed Tomography Versus Magnetic Resonance Imaging. Hepatol Commun 2021; 5:2009-2018. [PMID: 34559470 PMCID: PMC8631089 DOI: 10.1002/hep4.1774] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 06/04/2021] [Accepted: 06/09/2021] [Indexed: 02/06/2023] Open
Abstract
We compared the performance of computed tomography (CT) and magnetic resonance imaging (MRI) for preoperative clinical staging of mass‐forming intrahepatic cholangiocarcinoma (iCCA), using the eighth American Joint Committee on Cancer (AJCC) system. This retrospective, multicenter, cohort study consecutively identified patients who underwent partial hepatectomy for mass‐forming iCCA and had preoperative CT and MRI performed from January 2009 to December 2015. CT and MRI characteristics were used to determine clinical stage based on the eighth AJCC system. Performances of CT and MRI for clinical T and N staging were compared using generalized estimating equations. In 334 patients (median age, 63 years; 221 men), MRI sensitivities were significantly higher than CT sensitivities for detecting T1b or higher stages (91.0% vs. 80.5%, respectively, P < 0.001), T2 or higher stages (89.1% vs. 73.8%, respectively, P < 0.001), and T3 or T4 stage (77.8% vs. 58.0%, respectively, P < 0.001). MRI was also more sensitive at identifying multiple tumors than CT (66.7% vs. 50.0%, respectively, P = 0.026), without a significant difference in specificity (78.1% vs. 80.1%, respectively, P = 0.342). Sensitivities were comparable between CT and MRI for determination of size >5 cm (i.e., T1b for single tumor) and extrahepatic organ invasion (i.e., T4). Sensitivities of CT and MRI were not different for N stage (65.0% vs. 64.0%, respectively, P = 0.808), but the specificity of CT was significantly higher than that of MRI (80.7% vs. 72.9%, respectively, P = 0.001) when using a composite reference standard. Conclusion: MRI showed superior sensitivity to CT for diagnosing T2 and T3 stages, particularly multiple tumors. CT and MRI had comparable sensitivity for N staging, but CT provided higher specificity than MRI.
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Affiliation(s)
- Yeun-Yoon Kim
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Suk-Keu Yeom
- Department of Radiology, Korea University Ansan Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| | - Hyejung Shin
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, 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
| | - Hyungjin Rhee
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Ji Hoon Park
- Department of Radiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, Republic of Korea
| | - Eun-Suk Cho
- Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sumi Park
- Department of Radiology, National Health Insurance Service Ilsan Hospital, Goyang, 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
| | - Mi-Suk Park
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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16
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Wada Y, Shimada M, Yamamura K, Toshima T, Banwait JK, Morine Y, Ikemoto T, Saito Y, Baba H, Mori M, Goel A. A Transcriptomic Signature for Risk-Stratification and Recurrence Prediction in Intrahepatic Cholangiocarcinoma. Hepatology 2021; 74:1371-1383. [PMID: 33725402 PMCID: PMC8443691 DOI: 10.1002/hep.31803] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 01/06/2021] [Accepted: 02/23/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS Tumor recurrence is frequent even in intrahepatic cholangiocarcinoma (ICC), and improved strategies are needed to identify patients at highest risk for such recurrence. We performed genome-wide expression profile analyses to discover and validate a gene signature associated with recurrence in patients with ICC. APPROACH AND RESULTS For biomarker discovery, we analyzed genome-wide transcriptomic profiling in ICC tumors from two public data sets: The Cancer Genome Atlas (n = 27) and GSE107943 (n = 28). We identified an eight-gene panel (BIRC5 [baculoviral IAP repeat containing 5], CDC20 [cell division cycle 20], CDH2 [cadherin 2], CENPW [centromere protein W], JPH1 [junctophilin 1], MAD2L1 [mitotic arrest deficient 2 like 1], NEIL3 [Nei like DNA glycosylase 3], and POC1A [POC1 centriolar protein A]) that robustly identified patients with recurrence in the discovery (AUC = 0.92) and in silico validation cohorts (AUC = 0.91). We next analyzed 241 specimens from patients with ICC (training cohort, n = 64; validation cohort, n = 177), followed by Cox proportional hazard regression analysis, to develop an integrated transcriptomic panel and establish a risk-stratification model for recurrence in ICC. We subsequently trained this transcriptomic panel in a clinical cohort (AUC = 0.89; 95% confidence interval [CI] = 0.79-0.95), followed by evaluating its performance in an independent validation cohort (AUC = 0.86; 95% CI = 0.80-0.90). By combining our transcriptomic panel with various clinicopathologic features, we established a risk-stratification model that was significantly superior for the identification of recurrence (AUC = 0.89; univariate HR = 6.08, 95% CI = 3.55-10.41, P < 0.01; and multivariate HR = 3.49, 95% CI = 1.81-6.71, P < 0.01). The risk-stratification model identified potential recurrence in 85% of high-risk patients and nonrecurrence in 76% of low-risk patients, which is dramatically superior to currently used pathological features. CONCLUSIONS We report a transcriptomic signature for risk-stratification and recurrence prediction that is superior to currently used clinicopathological features in patients with ICC.
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Affiliation(s)
- Yuma Wada
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
- Department of Surgery, Tokushima University, Tokushima, Japan
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Mitsuo Shimada
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Kensuke Yamamura
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Takeo Toshima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Jasjit K Banwait
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
| | - Yuji Morine
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Tetsuya Ikemoto
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Yu Saito
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Masaki Mori
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Ajay Goel
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA
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17
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Hobeika C, Cauchy F, Fuks D, Barbier L, Fabre JM, Boleslawski E, Regimbeau JM, Farges O, Pruvot FR, Pessaux P, Salamé E, Soubrane O, Vibert E, Scatton O. Laparoscopic versus open resection of intrahepatic cholangiocarcinoma: nationwide analysis. Br J Surg 2021; 108:419-426. [PMID: 33793726 DOI: 10.1093/bjs/znaa110] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 05/28/2020] [Accepted: 11/03/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND The relevance of laparoscopic resection of intrahepatic cholangiocarcinoma (ICC) remains debated. The aim of this study was to compare laparoscopic (LLR) and open (OLR) liver resection for ICC, with specific focus on textbook outcome and lymph node dissection (LND). METHODS Patients undergoing LLR or OLR for ICC were included from two French, nationwide hepatopancreatobiliary surveys undertaken between 2000 and 2017. Patients with negative margins, and without transfusion, severe complications, prolonged hospital stay, readmission or death were considered to have a textbook outcome. Patients who achieved both a textbook outcome and LND were deemed to have an adjusted textbook outcome. OLR and LLR were compared after propensity score matching. RESULTS In total, 548 patients with ICC (127 LLR, 421 OLR) were included. Textbook-outcome and LND completion rates were 22.1 and 48.2 per cent respectively. LLR was independently associated with a decreased rate of LND (odds ratio 0.37, 95 per cent c.i. 0.20 to 0.69). After matching, 109 patients remained in each group. LLR was associated with a decreased rate of transfusion (7.3 versus 21.1 per cent; P = 0.001) and shorter hospital stay (median 7 versus 14 days; P = 0.001), but lower rate of LND (33.9 versus 73.4 per cent; P = 0.001). Patients who underwent LLR had lower rate of adjusted TO completion than patients who had OLR (6.5 versus 17.4 per cent; P = 0.012). CONCLUSION The laparoscopic approach did not substantially improve quality of care of patients with resectable ICC.
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Affiliation(s)
- C Hobeika
- Department of Hepatobiliary Surgery and Liver Transplantation, Hôpital Beaujon, Assistance Publique-Hopitaux de Paris, Université de Paris, Paris, France.,Department of Hepatobiliary Surgery and Liver Transplantation, Hôpital de la Pitié Salpêtrière, Assistance Publique-Hopitaux de Paris and Sorbonne University, Paris, France
| | - F Cauchy
- Department of Hepatobiliary Surgery and Liver Transplantation, Hôpital Beaujon, Assistance Publique-Hopitaux de Paris, Université de Paris, Paris, France
| | - D Fuks
- Department of Digestive Surgery, Institut Mutualiste Montsouris, Université Paris V, Paris, France
| | - L Barbier
- Department of Digestive, Endocrine, Hepatopancreatobiliary Surgery and Liver Transplantation, Hôpital Trousseau, Centre Hospitalier Régional Universitaire Tours, Tours, France
| | - J M Fabre
- Department of Digestive, Hepatopancreatobiliary Surgery and Liver Transplantation, Centre Hospitalier Universitaire de Montpellier, Montpellier, France
| | - E Boleslawski
- Department of Digestive Surgery and Liver Transplantation, Hôpital Huriez, Centre Hospitalier Universitaire de Lille, Université Nord de France, Lille, France
| | - J M Regimbeau
- Department of Digestive Surgery, Centre Hospitalier Universitaire Amiens-Picardie, Amiens, France
| | - O Farges
- Department of Hepatobiliary Surgery and Liver Transplantation, Hôpital Beaujon, Assistance Publique-Hopitaux de Paris, Université de Paris, Paris, France
| | - F R Pruvot
- Department of Digestive Surgery and Liver Transplantation, Hôpital Huriez, Centre Hospitalier Universitaire de Lille, Université Nord de France, Lille, France
| | - P Pessaux
- Department of Digestive Surgery, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
| | - E Salamé
- Department of Digestive, Endocrine, Hepatopancreatobiliary Surgery and Liver Transplantation, Hôpital Trousseau, Centre Hospitalier Régional Universitaire Tours, Tours, France
| | - O Soubrane
- Department of Hepatobiliary Surgery and Liver Transplantation, Hôpital Beaujon, Assistance Publique-Hopitaux de Paris, Université de Paris, Paris, France
| | - E Vibert
- Department of Hepatobiliary Surgery and Liver Transplantation, Hôpital Paul Brousse, Assistance Publique-Hopitaux de Paris and Université Paris XI, Paris, France
| | - O Scatton
- Department of Hepatobiliary Surgery and Liver Transplantation, Hôpital de la Pitié Salpêtrière, Assistance Publique-Hopitaux de Paris and Sorbonne University, Paris, France
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18
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Mar WA, Chan HK, Trivedi SB, Berggruen SM. Imaging of Intrahepatic Cholangiocarcinoma. Semin Ultrasound CT MR 2021; 42:366-380. [PMID: 34130849 DOI: 10.1053/j.sult.2021.04.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Cholangiocarcinoma is the second most common primary hepatic malignancy and is a heterogeneous tumor of biliary epithelium. We discuss the risk factors, anatomic classification of cholangiocarcinoma (CC) as well as the different morphologic subtypes of CC. Imaging findings of CC on different modalities are described, focusing on intrahepatic CC. Recently recognized imaging features that carry prognostic significance, such as a worse prognosis in tumors that have more desmoplastic stroma, are detailed. Other benign and malignant entities that should be considered in the differential diagnosis of CC will also be discussed.
