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Bos AK, Willemsen AECAB, Visser LE, Stoker LJ, Kingma JS, Rommers MK, Kuck EM, van der Linden PD, van Nuland M. Palbociclib Is Safe for Breast Cancer Patients With Mild Hepatic Impairment: A Multicenter Retrospective Study Using Real-World Data. Clin Pharmacol Ther 2025; 117:1115-1122. [PMID: 39856030 DOI: 10.1002/cpt.3574] [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: 10/22/2024] [Accepted: 01/09/2025] [Indexed: 01/27/2025]
Abstract
The liver is crucial for metabolizing the anticancer drug palbociclib, but limited information is available on the impact of hepatic impairment on its toxicity and efficacy, with no real-world data available. This study aims to evaluate how hepatic impairment affects hematological toxicity and progression-free survival (PFS) of palbociclib in advanced hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer, using the National Cancer Institute scoring system, in a large real-world dataset. This multicenter retrospective observational study included female patients treated with palbociclib between August 2017 and February 2024. Regression analysis was used to compare the risk of developing grade 3/4 hematological toxicity and PFS between patients with normal and mild impaired liver function. In total, 478 female patients were included. Patients with mild hepatic impairment (n = 205) did not have an increased risk of developing grade 3/4 neutropenia compared with patients with normal hepatic function (n = 273) (hazard ratio (HR) = 1.11; 95% CI 0.83-1.47). In addition, the PFS was not significantly different between both groups (HR = 1.15; 95% CI 0.93-1.42). In real-world settings, patients with mild hepatic impairment do not have a higher risk of developing palbociclib-induced neutropenia or disease progression than patients with normal hepatic function. These findings can guide clinicians when treating breast cancer patients with mild hepatic impairment.
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Affiliation(s)
- Alieke K Bos
- Department of Clinical Pharmacy, Tergooi Medical Centre, Hilversum, The Netherlands
| | | | - Loes E Visser
- Department of Pharmacy, Haga Teaching Hospital, The Hague, The Netherlands
- Department of Hospital Pharmacy, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - Lennart J Stoker
- Department of Clinical Pharmacy, Haaglanden Medical Centre, The Hague, The Netherlands
| | - Jurjen S Kingma
- Department of Clinical Pharmacy, Hospital Group Twente, Almelo and Hengelo, The Netherlands
| | - Mirjam K Rommers
- Department of Pharmacy, Noordwest Ziekenhuisgroep, Alkmaar, The Netherlands
| | - Emile M Kuck
- Department of Hospital Pharmacy, Diakonessenhuis, Utrecht, The Netherlands
| | | | - Merel van Nuland
- Department of Clinical Pharmacy, Tergooi Medical Centre, Hilversum, The Netherlands
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Kim Y, Kang M, Mamo MG, Adisasmita M, Huch M, Choi D. Liver organoids: Current advances and future applications for hepatology. Clin Mol Hepatol 2025; 31:S327-S348. [PMID: 39722609 PMCID: PMC11925438 DOI: 10.3350/cmh.2024.1040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 12/24/2024] [Indexed: 12/28/2024] Open
Abstract
The creation of self-organizing liver organoids represents a significant, although modest, step toward addressing the ongoing organ shortage crisis in allogeneic liver transplantation. However, researchers have recognized that achieving a fully functional whole liver remains a distant goal, and the original ambition of organoid-based liver generation has been temporarily put on hold. Instead, liver organoids have revolutionized the field of hepatology, extending their influence into various domains of precision and molecular medicine. These 3D cultures, capable of replicating key features of human liver function and pathology, have opened new avenues for human-relevant disease modeling, CRISPR gene editing, and high-throughput drug screening that animal models cannot accomplish. Moreover, advancements in creating more complex systems have led to the development of multicellular assembloids, dynamic organoid-on-chip systems, and 3D bioprinting technologies. These innovations enable detailed modeling of liver microenvironments and complex tissue interactions. Progress in regenerative medicine and transplantation applications continues to evolve and strives to overcome the obstacles of biocompatibility and tumorigenecity. In this review, we examine the current state of liver organoid research by offering insights into where the field currently stands, and the pivotal developments that are shaping its future.
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Affiliation(s)
- Yohan Kim
- Department of MetaBioHealth, Sungkyunkwan University, Suwon, Korea
- Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon, Korea
- Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, Suwon, Korea
| | - Minseok Kang
- Department of Surgery, Hanyang University College of Medicine, Seoul, Korea
| | - Michael Girma Mamo
- Department of Surgery, Hanyang University College of Medicine, Seoul, Korea
- Research Institute of Regenerative Medicine and Stem Cells, Hanyang University, Seoul, Korea
| | - Michael Adisasmita
- Department of Surgery, Hanyang University College of Medicine, Seoul, Korea
- Research Institute of Regenerative Medicine and Stem Cells, Hanyang University, Seoul, Korea
| | - Meritxell Huch
- Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
| | - Dongho Choi
- Department of Surgery, Hanyang University College of Medicine, Seoul, Korea
- Research Institute of Regenerative Medicine and Stem Cells, Hanyang University, Seoul, Korea
- Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul, Korea
- Department of HY-KIST Bio-convergence, Hanyang University, Seoul, Korea
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Badran O, Cohen I, Bar-Sela G. The Impact of Iron on Cancer-Related Immune Functions in Oncology: Molecular Mechanisms and Clinical Evidence. Cancers (Basel) 2024; 16:4156. [PMID: 39766056 PMCID: PMC11674619 DOI: 10.3390/cancers16244156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Revised: 12/08/2024] [Accepted: 12/10/2024] [Indexed: 01/11/2025] Open
Abstract
Iron metabolism plays a dual role in cancer, serving as an essential nutrient for cellular functions and a potential catalyst for tumor growth and immune evasion. Here, we cover the complex interplay between iron levels within the serum or in the microenvironment and cancer therapy, focusing on how iron deficiency and overload can impact immune function, tumor progression, and treatment efficacy. On the one hand, we highlight iron deficiency as a factor of primary immune responses and its adverse effects on anti-cancer immunotherapy efficacy. On the other hand, we also stress the impact of iron overload as an essential factor contributing to tumor growth, creating a suppressive tumor microenvironment that hinders immune checkpoint inhibitor immunotherapy. Overall, we emphasize the necessity of the personalized management of iron levels in oncology patients as a critical element in treatment optimization to achieve favorable outcomes. Based on these considerations, we believe that close and careful monitoring and the tailored balancing of iron supplementation strategies should be the subject of further clinical studies, and routine iron management should be implemented in oncology clinical practice and integrated into cancer therapy protocols.
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Affiliation(s)
- Omar Badran
- Department of Oncology, Emek Medical Center, Afula 1834111, Israel; (O.B.); (I.C.)
- Technion Integrated Cancer Center, Faculty of Medicine, Technion, Haifa 3525422, Israel
| | - Idan Cohen
- Department of Oncology, Emek Medical Center, Afula 1834111, Israel; (O.B.); (I.C.)
| | - Gil Bar-Sela
- Department of Oncology, Emek Medical Center, Afula 1834111, Israel; (O.B.); (I.C.)
- Technion Integrated Cancer Center, Faculty of Medicine, Technion, Haifa 3525422, Israel
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Gamal RM, Hazem SH, Hamed MF, Abdelaziz RR. PI3K inhibitor "alpelisib" alleviates methotrexate induced liver injury in mice and potentiates its cytotoxic effect against MDA-MB-231 triple negative breast cancer cell line. Toxicol Appl Pharmacol 2024; 488:116979. [PMID: 38797265 DOI: 10.1016/j.taap.2024.116979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 05/15/2024] [Accepted: 05/23/2024] [Indexed: 05/29/2024]
Abstract
Hepatotoxicity is the main off-target effect of methotrexate (MTX) limiting its effective clinical use. Besides, MDA-MB231 breast cancer cells show chemoresistance, partly via PI3K/AKT pathway. Therefore, we investigated the ameliorative potentials of the PI3K inhibitor, alpelisib (ALP) on MTX-induced hepatotoxicity (in vivo) and the restraining potentials of ALP on MDA-MB231 chemoresistance to MTX (in vitro). Twenty-eight male BALB/c mice were divided into 4 groups. In treatment groups, mice were administered ALP (2.5 and 5 mg/kg) for 5 days and MTX (20 mg/kg) from day 2 till day 5. The results showed that ALP restored hepatic architecture, reduced immune cell infiltration (F4/80, Ly6G and MPO) and repressed the rise in liver enzymes (AST and ALT) induced by MTX. Additionally, ALP rectified the MTX-induced disruption of cellular oxidant status by boosting antioxidant defense systems (HO-1 and GSH) and repressing lipid peroxidation (MDA and 4-HNE). Finally, ALP curbed MTX-induced hepatocyte apoptosis (NF-κB and BAX) and shifted the cytokine milieu away from inflammation (IL-17, IL-22, IL-6 and IL- 10). The results of the in vitro experiments revealed that ALP alone and in combination with MTX, synergistically, reduced cancer cell viability (MTT assay), migration (wound healing assay) and their capacity to establish colonies (colony formation assay) as compared to MTX alone. RT-PCR revealed the antiproliferative (Bcl-2) and proapoptotic (BAX) potentials of ALP and ALP/MTX combination especially after 24 h. In conclusion, targeting PI3K/AKT pathway is a promising strategy in triple negative breast cancer patients by ameliorating hepatotoxicity and restraining chemoresistance to chemotherapy.
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Affiliation(s)
- Rana M Gamal
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Sara H Hazem
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
| | - Mohamed F Hamed
- Department of Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.
| | - Rania R Abdelaziz
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
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Wang Y, Yin L, Du YY, Liao HM, Li J, Yao W, Yuan XQ, Guo QC, Deng TR, Guo N, Zhang M, Zeng Q, Liu C, Li YF. Associations between exposure to phthalates and liver function among women undergoing assisted reproductive technology. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2024; 108:104463. [PMID: 38734395 DOI: 10.1016/j.etap.2024.104463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 03/28/2024] [Accepted: 05/04/2024] [Indexed: 05/13/2024]
Abstract
Phthalates can induce hepatotoxicity in animal studies. We aimed to assess the associations of individual and mixture of urinary phthalate metabolites with serum liver function indicators among 764 women undergoing assisted reproductive technology (ART). In linear models, we observed inverse correlations between urinary mono-benzyl phthalate and serum total protein (TP) as well as globulin (β=-0.27 and -0.23, respectively, P<0.05). Additionally, negative associations were identified between mono-isobutyl phthalate and mono-butyl phthalate (MBP) and aspartate aminotransferase-to-alanine transaminase ratio (AST/ALT) (P<0.05). MBP and the sum of all phthalate metabolites (∑all.phth.m) were positively associated with bilirubin, with β ranging from 0.14 to 0.47. Most phthalate metabolites were also positively related to gamma-glutamyl transferase (GGT) (all P<0.05). In Bayesian kernel machine regression models, phthalate mixture was positively associated with bilirubin and GGT, whereas inversely associated with AST/ALT and TP. Our results suggest that phthalate exposure may impair liver function among women undergoing ART.
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Affiliation(s)
- Yi Wang
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
| | - Li Yin
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
| | - Yao-Yao Du
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
| | - Hong-Mei Liao
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
| | - Juan Li
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
| | - Wen Yao
- General Hospital of Central Theater Command, Wuhan, Hubei, PR China
| | - Xiao-Qiong Yuan
- The Reproductive Center, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China
| | - Qing-Chun Guo
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
| | - Tao-Ran Deng
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
| | - Na Guo
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
| | - Min Zhang
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
| | - Qiang Zeng
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
| | - Chong Liu
- Department of Environmental Health, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
| | - Yu-Feng Li
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
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Xiao Y, Hu J, Chen R, Xu Y, Pan B, Gao Y, Deng Y, Li W, Kan H, Chen S. Impact of fine particulate matter on liver injury: evidence from human, mice and cells. JOURNAL OF HAZARDOUS MATERIALS 2024; 469:133958. [PMID: 38479138 DOI: 10.1016/j.jhazmat.2024.133958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Revised: 02/29/2024] [Accepted: 03/03/2024] [Indexed: 04/07/2024]
Abstract
BACKGROUND A recently discovered risk factor for chronic liver disease is ambient fine particulate matter (PM2.5). Our research aims to elucidate the effects of PM2.5 on liver injury and the potential molecular mechanisms. METHODS AND RESULTS A population-based longitudinal study involving 102,918 participants from 15 Chinese cities, using linear mixed-effect models, found that abnormal alterations in liver function were significantly associated with long-term exposure to PM2.5. The serum levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, direct bilirubin, and triglyceride increased by 2.05%, 2.04%, 0.58%, 2.99%, and 1.46% with each 10 µg/m3 increase in PM2.5. In contrast, the serum levels of total protein, albumin, and prealbumin decreased by 0.27%, 0.48%, and 2.42%, respectively. Mice underwent chronic inhalation exposure to PM2.5 experienced hepatic inflammation, steatosis and fibrosis. In vitro experiments found that hepatocytes experienced an inflammatory response and lipid metabolic dysregulation due to PM2.5, which also activated hepatic stellate cells. The down-regulation and mis-localization of polarity protein Par3 mediated PM2.5-induced liver injury. CONCLUSIONS PM2.5 exposure induced liver injury, mainly characterized by steatosis and fibrosis. The down-regulation and mis-localization of Par3 were important mechanisms of liver injury induced by PM2.5.
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Affiliation(s)
- Yalan Xiao
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai 200032, China; NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
| | - Jialu Hu
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Renjie Chen
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai 200032, China
| | - Yanyi Xu
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai 200032, China
| | - Bin Pan
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai 200032, China
| | - Ya Gao
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai 200032, China
| | - Yiran Deng
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
| | - Wenshu Li
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai 200032, China
| | - Haidong Kan
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai 200032, China; National Center for Children's Health, Children's Hospital of Fudan University, Shanghai 201102, China.
| | - She Chen
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
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Shao J, Jiang Z, Jiang H, Ye Q, Jiang Y, Zhang W, Huang Y, Shen X, Lu X, Wang X. Machine Learning Radiomics Liver Function Model for Prognostic Prediction After Radical Resection of Advanced Gastric Cancer: A Retrospective Study. Ann Surg Oncol 2024; 31:1749-1759. [PMID: 38112885 DOI: 10.1245/s10434-023-14619-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Accepted: 11/02/2023] [Indexed: 12/21/2023]
Abstract
PURPOSE We aimed to establish a machine learning radiomics liver function model to explore how liver function affects the prognosis of patients with gastric cancer (GC). METHODS Patients with advanced GC were retrospectively enrolled in this study. Eight machine learning radiomic models were constructed by extracting radiomic features from portal-vein-phase contrast-enhanced computed tomography (CE-CT) images. Clinicopathological features were determined using univariate and multifactorial Cox regression analyses. These features were used to construct a GC survival nomogram. RESULTS A total of 510 patients with GC were split into training and test cohorts in an 8:2 ratio. Kaplan-Meier analysis showed that patients with type I liver function had a better prognosis. Fifteen significant features were retained to establish the machine learning model. LightBGM showed the best predictive performance in the training (area under the receiver operating characteristic curve [AUC] 0.978) and test cohorts (AUC 0.714). Multivariate analysis revealed that gender, age, liver function, Nutritional Risk Screening 2002 (NRS-2002) score, tumor-lymph node-metastasis stage, tumor size, and tumor differentiation were independent risk factors for GC prognosis. The survival nomogram based on machine learning radiomics, instead of liver biochemical indicators, still had high accuracy (C-index of 0.771 vs. 0.773). CONCLUSION The machine learning radiomics liver function model has high diagnostic value in predicting the influence of liver function on prognosis in patients with GC.
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Affiliation(s)
- Jiancan Shao
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
- Zhejiang International Scientific and Technological Cooperation Base of Translational Cancer Research, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Zhixuan Jiang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
- Zhejiang International Scientific and Technological Cooperation Base of Translational Cancer Research, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Hao Jiang
- School of Nursing, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Qinfan Ye
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
- Zhejiang International Scientific and Technological Cooperation Base of Translational Cancer Research, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yiwei Jiang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
- Zhejiang International Scientific and Technological Cooperation Base of Translational Cancer Research, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Weiteng Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yingpeng Huang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
- Zhejiang International Scientific and Technological Cooperation Base of Translational Cancer Research, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xian Shen
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
- Zhejiang International Scientific and Technological Cooperation Base of Translational Cancer Research, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
| | - Xufeng Lu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
- Zhejiang International Scientific and Technological Cooperation Base of Translational Cancer Research, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
- Research Center of Basic Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
| | - Xiang Wang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
- Zhejiang International Scientific and Technological Cooperation Base of Translational Cancer Research, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
- Research Center of Basic Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
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Ningarhari M, Bertez M, Ploquin A, Bertrand N, Desauw C, Cattan S, Catala P, Vandamme H, Cheymol C, Truant S, Lassailly G, Louvet A, Mathurin P, Dharancy S, Turpin A. Conventional cytotoxic chemotherapy for gastrointestinal cancer in patients with cirrhosis: A multicentre case-control study. Liver Int 2024; 44:682-690. [PMID: 38031969 DOI: 10.1111/liv.15813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 11/08/2023] [Accepted: 11/23/2023] [Indexed: 12/01/2023]
Abstract
BACKGROUND & AIMS Progresses in management make a higher proportion of cirrhotic patients with gastrointestinal (GI) cancer candidates to chemotherapy. Data are needed on the safety and liver-related events associated with the use of chemotherapy in these patients. METHODS Forty-nine patients with cirrhosis receiving chemotherapy against GI cancer from 2013 to 2018 were identified in the French Health Insurance Database using ICD-10 codes K70-K74, and matched 1:2 to non-cirrhotic controls (n = 98) on age, tumour type and type of treatment. Adverse events (AE), dose tapering, discontinuation rate, liver-related events and survival rate were compared. RESULTS Patients with cirrhosis (Child-Pugh A 91%) more often received lower doses (38.8% vs 7.1%, p < .001), without significant differences in terms of grade 3/4 AE or dose tapering rates (29.6% vs. 36.7%; 22.3% vs 24.4%, respectively). Treatment discontinuation rate was higher in patients with cirrhosis (23.3% vs. 11.3%, p = .005). Child-Pugh (p = .007) and MELD (p = .025) scores increased under chemotherapy. Five patients with cirrhosis (10.2%) had liver decompensation within 12 months, and 17.2% of deaths in the cirrhosis group were liver-related versus 0% in matched controls. WHO-PS stage > 1 (HR 3.74, CI95%: 2.13-6.57, p < .001), TNM-stage M1 (HR 3.61, CI 95%: 1.82-7.16, p < .001), non-colorectal cancer (HR 1.73, CI 95%: 1.05-2.86, p = .032) and bilirubin higher than 5 mg/dL (HR 2.26, CI 95%: 1.39-3.70, p < .001) were independent prognostic factors of 2-year mortality, whereas cirrhosis was not. CONCLUSIONS Chemotherapy should be proposed only in patients with compensated cirrhosis with close monitoring of liver function. Dose management remains challenging. Multidisciplinary management is warranted to improve these patients' outcomes.