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Affiliation(s)
- Winnie A Mar
- Department of Radiology, University of Illinois at Chicago
| | - Hing Kiu Chan
- Department of Radiology, University of Illinois at Chicago
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19
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Vitzthum LK, Riviere P, Sheridan P, Nalawade V, Deka R, Furnish T, Mell LK, Rose B, Wallace M, Murphy JD. Predicting Persistent Opioid Use, Abuse, and Toxicity Among Cancer Survivors. J Natl Cancer Inst 2021; 112:720-727. [PMID: 31754696 DOI: 10.1093/jnci/djz200] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Revised: 09/08/2019] [Accepted: 09/27/2019] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Although opioids play a critical role in the management of cancer pain, the ongoing opioid epidemic has raised concerns regarding their persistent use and abuse. We lack data-driven tools in oncology to understand the risk of adverse opioid-related outcomes. This project seeks to identify clinical risk factors and create a risk score to help identify patients at risk of persistent opioid use and abuse. METHODS Within a cohort of 106 732 military veteran cancer survivors diagnosed between 2000 and 2015, we determined rates of persistent posttreatment opioid use, diagnoses of opioid abuse or dependence, and admissions for opioid toxicity. A multivariable logistic regression model was used to identify patient, cancer, and treatment risk factors associated with adverse opioid-related outcomes. Predictive risk models were developed and validated using a least absolute shrinkage and selection operator regression technique. RESULTS The rate of persistent opioid use in cancer survivors was 8.3% (95% CI = 8.1% to 8.4%); the rate of opioid abuse or dependence was 2.9% (95% CI = 2.8% to 3.0%); and the rate of opioid-related admissions was 2.1% (95% CI = 2.0% to 2.2%). On multivariable analysis, several patient, demographic, and cancer and treatment factors were associated with risk of persistent opioid use. Predictive models showed a high level of discrimination when identifying individuals at risk of adverse opioid-related outcomes including persistent opioid use (area under the curve [AUC] = 0.85), future diagnoses of opioid abuse or dependence (AUC = 0.87), and admission for opioid abuse or toxicity (AUC = 0.78). CONCLUSION This study demonstrates the potential to predict adverse opioid-related outcomes among cancer survivors. With further validation, personalized risk-stratification approaches could guide management when prescribing opioids in cancer patients.
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Affiliation(s)
- Lucas K Vitzthum
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA.,Center for Precision Radiation Medicine, University of California San Diego, La Jolla, CA
| | - Paul Riviere
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA
| | - Paige Sheridan
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA
| | - Vinit Nalawade
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA
| | - Rishi Deka
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA
| | - Timothy Furnish
- Department of Family Medicine and Public Health and Division of Pain Medicine, Department of Internal Medicine, University of California San Diego, La Jolla, CA
| | - Loren K Mell
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA.,Center for Precision Radiation Medicine, University of California San Diego, La Jolla, CA
| | - Brent Rose
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA.,Center for Precision Radiation Medicine, University of California San Diego, La Jolla, CA
| | | | - James D Murphy
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA.,Center for Precision Radiation Medicine, University of California San Diego, La Jolla, CA
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20
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Prognostic impact of tumor microvessels in intrahepatic cholangiocarcinoma: association with tumor-infiltrating lymphocytes. Mod Pathol 2021; 34:798-807. [PMID: 33077921 DOI: 10.1038/s41379-020-00702-9] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 09/18/2020] [Accepted: 10/05/2020] [Indexed: 12/12/2022]
Abstract
Tumor microvessel density (MVD) is a prognostic factor for patients with intrahepatic cholangiocarcinoma (ICC). Tumor-infiltrating lymphocytes (TILs) are also key components of the tumor microenvironment that play important roles in ICC progression. This study aimed to clarify the relationships between the MVD and immune status and prognosis in patients with ICC. Immunohistochemical staining for cluster of differentiation 34 (CD34), cluster of differentiation 8 (CD8), forkhead box protein P3 (Foxp3), and programmed death-ligand 1 (PD-L1) was performed. The relationships between the MVD and clinicopathological characteristics and outcomes were analyzed. Additionally, the correlations between the MVD, CD8+ and Foxp3+ TIL counts, and PD-L1 expression were evaluated. One hundred ICC patients were classified into high (n = 50) and low (n = 50) MVD groups. The serum platelet and carbohydrate antigen 19-9 levels were higher in the low MVD group than in the high MVD group (P = 0.017 and P = 0.008, respectively). The low MVD group showed a significantly larger tumor size (P = 0.016), more frequent microvascular invasion (P = 0.001), and a higher rate of intrahepatic (P = 0.023) and lymph node (P < 0.001) metastasis than the high MVD group. Moreover, the MVD showed a high positive correlation with CD8+ TILs (r = 0.754, P < 0.001) and a negative correlation with Foxp3+ TILs (r = -0.302, P = 0.003). In contrast, no significant correlation was observed between the MVD and PD-L1 expression in cancer cells (P = 0.817). Patients with low MVDs had a significantly worse prognosis than those with high MVDs. Furthermore, multivariable analyses revealed that a low MVD influenced recurrence-free survival. A decreased intratumoral MVD might predict ICC patient outcomes. Tumor microvessels might be associated with ICC progression, possibly by altering TIL recruitment.
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21
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Fong ZV, Brownlee SA, Qadan M, Tanabe KK. The Clinical Management of Cholangiocarcinoma in the United States and Europe: A Comprehensive and Evidence-Based Comparison of Guidelines. Ann Surg Oncol 2021; 28:2660-2674. [PMID: 33646431 DOI: 10.1245/s10434-021-09671-y] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 01/18/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND The incidence of cholangiocarcinoma has doubled over the last 15 years with a similar rise in mortality, which provides the impetus for standardization of evidence-based care through the establishment of guidelines. METHODS We compared available guidelines on the clinical management of cholangiocarcinoma in the United States and Europe, which included the National Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO), British Society of Gastroenterology (BSG) and the International Liver Cancer Association (ILCA) guidelines. RESULTS There is discordance in the recommendation for biopsy in patients with potentially resectable cholangiocarcinoma and in the recommendation for use of fluorodeoxyglucose positron emission tomography scans. Similarly, the recommendation for preoperative biliary drainage for extrahepatic and perihilar cholangiocarcinoma in the setting of jaundice is inconsistent across all four guidelines. The BILCAP (capecitabine) and ABC-02 trials (gemcitabine with cisplatin) have provided the strongest evidence for systemic therapy in the adjuvant and palliative settings, respectively, but all guidelines have refrained from setting them as standard of care, given heterogeneity in the study cohorts and ABC-02's negative intention-to-treat results. CONCLUSIONS Future progress in enhancing survivorship of patients with cholangiocarcinoma would likely entail improvements in diagnostic biomarkers and novel systemic therapies. Based on recent results from studies of targeted therapy, future iterations of the guidelines will likely incorporate molecular profiling.
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Affiliation(s)
- Zhi Ven Fong
- Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Sarah A Brownlee
- Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Motaz Qadan
- Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Kenneth K Tanabe
- Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
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22
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Zeng JT, Zhang JF, Wang Y, Qing Z, Luo ZH, Zhang YL, Zhang Y, Luo XZ. Intrahepatic cholangiocarcinoma is more complex than we thought: A case report. World J Clin Cases 2021; 9:1469-1474. [PMID: 33644217 PMCID: PMC7896692 DOI: 10.12998/wjcc.v9.i6.1469] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 12/15/2020] [Accepted: 01/06/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Brain metastasis from intrahepatic cholangiocarcinoma is rare. To the best of our knowledge, only a few cases have been reported. The biological behavior was complex, and treatment requires further investigation.
CASE SUMMARY A 62-year-old woman complained of left limb weakness. Abdominal computed tomography showed a 5.0 cm × 5.6 cm lesion in the left lobe of the liver. Tumor markers were normal. Serological analysis indicated absence of hepatitis virus. Brain magnetic resonance imaging revealed a 1.0 cm × 1.3 cm mass in the right frontal lobe. Intrahepatic cholangiocarcinoma with brain metastasis was diagnosed by our liver cancer multidisciplinary team. After sufficient preparation, the patient underwent partial frontal lobotomy and left hemihepatectomy. Histopathological results confirmed that both the lesions were cholangiocarcinoma. Six cycles of gemcitabine combined with S1 were administered. During a 39 mo postoperative follow-up, no sign of local recurrence or distant metastasis was observed.
CONCLUSION This case expands our knowledge concerning the complex and heterogeneous nature of tumor metastasis.
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Affiliation(s)
- Jian-Ting Zeng
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, Chongqing University, Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Jie-Feng Zhang
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Yu Wang
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Zhou Qing
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, Chongqing University, Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Zhen-Hua Luo
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, Chongqing University, Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Yan-Lin Zhang
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, Chongqing University, Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Yi Zhang
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, Chongqing University, Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Xian-Zhang Luo
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, Chongqing University, Chongqing University Cancer Hospital, Chongqing 400030, China
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Abstract
Cholangiocarcinoma is the second most common primary malignancy of the liver. This review will focus on the mass-forming intrahepatic type of this disease and discuss the role of medical, surgical, and radiation oncology in managing this difficult disease. A global understanding to the management of intrahepatic cholangiocarcinoma (ICC) can help the interventional radiologist understand the role of locoregional therapies such as ablation, transarterial chemoembolization, and radioembolization in the management of ICC.
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Affiliation(s)
- Pouya Entezari
- Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Ahsun Riaz
- Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
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24
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Saleh M, Virarkar M, Bura V, Valenzuela R, Javadi S, Szklaruk J, Bhosale P. Intrahepatic cholangiocarcinoma: pathogenesis, current staging, and radiological findings. Abdom Radiol (NY) 2020; 45:3662-3680. [PMID: 32417933 DOI: 10.1007/s00261-020-02559-7] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
To this date, it is a major oncological challenge to optimally diagnose, stage, and manage intrahepatic cholangiocarcinoma (ICC). Imaging can not only diagnose and stage ICC, but it can also guide management. Hence, imaging is indispensable in the management of ICC. In this article, we review the pathology, epidemiology, genetics, clinical presentation, staging, pathology, radiology, and treatment of ICC.
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Affiliation(s)
- Mohammed Saleh
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
| | - Mayur Virarkar
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - Vlad Bura
- Department of Radiology, County Clinical Emergency Hospital, 400006, Cluj-Napoca, Cluj, Romania
| | - Raul Valenzuela
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - Sanaz Javadi
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - Janio Szklaruk
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - Priya Bhosale
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
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25
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Ito T, Shinkawa H, Takemura S, Tanaka S, Nishioka T, Miyazaki T, Ishihara A, Kubo S. Impact of the Preoperative C-reactive Protein to Albumin Ratio on the Long-Term Outcomes of Hepatic Resection for Intrahepatic Cholangiocarcinoma. Asian Pac J Cancer Prev 2020; 21:2373-2379. [PMID: 32856868 PMCID: PMC7771946 DOI: 10.31557/apjcp.2020.21.8.2373] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Indexed: 12/27/2022] Open
Abstract
Objective: The present study aimed to investigate the impact of preoperative C-reactive protein to albumin (CRP/Alb) ratio on the long-term outcomes of patients with intrahepatic cholangiocarcinoma (ICC). Methods: 82 patients who underwent hepatic resection for mass-forming type of ICC were evaluated. The relationship between preoperative CRP/Alb ratio and survival outcomes was investigated. Results: The optimal cutoff value of CRP/Alb ratio for assessing overall survival (OS) was determined as 0.089. Univariate analysis for recurrence-free survival (RFS) showed that CRP/Alb ratio >0.089, carbohydrate antigen 19-9 (CA 19-9) >37 U/mL, lymph node metastasis, vascular invasion, and multiple tumors were significantly associated with postoperative recurrence. On multivariate analysis, the independent prognostic factors identified were CRP/Alb ratio >0.089 (p < 0.001), lymph node metastasis (p = 0.006), and multiple tumors (p < 0.001). Univariate analysis for OS showed that CRP/Alb ratio >0.089, CA 19-9 >37 U/mL, lymph node metastasis, vascular invasion, multiple tumors, and positive surgical margin were significantly associated with overall death. On multivariate analysis, the independent prognostic factors identified were CRP/Alb ratio >0.089 (p < 0.001), lymph node metastasis (p = 0.01), and multiple tumors (p = 0.005). Conclusion: Preoperative CRP/Alb ratio may predict poor long-term outcomes after hepatic resection in patients with ICC.
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Affiliation(s)
- Tokuji Ito
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka, 545-8585, Japan
| | - Hiroji Shinkawa
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka, 545-8585, Japan
| | - Shigekazu Takemura
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka, 545-8585, Japan
| | - Shogo Tanaka
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka, 545-8585, Japan
| | - Takayoshi Nishioka
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka, 545-8585, Japan
| | - Toru Miyazaki
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka, 545-8585, Japan
| | - Atsushi Ishihara
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka, 545-8585, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka, 545-8585, Japan
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Khuntikeo N, Koonmee S, Sa-Ngiamwibool P, Chamadol N, Laopaiboon V, Titapun A, Yongvanit P, Loilome W, Namwat N, Andrews RH, Petney TN, Thinkhamrop K, Chaichaya N, Tawarungruang C, Thuanman J, Thinkhamrop B. A comparison of the proportion of early stage cholangiocarcinoma found in an ultrasound-screening program compared to walk-in patients. HPB (Oxford) 2020; 22:874-883. [PMID: 31662222 DOI: 10.1016/j.hpb.2019.10.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Revised: 08/30/2019] [Accepted: 10/01/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Patients with cholangiocarcinoma (CCA) usually have no specific symptoms until an advance stage of the disease and curative treatment is not possible. Patients with early stage, operable disease can be found using ultrasonography (US). A US-screening program was implemented in Thailand where CCA incidence is the highest worldwide. Here we evaluate the effectiveness of the program by comparing the proportion of individuals with early stage CCA in the screening group with that of the walk-in group presenting at hospitals with clinical symptoms. METHODS All patients had a pathological diagnosis of CCA. The difference in the proportions and the 95% confidence interval (CI) were obtained using binomial regression. RESULTS Of the 762 histologically proven CCA cases, 161 were from the screening group and 601 from the walk-in group. The proportion of early stage CCA (stages 0 to II) diagnosed was 84.5% in the screening and 21.6% in the walk-in groups. After adjustment age, gender, and liver fluke infection, there was a significantly higher proportion (P < 0.001) and higher chance (P < 0.001) of having early stage CCA in the screening group than in the walk-in group. CONCLUSIONS US-screening is an effective tool for detecting early stage, operable CCA in high incidence areas.
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Affiliation(s)
- Narong Khuntikeo
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Supinda Koonmee
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Prakasit Sa-Ngiamwibool
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Nittaya Chamadol
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Vallop Laopaiboon
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Attapol Titapun
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Puangrat Yongvanit
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Watcharin Loilome
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Nisana Namwat
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Ross H Andrews
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Faculty of Medicine, St Mary's Campus, Imperial College, London, United Kingdom
| | - Trevor N Petney
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; State Museum of Natural History Karlsruhe, Erbprinzenstrasse 13, 76133 Karlsruhe, Germany
| | - Kavin Thinkhamrop
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Data Management and Statistical Analysis Center (DAMASAC), Faculty of Public Health, Khon Kaen University, Thailand
| | - Nathaphop Chaichaya
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Data Management and Statistical Analysis Center (DAMASAC), Faculty of Public Health, Khon Kaen University, Thailand
| | - Chaiwat Tawarungruang
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Data Management and Statistical Analysis Center (DAMASAC), Faculty of Public Health, Khon Kaen University, Thailand
| | - Jaruwan Thuanman
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Data Management and Statistical Analysis Center (DAMASAC), Faculty of Public Health, Khon Kaen University, Thailand
| | - Bandit Thinkhamrop
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand; Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand; Data Management and Statistical Analysis Center (DAMASAC), Faculty of Public Health, Khon Kaen University, Thailand.
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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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Yamamoto Y, Sugiura T, Okamura Y, Ito T, Ashida R, Ohgi K, Nakanuma Y, Uesaka K. The Evaluation of the Eighth Edition of the AJCC/UICC Staging System for Intrahepatic Cholangiocarcinoma: a Proposal of a Modified New Staging System. J Gastrointest Surg 2020; 24:786-795. [PMID: 31012045 DOI: 10.1007/s11605-019-04185-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Accepted: 02/25/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND The objective was to clarify the prognostic impact of the 8th edition of American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) of intrahepatic cholangiocarcinoma (ICC). METHODS A total of 103 ICC patients who underwent hepatectomy between 2002 and 2016 were enrolled. The survival impact of AJCC/UICC 8th edition was examined. RESULTS The 5-year disease-specific survival (DSS) rate was 75.9% in T1a (n = 23), 88.9% in T1b (n = 10), 14.9% in T2 (n = 24), 52.5% in T3 (n = 11), and 15.2% in T4 (n = 35). The DSS was comparable among T2, T3, and T4 (T2 vs. T3; p = 0.345, T3 vs. T4; 0.295). A multivariate analysis identified multiple tumors (hazard ratio [HR] 2.821), periductal infiltrating (HR 2.439), perforation of the visceral peritoneum (HR 1.850), and vascular invasion (HR 1.872) as independent prognostic factors that were associated with the DSS. The optimum tumor size with the greatest difference in the DSS was 2 cm (p = 0.014). The new T classification was developed as follows: T1, size ≤ 2 cm without other factors; T2, size > 2 cm without other factors; T3, vascular invasion or perforation of the visceral peritoneum; and T4, multiple tumors or periductal infiltrating. The 5-year DSS was 100% in T1 (n = 7), 76.6% in T2 (n = 28), 45.1% in T3 (n = 28), and 3.4% in T4 (n = 40). There were differences in the DSS between T2 and T3 (p = 0.035) and between T3 and T4 (p = 0.003). CONCLUSIONS T2, T3, and T4 of AJCC/UICC overlapped with regard to the DSS. The new staging can classify ICC patients with sufficient prognostic differences.
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Affiliation(s)
- Yusuke Yamamoto
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 4118777, Japan.
| | - Teiichi Sugiura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 4118777, Japan
| | - Yukiyasu Okamura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 4118777, Japan
| | - Takaaki Ito
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 4118777, Japan
| | - Ryo Ashida
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 4118777, Japan
| | - Katsuhisa Ohgi
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 4118777, Japan
| | - Yasuni Nakanuma
- Division of Pathology, Shizuoka Cancer Center, Sunto-Nagaizumi, Shizuoka, Japan
| | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 4118777, Japan
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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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Tiemin P, Peng X, Qingfu L, Yan W, Junlin X, Zhefeng H, Ming Z, Desen L, Qinghui M. Dysregulation of the miR-148a-GLUT1 axis promotes the progression and chemoresistance of human intrahepatic cholangiocarcinoma. Oncogenesis 2020; 9:19. [PMID: 32054829 PMCID: PMC7018977 DOI: 10.1038/s41389-020-0207-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 01/30/2020] [Accepted: 02/04/2020] [Indexed: 11/09/2022] Open
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is a highly fatal malignant cancer worldwide. Elucidating the underlying molecular mechanism of iCCA progression is critical for the identification of new therapeutic targets. The present study explored the role of the miR-148a-GLUT1 axis in the progression of iCCA. The expression of GLUT1 was detected by using immunohistochemistry, western blot assays, and real-time polymerase chain reaction. The effects of GLUT1 on cell proliferation, invasion, and chemoresistance were investigated both in vitro and in vivo. A luciferase reporter assay was used to explore the effect of miR-148a on GLUT1 expression. GLUT1 was overexpressed in iCCA tissues. GLUT1 overexpression was associated with shorter overall and disease-free survival. Knockdown of GLUT1 reduced, while overexpression of GLUT1 promoted, the proliferation, motility, and invasiveness of iCCA cells in vitro and in vivo. Silencing GLUT1 significantly sensitized iCCA cells to gemcitabine in vitro and in vivo. GLUT1 was directly regulated by miR-148a, whose downregulation was associated with the proliferation, migration, and invasion of iCCA cells. WZB117, a GLUT1 inhibitor, inhibited tumor growth in an iCCA patient-derived xenograft model. These results indicate that downregulation of miR-148a levels results in GLUT1 overexpression in iCCA, leading to iCCA progression and gemcitabine resistance.