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Affiliation(s)
- Massih Ningarhari
- CHU Lille, Hôpital Huriez, Maladies de l'Appareil Digestif, Lille, France
| | - Marlène Bertez
- CHU Lille, Hôpital Huriez, Maladies de l'Appareil Digestif, Lille, France
| | - Anne Ploquin
- Université de Lille, CNRS INSERM UMR9020-U1277, CANTHER Cancer Heterogeneity Plasticity and Resistance to Therapies, Lille, France
- CHU Lille, Hôpital Huriez, Medical Oncology Department, Lille, France
| | - Nicolas Bertrand
- Université de Lille, CNRS INSERM UMR9020-U1277, CANTHER Cancer Heterogeneity Plasticity and Resistance to Therapies, Lille, France
- CHU Lille, Hôpital Huriez, Medical Oncology Department, Lille, France
| | - Christophe Desauw
- Université de Lille, CNRS INSERM UMR9020-U1277, CANTHER Cancer Heterogeneity Plasticity and Resistance to Therapies, Lille, France
- CHU Lille, Hôpital Huriez, Medical Oncology Department, Lille, France
| | - Stéphane Cattan
- CHU Lille, Hôpital Huriez, Maladies de l'Appareil Digestif, Lille, France
| | - Pascale Catala
- Centre Hospitalier de Béthune, Hépato-Gastro-Entérologie, Beuvry, France
| | - Hélène Vandamme
- Centre Hospitalier de Béthune, Hépato-Gastro-Entérologie, Beuvry, France
| | - Claire Cheymol
- GHICL Hôpital Saint-Vincent, Oncologie Médicale, Lille, France
| | - Stéphanie Truant
- CHU Lille, Hôpital Huriez, Chirurgie Digestive et Transplantation, Lille, France
| | | | - Alexandre Louvet
- CHU Lille, Hôpital Huriez, Maladies de l'Appareil Digestif, Lille, France
| | - Philippe Mathurin
- CHU Lille, Hôpital Huriez, Maladies de l'Appareil Digestif, Lille, France
| | - Sébastien Dharancy
- CHU Lille, Hôpital Huriez, Maladies de l'Appareil Digestif, Lille, France
| | - Anthony Turpin
- Université de Lille, CNRS INSERM UMR9020-U1277, CANTHER Cancer Heterogeneity Plasticity and Resistance to Therapies, Lille, France
- CHU Lille, Hôpital Huriez, Medical Oncology Department, Lille, France
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Senk K, Rio Bartulos C, Wilcke J, Einspieler I, Luerken L, Baeumler W, Stroszczynski C, Wiggermann P. Peri-interventional LiMAx test for liver ablation - A feasibility study. Clin Hemorheol Microcirc 2024; 86:213-224. [PMID: 37638427 DOI: 10.3233/ch-238107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/29/2023]
Abstract
BACKGROUND Local ablation is an important treatment for liver cancer in cases of cirrhosis. Liver failure may occur after ablation, especially in advanced liver diseases. Currently, there is no standardization for peri-interventional risk assessment. The liver maximum capacity test (LiMAx) is used to assess functional liver capacity, but there is a lack of exploration of its use in this context. OBJECTIVE The aim of this study was to retrospectively evaluate the usefulness of peri-interventional LiMAx measurements in patients with primary or secondary liver cancer who underwent ablation treatment. METHODS A LiMAx test was performed at 24 hours pre- and postablation in 49 patients. Blood parameters were collected to determine liver function using MELD and ALBI scores. The results of the LiMAx test were related with these scores and to critical postintervention LiMAx values. RESULTS LiMAx values correlated strongly with MELD and ALBI scores before the intervention and reflected the change in liver function, as shown by an increase in scores after the intervention. Notably, LiMAx values decreased during the intervention. AUC analysis for patients at risk of reaching a critical liver level after the intervention showed a cutoff value of 186μg/kg/h. CONCLUSIONS The LiMAx test may be a valuable tool in liver ablation for both peri-interventional monitoring of liver function and preintervention risk assessment.
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Affiliation(s)
- Karin Senk
- Institut für Röntgendiagnostik, Universitätsklinikum Regensburg, Regensburg, Germany
| | - Carolina Rio Bartulos
- Institut für Röntgendiagnostik und Nuklearmedizin, Städtisches Klinikum Braunschweig gGmbH, Braunschweig, Germany
| | - Juliane Wilcke
- Institut für Psychologie, Universität Kassel, Kassel, Germany
- Medizinische Fakultät, Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie (IBE), LMU München, München, Germany
| | - Ingo Einspieler
- Institut für Röntgendiagnostik, Universitätsklinikum Regensburg, Regensburg, Germany
| | - Lukas Luerken
- Institut für Röntgendiagnostik, Universitätsklinikum Regensburg, Regensburg, Germany
| | - Wolf Baeumler
- Institut für Röntgendiagnostik, Universitätsklinikum Regensburg, Regensburg, Germany
| | | | - Philipp Wiggermann
- Institut für Röntgendiagnostik und Nuklearmedizin, Städtisches Klinikum Braunschweig gGmbH, Braunschweig, Germany
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10
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Sousa Da Silva RX, Breuer E, Shankar S, Kawakatsu S, Hołówko W, Santos Coelho J, Jeddou H, Sugiura T, Ghallab M, Da Silva D, Watanabe G, Botea F, Sakai N, Addeo P, Tzedakis S, Bartsch F, Balcer K, Lim C, Werey F, Lopez-Lopez V, Peralta Montero L, Sanchez Claria R, Leiting J, Vachharajani N, Hopping E, Torres OJM, Hirano S, Andel D, Hagendoorn J, Psica A, Ravaioli M, Ahn KS, Reese T, Montes LA, Gunasekaran G, Alcázar C, Lim JH, Haroon M, Lu Q, Castaldi A, Orimo T, Moeckli B, Abadía T, Ruffolo L, Dib Hasan J, Ratti F, Kauffmann EF, de Wilde RF, Polak WG, Boggi U, Aldrighetti L, McCormack L, Hernandez-Alejandro R, Serrablo A, Toso C, Taketomi A, Gugenheim J, Dong J, Hanif F, Park JS, Ramia JM, Schwartz M, Ramisch D, De Oliveira ML, Oldhafer KJ, Kang KJ, Cescon M, Lodge P, Rinkes IHMB, Noji T, Thomson JE, Goh SK, Chapman WC, Cleary SP, Pekolj J, Regimbeau JM, Scatton O, Truant S, Lang H, Fuks D, Bachellier P, Ohtsuka M, Popescu I, Hasegawa K, Lesurtel M, Adam R, Cherqui D, Uesaka K, Boudjema K, Pinto-Marques H, Grąt M, Petrowsky H, Ebata T, Prachalias A, Robles-Campos R, Clavien PA. Novel Benchmark Values for Open Major Anatomic Liver Resection in Non-cirrhotic Patients: A Multicentric Study of 44 International Expert Centers. Ann Surg 2023; 278:748-755. [PMID: 37465950 DOI: 10.1097/sla.0000000000006012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/20/2023]
Abstract
OBJECTIVE This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities. BACKGROUND Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures. METHODS A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a 5-year period (2016-2020). Benchmark cases were low-risk non-cirrhotic patients without significant comorbidities treated in high-volume centers (≥30 major liver resections/year). Benchmark values were set at the 75th percentile of median values of all centers. Minimum follow-up period was 1 year in each patient. RESULTS Of 8044 patients, 2908 (36%) qualified as benchmark (low-risk) cases. Benchmark cutoffs for all indications include R0 resection ≥78%; liver failure (grade B/C) ≤10%; bile leak (grade B/C) ≤18%; complications ≥grade 3 and CCI ® ≤46% and ≤9 at 3 months, respectively. Benchmark values differed significantly between malignant and benign conditions so that reference values must be adjusted accordingly. Extended right hepatectomy (H1, 4-8 or H4-8) disclosed a higher cutoff for liver failure, while extended left (H1-5,8 or H2-5,8) were associated with higher cutoffs for bile leaks, but had superior oncologic outcomes, when compared to formal left hepatectomy (H1-4 or H2-4). The minimal follow-up for a conclusive outcome evaluation following open anatomic major resection must be 3 months. CONCLUSION These new benchmark cutoffs for open major hepatectomy provide a powerful tool to convincingly evaluate other approaches including parenchymal-sparing procedures, laparoscopic/robotic approaches, and alternative treatments, such as ablation therapy, irradiation, or novel chemotherapy regimens.
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Affiliation(s)
- Richard X Sousa Da Silva
- Swiss HPB and Transplant Center Zurich, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Eva Breuer
- Swiss HPB and Transplant Center Zurich, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Sadhana Shankar
- Department of Hepatobiliary and Pancreatic Surgery, King's College Hospital, London, UK
| | - Shoji Kawakatsu
- Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Wacław Hołówko
- Department of General, Transplant and Liver Surgery, Medical University Warsaw, Warsaw, Poland
| | - João Santos Coelho
- Hepato-Biliary-Pancreatic and Transplantation Centre, Curry Cabral Hospital, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
| | - Heithem Jeddou
- Department of Hepatobiliary and Digestive Surgery, Rennes University Hospital, Rennes, France
| | - Teiichi Sugiura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Mohammed Ghallab
- Paul Brousse Hospital, AP-HP, University Paris-Saclay, Villejuif, France
| | - Doris Da Silva
- Department of HPB Surgery and Liver Transplantation, AP-HP Beaujon Hospital, University of Paris Cité, Clichy, France
| | - Genki Watanabe
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Florin Botea
- Department of Surgery and Transplantation, Fundeni Clinical Institute, Bucharest, Romania
| | - Nozomu Sakai
- Department of General Surgery, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Pietro Addeo
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, University Hospital, Strasbourg University, Strasbourg, France
| | - Stylianos Tzedakis
- Department of Hepatobiliary, Digestive and Endocrine Surgery, Cochin Hospital, Paris Cité University, Paris, France
| | - Fabian Bartsch
- Department of General, Visceral and Transplantation Surgery, University Hospital of Mainz, Mainz, Germany
| | - Kaja Balcer
- Department of Digestive Surgery and Transplantation, CHU Lille, University Lille, Lille, France
| | - Chetana Lim
- Department of Digestive, Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpêtrière, Sorbonne Université, Centre de Recherche de Saint-Antoine, Paris, France
| | - Fabien Werey
- Department of Oncology and Digestive Surgery, CHU Amiens-Picardie, Amiens, France
| | - Victor Lopez-Lopez
- Clinic and University Virgen de la Arrixaca Hospital, IMIB, Murcia, Spain
| | - Luciana Peralta Montero
- Hepato-Pancreato-Biliary Surgery Section and Liver Transplant Unit, General Surgery Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Rodrigo Sanchez Claria
- Hepato-Pancreato-Biliary Surgery Section and Liver Transplant Unit, General Surgery Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Jennifer Leiting
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN
| | - Neeta Vachharajani
- Department of Surgery, Section of Abdominal Organ Transplant, Washington University School of Medicine, St Louis, MO
| | - Eve Hopping
- Hepatobiliary Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide & Hepatobiliary Unit, Department of Surgery, Flinders Medical Centre, Adelaide, Australia
| | - Orlando J M Torres
- Department of Gastrointestinal Surgery, Hepatopancreatobiliary Unit, Presidente Dutra Hospital, São Luiz, Brazil
| | - Satoshi Hirano
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Hokkaido, Japan
| | - Daan Andel
- Department of Surgical Oncology, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
| | - Jeroen Hagendoorn
- Department of Surgical Oncology, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
| | - Alicja Psica
- Department of Transplantation and Hepatobiliary Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Matteo Ravaioli
- Hepato-biliary surgery and Transplant Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Keun Soon Ahn
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, School of Medicine, Keimyung University, Dongsan Hospital, Daegu, Republic of Korea
| | - Tim Reese
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Asklepios Hospital Barmbek, Semmelweis University of Medicine, Asklepios Campus Hamburg, Hamburg, Germany
| | - Leonardo A Montes
- General Surgery Department Liver, Pancreas and Intestinal Transplant Unit, Favaloro Foundation University Hospital, Buenos Aires, Argentina
| | - Ganesh Gunasekaran
- Department of Surgery, Division of HPB Service, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Cándido Alcázar
- Department of Surgery, HPB and Transplant Unit, General Universitary Hospital Alicante and Health and Biomedical Research Institute of Alicante, Alicante, Spain
| | - Jin Hong Lim
- Department of Surgery, Division of HBP Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Muhammad Haroon
- Department of HPB and Liver Transplant, Bahria International Hospital Orchard, Lahore, Pakistan
| | - Qian Lu
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Antonio Castaldi
- Department of Digestive Surgery and Liver Transplant Unit, University Côte d'Azur, CHU de Nice, Nice, France
| | - Tatsuya Orimo
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Hokkaido, Japan
| | - Beat Moeckli
- Division of Abdominal and Transplantation Surgery, University Hospitals of Geneva, Geneva, Switzerland
| | - Teresa Abadía
- HPB Surgical Division, Miguel Servet University Hospital, Zaragoza, Spain
| | - Luis Ruffolo
- Department of HPB and Transplant Surgery, University of Rochester, Rochester, NY
| | - Josefina Dib Hasan
- Transplant Unit, Hospital Aleman de Buenos Aires, Buenos Aires, Argentina
| | - Francesca Ratti
- Division of Hepatobiliary Surgery, IRCCS San Raffaele Hospital, Vita-Salute University, Milan, Italy
| | | | - Roeland F de Wilde
- Department of Surgery, Division of HPB and Transplant Surgery, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Wojciech G Polak
- Department of Surgery, Division of HPB and Transplant Surgery, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Ugo Boggi
- Division of General and Transplant Surgery, University of Pisa, Pisa, Italy
| | - Luca Aldrighetti
- Division of Hepatobiliary Surgery, IRCCS San Raffaele Hospital, Vita-Salute University, Milan, Italy
| | - Lucas McCormack
- Transplant Unit, Hospital Aleman de Buenos Aires, Buenos Aires, Argentina
| | | | - Alejandro Serrablo
- HPB Surgical Division, Miguel Servet University Hospital, Zaragoza, Spain
| | - Christian Toso
- Division of Abdominal and Transplantation Surgery, University Hospitals of Geneva, Geneva, Switzerland
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Hokkaido, Japan
| | - Jean Gugenheim
- Department of Digestive Surgery and Liver Transplant Unit, University Côte d'Azur, CHU de Nice, Nice, France
| | - Jiahong Dong
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Faisal Hanif
- Department of HPB and Liver Transplant, Bahria International Hospital Orchard, Lahore, Pakistan
| | - Joon Seong Park
- Department of Surgery, Division of HBP Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - José M Ramia
- Department of Surgery, HPB and Transplant Unit, General Universitary Hospital Alicante and Health and Biomedical Research Institute of Alicante, Alicante, Spain
| | - Myron Schwartz
- Department of Surgery, Division of HPB Service, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Diego Ramisch
- General Surgery Department Liver, Pancreas and Intestinal Transplant Unit, Favaloro Foundation University Hospital, Buenos Aires, Argentina
| | - Michelle L De Oliveira
- Swiss HPB and Transplant Center Zurich, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Karl J Oldhafer
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Asklepios Hospital Barmbek, Semmelweis University of Medicine, Asklepios Campus Hamburg, Hamburg, Germany
| | - Koo Jeong Kang
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, School of Medicine, Keimyung University, Dongsan Hospital, Daegu, Republic of Korea
| | - Matteo Cescon
- Hepato-biliary surgery and Transplant Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Peter Lodge
- Department of Transplantation and Hepatobiliary Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Inne H M Borel Rinkes
- Department of Surgical Oncology, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
| | - Takehiro Noji
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Hokkaido, Japan
| | - John-Edwin Thomson
- Hepatobiliary Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide & Hepatobiliary Unit, Department of Surgery, Flinders Medical Centre, Adelaide, Australia
| | - Su Kah Goh
- Hepatobiliary Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide & Hepatobiliary Unit, Department of Surgery, Flinders Medical Centre, Adelaide, Australia
| | - William C Chapman
- Department of Surgery, Section of Abdominal Organ Transplant, Washington University School of Medicine, St Louis, MO
| | - Sean P Cleary
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN
| | - Juan Pekolj
- Hepato-Pancreato-Biliary Surgery Section and Liver Transplant Unit, General Surgery Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Jean-Marc Regimbeau
- Department of Oncology and Digestive Surgery, CHU Amiens-Picardie, Amiens, France
| | - Olivier Scatton
- Department of Digestive, Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpêtrière, Sorbonne Université, Centre de Recherche de Saint-Antoine, Paris, France
| | - Stéphanie Truant
- Department of Digestive Surgery and Transplantation, CHU Lille, University Lille, Lille, France
| | - Hauke Lang
- Department of General, Visceral and Transplantation Surgery, University Hospital of Mainz, Mainz, Germany
| | - David Fuks
- Department of Hepatobiliary, Digestive and Endocrine Surgery, Cochin Hospital, Paris Cité University, Paris, France
| | - Philippe Bachellier
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, University Hospital, Strasbourg University, Strasbourg, France
| | - Masayuki Ohtsuka
- Department of General Surgery, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Irinel Popescu
- Department of Surgery and Transplantation, Fundeni Clinical Institute, Bucharest, Romania
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Mickaël Lesurtel
- Department of HPB Surgery and Liver Transplantation, AP-HP Beaujon Hospital, University of Paris Cité, Clichy, France
| | - René Adam
- Paul Brousse Hospital, AP-HP, University Paris-Saclay, Villejuif, France
| | - Daniel Cherqui
- Paul Brousse Hospital, AP-HP, University Paris-Saclay, Villejuif, France
| | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Karim Boudjema
- Department of Hepatobiliary and Digestive Surgery, Rennes University Hospital, Rennes, France
| | - Hugo Pinto-Marques
- Hepato-Biliary-Pancreatic and Transplantation Centre, Curry Cabral Hospital, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
| | - Michał Grąt
- Department of General, Transplant and Liver Surgery, Medical University Warsaw, Warsaw, Poland
| | - Henrik Petrowsky
- Swiss HPB and Transplant Center Zurich, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Tomoki Ebata
- Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Andreas Prachalias
- Department of Hepatobiliary and Pancreatic Surgery, King's College Hospital, London, UK
| | | | - Pierre-Alain Clavien
- Swiss HPB and Transplant Center Zurich, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
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11
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Morin CE, Kolbe AB, Alazraki A, Chavhan GB, Gill A, Infante J, Khanna G, Nguyen HN, O'Neill AF, Rees MA, Sharma A, Squires JE, Squires JH, Syed AB, Tang ER, Towbin AJ, Schooler GR. Cancer Therapy-related Hepatic Injury in Children: Imaging Review from the Pediatric LI-RADS Working Group. Radiographics 2023; 43:e230007. [PMID: 37616168 DOI: 10.1148/rg.230007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/25/2023]
Abstract
The liver is the primary organ for the metabolism of many chemotherapeutic agents. Treatment-induced liver injury is common in children undergoing cancer therapy. Hepatic injury occurs due to various mechanisms, including biochemical cytotoxicity, hepatic vascular injury, radiation-induced cytotoxicity, and direct hepatic injury through minimally invasive and invasive surgical treatments. Treatment-induced liver injury can be seen contemporaneous with therapy and months to years after therapy is complete. Patients can develop a combination of hepatic injuries manifesting during and after treatment. Acute toxic effects of cancer therapy in children include hepatitis, steatosis, steatohepatitis, cholestasis, hemosiderosis, and vascular injury. Longer-term effects of cancer therapy include hepatic fibrosis, chronic liver failure, and development of focal liver lesions. Quantitative imaging techniques can provide useful metrics for disease diagnosis and monitoring, especially in treatment-related diffuse liver injury such as hepatic steatosis and steatohepatitis, hepatic iron deposition, and hepatic fibrosis. Focal liver lesions, including those developing as a result of treatment-related vascular injury such as focal nodular hyperplasia-like lesions and hepatic perfusion anomalies, as well as hepatic infections occurring as a consequence of immune suppression, can be anxiety provoking and confused with recurrent malignancy or hepatic metastases, although there often are imaging features that help elucidate the correct diagnosis. Radiologic evaluation, in conjunction with clinical and biochemical screening, is integral to diagnosing and monitoring hepatic complications of cancer therapy in pediatric patients during therapy and after therapy completion for long-term surveillance. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material See the invited commentary by Ferraciolli and Gee in this issue.