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Affiliation(s)
- Pei Tiemin
- Department of General Surgery, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xiao Peng
- Department of General Surgery, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Lang Qingfu
- Department of General Surgery, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Wang Yan
- Department of General Surgery, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xue Junlin
- Department of General Surgery, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - He Zhefeng
- Department of General Surgery, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Zhao Ming
- Department of General Surgery, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Liang Desen
- Department of General Surgery, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Meng Qinghui
- Department of General Surgery, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
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31
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Watanabe Y, Matsuyama Y, Izumi N, Kubo S, Kokudo N, Sakamoto M, Shiina S, Takayama T, Nakashima O, Kudo M. Effect of surgical margin width after R0 resection for intrahepatic cholangiocarcinoma: A nationwide survey of the Liver Cancer Study Group of Japan. Surgery 2020; 167:793-802. [PMID: 32044110 DOI: 10.1016/j.surg.2019.12.009] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 12/13/2019] [Accepted: 12/18/2019] [Indexed: 01/22/2023]
Abstract
BACKGROUND Data are inconsistent regarding the effects of a wide surgical margin for intrahepatic cholangiocarcinoma on recurrence-free survival and overall survival. This study was performed to investigate the effect of surgical margin width in patients undergoing R0 resection for intrahepatic cholangiocarcinoma, using a nationwide database in Japan. METHODS In total, 635 patients with intrahepatic cholangiocarcinoma who were treated by an R0 resection from 2000 to 2007 were identified from the database of a Japanese nationwide survey. Patients were divided into quartiles of the surgical margin width as follows: marginal (<1 mm), narrow (1-4 mm), intermediate (5-9 mm), and wide groups (≥10 mm). Multivariable Cox regression models for recurrence-free survival and overall survival were constructed with adjustment for preoperative and postoperative clinicopathologic factors. RESULTS Compared with the marginal group, the risk-adjusted hazard ratios (95% confidence intervals) in the narrow, intermediate, and wide groups for recurrence-free survival were 0.92 (0.62-1.37), 0.91 (0.61-1.37), and 0.81 (0.56-1.17), and those for overall survival were 0.79 (0.51-1.24), 0.93 (0.59-1.47), and 0.70 (0.46-1.08), respectively. In 398 patients without lymph node metastasis, the hazard ratios for overall survival were 0.62 (0.34-1.11), 0.63 (0.34-1.17), and 0.51 (0.29-0.90), and those of mass-forming type intrahepatic cholangiocarcinoma were 0.48 (0.21-1.08), 0.43 (0.19-0.96), and 0.40 (0.19-0.82), respectively. CONCLUSION Surgical margin width appears to have a limited effect on the prognosis of intrahepatic cholangiocarcinoma except in patients without lymph node metastasis, where a wide surgical margin is associated with favorable outcomes. This survival benefit of a wide surgical margin is especially apparent for the mass-forming type intrahepatic cholangiocarcinoma.
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Affiliation(s)
- Yukihiro Watanabe
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Saitama, Japan; Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
| | - Yutaka Matsuyama
- Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Namiki Izumi
- Department of Gastroenterology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Norihiro Kokudo
- National Center for Global Health and Medicine, Tokyo, Japan
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Shuichiro Shiina
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Osamu Nakashima
- Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka, Japan
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Mazzaferro V, Gorgen A, Roayaie S, Droz Dit Busset M, Sapisochin G. Liver resection and transplantation for intrahepatic cholangiocarcinoma. J Hepatol 2020; 72:364-377. [PMID: 31954498 DOI: 10.1016/j.jhep.2019.11.020] [Citation(s) in RCA: 224] [Impact Index Per Article: 44.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 11/25/2019] [Accepted: 11/29/2019] [Indexed: 02/06/2023]
Abstract
The incidence of intrahepatic cholangiocarcinoma (iCCA) is increasing worldwide. Although several advances have been made in the past decades to better understand this complex malignancy and to develop new treatment strategies, the prognosis of iCCA remains dismal. Liver resection (LR) is the mainstay of treatment but only a minority of patients are amenable to surgery. In most cases, patients with iCCA will require a major hepatectomy for complete resection of the tumour. This may be contraindicated or increase the surgical burden in patients with chronic liver disease and small remnant liver volume. Lymphadenectomy with a minimal harvest of 6 lymph nodes is considered adequate, as microscopic nodal metastases have been shown in more than 40% of patients. Current 5-year overall survival following LR is in the range of 25%-40%. For locally advanced disease not amenable to upfront LR, neoadjuvant locoregional therapies may be used with the aim of converting these patients to resectability or even to transplantation in well-selected cases. Recent studies have shown that liver transplantation (LT) might be a treatment option for patients with unresectable very-early iCCA (i.e. ≤2 cm), with survival outcomes comparable to those of hepatocellular carcinoma. In patients with unresectable, advanced tumours, confined to the liver who achieve sustained response to neoadjuvant treatment, LT may be considered an option within prospective protocols. The role of adjuvant therapies in iCCA is still under debate. Herein, we review the recent advances in the surgical treatment of iCCA and examine its correlation with locoregional therapies, adjuvant and neo-adjuvant strategies.
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Affiliation(s)
- Vincenzo Mazzaferro
- General Surgery and Liver Transplantation Unit, University of Milan and Istituto Nazionale Tumouri (National Cancer Institute), IRCCS Foundation, Milan, Italy.
| | - Andre Gorgen
- Multi-Organ Transplant and HPB Surgical Oncology, Division of General Surgery, University Health Network, Department of Surgery, University of Toronto, Canada
| | - Sasan Roayaie
- Liver Cancer Program, White Plains Hospital - Montefiore Health System, White Plains, NY, USA
| | - Michele Droz Dit Busset
- General Surgery and Liver Transplantation Unit, University of Milan and Istituto Nazionale Tumouri (National Cancer Institute), IRCCS Foundation, Milan, Italy
| | - Gonzalo Sapisochin
- Multi-Organ Transplant and HPB Surgical Oncology, Division of General Surgery, University Health Network, Department of Surgery, University of Toronto, Canada
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Sun D, Luo T, Dong P, Zhang N, Chen J, Zhang S, Liu L, Dong L, Zhang S. CD86 +/CD206 + tumor-associated macrophages predict prognosis of patients with intrahepatic cholangiocarcinoma. PeerJ 2020; 8:e8458. [PMID: 32002338 PMCID: PMC6982414 DOI: 10.7717/peerj.8458] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Accepted: 12/24/2019] [Indexed: 12/13/2022] Open
Abstract
Background As the main cellular ingredients of tumor microenvironment, tumor-associated macrophages (TAMs) play a vital role in tumor development and progression. Recent studies have suggested that TAMs are sensitive and specific prognostic factors in numerous cancers. The primary purpose of this study is to determine the prognostic significance of TAMs in intrahepatic cholangiocarcinoma (ICC). Methods Immunohistochemical staining of CD68, CD86 and CD206 were performed in tissue microarrays containing 322 patients, who underwent surgical resection and were pathologically diagnosed with ICC. The prognostic value of CD68, CD86 and CD206 were evaluated by Kaplan–Meier analysis (log-rank test) and nomogram models. Results We demonstrated that the CD86+/CD206+ TAMs model was an independent prognostic index for ICC patients. Patients with low CD86+ TAMs and high CD206+ TAMs infiltration had a markedly worse prognosis and increased risk of post-operative recurrence when compared to high CD86+ TAMs and low CD206+ TAMs intratumoral infiltration. Furthermore, subgroup analysis indicated that the CD86+/CD206+ TAMs model predicted prognosis of ICC patients more powerfully than single macrophage immunomarker. Interestingly, the CD86+/CD206+ TAMs model could further distinguish prognosis of CA-199 negative ICC patients, who were generally presumed to have a more favorable outcome. In order to further perfect the prognostic value of the CD86+/CD206+ TAMs model, we constructed and validated a postoperative nomogram to predict overall survival and recurrence-free survival time in ICC patients. Conclusions These findings indicate that the CD86+/CD206+ TAMs model possess potential value as a novel prognostic indicator for ICC patients.
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Affiliation(s)
- Dalong Sun
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.,Department of Gastroenterology and Hepatology, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, China.,Shanghai Institute of Liver Disease, Shanghai, China
| | - Tiancheng Luo
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.,Shanghai Institute of Liver Disease, Shanghai, China
| | - Pingping Dong
- Department of Surgery, Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Ningping Zhang
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.,Shanghai Institute of Liver Disease, Shanghai, China
| | - Jing Chen
- Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Shuncai Zhang
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.,Shanghai Institute of Liver Disease, Shanghai, China
| | - Longzi Liu
- Department of General Surgery, The First Affliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Ling Dong
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.,Shanghai Institute of Liver Disease, Shanghai, China
| | - Si Zhang
- NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China
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Wang T, Kong J, Yang X, Shen S, Zhang M, Wang W. Clinical features of sarcomatoid change in patients with intrahepatic cholangiocarcinoma and prognosis after surgical liver resection: A Propensity Score Matching analysis. J Surg Oncol 2019; 121:524-537. [PMID: 31867746 DOI: 10.1002/jso.25815] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Accepted: 12/10/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma with sarcomatoid change (iCCA-SC) is a rare histological subtype of iCCA, the clinical features and outcomes after surgical resection on the prognosis is still unknown. METHODS We retrospectively reviewed the clinical data of patients with histologically proven iCCA who underwent curative liver resection at our hospital between January 2008 and December 2018. Propensity score matching analysis was used to match patients with and without sarcomatoid change at a ratio of 1:4. The nomogram integrating all significant independent factors for overall survival (OS) and recurrence-free survival (RFS) was constructed to predict prognosis for iCCA. The predictive accuracy ability of the nomogram was determined by Harrell's index (C-index). RESULTS A total of 40 iCCA-SC and 160 ordinary iCCA patients were included in this study. RFS and OS in the iCCA-SC group were significantly lower than those in the ordinary iCCA group (P<.001 and P = .002, respectively). The calibration curve for the probability of survival showed good agreement between the nomogram prediction and actual observation. CONCLUSION The histological sarcomatoid subtype is an independent predictor of tumor recurrence and shorter OS in iCCA patients. The nomogram we established could provide more accurate prognostic prediction for iCCA patients.
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Affiliation(s)
- Tao Wang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China
| | - Junjie Kong
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China
| | - Xianwei Yang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China
| | - Shu Shen
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China
| | - Menglan Zhang
- Department of Pathology, West China Hospital of Sichuan University, Chengdu, China
| | - Wentao Wang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China
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Zhou KQ, Liu WF, Yang LX, Sun YF, Hu J, Chen FY, Zhou C, Zhang XY, Peng YF, Yu L, Zhou J, Fan J, Wang Z. Circulating osteopontin per tumor volume as a prognostic biomarker for resectable intrahepatic cholangiocarcinoma. Hepatobiliary Surg Nutr 2019; 8:582-596. [PMID: 31929985 DOI: 10.21037/hbsn.2019.03.14] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Background The role of osteopontin (OPN) in intrahepatic cholangiocarcinoma (ICC) remains controversial. This study aimed to explore the prognostic value of OPN in patients with ICC undergoing curative resection. Methods Patients undergoing curative resection from 2005 to 2016 were identified for inclusion in this retrospective study. The expression level of OPN in tumors was measured in each of the 228 patients by immunohistochemistry. Circulating OPN in serum was tested in 124 patients by ELISA. Tumor volume was calculated according to preoperative imaging or operation record. Proliferation assay, wound healing assay, and invasion assay were performed to investigate the biological function. Results Low expression of OPN in tissue was associated with lymph node metastasis (P=0.009) and shorter overall survival (OS) (P=0.001). A low level of circulating OPN/volume was associated with multiple tumors (P<0.001), vascular invasion (P=0.027), visceral peritoneal perforation (P=0.001), and lymph node metastasis (P=0.002). It was also able to predict the invasive behavior, lymph node metastasis, and early recurrence with the area under the receiver operating curve (AUC) of being 0.719, 0.708 and 0.622 respectively. Patients with a low level of circulating OPN/volume had shorter OS (P=0.028) and disease-free survival (DFS) (P=0.004) and could benefit from adjuvant chemotherapy (P=0.011). Compared with negative controlled cells, ICC cell lines, which expressed more OPN, showed a decelerated proliferation rate, the weaker ability of migration and invasion, while the opposite was true for the cells expressed less OPN. MMP1, MMP10, and CXCR4 were negatively regulated by OPN. Conclusions A low level of circulating OPN/volume could indicate aggressive characteristics, along with poor prognosis and efficacy of adjuvant chemotherapy in ICC patients. Over expression of OPN may inhibit phenotypes facilitating ICC metastasis by negatively regulating MMP1, MMP10, and CXCR4.
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Affiliation(s)
- Kai-Qian Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai 200032, China
| | - Wei-Feng Liu
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai 200032, China.,Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Liu-Xiao Yang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai 200032, China
| | - Yun-Fan Sun
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai 200032, China.,Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jie Hu
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai 200032, China.,Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Fei-Yu Chen
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai 200032, China
| | - Cheng Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai 200032, China
| | - Xiang-Yu Zhang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai 200032, China
| | - Yuan-Fei Peng
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai 200032, China.,Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Lei Yu
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai 200032, China.,Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jian Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai 200032, China.,Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.,Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
| | - Jia Fan
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai 200032, China.,Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.,Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
| | - Zheng Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai 200032, China.,Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Qiu B, Chen T, Sun R, Liu Z, Zhang X, Li Z, Xu Y, Zhang Z. Sprouty4 correlates with favorable prognosis in perihilar cholangiocarcinoma by blocking the FGFR-ERK signaling pathway and arresting the cell cycle. EBioMedicine 2019; 50:166-177. [PMID: 31761616 PMCID: PMC6921364 DOI: 10.1016/j.ebiom.2019.11.021] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 11/09/2019] [Accepted: 11/12/2019] [Indexed: 12/22/2022] Open
Abstract
Background Perihilar cholangiocarcinoma (PHCC) is the most common subtype of cholangiocarcinoma(CCA). We previously investigated the expression pattern of Sprouty(SPRY) in intrahepatic cholangiocarcinoma(ICC), but the expression and clinical significance of SPRY family members in PHCC are still unknown. Methods The expression of SPRY family members(SPRY1-4) was detected in different subtypes of CCA and corresponding adjacent tissues. SPRY4 expression in 142 cases of PHCC was detected by immunohistochemistry, and its clinical significance was evaluated using univariate and multivariate analyses. The functions of SPRY4 in the FGFR-induced proliferation and migration of PHCC cells were investigated through in vitro and in vivo experiments. We further investigated the effects and mechanisms of SPRY4 on FGFR-induced ERK phosphorylation and cell cycle distribution in the presence of FGFR and ERK inhibitors. Findings SPRY4 was the only SPRY family member associated with PHCC prognosis, and it was identified as an independent factor predicting favorable prognosis. In PHCC, SPRY4 expression was extensively associated with FGFR2, and its expression can be induced by ectopic FGFR2 activation. Through in vitro and in vivo experiments, we demonstrated that SPRY4 suppressed FGFR-induced proliferation and migration by inhibiting ERK phosphorylation. Moreover, SPRY4 knockdown was shown to decrease the percentage of cells in the G1 phase and promote the percentage of cells in the S and G2/M phases by increasing cyclin D1 expression, which also required FGFR-induced ERK phosphorylation. Interpretation High expression of SPRY4 was an independent biomarker of favorable prognosis in PHCC. SPRY4 expression can be induced by ectopic FGFR2 activation in PHCC. SPRY4 arrested the cell cycle at G1 phase and suppressed FGFR-induced proliferation and migration by inhibiting ERK phosphorylation, indicating that SPRY4 may be a potential therapeutic target in PHCC.
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Affiliation(s)
- Bo Qiu
- Department of General Surgery, Qilu Hospital of Shandong University, 107 Wenhua Road, Jinan, Shandong, China
| | - Tianli Chen
- Department of General Surgery, Qilu Hospital of Shandong University, 107 Wenhua Road, Jinan, Shandong, China
| | - Rongqi Sun
- Department of General Surgery, Qilu Hospital of Shandong University, 107 Wenhua Road, Jinan, Shandong, China
| | - Zengli Liu
- Department of General Surgery, Qilu Hospital of Shandong University, 107 Wenhua Road, Jinan, Shandong, China
| | - Xiaoming Zhang
- Department of General Surgery, Linyi People's Hospital, Linyi, China
| | - Zhipeng Li
- Department of General Surgery, Shandong Provincial Hospital, Jinan, China
| | - Yunfei Xu
- Department of General Surgery, Qilu Hospital of Shandong University, 107 Wenhua Road, Jinan, Shandong, China.
| | - Zongli Zhang
- Department of General Surgery, Qilu Hospital of Shandong University, 107 Wenhua Road, Jinan, Shandong, China.
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Moustafa M, Fasolo E, Bassi D, D'amico FE, Gringeri E, Pawlik TM, Cillo U. The impact of liver resection on survival for locally advanced intrahepatic cholangiocarcinoma tumors: A propensity score analysis. Eur J Surg Oncol 2019; 46:632-637. [PMID: 31812289 DOI: 10.1016/j.ejso.2019.11.502] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Revised: 11/11/2019] [Accepted: 11/15/2019] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Aim of work was to investigate the prognostic impact of liver resection (LR) on locally advanced Intrahepatic Cholangiocarcinoma (IC) in comparison to alternative palliative chemotherapy (CTx). METHOD A retrospective cohort study performed utilizing Surveillance, Epidemiology, and End Results (SEER) database to identify Locally advanced IC patients. Based on the American Joint Committee on Cancer (AJCC) Staging System, locally advanced IC was defined as: Stage III and IVa - 7th edition (7th-ed) or stage III - 8th edition (8th-ed). Study population were sub-classified into: LR group and a propensity score (PS) matched CTx group. RESULTS In 7th-ed module, the median survival for LR group (n = 154) was 35 months, and the 3-year survival rate was 40.8%. In PS matched CTx group (n = 154); the median survival was 14 months and the 3-year survival rate was 5.5% (P = 0.007). Survival rates were superior for LR group over PS matched CTx group in 8th-ed module as well. Worse prognosis has been reported in LR patients above 65 years old (HR 2.618, P = 001) and in multifocal lesions (HR 1.890, P = 0.025). CONCLUSION Hepatic resection was associated with a favorable impact on prognosis over chemotherapy for IC stage III and IVa of the 7th edition and for stage IIIb of 8th edition of AJCC staging system. Worse outcome has been observed in LR patients >65 years and with multifocal lesions. Randomized control studies are recommended to confirm the role of surgical resection in the management for advanced cases of IC, and to clarify the related prognostic factors.