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Affiliation(s)
- Cara E Morin
- From the Department of Radiology, Cincinnati Children's Hospital and University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229 (C.E.M., A.J.T.); Department of Radiology, Mayo Clinic, Rochester, Minn (A.B.K.); Department of Radiology and Imaging Sciences, Emory University and Children's Healthcare of Atlanta, Atlanta, Ga (A.A., A.G., G.K.); Diagnostic Imaging Department, The Hospital for Sick Children and Department of Medical Imaging, University of Toronto, Ontario, Canada (G.B.C.); Department of Radiology, Nicklaus Children's Hospital, Miami, Fla (J.I.); Department of Radiology, Children's Hospital Los Angeles, Los Angeles, Calif (H.N.N.); Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Mass (A.F.O.); Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio (M.A.R.); Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tenn (A.S.); Division of Gastroenterology, Hepatology, and Nutrition (J.E.S.) and Department of Radiology (J.H.S.), UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pa; Department of Radiology, Stanford University, Stanford, Calif (A.B.S.); Department of Radiology, Section of Pediatric Radiology, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colo (E.R.T.); and Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (G.R.S.)
| | - Amy B Kolbe
- From the Department of Radiology, Cincinnati Children's Hospital and University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229 (C.E.M., A.J.T.); Department of Radiology, Mayo Clinic, Rochester, Minn (A.B.K.); Department of Radiology and Imaging Sciences, Emory University and Children's Healthcare of Atlanta, Atlanta, Ga (A.A., A.G., G.K.); Diagnostic Imaging Department, The Hospital for Sick Children and Department of Medical Imaging, University of Toronto, Ontario, Canada (G.B.C.); Department of Radiology, Nicklaus Children's Hospital, Miami, Fla (J.I.); Department of Radiology, Children's Hospital Los Angeles, Los Angeles, Calif (H.N.N.); Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Mass (A.F.O.); Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio (M.A.R.); Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tenn (A.S.); Division of Gastroenterology, Hepatology, and Nutrition (J.E.S.) and Department of Radiology (J.H.S.), UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pa; Department of Radiology, Stanford University, Stanford, Calif (A.B.S.); Department of Radiology, Section of Pediatric Radiology, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colo (E.R.T.); and Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (G.R.S.)
| | - Adina Alazraki
- From the Department of Radiology, Cincinnati Children's Hospital and University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229 (C.E.M., A.J.T.); Department of Radiology, Mayo Clinic, Rochester, Minn (A.B.K.); Department of Radiology and Imaging Sciences, Emory University and Children's Healthcare of Atlanta, Atlanta, Ga (A.A., A.G., G.K.); Diagnostic Imaging Department, The Hospital for Sick Children and Department of Medical Imaging, University of Toronto, Ontario, Canada (G.B.C.); Department of Radiology, Nicklaus Children's Hospital, Miami, Fla (J.I.); Department of Radiology, Children's Hospital Los Angeles, Los Angeles, Calif (H.N.N.); Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Mass (A.F.O.); Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio (M.A.R.); Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tenn (A.S.); Division of Gastroenterology, Hepatology, and Nutrition (J.E.S.) and Department of Radiology (J.H.S.), UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pa; Department of Radiology, Stanford University, Stanford, Calif (A.B.S.); Department of Radiology, Section of Pediatric Radiology, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colo (E.R.T.); and Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (G.R.S.)
| | - Govind B Chavhan
- From the Department of Radiology, Cincinnati Children's Hospital and University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229 (C.E.M., A.J.T.); Department of Radiology, Mayo Clinic, Rochester, Minn (A.B.K.); Department of Radiology and Imaging Sciences, Emory University and Children's Healthcare of Atlanta, Atlanta, Ga (A.A., A.G., G.K.); Diagnostic Imaging Department, The Hospital for Sick Children and Department of Medical Imaging, University of Toronto, Ontario, Canada (G.B.C.); Department of Radiology, Nicklaus Children's Hospital, Miami, Fla (J.I.); Department of Radiology, Children's Hospital Los Angeles, Los Angeles, Calif (H.N.N.); Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Mass (A.F.O.); Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio (M.A.R.); Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tenn (A.S.); Division of Gastroenterology, Hepatology, and Nutrition (J.E.S.) and Department of Radiology (J.H.S.), UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pa; Department of Radiology, Stanford University, Stanford, Calif (A.B.S.); Department of Radiology, Section of Pediatric Radiology, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colo (E.R.T.); and Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (G.R.S.)
| | - Annie Gill
- From the Department of Radiology, Cincinnati Children's Hospital and University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229 (C.E.M., A.J.T.); Department of Radiology, Mayo Clinic, Rochester, Minn (A.B.K.); Department of Radiology and Imaging Sciences, Emory University and Children's Healthcare of Atlanta, Atlanta, Ga (A.A., A.G., G.K.); Diagnostic Imaging Department, The Hospital for Sick Children and Department of Medical Imaging, University of Toronto, Ontario, Canada (G.B.C.); Department of Radiology, Nicklaus Children's Hospital, Miami, Fla (J.I.); Department of Radiology, Children's Hospital Los Angeles, Los Angeles, Calif (H.N.N.); Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Mass (A.F.O.); Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio (M.A.R.); Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tenn (A.S.); Division of Gastroenterology, Hepatology, and Nutrition (J.E.S.) and Department of Radiology (J.H.S.), UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pa; Department of Radiology, Stanford University, Stanford, Calif (A.B.S.); Department of Radiology, Section of Pediatric Radiology, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colo (E.R.T.); and Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (G.R.S.)
| | - Juan Infante
- From the Department of Radiology, Cincinnati Children's Hospital and University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229 (C.E.M., A.J.T.); Department of Radiology, Mayo Clinic, Rochester, Minn (A.B.K.); Department of Radiology and Imaging Sciences, Emory University and Children's Healthcare of Atlanta, Atlanta, Ga (A.A., A.G., G.K.); Diagnostic Imaging Department, The Hospital for Sick Children and Department of Medical Imaging, University of Toronto, Ontario, Canada (G.B.C.); Department of Radiology, Nicklaus Children's Hospital, Miami, Fla (J.I.); Department of Radiology, Children's Hospital Los Angeles, Los Angeles, Calif (H.N.N.); Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Mass (A.F.O.); Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio (M.A.R.); Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tenn (A.S.); Division of Gastroenterology, Hepatology, and Nutrition (J.E.S.) and Department of Radiology (J.H.S.), UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pa; Department of Radiology, Stanford University, Stanford, Calif (A.B.S.); Department of Radiology, Section of Pediatric Radiology, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colo (E.R.T.); and Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (G.R.S.)
| | - Geetika Khanna
- From the Department of Radiology, Cincinnati Children's Hospital and University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229 (C.E.M., A.J.T.); Department of Radiology, Mayo Clinic, Rochester, Minn (A.B.K.); Department of Radiology and Imaging Sciences, Emory University and Children's Healthcare of Atlanta, Atlanta, Ga (A.A., A.G., G.K.); Diagnostic Imaging Department, The Hospital for Sick Children and Department of Medical Imaging, University of Toronto, Ontario, Canada (G.B.C.); Department of Radiology, Nicklaus Children's Hospital, Miami, Fla (J.I.); Department of Radiology, Children's Hospital Los Angeles, Los Angeles, Calif (H.N.N.); Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Mass (A.F.O.); Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio (M.A.R.); Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tenn (A.S.); Division of Gastroenterology, Hepatology, and Nutrition (J.E.S.) and Department of Radiology (J.H.S.), UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pa; Department of Radiology, Stanford University, Stanford, Calif (A.B.S.); Department of Radiology, Section of Pediatric Radiology, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colo (E.R.T.); and Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (G.R.S.)
| | - HaiThuy N Nguyen
- From the Department of Radiology, Cincinnati Children's Hospital and University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229 (C.E.M., A.J.T.); Department of Radiology, Mayo Clinic, Rochester, Minn (A.B.K.); Department of Radiology and Imaging Sciences, Emory University and Children's Healthcare of Atlanta, Atlanta, Ga (A.A., A.G., G.K.); Diagnostic Imaging Department, The Hospital for Sick Children and Department of Medical Imaging, University of Toronto, Ontario, Canada (G.B.C.); Department of Radiology, Nicklaus Children's Hospital, Miami, Fla (J.I.); Department of Radiology, Children's Hospital Los Angeles, Los Angeles, Calif (H.N.N.); Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Mass (A.F.O.); Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio (M.A.R.); Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tenn (A.S.); Division of Gastroenterology, Hepatology, and Nutrition (J.E.S.) and Department of Radiology (J.H.S.), UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pa; Department of Radiology, Stanford University, Stanford, Calif (A.B.S.); Department of Radiology, Section of Pediatric Radiology, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colo (E.R.T.); and Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (G.R.S.)
| | - Allison F O'Neill
- From the Department of Radiology, Cincinnati Children's Hospital and University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229 (C.E.M., A.J.T.); Department of Radiology, Mayo Clinic, Rochester, Minn (A.B.K.); Department of Radiology and Imaging Sciences, Emory University and Children's Healthcare of Atlanta, Atlanta, Ga (A.A., A.G., G.K.); Diagnostic Imaging Department, The Hospital for Sick Children and Department of Medical Imaging, University of Toronto, Ontario, Canada (G.B.C.); Department of Radiology, Nicklaus Children's Hospital, Miami, Fla (J.I.); Department of Radiology, Children's Hospital Los Angeles, Los Angeles, Calif (H.N.N.); Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Mass (A.F.O.); Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio (M.A.R.); Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tenn (A.S.); Division of Gastroenterology, Hepatology, and Nutrition (J.E.S.) and Department of Radiology (J.H.S.), UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pa; Department of Radiology, Stanford University, Stanford, Calif (A.B.S.); Department of Radiology, Section of Pediatric Radiology, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colo (E.R.T.); and Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (G.R.S.)
| | - Mitchell A Rees
- From the Department of Radiology, Cincinnati Children's Hospital and University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229 (C.E.M., A.J.T.); Department of Radiology, Mayo Clinic, Rochester, Minn (A.B.K.); Department of Radiology and Imaging Sciences, Emory University and Children's Healthcare of Atlanta, Atlanta, Ga (A.A., A.G., G.K.); Diagnostic Imaging Department, The Hospital for Sick Children and Department of Medical Imaging, University of Toronto, Ontario, Canada (G.B.C.); Department of Radiology, Nicklaus Children's Hospital, Miami, Fla (J.I.); Department of Radiology, Children's Hospital Los Angeles, Los Angeles, Calif (H.N.N.); Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Mass (A.F.O.); Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio (M.A.R.); Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tenn (A.S.); Division of Gastroenterology, Hepatology, and Nutrition (J.E.S.) and Department of Radiology (J.H.S.), UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pa; Department of Radiology, Stanford University, Stanford, Calif (A.B.S.); Department of Radiology, Section of Pediatric Radiology, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colo (E.R.T.); and Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (G.R.S.)
| | - Akshay Sharma
- From the Department of Radiology, Cincinnati Children's Hospital and University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229 (C.E.M., A.J.T.); Department of Radiology, Mayo Clinic, Rochester, Minn (A.B.K.); Department of Radiology and Imaging Sciences, Emory University and Children's Healthcare of Atlanta, Atlanta, Ga (A.A., A.G., G.K.); Diagnostic Imaging Department, The Hospital for Sick Children and Department of Medical Imaging, University of Toronto, Ontario, Canada (G.B.C.); Department of Radiology, Nicklaus Children's Hospital, Miami, Fla (J.I.); Department of Radiology, Children's Hospital Los Angeles, Los Angeles, Calif (H.N.N.); Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Mass (A.F.O.); Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio (M.A.R.); Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tenn (A.S.); Division of Gastroenterology, Hepatology, and Nutrition (J.E.S.) and Department of Radiology (J.H.S.), UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pa; Department of Radiology, Stanford University, Stanford, Calif (A.B.S.); Department of Radiology, Section of Pediatric Radiology, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colo (E.R.T.); and Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (G.R.S.)
| | - James E Squires
- From the Department of Radiology, Cincinnati Children's Hospital and University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229 (C.E.M., A.J.T.); Department of Radiology, Mayo Clinic, Rochester, Minn (A.B.K.); Department of Radiology and Imaging Sciences, Emory University and Children's Healthcare of Atlanta, Atlanta, Ga (A.A., A.G., G.K.); Diagnostic Imaging Department, The Hospital for Sick Children and Department of Medical Imaging, University of Toronto, Ontario, Canada (G.B.C.); Department of Radiology, Nicklaus Children's Hospital, Miami, Fla (J.I.); Department of Radiology, Children's Hospital Los Angeles, Los Angeles, Calif (H.N.N.); Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Mass (A.F.O.); Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio (M.A.R.); Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tenn (A.S.); Division of Gastroenterology, Hepatology, and Nutrition (J.E.S.) and Department of Radiology (J.H.S.), UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pa; Department of Radiology, Stanford University, Stanford, Calif (A.B.S.); Department of Radiology, Section of Pediatric Radiology, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colo (E.R.T.); and Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (G.R.S.)
| | - Judy H Squires
- From the Department of Radiology, Cincinnati Children's Hospital and University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229 (C.E.M., A.J.T.); Department of Radiology, Mayo Clinic, Rochester, Minn (A.B.K.); Department of Radiology and Imaging Sciences, Emory University and Children's Healthcare of Atlanta, Atlanta, Ga (A.A., A.G., G.K.); Diagnostic Imaging Department, The Hospital for Sick Children and Department of Medical Imaging, University of Toronto, Ontario, Canada (G.B.C.); Department of Radiology, Nicklaus Children's Hospital, Miami, Fla (J.I.); Department of Radiology, Children's Hospital Los Angeles, Los Angeles, Calif (H.N.N.); Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Mass (A.F.O.); Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio (M.A.R.); Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tenn (A.S.); Division of Gastroenterology, Hepatology, and Nutrition (J.E.S.) and Department of Radiology (J.H.S.), UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pa; Department of Radiology, Stanford University, Stanford, Calif (A.B.S.); Department of Radiology, Section of Pediatric Radiology, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colo (E.R.T.); and Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (G.R.S.)
| | - Ali B Syed
- From the Department of Radiology, Cincinnati Children's Hospital and University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229 (C.E.M., A.J.T.); Department of Radiology, Mayo Clinic, Rochester, Minn (A.B.K.); Department of Radiology and Imaging Sciences, Emory University and Children's Healthcare of Atlanta, Atlanta, Ga (A.A., A.G., G.K.); Diagnostic Imaging Department, The Hospital for Sick Children and Department of Medical Imaging, University of Toronto, Ontario, Canada (G.B.C.); Department of Radiology, Nicklaus Children's Hospital, Miami, Fla (J.I.); Department of Radiology, Children's Hospital Los Angeles, Los Angeles, Calif (H.N.N.); Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Mass (A.F.O.); Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio (M.A.R.); Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tenn (A.S.); Division of Gastroenterology, Hepatology, and Nutrition (J.E.S.) and Department of Radiology (J.H.S.), UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pa; Department of Radiology, Stanford University, Stanford, Calif (A.B.S.); Department of Radiology, Section of Pediatric Radiology, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colo (E.R.T.); and Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (G.R.S.)
| | - Elizabeth R Tang
- From the Department of Radiology, Cincinnati Children's Hospital and University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229 (C.E.M., A.J.T.); Department of Radiology, Mayo Clinic, Rochester, Minn (A.B.K.); Department of Radiology and Imaging Sciences, Emory University and Children's Healthcare of Atlanta, Atlanta, Ga (A.A., A.G., G.K.); Diagnostic Imaging Department, The Hospital for Sick Children and Department of Medical Imaging, University of Toronto, Ontario, Canada (G.B.C.); Department of Radiology, Nicklaus Children's Hospital, Miami, Fla (J.I.); Department of Radiology, Children's Hospital Los Angeles, Los Angeles, Calif (H.N.N.); Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Mass (A.F.O.); Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio (M.A.R.); Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tenn (A.S.); Division of Gastroenterology, Hepatology, and Nutrition (J.E.S.) and Department of Radiology (J.H.S.), UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pa; Department of Radiology, Stanford University, Stanford, Calif (A.B.S.); Department of Radiology, Section of Pediatric Radiology, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colo (E.R.T.); and Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (G.R.S.)
| | - Alexander J Towbin
- From the Department of Radiology, Cincinnati Children's Hospital and University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229 (C.E.M., A.J.T.); Department of Radiology, Mayo Clinic, Rochester, Minn (A.B.K.); Department of Radiology and Imaging Sciences, Emory University and Children's Healthcare of Atlanta, Atlanta, Ga (A.A., A.G., G.K.); Diagnostic Imaging Department, The Hospital for Sick Children and Department of Medical Imaging, University of Toronto, Ontario, Canada (G.B.C.); Department of Radiology, Nicklaus Children's Hospital, Miami, Fla (J.I.); Department of Radiology, Children's Hospital Los Angeles, Los Angeles, Calif (H.N.N.); Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Mass (A.F.O.); Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio (M.A.R.); Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tenn (A.S.); Division of Gastroenterology, Hepatology, and Nutrition (J.E.S.) and Department of Radiology (J.H.S.), UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pa; Department of Radiology, Stanford University, Stanford, Calif (A.B.S.); Department of Radiology, Section of Pediatric Radiology, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colo (E.R.T.); and Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (G.R.S.)
| | - Gary R Schooler
- From the Department of Radiology, Cincinnati Children's Hospital and University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH 45229 (C.E.M., A.J.T.); Department of Radiology, Mayo Clinic, Rochester, Minn (A.B.K.); Department of Radiology and Imaging Sciences, Emory University and Children's Healthcare of Atlanta, Atlanta, Ga (A.A., A.G., G.K.); Diagnostic Imaging Department, The Hospital for Sick Children and Department of Medical Imaging, University of Toronto, Ontario, Canada (G.B.C.); Department of Radiology, Nicklaus Children's Hospital, Miami, Fla (J.I.); Department of Radiology, Children's Hospital Los Angeles, Los Angeles, Calif (H.N.N.); Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Mass (A.F.O.); Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio (M.A.R.); Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tenn (A.S.); Division of Gastroenterology, Hepatology, and Nutrition (J.E.S.) and Department of Radiology (J.H.S.), UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pa; Department of Radiology, Stanford University, Stanford, Calif (A.B.S.); Department of Radiology, Section of Pediatric Radiology, Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colo (E.R.T.); and Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Tex (G.R.S.)
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Toyoshima MTK, Cukier P, Damascena AS, Batista RL, de Azevedo Correa F, Zanatta Kawahara E, Minanni CA, Hoff AO, Nery M. Fructosamine and glycated hemoglobin as biomarkers of glycemic control in people with type 2 diabetes mellitus and cancer (GlicoOnco study). Clinics (Sao Paulo) 2023; 78:100240. [PMID: 37390617 PMCID: PMC10338289 DOI: 10.1016/j.clinsp.2023.100240] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 05/09/2023] [Accepted: 06/12/2023] [Indexed: 07/02/2023] Open
Abstract
INTRODUCTION Glycemic control is important to avoid diabetes complications in individuals with cancer. There is no evidence for HbA1c and fructosamine as reliable biomarkers in these conditions. There are particularities in caring for patients with diabetes and cancer that can alter these biomarkers. OBJECTIVE The aim of this study was to evaluate HbA1c and fructosamine as glycemic biomarkers in people with type 2 diabetes and cancer, undergoing clinical or surgical oncological treatment. METHODS The authors conducted a single-center, retrospective analysis with people who have cancer and diabetes. Comparison of glycemic biomarkers (HbA1c, fructosamine, and Self-Monitoring of Blood Glucose [SMBG]) was performed including evaluation in individuals undergoing chemotherapy, using glucocorticoids, with anemia, hypoproteinemia or with reduced estimated Glomerular Filtration Rate (eGFR). RESULTS There was a strong positive correlation between fructosamine and HbA1c (n = 318, r = 0.66, p < 0.001) in people with diabetes and cancer even in those under chemotherapy (n = 101, r = 0.61, p < 0.001) or using glucocorticoids (n = 96, r = 0.67, p<0.001). There was a strong correlation between HbA1c and fructosamine in subjects with anemia (n = 111, r = 0.66, p < 0.001), hypoproteinemia (n = 54, r = 0.67, p < 0.001), or with eGFR ≥ 60 mL/min/1.73 m2 (n = 189, r = 0.70, p < 0.001), and moderate correlation with hypoalbuminemia (n = 21, r = 0.54, p = 0.001) and with reduced eGFR (n = 67, r = 0.57, p < 0.001). The correlations between fructosamine and HbA1c with SMBG were moderate (n = 164, r = 0.49, p < 0.001; n = 111, r = 0.55, p < 0.001, respectively), strong in subjects undergoing chemotherapy, with hypoalbuminemia or hypoproteinemia, and at least moderate, if eGFR < 60 mL/min/1.73 m2 or with anemia. CONCLUSIONS Fructosamine and HbA1c can be used as glycemic biomarkers in people with diabetes and cancer, even in those with anemia, hypoproteinemia, or undergoing chemotherapy.
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Affiliation(s)
- Marcos Tadashi Kakitani Toyoshima
- Serviço de Onco-Endocrinologia, Instituto do Câncer do Estado de São Paulo Octávio Frias de Oliveira; Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
| | - Priscilla Cukier
- Serviço de Onco-Endocrinologia, Instituto do Câncer do Estado de São Paulo Octávio Frias de Oliveira; Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil; Serviço de Endocrinologia e Metabologia. Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
| | - Aline Santos Damascena
- Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
| | - Rafael Loch Batista
- Serviço de Onco-Endocrinologia, Instituto do Câncer do Estado de São Paulo Octávio Frias de Oliveira; Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
| | - Fernanda de Azevedo Correa
- Serviço de Onco-Endocrinologia, Instituto do Câncer do Estado de São Paulo Octávio Frias de Oliveira; Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
| | - Eduardo Zanatta Kawahara
- Serviço de Endocrinologia e Metabologia. Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
| | - Carlos André Minanni
- Serviço de Endocrinologia e Metabologia. Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil; Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
| | - Ana O Hoff
- Serviço de Onco-Endocrinologia, Instituto do Câncer do Estado de São Paulo Octávio Frias de Oliveira; Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
| | - Marcia Nery
- Serviço de Endocrinologia e Metabologia. Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
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Ali YA, Soliman HA, Abdel-Gabbar M, Ahmed NA, Attia KAA, Shalaby FM, El-Nahass ES, Ahmed OM. Rutin and Hesperidin Revoke the Hepatotoxicity Induced by Paclitaxel in Male Wistar Rats via Their Antioxidant, Anti-Inflammatory, and Antiapoptotic Activities. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2023; 2023:2738351. [PMID: 37275575 PMCID: PMC10238143 DOI: 10.1155/2023/2738351] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 09/09/2022] [Accepted: 09/29/2022] [Indexed: 06/07/2023]
Abstract
Paclitaxel, one of the most effective chemotherapeutic drugs, is used to treat various cancers but it is exceedingly toxic when used long-term and can harm the liver. This study aimed to see if rutin, hesperidin, and their combination could protect male Wistar rats against paclitaxel (Taxol)-induced hepatotoxicity. Adult male Wistar rats were subdivided into 5 groups (each of six rats). The normal group was orally given the equivalent volume of vehicles for 6 weeks. The paclitaxel-administered control group received intraperitoneal injection of paclitaxel at a dose of 2 mg/Kg body weight twice a week for 6 weeks. Treated paclitaxel-administered groups were given paclitaxel similar to the paclitaxel-administered control group together with oral supplementation of rutin, hesperidin, and their combination at a dose of 10 mg/Kg body weight every other day for 6 weeks. The treatment of paclitaxel-administered rats with rutin and hesperidin significantly reduced paclitaxel-induced increases in serum alanine transaminase, aspartate transaminase, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transferase activities as well as total bilirubin level and liver lipid peroxidation. However, the levels of serum albumin, liver glutathione content, and the activities of liver superoxide dismutase and glutathione peroxidase increased. Furthermore, paclitaxel-induced harmful hepatic histological changes (central vein and portal area blood vessel congestion, fatty changes, and moderate necrotic changes with focal nuclear pyknosis, focal mononuclear infiltration, and Kupffer cell proliferation) were remarkably enhanced by rutin and hesperidin treatments. Moreover, the elevated hepatic proapoptotic mediator (caspase-3) and pro-inflammatory cytokine (tumor necrosis factor-α) expressions were decreased by the three treatments in paclitaxel-administered rats. The cotreatment with rutin and hesperidin was the most effective in restoring the majority of liver function and histological integrity. Therefore, rutin, hesperidin, and their combination may exert hepatic protective effects in paclitaxel-administered rats by improving antioxidant defenses and inhibiting inflammation and apoptosis.
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Affiliation(s)
- Yasmine A. Ali
- Biochemistry Department, Faculty of Science, Beni-Suef University, P.O. Box 62521, Beni-Suef, Egypt
| | - Hanan A. Soliman
- Biochemistry Department, Faculty of Science, Beni-Suef University, P.O. Box 62521, Beni-Suef, Egypt
| | - Mohamed Abdel-Gabbar
- Biochemistry Department, Faculty of Science, Beni-Suef University, P.O. Box 62521, Beni-Suef, Egypt
| | - Noha A. Ahmed
- Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, P.O. Box 62521, Beni-Suef, Egypt
| | - Kandil A. A. Attia
- Clinical Nutrition Department, College of Applied Medical Sciences, Jazan University, P.O. Box 114, Jazan 45142, Saudi Arabia
- Department of Evaluation of Natural Resources, Environmental Studies and Research Institute, El-Sadat City University, El-Sadat City 32897, Egypt
| | - Fatma M. Shalaby
- Biology Department, Faculty of Science, King Khalid University, Abha, Saudi Arabia
- Department of Zoology, Faculty of Science, Mansoura University, Mansoura, Egypt
| | - El-Shaymaa El-Nahass
- Department of Pathology, Faculty of Veterinary Medicine, Beni-Suef University, P.O. Box 62521, Beni-Suef, Egypt
| | - Osama M. Ahmed
- Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, P.O. Box 62521, Beni-Suef, Egypt
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Escudero-Duch C, Muñoz-Moreno L, Martin-Saavedra F, Sanchez-Casanova S, Lerma-Juarez MA, Vilaboa N. Remote control of transgene expression using noninvasive near-infrared irradiation. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY. B, BIOLOGY 2023; 242:112697. [PMID: 36963296 DOI: 10.1016/j.jphotobiol.2023.112697] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Revised: 03/09/2023] [Accepted: 03/13/2023] [Indexed: 03/26/2023]
Abstract
This study investigated whether noninvasive near-infrared (NIR) energy could be transduced into heat in deep-seated organs in which adenovirus type-5 vectors tend to accumulate, thereby activating heat shock protein (HSP) promoter-mediated transgene expression, without local administration of photothermal agents. NIR irradiation of the subdiaphragmatic and left dorsocranial part of the abdominal cavity of adult immunocompetent C3H/HeNRj mice with an 808-nm laser effectively increased the temperature of the irradiated regions of the liver and spleen, respectively, resulting in the accumulation of the heat-inducible HSP70 protein. Spatial control of transgene expression was achieved in the NIR-irradiated regions of the mice administered an adenoviral vector carrying a firefly luciferase (fLuc) coding sequence controlled by a human HSP70B promoter, as assessed by bioluminescence and immunohistochemistry analyses. Levels of reporter gene expression were modulated by controlling NIR power density. Spatial control of transgene expression through NIR-focused activation of the HSP70B promoter, as well as temporal regulation by administering rapamycin was achieved in the spleens of mice inoculated with an adenoviral vector encoding a rapamycin-dependent transactivator driven by the HSP70B promoter and an adenoviral vector carrying a fLuc coding sequence controlled by the rapamycin-activated transactivator. Mice that were administered rapamycin and exposed to NIR light expressed fLuc activity in the splenic region, whereas no activity was detected in mice that were only administered rapamycin or vehicle or only NIR-irradiated. Thus, in the absence of any exogenously supplied photothermal material, remote control of heat-induced transgene expression can be achieved in the liver and spleen by means of noninvasive NIR irradiation.
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Affiliation(s)
- Clara Escudero-Duch
- CIBER de Bioingenieria, Biomateriales y Nanomedicina, CIBER-BBN, Madrid, Spain; Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain
| | - Laura Muñoz-Moreno
- CIBER de Bioingenieria, Biomateriales y Nanomedicina, CIBER-BBN, Madrid, Spain; Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain
| | - Francisco Martin-Saavedra
- CIBER de Bioingenieria, Biomateriales y Nanomedicina, CIBER-BBN, Madrid, Spain; Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain
| | - Silvia Sanchez-Casanova
- CIBER de Bioingenieria, Biomateriales y Nanomedicina, CIBER-BBN, Madrid, Spain; Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain
| | - Miguel Angel Lerma-Juarez
- CIBER de Bioingenieria, Biomateriales y Nanomedicina, CIBER-BBN, Madrid, Spain; Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain
| | - Nuria Vilaboa
- CIBER de Bioingenieria, Biomateriales y Nanomedicina, CIBER-BBN, Madrid, Spain; Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain.
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15
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Zhang D, Pan Y, Yang Z, Zeng H, Wang X, Chen J, Wang J, Zhang Y, Zhou Z, Chen M, Hu D. A Nomogram Based on Preoperative Lab Tests, BMI, ICG-R15, and EHBF for the Prediction of Post-Hepatectomy Liver Failure in Patients with Hepatocellular Carcinoma. J Clin Med 2022; 12:jcm12010324. [PMID: 36615125 PMCID: PMC9821206 DOI: 10.3390/jcm12010324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 12/15/2022] [Accepted: 12/29/2022] [Indexed: 01/03/2023] Open
Abstract
Background: Liver cancer is one of the most common malignant tumors, and worldwide, its incidence ranks sixth, and its morality third. Post-hepatectomy liver failure (PHLF) is the leading cause of death in patients who have undergone liver resection. This retrospective study investigated the risk factors for PHLF by predicting and constructing an index to evaluate the risk. This was achieved by combining the lab tests with an indocyanine green (ICG) clearance test. Methods: The study analyzed 1081 hepatocellular carcinoma (HCC) patients who had received liver resection at Sun Yat-sen University Cancer Center between 2005 and 2020. The patients were divided into a PHLF group (n = 113) and a non-PHLF group (n = 968), according to the International Study Group of Liver Surgery (ISGLS) criteria. Receiver operating characteristics (ROC) curves were then used to estimate the optimal cut-off values. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors. Finally, a nomogram was constructed where the calibration plot, the areas under the ROC curve (AUC), and the decision curve analysis (DCA) showed good predictive ability. Results: Correlation analysis revealed that body mass index (BMI) was positively correlated with ICG-R15 and with effective hepatic blood flow (EHBF). Univariate and multivariate logistics regression analysis revealed that BMI, ICG-R15, international normalized ratio (INR), tumor size, hepatic inflow occlusion (HIO) time, and operation method were independent predictive factors for PHLF. When these factors and EHBF were included in the nomogram, the nomogram showed a good predictive value, with a C-index of 0.773 (95% Confidence Interval [CI]: 0.729-0.818). The INR had the largest ROC areas (AUC INR = 0.661). Among the variables, ICG-R15 (AUC ICG-R15 = 0.604) and EHBF (AUC EHBF = 0.609) also showed good predictive power. Conclusions: The risk of PHLF in HCC patients can be precisely predicted by this model prior to the operation. By integrating EHBF into the model, HCC patients at higher risk for PHLF can be identified more effectively.
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Affiliation(s)
- Deyao Zhang
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Yangxun Pan
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Zhenyun Yang
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Huilan Zeng
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Xin Wang
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Jinbin Chen
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Juncheng Wang
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Yaojun Zhang
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Zhongguo Zhou
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Minshan Chen
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
- Correspondence: (M.C.); (D.H.); Tel.: +86-18676630499 (D.H.)
| | - Dandan Hu
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
- Correspondence: (M.C.); (D.H.); Tel.: +86-18676630499 (D.H.)
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16
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Ma L, Wang R, He Q, Huang L, Wei X, Lu X, Du Y, Luo J, Liao H. Artificial intelligence-based ultrasound imaging technologies for hepatic diseases. ILIVER 2022; 1:252-264. [DOI: 10.1016/j.iliver.2022.11.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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17
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A new NIR emission mitochondrial targetable fluorescent probe and its application in detecting viscosity changes in mouse liver and kidney injury. Talanta 2022; 249:123647. [DOI: 10.1016/j.talanta.2022.123647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 05/30/2022] [Accepted: 06/01/2022] [Indexed: 11/19/2022]
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18
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Ahmed OM, Galaly SR, Mostafa MAMA, Eed EM, Ali TM, Fahmy AM, Zaky MY. Thyme Oil and Thymol Counter Doxorubicin-Induced Hepatotoxicity via Modulation of Inflammation, Apoptosis, and Oxidative Stress. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:6702773. [PMID: 35178158 PMCID: PMC8844103 DOI: 10.1155/2022/6702773] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 11/26/2021] [Accepted: 01/02/2022] [Indexed: 12/14/2022]
Abstract
Doxorubicin (DOX) is an effective anticancer agent with a wide spectrum of activities. However, it has many adverse effects on various organs especially on the liver. Thymol, one of the major components of thyme oil, has biological properties that include anti-inflammatory and antioxidant activities. Thus, this study was designed to examine thyme oil and thymol for their ability to prevent doxorubicin-induced hepatotoxicity in Wistar rats. Hepatotoxicity was induced by an intraperitoneal injection of doxorubicin, at a dose of 2 mg/kg bw/week, for seven weeks. Doxorubicin-injected rats were supplemented with thyme oil and thymol at doses 250 and 100 mg/kg bw, respectively, four times/week by oral gavage for the same period. Treatment of rats with thyme oil and thymol reversed the high serum activities of AST, ALT, and ALP and total bilirubin, AFP, and CA19.9 levels, caused by doxorubicin. Thyme oil and thymol also reduced the high levels of TNF-α and the decreased levels of both albumin and IL-4. These agents ameliorated doxorubicin-induced elevation in hepatic lipid peroxidation and associated reduction in GSH content and GST and GPx activities. Further, the supplementation with thyme oil and thymol significantly augmented mRNA expression of the level of antiapoptotic protein Bcl-2 and significantly downregulated nuclear and cytoplasmic levels of the hepatic apoptotic mediator p53. Thus, thyme oil and thymol successfully counteracted doxorubicin-induced experimental hepatotoxicity via their anti-inflammatory, antioxidant, and antiapoptotic properties.
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Affiliation(s)
- Osama M. Ahmed
- Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, P.O. Box 62521, Beni-Suef, Egypt
| | - Sanaa R. Galaly
- Cell Biology and Histology Division, Department of Zoology, Faculty of Science, Beni-Suef University, P.O. Box 62521, Beni-Suef, Egypt
| | - Mennah-Allah M. A. Mostafa
- Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, P.O. Box 62521, Beni-Suef, Egypt
| | - Emad M. Eed
- Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
| | - Tarek M. Ali
- Department of Physiology, College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
| | - Alzhraa M. Fahmy
- Tropical Medicine and Infectious Diseases Department, Beni-Suef University Faculty of Medicine, Beni-Suef, Egypt
| | - Mohamed Y. Zaky
- Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, P.O. Box 62521, Beni-Suef, Egypt
- Department of Medical Oncology Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China
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19
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Ravaioli F, Marconi G, Martinelli G, Dajti E, Sartor C, Abbenante MC, Alemanni LV, Nanni J, Rossini B, Parisi S, Colecchia L, Cristiano G, Marasco G, Vestito A, Paolini S, Bonifazi F, Curti A, Festi D, Cavo M, Colecchia A, Papayannidis C. Assessment of liver stiffness measurement and ultrasound findings change during inotuzumab ozogamicin cycles for relapsed or refractory acute lymphoblastic leukemia. Cancer Med 2021; 11:618-629. [PMID: 34970853 PMCID: PMC8817094 DOI: 10.1002/cam4.4390] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 09/10/2021] [Accepted: 09/16/2021] [Indexed: 12/20/2022] Open
Abstract
In adult patients, acute lymphoblastic leukemia (ALL) is a rare hematological cancer with a cure rate below 50% and frequent relapses. With traditional therapies, patients with relapsed or refractory (R/R) ALL have a survival that may be measured in months; in these patients, inotuzumab ozogamicin (IO) is an effective therapy. IO was linked to increased risk of veno-occlusive disease/sinusoid obstruction syndrome (VOD/SOS), liver injury, and various grade of liver-related complications during clinical trials and real-life settings; however, hepatologic monitoring protocol is not established in this population. In our institution, 21 patients who received IO (median of 6 doses of IO administered) for R/R ALL were prospectively followed for hepatologic surveillance, including clinical evaluation, ultrasonography, and liver stiffness measurement (LSM) biochemistry. After a median follow-up of 17.2 months, two SOS events were reported (both after allogeneic transplant) as IO potentially related clinically relevant adverse event. Mild alterations were reported in almost the totality of patients and moderate-severe liver biochemical alterations in a quarter of patients. Within biochemicals value, AST and ALP showed an augment related to IO administration. LSM linearly augmented for each IO course administered. Baseline LSM was related to liver-related changes, especially with the severity of portal hypertension (PH)-related complications. Pre-transplant LSM was higher in patients receiving IO when compared with a control cohort. PH-related complications were discovered in nearly 77% of patients, with clinically significant PH occurrence and development of ascites in 38% and 14%, respectively. This prospective experience constitutes the rationale to design a hepatologic monitoring program in patients receiving IO. LSM may be of pivotal importance in this program, constituting a rapid and effective screening that quantitatively correlates with liver alterations.