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Yu W, Hu C, Shui Y, Wu K, Zhang L, Chen Y, Li C, Xu J, Wei Q. Failure patterns after curative resection for intrahepatic cholangiocarcinoma: possible implications for postoperative radiotherapy. BMC Cancer 2019; 19:1108. [PMID: 31727017 PMCID: PMC6857295 DOI: 10.1186/s12885-019-6328-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Accepted: 11/04/2019] [Indexed: 01/06/2023] Open
Abstract
Background To explore the patterns of failures and areas at highest risk of recurrence for postoperative intrahepatic cholangiocarcinoma (IHCC), with the aim to guide IHCC adjuvant radiotherapy. Methods Patients with IHCC who had undergone radical surgery at our institution from July 2010 to August 2017 were retrospectively analyzed. The survival and prognostic factors were analyzed by univariate and multivariate analysis. All sites of recurrence were found out and classified as the surgical margin, regional lymph nodes, liver remnant and distant metastasis. According to the recurring area at highest risk, the target volume of adjuvant radiotherapy was proposed. Results The median follow-up time was 23.5 months (2–85 months). The median recurrence free survival (RFS) and overall survival (OS) were 12.1 months and 24.8 months, respectively. Seventy-three (73/127, 57.5%) IHCC patients developed tumor recurrence. Initial recurrences occurred in the potential postoperative radiotherapy (PORT) volume, remnant liver and distant sits were 46 (46/73, 63.0%), 36 (36/73, 49.3%) and 22 (22/73, 30.1%) cases, respectively. Of the 46 patients whose initial recurrence inside the potential PORT volume, 29 (29/73, 39.7%) developed recurrence only inside the potential PORT volume, including 13 tumor bed recurrences, 7 lymph node metastases, and 9 with both tumor bed recurrences and lymph node metastases. The most common lymph node metastases sites were nodes around the abdominal aorta, followed by lymph nodes along the celiac artery, the common hepatic artery, and in the hepatoduodenal ligament. Conclusions High proportion of the recurrences occurred only inside the potential PORT volume, implying adjuvant radiotherapy might improve the local-regional control. Surgical margins and lymph node stations No.16a2, 9, 8, 12, 13, and 14 are suggested to be included in the radiation volume.
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Affiliation(s)
- Wei Yu
- Department of Radiation Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Jiefang Road 88, Hangzhou, 310009, People's Republic of China.,Ministry of Education Key Laboratory of Cancer Prevention and Intervention, Zhejiang University School of Medicine, Hangzhou, 310009, People's Republic of China
| | - Chunxiu Hu
- Department of Radiation Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Jiefang Road 88, Hangzhou, 310009, People's Republic of China.,Department of Radiation Oncology, Zhejiang Quhua Hospital, Quzhou, 324000, People's Republic of China
| | - Yongjie Shui
- Department of Radiation Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Jiefang Road 88, Hangzhou, 310009, People's Republic of China
| | - Kui Wu
- Department of Radiation Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Jiefang Road 88, Hangzhou, 310009, People's Republic of China
| | - Lili Zhang
- Department of Radiation Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Jiefang Road 88, Hangzhou, 310009, People's Republic of China
| | - Ying Chen
- Department of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, People's Republic of China
| | - Chao Li
- Department of Radiation Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Jiefang Road 88, Hangzhou, 310009, People's Republic of China
| | - Jing Xu
- Department of Radiation Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Jiefang Road 88, Hangzhou, 310009, People's Republic of China
| | - Qichun Wei
- Department of Radiation Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Jiefang Road 88, Hangzhou, 310009, People's Republic of China. .,Ministry of Education Key Laboratory of Cancer Prevention and Intervention, Zhejiang University School of Medicine, Hangzhou, 310009, People's Republic of China.
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Yugawa K, Itoh S, Kurihara T, Yoshiya S, Mano Y, Takeishi K, Harada N, Ikegami T, Soejima Y, Mori M, Yoshizumi T. Skeletal muscle mass predicts the prognosis of patients with intrahepatic cholangiocarcinoma. Am J Surg 2019; 218:952-958. [DOI: 10.1016/j.amjsurg.2019.03.010] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 02/15/2019] [Accepted: 03/08/2019] [Indexed: 12/16/2022]
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Ejaz A, Cloyd JM, Pawlik TM. Advances in the Diagnosis and Treatment of Patients with Intrahepatic Cholangiocarcinoma. Ann Surg Oncol 2019; 27:552-560. [PMID: 31555936 DOI: 10.1245/s10434-019-07873-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Indexed: 12/27/2022]
Abstract
Intrahepatic cholangiocarcinoma (ICC) is an aggressive biliary tract cancer (BTC) that arises from the biliary tract epithelium distal to the secondary biliary radicals. Over the past decade, significant advances have been made in the diagnosis, staging, and treatment of ICC. Emerging data have highlighted the importance of lymphadenectomy for elucidating patient prognosis as well as the at-risk nodal basins based on tumor location (de Jong et al. in J Clin Oncol 29(23):3140-3145, 2011). Several large randomized controlled trials have recently been published clarifying the role of adjuvant therapy for BTCs (Cloyd and Pawlik in J Oncol Pract 14(12):723-724, 2018). In addition, the molecular understanding of ICC pathogenesis has increased over time, leading to new potential molecular biomarkers and opening opportunities for novel targeted and immunologic therapies (Rizvi et al. in Nat Rev Clin Oncol 15(2):95-111, 2018). These recent advances serve to only improve our understanding of the optimal multidisciplinary treatment of this difficult disease.
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Affiliation(s)
- Aslam Ejaz
- James Cancer Center, The Ohio State University, Columbus, OH, USA. .,Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
| | - Jordan M Cloyd
- James Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Timothy M Pawlik
- James Cancer Center, The Ohio State University, Columbus, OH, USA
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Addeo P, Jedidi I, Locicero A, Faitot F, Oncioiu C, Onea A, Bachellier P. Prognostic Impact of Tumor Multinodularity in Intrahepatic Cholangiocarcinoma. J Gastrointest Surg 2019; 23:1801-1809. [PMID: 30478531 DOI: 10.1007/s11605-018-4052-y] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Accepted: 11/07/2018] [Indexed: 01/31/2023]
Abstract
BACKGROUND The prognostic value of tumor multinodularity in intrahepatic cholangiocarcinoma (ICC) remains debated. We aimed to evaluate the impact of tumor multinodularity according to the presence and distribution of multiples ICC's nodules. METHODS A retrospective review of a prospectively maintained database of patients undergoing resection for ICC from January 1995 to September 2017 was performed. Prognostic factors for survival were assessed by multivariate Cox analysis. Tumoral nodules were defined according to their number (single and multiple) and localization (satellites and contralateral). RESULTS Out of 120 selected patients, 64 (53%) had single and 56 (47%) had multiple lesions. Multiple lesions included tumors with satellites (n = 40; 71.5%) and tumors with contralateral lesions (n = 16; 28.5%). Patients with multiple tumors had significantly larger mean main lesion size (p = 0.02), required a higher rate of perioperative transfusion (p = 0.04), had a greater rate of lymph node involvement (p < 0.0001), vascular invasion (p = 0.04), and poor differentiation (p = 0.04) than single tumors. Patients with single tumors experienced a 5-year survival significantly longer (40%) than patients with multiple tumors (14%; p = 0.004). Patients having tumors with satellites had inferior median overall survival and 5-year survival rates (20 months, 7%) compared with patients with contralateral tumors (33.6 months, 29%) (p = 0.09). Multivariable analysis identified tumor multinodularity, morbidity, tumor size < 5 cm, poor differentiation, and lymph node involvement as independent prognostic factors for overall survival. CONCLUSIONS Tumor multinodularity represents an independent risk factor for survival in ICCs and identifies a category of patients in need of more effective perioperative treatment.
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Affiliation(s)
- Pietro Addeo
- Hepato-Pancreato-Biliary Surgery and Liver transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, 1, Avenue Molière, 67098, Strasbourg, France.
| | - Issam Jedidi
- Hepato-Pancreato-Biliary Surgery and Liver transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, 1, Avenue Molière, 67098, Strasbourg, France
| | - Andrea Locicero
- Hepato-Pancreato-Biliary Surgery and Liver transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, 1, Avenue Molière, 67098, Strasbourg, France
| | - François Faitot
- Hepato-Pancreato-Biliary Surgery and Liver transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, 1, Avenue Molière, 67098, Strasbourg, France
| | - Constantin Oncioiu
- Hepato-Pancreato-Biliary Surgery and Liver transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, 1, Avenue Molière, 67098, Strasbourg, France
| | - Alina Onea
- Department of Pathology, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France
| | - Philippe Bachellier
- Hepato-Pancreato-Biliary Surgery and Liver transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, 1, Avenue Molière, 67098, Strasbourg, France
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Liu J, Zhong M, Feng Y, Zeng S, Wang Y, Xu H, Zhou H. Prognostic Factors and Treatment Strategies for Intrahepatic Cholangiocarcinoma from 2004 to 2013: Population-Based SEER Analysis. Transl Oncol 2019; 12:1496-1503. [PMID: 31446308 PMCID: PMC6717067 DOI: 10.1016/j.tranon.2019.05.020] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Revised: 05/21/2019] [Accepted: 05/23/2019] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND: Seventy percent of intrahepatic cholangiocarcinoma (ICC) patients are inoperable. Treatment for unresectable patients is essential to improve poor survival. AIMS: We aimed to evaluate the prognostic factors for ICC patients, and investigate the potential treatment strategies for unresectable patients. METHODS: ICC patients were identified in SEER registry in 2004–2013. Univariate and multivariate Cox proportional hazard regression analysis were performed to evaluate the effect of treatment strategies. RESULTS: Of 2248 cases diagnosed in 2010–2013 and staged according to the American Joint Committee on Cancer (AJCC) 7th edition, 1706 (76.13%) did not receive cancer-directed surgery. This portion increased compared to those diagnosed between 2004 and 2009 and staged according to the AJCC 6th edition (72.87%). In addition, the percentage of stage 4 cases increased, while stage 3 cases decreased, because AJCC 7th staging system categorized both T4 and N1 patients into stage IV, which were previously categorized into stage III by AJCC 6th staging system. Patients with radiofrequency ablation (RFA) showed a poorer survival in 2004–2009 (P = .0213), but an almost the same survival as patients with tumor resection in 2010–2013 (P = .51), suggesting that RFA performed better in recent years. Lymphadenectomy showed protective effect for unresectable patients. Radiotherapy improved cancer-specific survival in non-surgery patients (P < .0001).The proportion of stage IV patients increased tremendously from 37.4% in 2004–2009 to 58.7% in 2010–2013. Among 1319 stage IV patients (2010–2013), surgery at distant metastatic sites improved cancer-specific survival. CONCLUSIONS: For unresectable tumors, RFA, radiotherapy, lymphadenectomy, and surgery of distant metastases showed significant benefits to improve cancer-specific survival.