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Affiliation(s)
- Federico Ravaioli
- IRCCS Azienda Ospedaliero-Universitaria di Bologna Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Università di Bologna, Bologna, Italy
| | - Giovanni Marconi
- IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia "Seràgnoli" Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy.,IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Giovanni Martinelli
- IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Elton Dajti
- IRCCS Azienda Ospedaliero-Universitaria di Bologna Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Università di Bologna, Bologna, Italy
| | - Chiara Sartor
- IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia "Seràgnoli" Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy
| | - Maria Chiara Abbenante
- IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia "Seràgnoli" Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy
| | - Luigina Vanessa Alemanni
- IRCCS Azienda Ospedaliero-Universitaria di Bologna Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Università di Bologna, Bologna, Italy
| | - Jacopo Nanni
- IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia "Seràgnoli", Bologna, Italy
| | - Benedetta Rossini
- IRCCS Azienda Ospedaliero-Universitaria di Bologna Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Università di Bologna, Bologna, Italy
| | - Sarah Parisi
- IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia "Seràgnoli", Bologna, Italy
| | - Luigi Colecchia
- IRCCS Azienda Ospedaliero-Universitaria di Bologna Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Università di Bologna, Bologna, Italy
| | - Gianluca Cristiano
- IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia "Seràgnoli", Bologna, Italy
| | - Giovanni Marasco
- IRCCS Azienda Ospedaliero-Universitaria di Bologna Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Università di Bologna, Bologna, Italy
| | - Amanda Vestito
- IRCCS Azienda Ospedaliero-Universitaria di Bologna Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Università di Bologna, Bologna, Italy
| | - Stefania Paolini
- IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia "Seràgnoli", Bologna, Italy
| | - Francesca Bonifazi
- Programma Dipartimentale di Terapie Cellulari Avanzate, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Antonio Curti
- IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia "Seràgnoli", Bologna, Italy
| | - Davide Festi
- IRCCS Azienda Ospedaliero-Universitaria di Bologna Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Università di Bologna, Bologna, Italy
| | - Michele Cavo
- IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia "Seràgnoli" Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy.,IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia "Seràgnoli", Bologna, Italy
| | - Antonio Colecchia
- Gastroenterology Unit, Department of Medical Specialties, University of Modena & Reggio Emilia and Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
| | - Cristina Papayannidis
- IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia "Seràgnoli", Bologna, Italy
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20
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Wang C, Yuan Z, Sun Y, Yao X, Li R, Li S. Effect of Chronic Exposure to Textile Wastewater Treatment Plant Effluents on Growth Performance, Oxidative Stress, and Intestinal Microbiota in Adult Zebrafish ( Danio rerio). Front Microbiol 2021; 12:782611. [PMID: 34899664 PMCID: PMC8656261 DOI: 10.3389/fmicb.2021.782611] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 10/28/2021] [Indexed: 01/30/2023] Open
Abstract
The ever-increasing production and processing of textiles will lead to greater risks of releasing pollutants into the environment. Textile wastewater treatment plants (TWTPs) effluent are an important source of persistent toxic pollutants in receiving water bodies. The effects of specific pollutants on organisms are usually studied under laboratory conditions, and therefore, comprehensive results are not obtained regarding the chronic combined effects of pollutants under aquatic environmental conditions. Thus, this study aimed to determine the combined effects of TWTP effluents on the growth performance, oxidative stress, inflammatory response, and intestinal microbiota of adult zebrafish (Danio rerio). Exposure to TWTP effluents significantly inhibited growth, exacerbated the condition factor, and increased the mortality of adult zebrafish. Moreover, markedly decreases were observed in the activities of antioxidant enzymes, such as CAT, GSH, GSH-Px, MDA, SOD, and T-AOC, mostly in the intestine and muscle tissues of zebrafish after 1 and 4 months of exposure. In addition, the results demonstrated that TWTP effluent exposure affected the intestinal microbial community composition and decreased community diversity. Slight changes were found in the relative abundance of probiotic Lactobacillus, Akkermansia, and Lactococcus in zebrafish guts after chronic TWTP effluent exposure. The chronic toxic effects of slight increases in opportunistic pathogens, such as Mycoplasma, Stenotrophomonas, and Vibrio, deserve further attention. Our results reveal that TWTP effluent exposure poses potential health risks to aquatic organisms through growth inhibition, oxidative stress impairment of the intestine and muscles, and intestinal microbial community alterations.
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Affiliation(s)
- Chun Wang
- School of Ecology and Environment, Beijing Technology and Business University, Beijing, China.,State Environmental Protection Key Laboratory of Food Chain Pollution Control, Beijing Technology and Business University, Beijing, China
| | - Zixi Yuan
- School of Ecology and Environment, Beijing Technology and Business University, Beijing, China.,State Environmental Protection Key Laboratory of Food Chain Pollution Control, Beijing Technology and Business University, Beijing, China
| | - Yingxue Sun
- School of Ecology and Environment, Beijing Technology and Business University, Beijing, China.,State Environmental Protection Key Laboratory of Food Chain Pollution Control, Beijing Technology and Business University, Beijing, China
| | - Xiaolong Yao
- School of Ecology and Environment, Beijing Technology and Business University, Beijing, China.,State Environmental Protection Key Laboratory of Food Chain Pollution Control, Beijing Technology and Business University, Beijing, China
| | - Ruixuan Li
- School of Ecology and Environment, Beijing Technology and Business University, Beijing, China.,State Environmental Protection Key Laboratory of Food Chain Pollution Control, Beijing Technology and Business University, Beijing, China
| | - Shuangshuang Li
- College of Energy and Environmental Engineering, Hebei University of Engineering, Handan, China
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21
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Calistri L, Rastrelli V, Nardi C, Maraghelli D, Vidali S, Pietragalla M, Colagrande S. Imaging of the chemotherapy-induced hepatic damage: Yellow liver, blue liver, and pseudocirrhosis. World J Gastroenterol 2021; 27:7866-7893. [PMID: 35046618 PMCID: PMC8678821 DOI: 10.3748/wjg.v27.i46.7866] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 06/15/2021] [Accepted: 11/29/2021] [Indexed: 02/06/2023] Open
Abstract
The liver is the major drug-metabolizing and drug-detoxifying organ. Many drugs can cause liver damage through various mechanisms; however, the liver response to injury includes a relatively narrow spectrum of alterations that, regardless of the cause, are represented by phlogosis, oxidative stress and necrosis. The combination of these alterations mainly results in three radiological findings: vascular alterations, structural changes and metabolic function reduction. Chemotherapy has changed in recent decades in terms of the drugs, protocols and duration, allowing patients a longer life expectancy. As a consequence, we are currently observing an increase in chemotherapy-associated liver injury patterns once considered unusual. Recognizing this form of damage in an early stage is crucial for reconsidering the therapy regimen and thus avoiding severe complications. In this frontier article, we analyze the role of imaging in detecting some of these pathological patterns, such as pseudocirrhosis, “yellow liver” due to chemotherapy-associated steatosis-steatohepatitis, and “blue liver”, including sinusoidal obstruction syndrome, veno-occlusive disease and peliosis.
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Affiliation(s)
- Linda Calistri
- Department of Experimental and Clinical Biomedical Sciences Mario Serio, University of Florence, Azienda Ospedaliera Universitaria Careggi, Florence 50134, Italy
| | - Vieri Rastrelli
- Department of Experimental and Clinical Biomedical Sciences Mario Serio, University of Florence, Azienda Ospedaliera Universitaria Careggi, Florence 50134, Italy
| | - Cosimo Nardi
- Department of Experimental and Clinical Biomedical Sciences Mario Serio, University of Florence, Azienda Ospedaliera Universitaria Careggi, Florence 50134, Italy
| | - Davide Maraghelli
- Department of Experimental and Clinical Biomedical Sciences Mario Serio, University of Florence, Azienda Ospedaliera Universitaria Careggi, Florence 50134, Italy
| | - Sofia Vidali
- Department of Experimental and Clinical Biomedical Sciences Mario Serio, University of Florence, Azienda Ospedaliera Universitaria Careggi, Florence 50134, Italy
| | - Michele Pietragalla
- Department of Experimental and Clinical Biomedical Sciences Mario Serio, University of Florence, Azienda Ospedaliera Universitaria Careggi, Florence 50134, Italy
| | - Stefano Colagrande
- Department of Experimental and Clinical Biomedical Sciences Mario Serio, University of Florence, Azienda Ospedaliera Universitaria Careggi, Florence 50134, Italy
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22
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Hepatotoxicity associated with PD-1 blockade antibodies in cancer patients co-infected with hepatitis B virus. Cancer Immunol Immunother 2021; 71:1247-1255. [PMID: 34647153 DOI: 10.1007/s00262-021-03082-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 10/01/2021] [Indexed: 12/19/2022]
Abstract
The use of anti-programmed cell death-1 (PD-1) antibodies in treating malignancies is increasing; however, most registered clinical trials on anti-PD-1 antibodies exclude patients infected with hepatitis B virus (HBV). This retrospective study aimed to assess hepatotoxicity in cancer patients infected with HBV undergoing anti-PD1 antibody therapy and identify the associated risk factors. A total of 301 cancer patients positive for hepatitis B core antibodies (HbcAb) (negative or positive hepatitis B surface antigen [HBsAg]) who received PD-1 inhibitors were enrolled. The primary and secondary endpoints were the incidence rate of hepatotoxicity related to PD-1 inhibitor treatment, and risk factors associated with hepatic toxicity, respectively. Of the enrolled analyzed, 16.9% (n = 51) developed any grade and 4.7% (n = 14) developed grade 3-4 hepatotoxicity, respectively. Higher risk for any-grade hepatotoxicity development was associated with sero-positive HBsAg (OR = 6.30; P = 0.020), existence of liver involvement (OR = 2.10; P = 0.030), and detectable baseline HBV DNA levels (OR = 2.39; P = 0.012). Patients with prophylactic antiviral therapy decreased hazard for the incidence of grade 3-4 hepatotoxicity (OR = 0.10; P = 0.016). Our results suggested chronic (HBsAg-positive)/resolved (HBsAg-negative and HBcAb-positive) HBV-infected cancer patients are at an increased risk of hepatotoxicity following PD-1 inhibitor therapy. Cancer patients should be tested for HBsAg/HBcAb prior to the commencement of immune checkpoint inhibitor therapy. For patients with chronic/resolved HBV infection, ALT/AST and HBV DNA should be closely monitored during the whole immunotherapy period.
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23
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Bardi E, Mulder RL, van Dalen EC, Bhatt NS, Ruble KA, Burgis J, Castellino SM, Constine LS, den Hoed CM, Green DM, Koot BGP, Levitt G, Szonyi L, Wallace WH, Skinner R, Hudson MM, Kremer LCM, Effinger KE, Bresters D. Late hepatic toxicity surveillance for survivors of childhood, adolescent and young adult cancer: Recommendations from the international late effects of childhood cancer guideline harmonization group. Cancer Treat Rev 2021; 100:102296. [PMID: 34571378 DOI: 10.1016/j.ctrv.2021.102296] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 09/13/2021] [Accepted: 09/14/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND Survivors of childhood, adolescent and young adult (CAYA) cancer may develop treatment-induced chronic liver disease. Surveillance guidelines can improve survivors' health outcomes. However, current recommendations vary, leading to uncertainty about optimal screening. The International Late Effects of Childhood Cancer Guideline Harmonization Group has developed recommendations for the surveillance of late hepatotoxicity after CAYA cancer. METHODS Evidence-based methods based on the GRADE framework were used in guideline development. A multidisciplinary guideline panel performed systematic literature reviews, developed evidence summaries, appraised the evidence, and formulated recommendations on the basis of evidence, clinical judgement, and consideration of benefits versus the harms of the surveillance while allowing for flexibility in implementation across different health care systems. RESULTS The guideline strongly recommends a physical examination and measurement of serum liver enzyme concentrations (ALT, AST, gGT, ALP) once at entry into long-term follow-up for survivors treated with radiotherapy potentially exposing the liver (moderate- to high-quality evidence). For survivors treated with busulfan, thioguanine, mercaptopurine, methotrexate, dactinomycin, hematopoietic stem cell transplantation (HSCT), or hepatic surgery, or with a history of chronic viral hepatitis or sinusoidal obstruction syndrome, similar surveillance for late hepatotoxicity once at entry into LTFU is reasonable (low-quality evidence/expert opinion, moderate recommendation). For survivors who have undergone HSCT and/or received multiple red blood cell transfusions, surveillance for iron overload with serum ferritin is strongly recommended once at long-term follow-up entry. CONCLUSIONS These evidence-based, internationally-harmonized recommendations for the surveillance of late hepatic toxicity in cancer survivors can inform clinical care and guide future research of health outcomes for CAYA cancer survivors.
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Affiliation(s)
- Edit Bardi
- St. Anna Children's Hospital, Vienna, Austria; Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Kepler University Hospital, Linz, Austria.
| | - Renée L Mulder
- Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands
| | | | - Neel S Bhatt
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Kathy A Ruble
- Division of Pediatric Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
| | - Jennifer Burgis
- Division of Pediatric Gastroenterology, University of California San Francisco, San Francisco, CA, USA
| | - Sharon M Castellino
- Department of Pediatrics at Emory University School of Medicine, and Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA, USA
| | - Louis S Constine
- Departments of Radiation Oncology and Pediatrics, University of Rochester Medical Center, Rochester, NY, USA
| | - Caroline M den Hoed
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
| | - Daniel M Green
- Departments of Oncology and Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Bart G P Koot
- Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Gill Levitt
- Department of Paediatric Oncology, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK
| | - László Szonyi
- Semmelweis University, I. Pediatric Department, Budapest, Hungary
| | - W Hamish Wallace
- Department of Paediatric Haematology and Oncology, Royal Hospital for Sick Children, Edinburgh, UK
| | - Roderick Skinner
- Department of Paediatric and Adolescent Haematology/Oncology, Great North Children's Hospital and Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK
| | - Melissa M Hudson
- Departments of Oncology and Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, USA
| | | | - Karen E Effinger
- Department of Pediatrics at Emory University School of Medicine, and Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA, USA
| | - Dorine Bresters
- Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands
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24
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Senk K, Wilcke J, Haimerl M, Verloh N, Rio Bartulos C, Bäumler W, Stroszczynski C, Wiggermann P. Prediction of transarterial chemoembolization (TACE) outcome by pre- and postinterventional 13C-methacetin breath test. Clin Hemorheol Microcirc 2021; 79:73-80. [PMID: 34487035 DOI: 10.3233/ch-219118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND AND OBJECTIVE Liver function is one of the most important parameters for the outcome of transarterial chemoembolization (TACE). The liver maximum capacity (LiMAx) test is a bedside test that provides a real-time option for liver function testing. The objective of this pilot study was to investigate the suitability of the LiMAX test for predicting the TACE outcome. METHODS 20 patients with intermediate-stage hepatocellular carcinoma (HCC) received a LiMAx test 24 h pre and post TACE. In addition, laboratory values were collected to determine liver function and model for endstage liver disease (MELD) scores. The success of TACE was assessed 6 weeks post intervention by morphological imaging tests using modified response evaluation criteria in solid tumors (mRECIST). RESULTS Patients with an objective response (OR = CR + PR) according to mRECIST post TACE had significantly higher values in the pre-interventional LiMAx test than patients with a non-OR (PD or SD) post TACE (r(14) = 0.62, p = 0.01). Higher pre-interventional LiMAx values therefore indicate OR. Patients with a disease control (DC = CR + PR + SD) according to mRECIST post TACE had significantly higher values in the pre-interventional LiMAx test than patients with a non-DC (PD) post TACE (r(14) = 0.65, p = 0.01). Higher pre-interventional LiMAx values therefore indicate DC. The point biserial correlations of LiMAx values pre and post TACE with the outcome OR or DC were descriptively stronger than those of MELD with OR or DC. This suggests that the LiMAx test correlates better with the treatment response than the MELD score. CONCLUSIONS For the first time, we were able to show in our study that patients who are scheduled for TACE could benefit from a LiMAx test to be able to estimate the benefit of TACE. The higher the pre-interventional LiMAx values, the higher the benefit of TACE. On the other hand, laboratory parameters summarized in the form of the MELD score had significantly less descriptive correlation with the TACE outcome.
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Affiliation(s)
- Karin Senk
- Institut für Röntgendiagnostik, Universtitätsklinikum Regensburg, Regensburg, Germany
| | - Juliane Wilcke
- Institut für Psychologie, Universität Kassel, Kassel, Germany
| | - Michael Haimerl
- Institut für Röntgendiagnostik, Universtitätsklinikum Regensburg, Regensburg, Germany
| | - Niklas Verloh
- Institut für Röntgendiagnostik, Universtitätsklinikum Regensburg, Regensburg, Germany
| | - Carolina Rio Bartulos
- Institut für Röntgendiagnostik und Nuklearmedizin, Städtisches Klinikum Braunschweig gGmbH, Braunschweig, Germany
| | - Wolf Bäumler
- Institut für Röntgendiagnostik, Universtitätsklinikum Regensburg, Regensburg, Germany
| | | | - Philipp Wiggermann
- Institut für Röntgendiagnostik und Nuklearmedizin, Städtisches Klinikum Braunschweig gGmbH, Braunschweig, Germany
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25
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Palmieri C, Macpherson IR. A review of the evidence base for utilizing Child-Pugh criteria for guiding dosing of anticancer drugs in patients with cancer and liver impairment. ESMO Open 2021; 6:100162. [PMID: 34098229 PMCID: PMC8190488 DOI: 10.1016/j.esmoop.2021.100162] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 04/12/2021] [Accepted: 05/05/2021] [Indexed: 12/24/2022] Open
Abstract
As the liver is vital for the metabolism of many anticancer drugs, determining the correct starting doses in cancer patients with liver impairment is key to safe prescription and prevention of unnecessary adverse effects. Clinicians typically use liver function tests when evaluating patients; however, prescribing information and summaries of product characteristics often suggest dosing of anticancer drugs in patients with liver impairment based on the Child-Pugh criteria, even though the criteria were not developed for this purpose. In this review, we assessed all the oncological small molecule and cytotoxic drugs approved by the United States Food and Drug Administration (FDA) over a 5-year period from 2014 to 2018. The various entry criteria related to these drugs—with respect to hepatic function—in key pivotal studies were compared with their approved dosing recommendations found in prescribing information and summaries of product characteristics. We found that 46% of drugs have dosing recommendations based on Child-Pugh criteria alone, despite the fact that only 8% of these drugs were tested within studies that used the Child-Pugh criteria as entry criteria. Moreover, we note that the data used to make recommendations based on Child-Pugh criteria are typically from small studies that may lack an appropriate patient population. We propose that these findings, along with details surrounding the development of the Child-Pugh criteria, call into question the validity and appropriateness of using Child-Pugh criteria for dosing recommendations of anticancer drugs.
Dosing information for anticancer drugs in patients with liver impairment is often based on the Child-Pugh criteria. Clinical trials and clinicians typically use liver function tests when evaluating patients. Of the 39 oncologic drugs examined, almost half (46%) had dosing recommendations based on Child-Pugh criteria alone. We question whether using Child-Pugh criteria for dosing recommendations of anticancer drugs is the best approach.
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Affiliation(s)
- C Palmieri
- Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK; Academic Department of Medical Oncology, The Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, UK.
| | - I R Macpherson
- Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
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26
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Ishikawa J, Takeo M, Iwadate A, Koya J, Kihira M, Oshima M, Suzuki Y, Taniguchi K, Kobayashi A, Tsuji T. Mechanical homeostasis of liver sinusoid is involved in the initiation and termination of liver regeneration. Commun Biol 2021; 4:409. [PMID: 33828226 PMCID: PMC8027462 DOI: 10.1038/s42003-021-01936-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Accepted: 02/23/2021] [Indexed: 12/12/2022] Open
Abstract
Organogenesis and regeneration are fundamental for developmental progress and are associated with morphogenesis, size control and functional properties for whole-body homeostasis. The liver plays an essential role in maintaining homeostasis of the entire body through various functions, including metabolic functions, detoxification, and production of bile, via the three-dimensional spatial arrangement of hepatic lobules and has high regenerative capacity. The regeneration occurs as hypertrophy, which strictly controls the size and lobule structure. In this study, we established a three-dimensional sinusoidal network analysis method and determined valuable parameters after partial hepatectomy by comparison to the static phase of the liver. We found that mechanical homeostasis, which is crucial for organ morphogenesis and functions in various phenomena, plays essential roles in liver regeneration for both initiation and termination of liver regeneration, which is regulated by cytokine networks. Mechanical homeostasis plays critical roles in the initiation and termination of organogenesis, tissue repair and organ regeneration in coordination with cytokine networks.
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Affiliation(s)
- Jun Ishikawa
- Laboratory for Organ Regeneration, RIKEN Center for Developmental Biology (CDB) and RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Hyogo, Japan
- Department of Biological Science and Technology, Graduate School of Industrial Science and Technology, Tokyo University of Science, Noda, Chiba, Japan
| | - Makoto Takeo
- Laboratory for Organ Regeneration, RIKEN Center for Developmental Biology (CDB) and RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Hyogo, Japan
| | - Ayako Iwadate
- Department of Biological Science and Technology, Graduate School of Industrial Science and Technology, Tokyo University of Science, Noda, Chiba, Japan
| | - Junko Koya
- Department of Biological Science and Technology, Graduate School of Industrial Science and Technology, Tokyo University of Science, Noda, Chiba, Japan
| | - Miho Kihira
- Department of Biological Science and Technology, Graduate School of Industrial Science and Technology, Tokyo University of Science, Noda, Chiba, Japan
| | - Masamitsu Oshima
- Laboratory for Organ Regeneration, RIKEN Center for Developmental Biology (CDB) and RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Hyogo, Japan
- Department of Stomatognathic Function and Occlusal Reconstruction, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan
| | - Yuki Suzuki
- Department of Biological Science and Technology, Graduate School of Industrial Science and Technology, Tokyo University of Science, Noda, Chiba, Japan
| | - Kazushi Taniguchi
- Department of Biological Science and Technology, Graduate School of Industrial Science and Technology, Tokyo University of Science, Noda, Chiba, Japan
| | - Ayaka Kobayashi
- Department of Biological Science and Technology, Graduate School of Industrial Science and Technology, Tokyo University of Science, Noda, Chiba, Japan
| | - Takashi Tsuji
- Laboratory for Organ Regeneration, RIKEN Center for Developmental Biology (CDB) and RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Hyogo, Japan.
- Department of Biological Science and Technology, Graduate School of Industrial Science and Technology, Tokyo University of Science, Noda, Chiba, Japan.
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27
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Sobotka LA, Chen JL, Wellner MR. Compression induced hepatic injury: an unusual case of abnormal liver function tests. Clin Res Hepatol Gastroenterol 2021; 45:101655. [PMID: 33636363 DOI: 10.1016/j.clinre.2021.101655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Accepted: 02/12/2021] [Indexed: 02/04/2023]
Affiliation(s)
- Lindsay A Sobotka
- Division of Internal Medicine, Department of Gastroenterology, Hepatology and Nutrition, The Ohio State Wexner Medical Center, 410 West 10th Avenue, Columbus, OH 43210, United States
| | - James L Chen
- Division of Internal Medicine, Department of Medical Oncology, The James Cancer Hospital Solove Research Institute, The Ohio State University, United States
| | - Michael R Wellner
- Division of Internal Medicine, Department of Gastroenterology, Hepatology and Nutrition, The Ohio State Wexner Medical Center, 410 West 10th Avenue, Columbus, OH 43210, United States.
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28
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Hamid N, Junaid M, Wang Y, Pu SY, Jia PP, Pei DS. Chronic exposure to PPCPs mixture at environmentally relevant concentrations (ERCs) altered carbohydrate and lipid metabolism through gut and liver toxicity in zebrafish. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2021; 273:116494. [PMID: 33486247 DOI: 10.1016/j.envpol.2021.116494] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Revised: 12/19/2020] [Accepted: 01/08/2021] [Indexed: 06/12/2023]
Abstract
Pharmaceuticals and personal care products (PPCPs) have been widely distributed and posed ecotoxicological risks in the aquatic environment. This study aims to evaluate the toxic effects after chronic exposure to PPCPs mixture at the environment relevant concentrations (ERCs). Our results indicated that PPCPs induced serious metabolic effects by disturbing the carbohydrate and lipid metabolism pathways. Chronic exposure caused a significant reduction in the hepatosomatic index (HSI), the gut weight ratios, and histological alterations in liver and gut tissues. Further, exposure to the combined PPCPs disrupted the carbohydrate metabolism via significant upregulation of hk1, gk, pck1, and insr genes. The lipid metabolism was affected with higher ppars expression levels that increased the fatty acid β-oxidation and ultimately decreased the lipidogenesis. Moreover, the altered responses of the insulin growth factor (IGF) pathway more in male gut tissue than that of female revealed sex-dependent disturbance in the gut homeostasis induced by PPCPs mixture. In conclusion, chronic exposure to PPCPs mixtures at ERCs can induce developmental effects and metabolic dysfunction in both male and female fish. The consumption and environmental disposal of these PPCPs should be regulated to ensure ecological health and environmental safety.
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Affiliation(s)
- Naima Hamid
- Key Laboratory of Reservoir Aquatic Environment, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, China; University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Muhammad Junaid
- Key Laboratory of Reservoir Aquatic Environment, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, China
| | - Yan Wang
- Key Laboratory of Reservoir Aquatic Environment, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, China; University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Shi-Ya Pu
- Key Laboratory of Reservoir Aquatic Environment, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, China; University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Pan-Pan Jia
- Key Laboratory of Reservoir Aquatic Environment, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, China
| | - De-Sheng Pei
- Key Laboratory of Reservoir Aquatic Environment, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, China; University of Chinese Academy of Sciences, Beijing, 100049, China; College of Life Science, Henan Normal University, Xinxiang, 453007, Henan, China.
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29
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Qader G, Aali M, Smail SW, Mahmood K, Hasan B, M-Amen K, Rahman DB, Qadir FA, Mohammad DK, Najmuldeen HH, Rahman FM, Ahmad SI, Salih NS, Khdhr ZM, Mohammed BA, Majeed AM, Hasan XM, Khidhir BH, Muhammad ES, Muhamadsalih BA, Hasan SK, Hamad AJ, Esmail ZK, Ismael CM, Husaen SM, Abdulla CA, Hussen BM, Housein Z, Shekha M, Salihi A. Cardiac, Hepatic and Renal Dysfunction and IL-18 Polymorphism in Breast, Colorectal, and Prostate Cancer Patients. Asian Pac J Cancer Prev 2021; 22:131-137. [PMID: 33507690 PMCID: PMC8184168 DOI: 10.31557/apjcp.2021.22.1.131] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Indexed: 11/25/2022] Open
Abstract
INTRODUCTION The present study aimed to determine the alterations in the serum levels of tumor markers used to evaluate cardiac, renal and liver function, and detect the interleukin (IL)-18 rs1946518 polymorphism in breast (BC), colorectal (CRC) and prostate cancer (PCa) patients. METHODS Blood samples were collected from 65 female BC, 116 CRC, 79 PCa and 88 myocardial infarction (MI) patients, and 110 healthy individuals to determine the concentration of tumor and cardiac markers. Furthermore, the IL-18 rs1946518 polymorphism was assessed using amplification refractory mutation system (ARMS)-PCR. RESULTS The serum levels of the tumor markers cancer antigen 15-3 (CA 15-3), carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA) and total prostate-specific antigen (TPSA) were significantly increased in cancer patients compared with healthy controls. Furthermore, the activity of high-sensitivity cardiac troponin T (hs-cTnT) and creatine kinase‑myocardial band (CK-MB) was enhanced in MI patients, however, their activity was unchanged in cancer patients. The activity of alkaline phosphatase (ALP), and the serum concentration of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and urea were markedly elevated in CRC and PCa patients, respectively, compared with the control group. Although, no significant differences were observed in the -607 C/A polymorphism and allele frequency of IL-18 among BC, CRC patients and healthy individuals, the odds ratio (OR) was 1.75 for both C and A allele in BC patients. Therefore, the -607 C/A polymorphism could be considered as a risk factor for BC. CONCLUSION The aforementioned results suggested that tumor markers could be considered as excellent biomarkers for the early detection of BC, CRC and PCa, whereas the concentration of liver enzymes could serve as an alternative indicator for the diagnosis of CRC and PCa. Additionally, the rs1946518 polymorphism in the IL-18 gene could be considered as a risk factor for the occurrence of BC, CRC and PCa.<br />.
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Affiliation(s)
- Govand Qader
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Mukhlis Aali
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Shukur W Smail
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq.,Department of Medical Analysis, Faculty of Science, Tishk International University, Erbil, Iraq
| | - Kazhan Mahmood
- Department of Midwifery, College of Nursing, Hawler Medical University, Erbil, Kurdistan Region, Iraq
| | - Bestoon Hasan
- Department of Cancer Registry, Cancer Control Unit, Erbil Directorate of Health, Erbil, Iraq
| | - Karwan M-Amen
- Department of Medical Analysis, Faculty of Science, Tishk International University, Erbil, Iraq.,Department of Nursing, College of Nursing, Hawler Medical University, Erbil, Kurdistan Region, Iraq
| | - Dlzar Bayz Rahman
- Internal Laboratory, Hawler Teaching Hospital, Erbil Directorate of Health, Erbil, Iraq
| | - Fikry A Qadir
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Dara K Mohammad
- College of Agricultural Engineering Sciences, Salahaddin University-Erbil, Erbil, Kurdistan Region, Iraq.,Center for Hematology and Regenerative Medicine (HERM), Department of Medicine Huddinge, Karolinska Institutet, 141 83 Stockholm, Sweden
| | - Hastyar H Najmuldeen
- Department of Biology, College of Science, University of Sulaimani, Kurdistan Region, Iraq.,Medical Laboratory Analysis, Cihan University-Sulaimaniya, Slemani, Iraq
| | - Fryad Majeed Rahman
- Department of Biology, College of Science, University of Sulaimani, Kurdistan Region, Iraq
| | - Seepal Ibrahim Ahmad
- Emergency Hospital, Duhok General Health Directorate, Duhok, Kurdistan Region, Iraq
| | - Nergz S Salih
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Zainab M Khdhr
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Bushra A Mohammed
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Asuda M Majeed
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Xanda M Hasan
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Bushra H Khidhir
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Eman S Muhammad
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Bahar A Muhamadsalih
- Department of Pathological Analysis, Faculty of Science, University of Knowledge, Erbil, Kurdistan Region, Iraq
| | - Simav K Hasan
- Department of Pathological Analysis, Faculty of Science, University of Knowledge, Erbil, Kurdistan Region, Iraq
| | - Aram J Hamad
- Department of Pathological Analysis, Faculty of Science, University of Knowledge, Erbil, Kurdistan Region, Iraq
| | - Zahra K Esmail
- Department of Pathological Analysis, Faculty of Science, University of Knowledge, Erbil, Kurdistan Region, Iraq
| | - Chra M Ismael
- Department of Pathological Analysis, Faculty of Science, University of Knowledge, Erbil, Kurdistan Region, Iraq
| | - Shan M Husaen
- Department of Pathological Analysis, Faculty of Science, University of Knowledge, Erbil, Kurdistan Region, Iraq
| | - Chiavan A Abdulla
- Department of Pathological Analysis, Faculty of Science, University of Knowledge, Erbil, Kurdistan Region, Iraq
| | - Bashdar M Hussen
- College of Pharmacy, Hawler Medical University, Kurdistan Region, Iraq
| | - Zjwan Housein
- Department of Medical Laboratory Technology, Health Technical College, Erbil Polytechnic University, Erbil, Iraq
| | - Mudhir Shekha
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Abbas Salihi
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq.,Department of Nursing, College of Nursing, Hawler Medical University, Erbil, Kurdistan Region, Iraq
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30
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Honmyo N, Kobayashi T, Kuroda S, Oshita A, Onoe T, Kohashi T, Fukuda S, Ohmori I, Abe T, Imaoka Y, Akita T, Tanaka J, Ohdan H. A novel model for predicting posthepatectomy liver failure based on liver function and degree of liver resection in patients with hepatocellular carcinoma. HPB (Oxford) 2021; 23:134-143. [PMID: 32563594 DOI: 10.1016/j.hpb.2020.05.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 04/23/2020] [Accepted: 05/13/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND The permissible liver resection rate for preventing posthepatectomy liver failure (PHLF) remains unclear. We aimed to develop a novel PHLF-predicting model and to strategize hepatectomy for hepatocellular carcinoma (HCC). METHODS This retrospective study included 335 HCC patients who underwent anatomical hepatectomy at eight institutions between 2013 and 2017. Risk factors, including volume-associated liver-estimating parameters, for PHLF grade B-C were analyzed in a training set (n = 122) via multivariate analysis, and a PHLF prediction model was developed. The utility of the model was evaluated in a validation set (n = 213). RESULTS Our model was based on the three independent risk factors for PHLF identified in the training set: volume-associated indocyanine green retention rate at 15 min, platelet count, and prothrombin time index (the VIPP score). The areas under the receiver operating characteristic curve of the VIPP scores for severe PHLF in the training and validation sets were 0.864 and 0.794, respectively. In both sets, the VIPP score stratified patients at risk for severe PHLF, with a score of 3 (specificity, 0.92) indicating higher risk. CONCLUSION Our model facilitates the selection of the appropriate hepatectomy procedure by providing permissible liver resection rates based on VIPP scores.
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Affiliation(s)
- Naruhiko Honmyo
- Department of Gastroenterological and Transplant Surgery, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan.
| | - Shintaro Kuroda
- Department of Gastroenterological and Transplant Surgery, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan
| | - Akihiko Oshita
- Department of Gastroenterological, Breast, and Transplant Surgery, Hiroshima Prefectural Hospital, 1-5-54 Ujinakanda, Minami-ku, Hiroshima, Japan
| | - Takashi Onoe
- Department of Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, 3-1 Aoyamacho, Kure, Japan
| | - Toshihiko Kohashi
- Department of Surgery, Hiroshima City Asa Citizens Hospital, 2-1-1 Kabeminami, Asakita-ku, Hiroshima, Japan
| | - Saburo Fukuda
- Department of Surgery, Chugoku Rosai Hospital, 1-5-1 Hirotagaya, Kure, Japan
| | - Ichiro Ohmori
- Department of Surgery, National Hospital Organization Higashihiroshima Medical Center, 513 Saijochojike, Higashihiroshima, Japan
| | - Tomoyuki Abe
- Department of Surgery, Onomichi General Hospital, 1-10-23 Hirahara, Onomichi, Japan
| | - Yasuhiro Imaoka
- Department of Surgery, National Hospital Organization Hiroshima-nishi Medical Center, 4-4-1 Kuba, Otake, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan
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Menakh M, Boutellaa S, Mahdi D, Zellagui A, Lahouel M, Ozturk M. Hepatoprotective effects of Hertia cheirifolia butanolic extract and selenium against CCl 4-induced toxicity in rats. JOURNAL OF REPORTS IN PHARMACEUTICAL SCIENCES 2021. [DOI: 10.4103/jrptps.jrptps_25_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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32
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O'Leary C, Soulen MC, Shamimi-Noori S. Interventional Oncology Approach to Hepatic Metastases. Semin Intervent Radiol 2020; 37:484-491. [PMID: 33328704 PMCID: PMC7732560 DOI: 10.1055/s-0040-1719189] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Metastatic liver disease is one of the major causes of cancer-related morbidity and mortality. Locoregional therapies offered by interventional oncologists alleviate cancer-related morbidity and in some cases improve survival. Locoregional therapies are often palliative in nature but occasionally can be used with curative intent. This review will discuss important factors to consider prior to palliative and curative intent treatment of metastatic liver disease with locoregional therapy. These factors include those specific to the tumor, liver function, liver reserve, differences between treatment modalities, and patient-specific considerations.
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Affiliation(s)
- Cathal O'Leary
- Division of Interventional Radiology, Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Michael C. Soulen
- Division of Interventional Radiology, Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Susan Shamimi-Noori
- Division of Interventional Radiology, Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
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Abdelgawad ME, El-Zakzok H, Salah M, El-Mezayen HA. Diagnostic accuracy of hepatocyte growth factor, Fas/CD95 and Endostatin for non-invasive assessment of hepatic fibrosis in biopsy-proven hepatitis C virus patients. INFECTION GENETICS AND EVOLUTION 2020; 85:104526. [PMID: 32890764 DOI: 10.1016/j.meegid.2020.104526] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 08/24/2020] [Accepted: 08/30/2020] [Indexed: 01/18/2023]
Abstract
BACKGROUND/AIM Evaluation of liver fibrosis in chronic hepatitis C patients (CHC) provides a high value, not only for the diagnosis of the disease, but also for the therapeutic decision. The aim of the current study is the construction of simple non-invasive and more accurate score for liver fibrosis staging in CHC patients and estimating its performance against three published non-invasive indexes. MATERIAL AND METHODS CHC patients were divided into two groups: an estimated group (n = 75) and validated group (n = 50). Liver fibrosis was tested in biopsies by Metavair score system. Fas/CD95, hepatocyte growth factor (HGF) and endostatin were assayed by enzyme linked immunosorbent assay (ELISA). Statistical analysis was performed by stepwise linear discriminate analysis and area under-receiver operating curves (AUCs). RESULTS The multivariate discriminate analysis (MDA) selects a function based on absolute values of five biochemical markers; FHEPA (Fas/CD95, HGF, Endostatin, Platelets&Albumin)-Test score = 1.2 × Fas/CD95 (ng/mL) + 0.006 × HGF (pg/mL) + 0.03 × Endostatin (ng/mL) - 0.007 × platelets count(109/L)-3.6 × Albumin (g/dL) - 8.6.FHEPA-Test producesAUCs 0.99, 0.877 and 0.847 to discriminate patients with significant fibrosis (F2-F4), advanced fibrosis (F3-F4) and cirrhosis (F4), respectively. CONCLUSION FHEPA-Test is considered a novel non-invasive test which could be applied in assessment of liver fibrosis in HCV infected patients. Our novel score was more efficient than Immune Fibrosis Index, Fibrosis Index and FibroQ and thus it could be more applicable, feasible & economic for Egyptian HCV patients. Our Novel Scoring system could be globalized to other populations to confirm its advantageous use in early diagnosis of liver fibrosis.