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Affiliation(s)
- Jieqiong Liu
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, China.
| | - Meizuo Zhong
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, China.
| | - Yuhua Feng
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, China.
| | - Shan Zeng
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, China.
| | - Yikai Wang
- Department of Biostatistics and Bioinformatics, Emory University Rollins School of Public Health, Atlanta, 30322, US.
| | - Hongbo Xu
- Department of Surgery The third Xiangya Hospital, Central South University, Changsha, 4100013, China.
| | - Hui Zhou
- Affiliated Cancer Hospital of Xiangya Medical School, Central South University / Hunan Cancer Hospital, Changsha, 410013, China.
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Yoon SB, Choi MH, Song M, Lee JH, Lee IS, Lee MA, Hong TH, Jung ES, Choi M. Impact of preoperative body compositions on survival following resection of biliary tract cancer. J Cachexia Sarcopenia Muscle 2019; 10:794-802. [PMID: 31037838 PMCID: PMC6711415 DOI: 10.1002/jcsm.12431] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Accepted: 03/18/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Although surgical resection is the only potentially curative treatment for biliary tract cancer, the prognosis remains poor after a major operation such as pancreatoduodenectomy or hepatectomy. We aimed to investigate the impact of preoperative body compositions on long-term survival of patients undergoing resection of biliary tract cancer. METHODS We analysed data of patients diagnosed with biliary tract cancer who underwent surgery from 2009 to 2015. Skeletal muscle area, skeletal muscle radiation attenuation, and visceral and subcutaneous adipose tissue areas were measured from the computed tomography images at L3 vertebral levels obtained before resection of cancer. Patients were divided into two groups based on the sex-specific median values for each parameter, and long-term survival was compared between the groups. RESULTS A total of 371 patients (women, 39.6%; mean age, 66.2 ± 9.6 years) were finally included in the analysis. Patients with low skeletal muscle index (SMI) had significantly shorter median survival than those with high SMI (29 vs. 39 months; P = 0.026). Patients with low skeletal muscle attenuation (SMA) also showed reduced survival compared with those with high SMA (median survival 25 vs. 60 months; P = 0.002). Combining these two factors, survival was highest in the high SMI/high SMA group (reference) and lowest in the low SMI/low SMA group (hazard ratio, 2.18; 95% confidence interval, 1.44-3.30). Visceral and subcutaneous adipose tissue areas were not associated with long-term survival. CONCLUSIONS Low SMI and low SMA on computed tomography scan have a negative impact on survival after resection of biliary tract cancer. They can be used in preoperative risk assessment to assist in treatment decision making.
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Affiliation(s)
- Seung Bae Yoon
- Cancer Research Institute, College of MedicineThe Catholic University of KoreaSeoulKorea
- Department of Internal Medicine, College of MedicineThe Catholic University of KoreaSeoulKorea
| | - Moon Hyung Choi
- Cancer Research Institute, College of MedicineThe Catholic University of KoreaSeoulKorea
- Department of Radiology, College of MedicineThe Catholic University of KoreaSeoulKorea
| | - Meiying Song
- Cancer Research Institute, College of MedicineThe Catholic University of KoreaSeoulKorea
| | - Ju Hyun Lee
- Department of Internal Medicine, College of MedicineThe Catholic University of KoreaSeoulKorea
| | - In Seok Lee
- Department of Internal Medicine, College of MedicineThe Catholic University of KoreaSeoulKorea
| | - Myung Ah. Lee
- Cancer Research Institute, College of MedicineThe Catholic University of KoreaSeoulKorea
- Department of Internal Medicine, College of MedicineThe Catholic University of KoreaSeoulKorea
| | - Tae Ho Hong
- Department of Surgery, College of MedicineThe Catholic University of KoreaSeoulKorea
| | - Eun Sun Jung
- Department of Hospital Pathology, College of MedicineThe Catholic University of KoreaSeoulKorea
| | - Myung‐Gyu Choi
- Department of Internal Medicine, College of MedicineThe Catholic University of KoreaSeoulKorea
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Ma K, Dong B, Wang L, Zhao C, Fu Z, Che C, Liu W, Yang Z, Liang R. Nomograms for predicting overall survival and cancer-specific survival in patients with surgically resected intrahepatic cholangiocarcinoma. Cancer Manag Res 2019; 11:6907-6929. [PMID: 31440084 PMCID: PMC6664419 DOI: 10.2147/cmar.s212149] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2019] [Accepted: 07/04/2019] [Indexed: 12/25/2022] Open
Abstract
Purpose To develop and validate nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) in patients with surgically resected intrahepatic cholangiocarcinoma (ICC). Patients and methods The nomograms were developed using a development cohort of 947 ICC patients after surgery selected from Surveillance, Epidemiology, and End Results database, and externally validated using a training cohort of 159 patients admitted at our institution. Nomograms for OS and CSS were established based on the independent prognostic factors identified by COX regression models and Fine and Grey’s models, respectively. The performance of the nomograms was validated internally and externally by using the concordance index (c-index), and calibration plot, and compared with that of AJCC 8th edition TNM staging system by using c-index and decision curve analysis. Results Age, T stage, M stage, lymph node ratio (LNR) level and tumor grade were independent prognostic predictors for OS in ICC patients, while T stage, M stage, LNR level and tumor grade were independent prognostic predictors for CSS. Nomogram predicting OS was with a c-index of 0.751 on internal validation and 0.725 up to external validation, while nomogram for CSS was with a c-index of 0.736 on internal validation and 0.718 up to external validation. Calibration plots exhibited that the nomograms-predicted and actual OS/CSS probabilities were fitted well on both internal and external validation. Additionally, the nomograms exhibited superiority over AJCC 8th edition TNM staging system with higher c-indices and net benefit gains, in predicting OS and CSS in ICC patients after surgery. Conclusion The constructed nomograms could predict OS and CSS with good performance, which could be served as an effective tool for prognostic evaluation and individual treatment strategies optimization in ICC patients after surgery in clinical practice.
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Affiliation(s)
- Kexin Ma
- Department of Hepatobiliary Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - Bing Dong
- Department of Hepatobiliary Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - Liming Wang
- Department of Hepatobiliary Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - Chongyu Zhao
- Department of Hepatobiliary Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - Zhaoyu Fu
- Department of Hepatobiliary Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - Chi Che
- Department of Hepatobiliary Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - Wuguang Liu
- Department of Hepatobiliary Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - Zexuan Yang
- Department of Hepatobiliary Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - Rui Liang
- Department of Hepatobiliary Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
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Zhou M, Ling W, Luo Y. Intrahepatic mass-forming cholangiocarcinoma growing in a giant hepatic hemangioma: A case report. Medicine (Baltimore) 2019; 98:e16410. [PMID: 31277198 PMCID: PMC6635132 DOI: 10.1097/md.0000000000016410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Revised: 05/09/2019] [Accepted: 06/13/2019] [Indexed: 02/05/2023] Open
Abstract
RATIONALE Hepatic hemangioma (HH) is a common benign tumor with a high number of normal or abnormal blood vessels. Intrahepatic cholangiocarcinoma (ICC) is a relatively common malignant primary hepatic carcinoma (10%-15%) with high incidence rate and high fatality, yet low discovery rate in the early stages. Ultrasonography (US), computed tomography, and magnetic resonance imaging (MRI) are frequently used and indispensable imaging techniques for the diagnosis of hepatic lesions. It is possible to differentiate a liver lesion from HH with high accuracy owing to their different patterns and hemodynamic characteristics. PATIENT CONCERNS A 59-year-old Asian woman was referred to hospital for a hepatic mass, which was 9.0 × 6.5 cm in size, The patient was tested positive for hepatitis B antigen but negative for serum alpha-fetoprotein and carbohydrate antigen 199 and had a slightly elevated carcinoembryonic antigen level (3.56 ng/ml). DIAGNOSIS Liver US and MRI were performed. Grey-scale US revealed a huge heterogeneous mass on the right lobe with a point and line-like blood flow signal on Doppler US. Dynamic contrast-enhanced MRI showed heterogeneous annular nodular enhancement in the arterial phase. An initial diagnosis of HH was made based on the clinical history and imaging results; however, histopathologic examination of the liver lesions revealed modest to severe atypical hyperplasia of intrahepatic bile duct epithelium, cancerization, and mid to high differentiated mass-forming type cholangiocarcinoma combined with focal organized hemangioma. INTERVENTIONS The intrahepatic mass-forming cholangiocarcinoma (IMCC) lesion was considered a focal organization of hemangioma during operation and was surgically removed. No routine chemotherapy was performed after the operation. OUTCOMES The IMCC recurred 23 months after surgery, with elevated serum CA19-9 and CA125. Liver damage was evident, and the patient developed jaundice. The patient was discharged without active treatment and died in 4 months. LESSONS Although preoperative imaging of focal hepatic lesions is indispensable, intraoperative frozen section analysis and histopathological examination remain essential for definitive diagnosis. This is particularly important for high-risk patients and those with suspected malignancy.