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Affiliation(s)
- Mohamed Essameldin Abdelgawad
- Biochemistry Division, Chemistry Department, Helwan University, Cairo, Egypt; Inserm UMR-S-MD 1197, Hôpital Paul Brousse, Villejuif, France; Paris-Saclay University, Villejuif, France
| | | | - Mona Salah
- Clinical Pathology Department, Cairo University, Cairo, Egypt
| | - Hatem A El-Mezayen
- Biochemistry Division, Chemistry Department, Helwan University, Cairo, Egypt; Gastroentrological Surgery Department, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
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Wang S, Guo XZ, Xu SX, Qi XS. Risk and treatment of non-hepatic cancers in patients with cirrhosis. Shijie Huaren Xiaohua Zazhi 2020; 28:655-659. [DOI: 10.11569/wcjd.v28.i15.655] [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: 02/06/2023] Open
Abstract
Patients with cirrhosis are at a high risk for hepatocellular carcinoma. However, it remains controversial about whether or not there is a high risk for non-hepatic cancers in patients with liver cirrhosis. Additionally, the management of non-hepatic cancers in cirrhotic patients is a clinical challenge, because the use of surgery and anticancer drugs is often compromised by the presence of liver dysfunction. This editorial aims to briefly summarize the findings on the risk and management of non-hepatic cancers in patients with cirrhosis.
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Affiliation(s)
- Shuo Wang
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China,Postgraduate College, China Medical University, Shenyang 110122, Liaoning Province, China
| | - Xiao-Zhong Guo
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China
| | - Shi-Xue Xu
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China,Postgraduate College, China Medical University, Shenyang 110122, Liaoning Province, China
| | - Xing-Shun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, Liaoning Province, China
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Diagnostic performance of extrinsic apoptosis pathway in hepatitis C virus patients: apoptosis fibrosis crosstalk. Eur J Gastroenterol Hepatol 2020; 32:990-997. [PMID: 31743229 DOI: 10.1097/meg.0000000000001603] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND/AIM Liver fibrosis assessment and evaluation of disease severity in hepatitis C virus (HCV) patients provides useful information for therapeutic decisions. Chronic HCV infection is associated with increased levels of peripheral T cell apoptosis. The aim was to study whether peripheral blood T lymphocyte apoptosis markers may contribute to clinical progression, and develop a simple index based on combination of apoptosis and routine biomarkers for accurate evaluation of fibrosis stages in HCV patients. PATIENTS AND METHODS Peripheral blood T lymphocytes were isolated from 72 patients with hepatitis C virus and 25 healthy control individuals. Serum samples were collected at time of liver biopsy. Liver fibrosis was tested in biopsies using the Metavair score system. Stepwise linear discriminate analysis and area under receiver-operating characteristic curves were utilized to produce a predictive score comprising significant apoptosis biomarkers. RESULTS A novel score named apoptosis fibrosis index (AFI) was created on the basis of a combination of CD8/Annexin, albumin and platelets. The multivariate discriminate analysis selected a score based on absolute values of the three biochemical markers; score = 5.8 + 0.008×CD8/Annexin-V (%) - 1.4×Albumin (g/dl) - 0.001×Platelet count (10/L), where 5.8 considered numerical constant. AFI produce an area under the curve of one for significant fibrosis, 0.80 for advanced fibrosis, and 0.889 for cirrhosis. CONCLUSION Apoptosis biomarkers in HCV patients were associated with liver fibrosis. AFI score, a novel noninvasive test, can be used easily for the prediction of liver fibrosis stage and may decrease the need for liver biopsy in hepatitis C virus Egyptian patients.
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Azar A, Devcic Z, Paz-Fumagalli R, Vidal LLC, McKinney JM, Frey G, Lewis AR, Ritchie C, Starr JS, Mody K, Toskich B. Albumin-bilirubin grade as a prognostic indicator for patients with non-hepatocellular primary and metastatic liver malignancy undergoing Yttrium-90 radioembolization using resin microspheres. J Gastrointest Oncol 2020; 11:715-723. [PMID: 32953155 DOI: 10.21037/jgo.2020.04.01] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Studies have shown that the albumin-bilirubin (ALBI) grade can be a superior prognosticator for patients undergoing Yttrium-90 (Y90) glass microsphere radioembolization for hepatocellular carcinoma (HCC) compared to the Child-Pugh (CP) scoring system. Less is known about the applicability of this score in non-hepatocellular malignancies using Y90 resin microspheres. This study evaluates the ALBI grade's ability to predict overall survival and biochemical toxicity in patients undergoing resin Y90 radioembolization and body surface area dosimetry (BSA) for non-hepatocellular primary and metastatic liver malignancies compared to the CP class and Model for End-Stage Liver Disease (MELD) score. Methods A retrospective review of patients with intrahepatic metastatic colorectal and neuroendocrine cancers and cholangiocarcinoma undergoing resin radioembolization from 2006-2015 at a single tertiary medical center was performed. ALBI, MELD, and CP scores were compared and correlated with biochemical toxicity and overall survival. Results There was a significant difference in overall survival between CP class A and class B liver function (P=0.04) for the entire patient cohort. ALBI grade (P=0.36) and MELD score (P=0.19) were not independently associated with survival. When stratified by CP class, the ALBI grade revealed a trend for survival difference in CP class B (P=0.05). Baseline ALBI grade was associated with post-procedural albumin reduction (P=0.01) and bilirubin elevation (P=0.007). Conclusions ALBI grade predicted post-procedural biochemical toxicity, but did not predict survival after resin radioembolization of non-hepatocellular liver malignancies using BSA dosimetry. Given the heterogeneity of this study population, dedicated prospective analyses are required.
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Affiliation(s)
- Antoine Azar
- Division of Diagnostic Radiology, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Zlatko Devcic
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL, USA
| | | | | | - J Mark McKinney
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Gregory Frey
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Andrew R Lewis
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Charles Ritchie
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Jason S Starr
- Division of Oncology, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Kabir Mody
- Division of Oncology, Mayo Clinic Florida, Jacksonville, FL, USA
| | - Beau Toskich
- Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL, USA
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Krens SD, Lassche G, Jansman FGA, Desar IME, Lankheet NAG, Burger DM, van Herpen CML, van Erp NP. Dose recommendations for anticancer drugs in patients with renal or hepatic impairment. Lancet Oncol 2020; 20:e200-e207. [PMID: 30942181 DOI: 10.1016/s1470-2045(19)30145-7] [Citation(s) in RCA: 75] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Revised: 02/19/2019] [Accepted: 02/19/2019] [Indexed: 01/22/2023]
Abstract
Renal or hepatic impairment is a common comorbidity for patients with cancer either because of the disease itself, toxicity of previous anticancer treatments, or because of other factors affecting organ function, such as increased age. Because renal and hepatic function are among the main determinants of drug exposure, the pharmacokinetic profile might be altered for patients with cancer who have renal or hepatic impairment, necessitating dose adjustments. Most anticancer drugs are dosed near their maximum tolerated dose and are characterised by a narrow therapeutic index. Consequently, selecting an adequate dose for patients who have either hepatic or renal impairment, or both, is challenging and definitive recommendations on dose adjustments are scarce. In this Review, we discuss the effect of renal and hepatic impairment on the pharmacokinetics of anticancer drugs. To guide clinicians in selecting appropriate dose adjustments, information from available drug labels and from the published literature were combined to provide a practical set of recommendations for dose adjustments of 160 anticancer drugs for patients with hepatic and renal impairment.
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Affiliation(s)
- Stefanie D Krens
- Department of Clinical Pharmacy, Radboud University Medical Center, Nijmegen, Netherlands
| | - Gerben Lassche
- Department of Medical Oncology, Radboud University Medical Center, Nijmegen, Netherlands
| | - Frank G A Jansman
- Department of Pharmacy, Deventer Hospital, Deventer, Netherlands; PharmacoTherapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, Netherlands
| | - Ingrid M E Desar
- Department of Medical Oncology, Radboud University Medical Center, Nijmegen, Netherlands
| | - Nienke A G Lankheet
- Department of Clinical Pharmacy, Radboud University Medical Center, Nijmegen, Netherlands; Department of Clinical Pharmacy, Medisch Spectrum Twente, Enschede, Netherlands
| | - David M Burger
- Department of Clinical Pharmacy, Radboud University Medical Center, Nijmegen, Netherlands
| | - Carla M L van Herpen
- Department of Medical Oncology, Radboud University Medical Center, Nijmegen, Netherlands
| | - Nielka P van Erp
- Department of Clinical Pharmacy, Radboud University Medical Center, Nijmegen, Netherlands.
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Liu Z, Gu J, Qin Z, Yang C, Yu S, Dai X, Wang K. Decreased Foxp3 and function of Tregs caused immune imbalance and liver injury in patients with autoimmune liver diseases post-liver transplantation. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:534. [PMID: 32411757 PMCID: PMC7214902 DOI: 10.21037/atm.2020.03.203] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Background Autoimmune liver diseases (AILD) is a type of autoimmune disease which may cause end-stage liver failure and require liver transplantation. Regulatory T cells (Tregs) play an irreplaceable role in maintaining immunological homeostasis. Methods In this study, we made a comparative analysis of the immune balance and graft function between AILD patients’ post-transplantation and the patients who have had liver failure with hepatitis B virus (HBV) infection post-transplantation. Immune cell phenotype of two groups were analyzed. We sorted CD4+CD25+CD127-Tregs both in vitro and vivo and did TSDR methylation status assay to explore further possible mechanisms. Results Our data showed that there is a worse prognosis with severe graft function in liver transplant patients with AILD compared to patients with HBV-induced liver failure. Immune cell phenotype analysis showed that more Tregs could be detected in AILD patients compared with HBV patients’ post-transplantation. We sorted CD4+CD25+CD127-Tregs in vivo and showed that Tregs presented decreased function both in vitro and vivo. Mechanism study also proved that modulation of the phosphorylation level of STAT1 and STAT3 as well as the methylation level of TSDR in Foxp3 might partially result in the function loss of Tregs. Conclusions These results suggest that loss of Foxp3 expression and suppressive function of Tregs may be the critical factor that causes graft loss for liver transplant patients after AILD.
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Affiliation(s)
- Zheng Liu
- Translational Medicine Research Center, Affiliated Jiangning Hospital, and Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China
| | - Jian Gu
- Translational Medicine Research Center, Affiliated Jiangning Hospital, and Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China
| | - Zhu Qin
- Translational Medicine Research Center, Affiliated Jiangning Hospital, and Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China
| | - Che Yang
- Medical college, Jiangsu University, Zhenjiang 212000, China
| | - Sun Yu
- Translational Medicine Research Center, Affiliated Jiangning Hospital, and Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China
| | - Xinzheng Dai
- Translational Medicine Research Center, Affiliated Jiangning Hospital, and Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China
| | - Ke Wang
- Translational Medicine Research Center, Affiliated Jiangning Hospital, and Liver Transplantation Center, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China
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Chen H, Jia W. Progress in hepatectomy for hepatocellular carcinoma and peri-operation management. Genes Dis 2020; 7:320-327. [PMID: 32884986 PMCID: PMC7452507 DOI: 10.1016/j.gendis.2020.02.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Revised: 01/22/2020] [Accepted: 02/06/2020] [Indexed: 12/18/2022] Open
Abstract
The global incidence of liver cancer continues to grow. Liver cancer, especially hepatocellular carcinoma, has high recurrence and mortality rates. Here, we review the past decade's diagnostic, therapeutic, and management strategies for hepatocellular carcinoma, and summarize new patient management approaches, including enhanced recovery after surgery, targeted therapy, and immunotherapy. We compare traditional and innovative management methods, which comprise developments in precision medicine, and consider their limitations. Ongoing innovation and technological advances enable surgeons to gain deeper understandings of the multidimensionality of hepatocellular carcinoma, thereby promoting the continuous development of precision therapy.
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Affiliation(s)
- Hao Chen
- Department of Hepatic Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, HeFei, Anhui, 230001, China
- Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, HeFei, Anhui, 230001, China
| | - Weidong Jia
- Department of Hepatic Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, HeFei, Anhui, 230001, China
- Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, HeFei, Anhui, 230001, China
- Corresponding author. Department of Hepatic Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, HeFei, Anhui, 230001, China. Fax: +86 551 62282121.
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Mashni O, Qasem K, Sara AA, Awad W. Etoposide dosage adjustment in two patients with neuroendocrine tumors and severe liver impairment. J Oncol Pharm Pract 2020; 26:500-506. [DOI: 10.1177/1078155219859630] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Introduction Limited data are available on dosing etoposide in patients with liver impairment. Case report We report the dosing strategies for etoposide utilized in two patients with neuroendocrine tumors and severe liver impairment. Management and outcomes Treatment consisted of platinum-based chemotherapy regimens, with the decision of whether to administer etoposide and at what doses being based on the liver function before each chemotherapy cycle. By the end of treatment, total bilirubin was normal, and the performance status of both patients had improved, with stable computed tomography scan findings. Discussion The reported two cases suggest that the administration of etoposide at reduced doses with close monitoring in patients with neuroendocrine tumors and severe liver impairment may still be considered as an option and may improve outcomes.
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Affiliation(s)
- Ola Mashni
- Department of Pharmacy, King Hussein Cancer Center, Amman, Jordan
| | - Khlood Qasem
- Department of Hematology and Medical Oncology, King Hussein Cancer Center, Amman, Jordan
| | - Aseel Abu Sara
- Department of Pharmacy, King Hussein Cancer Center, Amman, Jordan
| | - Wedad Awad
- Department of Pharmacy, King Hussein Cancer Center, Amman, Jordan
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Comparison of hepatic resection and systemic treatment of breast cancer liver metastases: A propensity score matching study. Am J Surg 2020; 220:945-951. [PMID: 32145919 DOI: 10.1016/j.amjsurg.2020.02.047] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Revised: 02/11/2020] [Accepted: 02/23/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND The role of surgery in breast cancer liver metastases (BCLM) remains elusive, and current application is limited. Our aim is to investigate whether hepatic resection (HR) of BCLM improves survival compared with non-hepatic resection (NHR) treatment. METHODS Three hundred and eighty-four patients with BCLM from 2008 to 2018 were divided into two groups. Propensity score matching (PSM) analysis was used to compare the clinical outcomes. RESULTS After PSM the mean overall survival (OS) and the 1, 3, and 5-year OS rates in HR group were 61.8 months, 92.6%, 54.7% and 54.7%, respectively; while for NHR group these values were 38.6 months, 79.2%, 45.6% and 21.9%, respectively (p < 0.007). Multivariate analysis indicated hormonal receptor status (p = 0.039) and hepatic resection (p = 0.032) were independent prognostic factors. CONCLUSION Our study revealed that hepatectomy yields a survival benefit safely compared with medical treatments, especially for patients with positive hormonal receptors.
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Multicenter-Based Population Pharmacokinetic Analysis of Ciclosporin in Hematopoietic Stem Cell Transplantation Patients. Pharm Res 2019; 37:15. [PMID: 31873806 DOI: 10.1007/s11095-019-2740-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Accepted: 11/25/2019] [Indexed: 12/13/2022]
Abstract
PURPOSE To explore the contribution of physiological characteristics to variability in ciclosporin pharmacokinetics in hematopoietic stem cell transplantation patients. METHODS Clinical data from 563 patients were collected from centers in three regions. Ciclosporin concentrations were measured using immunoassays. The patients' demographics, hematological and biological indicators, coadministered drugs, region, and disease diagnosis were recorded from medical records. Data analysis was performed using NONMEM based on a one-compartment model to describe the pharmacokinetics of ciclosporin. The reliability and stability of the final model were evaluated using bootstrap resampling, goodness-of-fit plots, and prediction-corrected visual predictive checks. RESULTS The population estimate of the clearance (CL) was 30.4 L/h, the volume of distribution (V) was 874.0 L and the bioavailability (F) was 81.1%. The between-subject variability in these parameters was 26.3, 68.0, and 110.8%, respectively. Coadministration of fluconazole, itraconazole, or voriconazole decreased CL by 17.6%, 28.4%, and 29.2%, respectively. Females' CL increased by approximately 12.0%. In addition, CL and V decreased with hematocrit, total protein, and uric acid increase, and CL also decreased with age and aspartate aminotransferase increase. However, CL increased with creatinine clearance increase. CONCLUSIONS A multicenter-based population pharmacokinetic model of ciclosporin was established. The pharmacokinetics of ciclosporin exhibited discrepancies among different regions.
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Barzakova ES, Schulze-Hagen M, Zimmermann M, Lurje G, Bednarsch J, Pedersoli F, Isfort P, Kuhl C, Bruners P. Monitoring Liver Function of Patients Undergoing Transarterial Chemoembolization (TACE) by a 13C Breath Test (LiMAx). Cardiovasc Intervent Radiol 2019; 42:1702-1708. [PMID: 31535181 DOI: 10.1007/s00270-019-02325-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Accepted: 08/23/2019] [Indexed: 02/07/2023]
Abstract
PURPOSE Transarterial chemoembolization (TACE) is associated with the risk of deteriorating liver function, especially in patients with preexisting liver damage. Current liver function tests may fail to accurately predict the functional liver reserve. Aim of this study was to investigate whether changes of liver function caused by TACE are associated with detectable changes of LiMAx values. METHODS AND MATERIALS Forty patients with primary or secondary liver cancer underwent TACE and LiMAx test on the day before, the day after, and 4 weeks after TACE. LiMAx results were evaluated, referenced to liver volume (CT/MR volumetry), correlated with the respective TACE volume (subsegmental vs. segmental vs. lobar), established liver function tests, and Child-Pugh and ALBI scores. RESULTS The individual LiMAx values were significantly reduced by 10% (p = 0.01) on the day after TACE and fully recovered to baseline 1 month after treatment. Similar changes were observed regarding levels of bilirubin, transaminases, albumin, INR, and creatinine. LiMAx did not correlate significantly with the treated liver volume, but did correlate with the baseline liver volume (< 1200 ml vs. > 1200 ml; p < 0.01). No significant changes were observed in the Child-Pugh score or ALBI score. CONCLUSION LiMAx is capable of detecting changes in liver function, even modulations caused by superselective TACE procedures. Accordingly, it could be used as a tool for patient selection and monitoring of transarterial therapy. In comparison, Child-Pugh and ALBI scores did not reflect any of these changes. Some biochemical parameters also changed significantly after TACE, but they tend to be less specific in providing sufficient information on actual cellular dysfunction.
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Affiliation(s)
- Emona S Barzakova
- Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Pauwelsstreet 30, 52074, Aachen, Germany.
| | - Maximilian Schulze-Hagen
- Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Pauwelsstreet 30, 52074, Aachen, Germany
| | - Markus Zimmermann
- Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Pauwelsstreet 30, 52074, Aachen, Germany
| | - Georg Lurje
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany
| | - Jan Bednarsch
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany
| | - Federico Pedersoli
- Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Pauwelsstreet 30, 52074, Aachen, Germany
| | - Peter Isfort
- Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Pauwelsstreet 30, 52074, Aachen, Germany
| | - Christiane Kuhl
- Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Pauwelsstreet 30, 52074, Aachen, Germany
| | - Philipp Bruners
- Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Pauwelsstreet 30, 52074, Aachen, Germany
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Hiratani S, Mori R, Ota Y, Matsuyama R, Kumamoto T, Nagashima Y, Morioka D, Endo I. A Simple and Easily Reproducible Model of Reversible Obstructive Jaundice in Rats. In Vivo 2019; 33:699-706. [PMID: 31028186 PMCID: PMC6559921 DOI: 10.21873/invivo.11528] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Revised: 02/06/2019] [Accepted: 02/08/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND/AIM Cholangiocarcinoma and pancreatic carcinoma are major malignancies that cause obstructive jaundice (OJ). This study aimed to develop a simple and easily reproducible rat model of reversible OJ (ROJ). MATERIALS AND METHODS OJ was induced by clamping the common bile duct (CBD) using a U-shaped titanium hemoclip and its base was attached by ligation using 2-cm long 4-0 polypropylene suture. An anti-adhesive sheet was placed around the CBD. OJ was mitigated by pulling the suture to remove the clip under laparotomy 3 days later. Serum chemistry and liver histopathology were compared between the ROJ group and sham surgery (SH) groups. RESULTS Three days after inducing OJ, serum total bilirubin, aspartate aminotransferase, and alanine aminotransferase were remarkably elevated in the ROJ group and thereafter reduced significantly after mitigating OJ. Similar findings were confirmed by histopathology. CONCLUSION Our rat model of reversible OJ was considered simple and easily reproducible.
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Affiliation(s)
- Seigo Hiratani
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Ryutaro Mori
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Yohei Ota
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Ryusei Matsuyama
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Takafumi Kumamoto
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Yoji Nagashima
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Daisuke Morioka
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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Sun Y, Gu J, Liu R, Zhou H, Lu L, Dai X, Qian X. IL‐2/IL‐6 ratio correlates with liver function and recovery in acute liver injury patients. APMIS 2019; 127:468-474. [PMID: 30802326 DOI: 10.1111/apm.12944] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Accepted: 02/07/2019] [Indexed: 12/29/2022]
Affiliation(s)
- Yu Sun
- Hepatobiliary Center The First Affiliated Hospital of Nanjing Medical University Nanjing China
| | - Jian Gu
- Hepatobiliary Center The First Affiliated Hospital of Nanjing Medical University Nanjing China
| | - Rui Liu
- Hepatobiliary Center The First Affiliated Hospital of Nanjing Medical University Nanjing China
| | - Haoming Zhou
- Hepatobiliary Center The First Affiliated Hospital of Nanjing Medical University Nanjing China
| | - Ling Lu
- Hepatobiliary Center The First Affiliated Hospital of Nanjing Medical University Nanjing China
| | - Xinzheng Dai
- Hepatobiliary Center The First Affiliated Hospital of Nanjing Medical University Nanjing China
| | - Xiaofeng Qian
- Hepatobiliary Center The First Affiliated Hospital of Nanjing Medical University Nanjing China
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Mulder RL, Bresters D, Van den Hof M, Koot BGP, Castellino SM, Loke YKK, Post PN, Postma A, Szőnyi LP, Levitt GA, Bardi E, Skinner R, van Dalen EC. Hepatic late adverse effects after antineoplastic treatment for childhood cancer. Cochrane Database Syst Rev 2019; 4:CD008205. [PMID: 30985922 PMCID: PMC6463806 DOI: 10.1002/14651858.cd008205.pub3] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Survival rates have greatly improved as a result of more effective treatments for childhood cancer. Unfortunately, the improved prognosis has been accompanied by the occurrence of late, treatment-related complications. Liver complications are common during and soon after treatment for childhood cancer. However, among long-term childhood cancer survivors, the risk of hepatic late adverse effects is largely unknown. To make informed decisions about future cancer treatment and follow-up policies, it is important to know the risk of, and associated risk factors for, hepatic late adverse effects. This review is an update of a previously published Cochrane review. OBJECTIVES To evaluate all the existing evidence on the association between antineoplastic treatment (that is, chemotherapy, radiotherapy involving the liver, surgery involving the liver and BMT) for childhood cancer and hepatic late adverse effects. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2018, Issue 1), MEDLINE (1966 to January 2018) and Embase (1980 to January 2018). In addition, we searched reference lists of relevant articles and scanned the conference proceedings of the International Society of Paediatric Oncology (SIOP) (from 2005 to 2017) and American Society of Pediatric Hematology/Oncology (ASPHO) (from 2013 to 2018) electronically. SELECTION CRITERIA All studies, except case reports, case series, and studies including fewer than 10 patients that examined the association between antineoplastic treatment for childhood cancer (aged 18 years or less at diagnosis) and hepatic late adverse effects (one year or more after the end of treatment). DATA COLLECTION AND ANALYSIS Two review authors independently performed the study selection and 'risk of bias' assessment. The 'risk of bias' assessment was based on earlier checklists for observational studies. For the original version of the review, two review authors independently performed data extraction. For the update of the review, the data extraction was performed by one reviewer and checked by another reviewer. MAIN RESULTS Thirteen new studies were identified for the update of this review. In total, we included 33 cohort studies including 7876 participants investigating hepatic late adverse effects after antineoplastic treatment (especially chemotherapy and radiotherapy) for different types of childhood cancer, both haematological and solid malignancies. All studies had methodological limitations. The prevalence of hepatic late adverse effects, all defined in a biochemical way, varied widely, between 0% and 84.2%. Selecting studies where the outcome of hepatic late adverse effects was well-defined as alanine aminotransferase (ALT) above the upper limit of normal, indicating cellular liver injury, resulted in eight studies. In this subgroup, the prevalence of hepatic late adverse effects ranged from 5.8% to 52.8%, with median follow-up durations varying from three to 23 years since cancer diagnosis in studies that reported the median follow-up duration. A more stringent selection process using the outcome definition of ALT as above twice the upper limit of normal, resulted in five studies, with a prevalence ranging from 0.9% to 44.8%. One study investigated biliary tract injury, defined as gamma-glutamyltransferase (γGT) above the upper limit of normal and above twice the upper limit of normal and reported a prevalence of 5.3% and 0.9%, respectively. Three studies investigated disturbance in biliary function, defined as bilirubin above the upper limit of normal and reported prevalences ranging from 0% to 8.7%. Two studies showed that treatment with radiotherapy involving the liver (especially after a high percentage of the liver irradiated), higher BMI, and longer follow-up time or older age at evaluation increased the risk of cellular liver injury in multivariable analyses. In addition, there was some suggestion that busulfan, thioguanine, hepatic surgery, chronic viral hepatitis C, metabolic syndrome, use of statins, non-Hispanic white ethnicity, and higher alcohol intake (> 14 units per week) increase the risk of cellular liver injury in multivariable analyses. Chronic viral hepatitis was shown to increase the risk of cellular liver injury in six univariable analyses as well. Moreover, one study showed that treatment with radiotherapy involving the liver, higher BMI, higher alcohol intake (> 14 units per week), longer follow-up time, and older age at cancer diagnosis increased the risk of biliary tract injury in a multivariable analysis. AUTHORS' CONCLUSIONS The prevalence of hepatic late adverse effects among studies with an adequate outcome definition varied considerably from 1% to 53%. Evidence suggests that radiotherapy involving the liver, higher BMI, chronic viral hepatitis and longer follow-up time or older age at follow-up increase the risk of hepatic late adverse effects. In addition, there may be a suggestion that busulfan, thioguanine, hepatic surgery, higher alcohol intake (>14 units per week), metabolic syndrome, use of statins, non-Hispanic white ethnicity, and older age at cancer diagnosis increase the risk of hepatic late adverse effects. High-quality studies are needed to evaluate the effects of different therapy doses, time trends, and associated risk factors after antineoplastic treatment for childhood cancer.
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Affiliation(s)
- Renée L Mulder
- Princess Máxima Center for Pediatric OncologyHeidelberglaan 25UtrechtNetherlands3584 CS
- Emma Children's Hospital, Amsterdam UMC, University of AmsterdamDepartment of Paediatric OncologyP.O. Box 22660AmsterdamNetherlands1100 DD
| | - Dorine Bresters
- Princess Máxima Center for Pediatric OncologyHeidelberglaan 25UtrechtNetherlands3584 CS
- Leiden University Medical CenterWillem Alexander Children's HospitalPO Box 9600LeidenNetherlands2300 RC
| | - Malon Van den Hof
- Emma Children's Hospital, Amsterdam UMC, University of AmsterdamDepartment of Paediatric OncologyP.O. Box 22660AmsterdamNetherlands1100 DD
| | - Bart GP Koot
- Emma Children's Hospital, Amsterdam UMC, University of AmsterdamDepartment of Paediatric Gastroenterology and NutritionP.O. Box 22660AmsterdamNetherlands1100 DD
| | - Sharon M Castellino
- Emory School of MedicineDepartment of Pediatrics, Division Hematology/OncologyAtlanta, GAUSA
| | | | - Piet N Post
- Dutch Institute for Healthcare Improvement CBOPO Box 20064UtrechtNetherlands3502 LB
| | - Aleida Postma
- University Medical Center Groningen and University of Groningen, Beatrix Children's HospitalDepartment of Paediatric OncologyPostbus 30.000GroningenNetherlands9700 RB
| | - László P Szőnyi
- King Feisal Specialist HospitalOrgan Transplant CentreRiyadhSaudi Arabia11211
| | - Gill A Levitt
- Great Ormond Street Hospital for Children NHS Foundation TrustOncologyGt Ormond StLondonUK
| | - Edit Bardi
- Kepler UniversitätsklinikumMed Campus IV26‐30 KrankenhausstraßeLinzAustria4020
| | - Roderick Skinner
- Great North Children’s HospitalDepartment of Paediatric and Adolescent Haematology / OncologyQueen Victoria RoadNewcastle upon TyneUKNE1 4LP
| | - Elvira C van Dalen
- Princess Máxima Center for Pediatric OncologyHeidelberglaan 25UtrechtNetherlands3584 CS
- Emma Children's Hospital, Amsterdam UMC, University of AmsterdamDepartment of Paediatric OncologyP.O. Box 22660AmsterdamNetherlands1100 DD
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Qian L, Zhang J, Chen X, Qi S, Wu P, Wang C, Wang C. Toxic effects of boscalid in adult zebrafish (Danio rerio) on carbohydrate and lipid metabolism. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2019; 247:775-782. [PMID: 30721868 DOI: 10.1016/j.envpol.2019.01.054] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/17/2018] [Revised: 01/08/2019] [Accepted: 01/15/2019] [Indexed: 06/09/2023]
Abstract
Boscalid as one of the most widely used succinate dehydrogenase inhibitor (SDHI) fungicides has been frequently detected in both freshwater and estuarine environments. Its acute toxic effects on zebrafish and freshwater algae have been reported in our previous studies. To further investigate its chronic toxic effects to aquatic organisms, adult zebrafish were exposed for 28 days to a series of environmentally relevant boscalid concentrations in this study. Growth indicators and histopathology were determined in this study. Results indicated that boscalid inhibited the growth of zebrafish and induced damage in the kidneys and liver. Carbohydrate and lipid metabolism as the key pathways of energy metabolism in growth of zebrafish were also investigated. Results showed boscalid caused an increase in the activity of hexokinase (HK), the content of glycogen, glucose-6-phosphatase (G6Pase), and insulin (INS) in liver and a decrease in blood glucose content and succinate dehydrogenase (SDH) activity. Boscalid reduced the total content of triacylglyceride (TG) and cholesterol (TC) and the activity of fatty acid synthase (FAS) and acetyl coenzyme A carboxylase (ACC) in the liver. Correspondingly, expression of the genes related to carbohydrate and lipid metabolism in liver and intestine was affected by boscalid, especially in the significant upregulation of G6Pase and pparα and downregulation of SGLT-1 and AMY. Results suggested that boscalid could affect carbohydrate metabolism of adult zebrafish via regulation of gluconeogenesis and glycolysis at 0.1 mg/L. Moreover, boscalid might induce an increase in β-oxidation and a decrease in lipid synthesis at 0.01 mg/L. In conclusion, our study identified that carbohydrate and lipid metabolism are the possible biological pathways that mediate boscalid-induced developmental effects.
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Affiliation(s)
- Le Qian
- College of Sciences, China Agricultural University, Beijing, China
| | - Jie Zhang
- College of Sciences, China Agricultural University, Beijing, China
| | - Xiangguang Chen
- College of Sciences, China Agricultural University, Beijing, China
| | - Suzhen Qi
- Risk Assessment Laboratory for Bee Products Quality and Safety of Ministry of Agriculture, Institute of Agricultural Research, Chinese Academy of Agricultural Sciences, Beijing, 100093, China
| | - Peizhuo Wu
- College of Sciences, China Agricultural University, Beijing, China
| | - Chen Wang
- State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, China
| | - Chengju Wang
- College of Sciences, China Agricultural University, Beijing, China.
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Kumar S, Singh AP, Senapati S, Maiti P. Controlling Drug Delivery Using Nanosheet-Embedded Electrospun Fibers for Efficient Tumor Treatment. ACS APPLIED BIO MATERIALS 2019; 2:884-894. [DOI: 10.1021/acsabm.8b00735] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Affiliation(s)
- Sunil Kumar
- School of Materials Science and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221 005, India
| | - Akhand Pratap Singh
- School of Materials Science and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221 005, India
| | - Sudipta Senapati
- School of Materials Science and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221 005, India
| | - Pralay Maiti
- School of Materials Science and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221 005, India
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Lucić Vrdoljak A, Fuchs N, Mikolić A, Žunec S, Brčić Karačonji I, Jurič A, Prester L, Micek V, Neuberg M, Čanović S, Mršić G, Kopjar N. Irinotecan and Δ⁸-Tetrahydrocannabinol Interactions in Rat Liver: A Preliminary Evaluation Using Biochemical and Genotoxicity Markers. Molecules 2018; 23:E1332. [PMID: 29865166 PMCID: PMC6100385 DOI: 10.3390/molecules23061332] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Revised: 05/23/2018] [Accepted: 05/31/2018] [Indexed: 01/27/2023] Open
Abstract
There is growing interest regarding the use of herbal preparations based on Cannabis sativa for medicinal purposes, despite the poorly understood interactions of their main constituent Δ⁸-tetrahydrocannabinol (THC) with conventional drugs, especially cytostatics. The objective of this pilot study was to prove whether the concomitant intake of THC impaired liver function in male Wistar rats treated with the anticancer drug irinotecan (IRI), and evaluate the toxic effects associated with this exposure. IRI was administered once intraperitoneally (at 100 mg/kg of the body weight (b.w.)), while THC was administered per os repeatedly for 1, 3, and 7 days (at 7 mg/kg b.w.). Functional liver impairments were studied using biochemical markers of liver function (aspartate aminotransferase-AST, alanine aminotransferase-ALP, alkaline phosphatase-AP, and bilirubin) in rats given a combined treatment, single IRI, single THC, and control groups. Using common oxidative stress biomarkers, along with measurement of primary DNA damage in hepatocytes, the degree of impairments caused at the cellular level was also evaluated. THC caused a time-dependent enhancement of acute toxicity in IRI-treated rats, which was confirmed by body and liver weight reduction. Although single THC affected ALP and AP levels more than single IRI, the levels of liver function markers measured after the administration of a combined treatment mostly did not significantly differ from control. Combined exposure led to increased oxidative stress responses in 3- and 7-day treatments, compared to single IRI. Single IRI caused the highest DNA damage at all timepoints. Continuous 7-day oral exposure to single THC caused an increased mean value of comet tail length compared to its shorter treatments. Concomitant intake of THC slightly affected the levels of IRI genotoxicity at all timepoints, but not in a consistent manner. Further studies are needed to prove our preliminary observations, clarify the underlying mechanisms behind IRI and THC interactions, and unambiguously confirm or reject the assumptions made herein.
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Affiliation(s)
- Ana Lucić Vrdoljak
- Institute for Medical Research and Occupational Health, HR-10001 Zagreb, Croatia.
| | - Nino Fuchs
- University Hospital Centre Zagreb, HR-10000 Zagreb, Croatia.
| | - Anja Mikolić
- Institute for Medical Research and Occupational Health, HR-10001 Zagreb, Croatia.
| | - Suzana Žunec
- Institute for Medical Research and Occupational Health, HR-10001 Zagreb, Croatia.
| | | | - Andreja Jurič
- Institute for Medical Research and Occupational Health, HR-10001 Zagreb, Croatia.
| | - Ljerka Prester
- Institute for Medical Research and Occupational Health, HR-10001 Zagreb, Croatia.
| | - Vedran Micek
- Institute for Medical Research and Occupational Health, HR-10001 Zagreb, Croatia.
| | - Marijana Neuberg
- University Centre Varaždin, University North, HR-42000 Varaždin, Croatia.
| | | | - Gordan Mršić
- Forensic Science Centre "Ivan Vučetić", HR-10000 Zagreb, Croatia.
| | - Nevenka Kopjar
- Institute for Medical Research and Occupational Health, HR-10001 Zagreb, Croatia.
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Mouli SK, Gupta R, Sheth N, Gordon AC, Lewandowski RJ. Locoregional Therapies for the Treatment of Hepatic Metastases from Breast and Gynecologic Cancers. Semin Intervent Radiol 2018; 35:29-34. [PMID: 29628613 DOI: 10.1055/s-0038-1636518] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Breast cancer is the most common women's malignancy in the United States and is the second leading cause of cancer death. More than half of patients with breast cancer will develop hepatic metastases; this portends a poorer prognosis. In the appropriately selected patient, there does appear to be a role for curative (surgery, ablation) or palliative (intra-arterial treatments) locoregional therapy. Gynecologic malignancies are less common and metastases to the liver are most often seen in the setting of disseminated disease. The role of locoregional therapies in these patients is not well reported. The purpose of this article is to review the outcomes data of locoregional therapies in the treatment of hepatic metastases from breast and gynecologic malignancies.
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Affiliation(s)
- Samdeep K Mouli
- Section of Interventional Radiology, Department of Radiology, Northwestern University, Chicago, Illinois
| | - Ramona Gupta
- Section of Interventional Radiology, Department of Radiology, Northwestern University, Chicago, Illinois
| | - Neil Sheth
- Section of Interventional Radiology, Department of Radiology, Northwestern University, Chicago, Illinois
| | - Andrew C Gordon
- Section of Interventional Radiology, Department of Radiology, Northwestern University, Chicago, Illinois
| | - Robert J Lewandowski
- Section of Interventional Radiology, Department of Radiology, Northwestern University, Chicago, Illinois.,Division of Hematology and Oncology, Department of Medicine, Northwestern University, Chicago, Illinois.,Division of Transplant Surgery, Department of Surgery, Northwestern University, Chicago, Illinois
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