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Transcription factor 7 promotes the progression of perihilar cholangiocarcinoma by inducing the transcription of c-Myc and FOS-like antigen 1. EBioMedicine 2019; 45:181-191. [PMID: 31248836 PMCID: PMC6642257 DOI: 10.1016/j.ebiom.2019.06.023] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 06/09/2019] [Accepted: 06/13/2019] [Indexed: 01/03/2023] Open
Abstract
Background Perihilar cholangiocarcinoma (PHCC) is the most common type of cholangiocarcinoma with the worst prognosis. Radical resection of PHCC is difficult; thus, few effective biomarkers or useful molecular profiles for PHCC have been reported in recent years. Therefore, in this study, we aimed to assess biomarkers for PHCC. Methods We screened potential biomarkers for PHCC using exome and transcriptome sequencing with PHCC tissues and paired normal tissues. Transcription factor 7 (TCF7) expression was evaluated using quantitative reverse transcription polymerase chain reaction, western blotting, and immunohistochemistry. The correlations between TCF7 and clinicopathological factors were analyzed with Chi-square test, and the prognostic significance of TCF7 was evaluated with univariate and multivariate analyses. The functions of TCF7 and its main effectors in PHCC cells were investigated in vitro and in vivo. Findings TCF7 expression was upregulated in PHCC and was an unfavorable prognostic biomarker. c-Myc was a main effector of TCF7 in PHCC cells and modulated TCF7-induced proliferation, invasion, and migration. FOS-like antigen 1 (FOSL1) was identified as a downstream target of TCF7 and was required in TCF7-induced PHCC proliferation. Triple-positive expression of TCF7, c-Myc, and FOSL1 predicted a much worse prognosis in patients with PHCC than TCF7 expression alone. Interpretation Postoperative detection of TCF7, c-Myc, and FOSL1 may be useful for stratifying patients with a high risk of unfavorable prognosis, and suppressing TCF7 or its downstream effectors may be a promising strategy for the treatment of PHCC.
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Cheng Z, Lei Z, Shen F. Coming of a precision era of the staging systems for intrahepatic cholangiocarcinoma? Cancer Lett 2019; 460:10-17. [PMID: 31212000 DOI: 10.1016/j.canlet.2019.114426] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Revised: 05/02/2019] [Accepted: 06/04/2019] [Indexed: 02/08/2023]
Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer. Appropriate treatment of this aggressive and heterogeneous cancer requires accurate staging and prognostic stratification, as does patient selection for clinical trials. Over the past two decades, several staging systems and prognostic models for ICC have been developed. Most include independent prognostic factors such as tumor extent, clinical parameters and histopathological features and are inaccurate. Accumulating findings offer new insights into the genetic and molecular basis of ICC progression. Hence, staging systems and prognostic models that incorporate in clinicalpathological factors, molecular and genomic information, and tumor biomarkers, and hence more accurately estimate prognosis, will become a reality. This review summarizes the current staging systems and prognostic models for ICC and highlights the need to establish more precise and personalized systems and models that incorporate tumor biologic factors.
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Affiliation(s)
- Zhangjun Cheng
- Hepato-Pancreato-Biliary Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China; Department of Hepatic Surgery IV, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, 200438, China.
| | - Zhengqing Lei
- Hepato-Pancreato-Biliary Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China; Department of Hepatic Surgery IV, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, 200438, China
| | - Feng Shen
- Department of Hepatic Surgery IV, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, 200438, China.
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48
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Tian MX, Luo LP, Liu WR, Deng W, Yin JC, Jin L, Jiang XF, Zhou YF, Qu WF, Tang Z, Wang H, Tao CY, Fang Y, Qiu SJ, Zhou J, Liu JF, Fan J, Shi YH. Development and validation of a prognostic score predicting recurrence in resected combined hepatocellular cholangiocarcinoma. Cancer Manag Res 2019; 11:5187-5195. [PMID: 31239773 PMCID: PMC6556465 DOI: 10.2147/cmar.s195964] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Accepted: 03/19/2019] [Indexed: 01/27/2023] Open
Abstract
Purpose: To develop and validate a decision aid to help make individualized estimates of tumor recurrence for patients with resected combined hepatocellular cholangiocarcinoma (CHC). Patients and methods: Risk factors of recurrence were identified in the derivation cohort of 208 patients who underwent liver resection between 1995 and 2014 at Zhongshan Hospital to develop a prediction score. The model was subsequently validated in an external cohort of 101 CHC patients using the C concordance statistic and net reclassification index (NRI). Results: On multivariate analysis, five independent predictors associated with tumor recurrence were identified, including sex, γ-glutamyl transferase, macrovascular invasion, hilar lymphoid metastasis and adjuvant transcatheter arterial chemoembolization. The prediction score was constructed using these 5 variables, with scores ranging from 0 to 5. A patient with a score of 0 had a predicted 1- and 5-year recurrence risk of 11.1% and 22.2%, respectively. In the validation cohort, the NRIs of prediction score vs American Joint Committee on Cancer 7th TNM staging system at 1-year and 5-year were 0.185 (95% CI, 0.090-0.279, P<0.001) and 0.425 (95% CI, 0.044-0.806, P=0.03), respectively. Conclusion: Our developed and validated prediction score might be a simple and reliable method in postoperative CHC patients and help clinicians identify candidates who may benefit from future adjuvant therapies.
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Affiliation(s)
- Meng-Xin Tian
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, People's Republic of China
| | - Liu-Ping Luo
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China.,The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China
| | - Wei-Ren Liu
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, People's Republic of China
| | - Wei Deng
- Department of Health Statistics and Social Medicine, Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, People's Republic of China
| | - Jia-Cheng Yin
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, People's Republic of China
| | - Lei Jin
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, People's Republic of China
| | - Xi-Fei Jiang
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, People's Republic of China
| | - Yu-Fu Zhou
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, People's Republic of China
| | - Wei-Feng Qu
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, People's Republic of China
| | - Zheng Tang
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, People's Republic of China
| | - Han Wang
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, People's Republic of China
| | - Chen-Yang Tao
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, People's Republic of China
| | - Yuan Fang
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, People's Republic of China
| | - Shuang-Jian Qiu
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, People's Republic of China
| | - Jian Zhou
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, People's Republic of China.,Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China
| | - Jing-Feng Liu
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China.,The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China
| | - Jia Fan
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, People's Republic of China.,Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China
| | - Ying-Hong Shi
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, People's Republic of China
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Li S, Chai Y, Ding Y, Yuan T, Wu C, Huang C. CHD1L is associated with poor survival and promotes the proliferation and metastasis of intrahepatic cholangiocarcinoma. Oncol Rep 2019; 42:657-669. [PMID: 31173252 PMCID: PMC6610041 DOI: 10.3892/or.2019.7174] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Accepted: 05/17/2019] [Indexed: 12/29/2022] Open
Abstract
Chromodomain helicase/ATPase DNA-binding protein 1-like gene (CHD1L) is a new oncogene which has been confirmed to be crucial to the progression of many solid tumors. In the present study, the expression of CHD1L was found to be upregulated in intrahepatic cholangiocarcinoma (ICC), which was significantly associated with histological differentiation (P=0.011), vascular invasion (P=0.002), lymph node metastasis (P=0.008) and TNM stage (P=0.001). Kaplan-Meier survival analysis revealed that ICC patients with positive CHD1L expression had shorter overall and disease-free survival than those with negative CHD1L expression. Functional study found that CHD1L exhibited strong oncogenic roles, including increased cell growth by CCK-8 assay, colony formation by plate colony formation assay, G1/S transition by flow cytometry and tumor formation in nude mice. In addition, RNAi-mediated silencing of CHD1L inhibited ICC invasion and metastasis by wound healing, Transwell migration and Matrigel invasion assays in vitro and in vivo. Collectively, our results show that CHD1L is upregulated and promotes the proliferation and metastasis of ICC cells. CHD1L acts as an oncogene and may be a prognostic factor or therapeutic target for patients with ICC.
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Affiliation(s)
- Shimiao Li
- Department of Hepatobiliary Surgery, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi 330006, P.R. China
| | - Yi Chai
- Department of Neurosurgery, Shangrao People's Hospital, Shangrao, Jiangxi 334000, P.R. China
| | - Yanbao Ding
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Tinghao Yuan
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Changwen Wu
- Department of Urology Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Changwen Huang
- Department of Hepatobiliary Surgery, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi 330006, P.R. China
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50
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Ng KK, Cheung TT, Pang HH, Wong TC, Dai JW, Ma KW, She WH, Kotewall CN, Lo CM. A simplified prediction model for early intrahepatic recurrence after hepatectomy for patients with unilobar hepatocellular carcinoma without macroscopic vascular invasion: An implication for adjuvant therapy and postoperative surveillance. Surg Oncol 2019; 30:6-12. [PMID: 31500787 DOI: 10.1016/j.suronc.2019.05.017] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 05/03/2019] [Accepted: 05/18/2019] [Indexed: 01/27/2023]
Abstract
BACKGROUND An accurate prediction model of early recurrence of hepatocellular carcinoma (HCC) after hepatectomy is important to ascertain the postoperative adjuvant treatment and surveillance. METHODS This is a retrospective cohort study including 1125 patients with HCC underwent curative hepatic resection. They were randomly divided into training (n = 562) and validation (n = 563) sets. Early intrahepatic recurrence within 18 months from surgery is the primary outcome. In the training set, a prediction scoring model (Recurrent Liver Cancer Score RLCS) was developed, which was legitimised in the validation set. RESULTS RLCS was developed based on four clinicopathologic risk factors (serum alpha fetoprotein, tumor size, multiple tumors or satellite nodules, and microvascular invasion). Low-risk and high-risk groups had statistically significant differences in early recurrence rates (18% vs. 43.8%). The 5-year recurrence-free survival rates of low risk and high risk groups were 52.9% and 27.8%, respectively. This model showed good calibration and discriminatory ability in the validation set (c-index of 0.647). CONCLUSION RLCS is a user-friendly prediction scoring model which can accurately predict the occurrence of early intrahepatic recurrence of HCC. It establishes the basis of postoperative adjuvant treatment and surveillance in future studies.
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Affiliation(s)
- Kelvin K Ng
- Department of Surgery, The University of Hong Kong, Hong Kong.
| | - Tan-To Cheung
- Department of Surgery, The University of Hong Kong, Hong Kong; State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong
| | - Herbert H Pang
- School of Public Health, The University of Hong Kong, Hong Kong
| | - Tiffany C Wong
- Department of Surgery, The University of Hong Kong, Hong Kong; State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong
| | - Jeff W Dai
- Department of Surgery, The University of Hong Kong, Hong Kong
| | - Ka-Wing Ma
- Department of Surgery, The University of Hong Kong, Hong Kong
| | - Wong-Hoi She
- Department of Surgery, The University of Hong Kong, Hong Kong
| | | | - Chung-Mau Lo
- Department of Surgery, The University of Hong Kong, Hong Kong; State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong
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