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Sato-Espinoza K, Valdivia-Herrera M, Chotiprasidhi P, Diaz-Ferrer J. Hepatocellular carcinoma in patients without cirrhosis. World J Gastroenterol 2025; 31:107100. [PMID: 40575339 PMCID: PMC12188760 DOI: 10.3748/wjg.v31.i23.107100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2025] [Revised: 04/22/2025] [Accepted: 05/27/2025] [Indexed: 06/20/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, the sixth most common cancer worldwide, and the third leading cause of cancer-related death. Cirrhosis is the predominant risk factor for HCC, driven by major etiologies including hepatitis B and C, excessive alcohol consumption, and metabolic dysfunction-associated steatotic liver disease (MASLD). While approximately 80% of HCC cases occur in patients with cirrhosis, its incidence among individuals without cirrhosis has significantly increased, particularly in developed countries, driven by the rising prevalence of MASLD. The prevalence of patients with non-cirrhotic HCC varies geographically, yet data on this subgroup remain limited. Consequently, screening and clinical management guidelines for patients with non-cirrhotic HCC are underdeveloped. Current surveillance is typically not recommended for non-cirrhotic populations, except for individuals with hepatitis B, and diagnostic criteria like Liver Imaging Reporting and Data System are designed explicitly for cirrhotic or hepatitis B-associated HCC. Furthermore, treatment strategies for non-cirrhotic HCC are often extrapolated from studies focused on patients with cirrhosis, leading to gaps in knowledge regarding treatment efficacy, survival outcomes, and etiological variability in non-cirrhotic cohorts. Thus, emerging evidence must be reviewed to guide the development of enhanced diagnostic and therapeutic strategies for patients with non-cirrhotic HCC. To address these gaps, we comprehensively reviewed the epidemiology, clinical and genetic characteristics, diagnostic modalities, and therapeutic approaches for patients with non-cirrhotic HCC.
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Affiliation(s)
- Karina Sato-Espinoza
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN 55902, United States
| | - Mayra Valdivia-Herrera
- Escuela de Medicina Humana, Facultad de Ciencias de la Salud, Universidad Cientifica del Sur, Lima 15067, Peru
| | - Perapa Chotiprasidhi
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN 55902, United States
| | - Javier Diaz-Ferrer
- Hepatology Service, Department of Digestive Diseases, Hospital Nacional Edgardo Rebagliati Martins, Lima 15072, Peru
- Department of Gastroenterology Service, Clinica Internacional, Lima 15036, Peru
- Medicine Faculty, Universidad San Martin de Porres, Lima 15024, Peru
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Monsel A, Sitbon A, Roux C, Eyraud D, Scatton O, Vezinet C, Oré MV, Gallet J, Wagner M, Thabut D, Boughdad S, Renaud F, Mazzola A, Goumard C, Allaire M. Current insights into anaesthesia and critical care management of patients with hepatocellular carcinoma: Multifaceted implications for the anaesthesiologist and intensive care physician. Eur J Anaesthesiol 2025; 42:435-448. [PMID: 39945138 DOI: 10.1097/eja.0000000000002141] [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: 10/10/2024] [Accepted: 01/23/2025] [Indexed: 04/03/2025]
Abstract
BACKGROUND The incidence of hepatocellular carcinoma (HCC) is on the rise worldwide, due to the increasing prevalence of liver diseases associated with metabolic dysfunction and better management of cirrhosis and its complications. The diversification of HCC treatments has recently increased, with the choice of strategy based on HCC characteristics, liver function and comorbidities. The combination of new therapies has transformed the prognosis, with up to 70% survival at 5 years. OBJECTIVE The aim of this review was to analyse the most recent data on preoperative evaluation, peri-operative anaesthetic management of liver resection, liver transplantation and other types of procedures, and to highlight the multidisciplinary aspect of such management. MAIN FINDINGS AND DISCUSSION The importance of preanaesthetic evaluation will depend largely on the procedure proposed, associated co-morbidities and the stage of liver disease. This assessment should verify stabilisation of all comorbidities, and evaluate the degree of portal hypertension, cirrhosis severity and sarcopenia. Liver resection and liver transplantation for HCC present specific surgical challenges, and minimally invasive techniques improve recovery. Nonsurgical procedures considered as therapeutic (ablation) or standby (regional embolisation) are diverse, and all expose patients to specific intra-anaesthetic complications, sometimes requiring intensive care management. Peri-operative anaesthetic strategies deployed in the management of liver resection or nonsurgical procedures involve specific management of fluids, coagulation, narcosis and analgesia, which can impact on patients' overall, and cancer prognosis. Lastly, new down-staging strategies combining several types of procedure and possibly immunotherapy, also call for collegial reflection on posthepatic transplant immunosuppression, which must remain tailored to each individual patient.
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Affiliation(s)
- Antoine Monsel
- From the Multidisciplinary Intensive Care Unit, Department of Anaesthesiology and Critical Care, La Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (APHP) Sorbonne University, Paris, France (AM, AS, DE, CV, MVO, JG), Sorbonne Université-INSERM UMRS_959, Immunology-Immunopathology-Immunotherapy (I3), 75013 Paris, France (AM), Sorbonne Université, INSERM, Centre de Recherche de Saint-Antoine (CRSA), UMRS-938, 75012, Paris, France (AM, AS, OS, CG), Department of Advanced Interventional Radiology, APHP, Sorbonne University, Hôpital Pitié-Salpétrière, Paris, France (CR), Hepatology and gastrenterology Unit, La Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (APHP) Sorbonne University, Paris, France (DT, AM, MA), Department of Hepatobiliary and Liver Transplantation Surgery, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne Université, Paris, France (OS, CG), Department of Radiology (SISU), APHP, Sorbonne University, Laboratoire d'imagerie biomédicale, Hôpital Pitié-Salpétrière, Paris, France (MW, SB), Nuclear Medicine Department, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France (SB), Pathology Department, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France (FR), Genomic Instability, Metabolism, Immunity and Liver Tumorigenesis laboratory, Equipe Labellisée LIGUE 2023, Paris, France (MA), Centre de Recherche des Cordeliers, Sorbonne Université, INSERM, Université de Paris, Paris, France (MA), Radiotherapy Department, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
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Bansal B, Pattilachan TM, Ross S, Christodoulou M, Sucandy I. Implications of robotic platforms for repeat hepatectomies: a propensity score matched study of clinical outcomes. Updates Surg 2025; 77:447-454. [PMID: 39946054 DOI: 10.1007/s13304-025-02117-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Accepted: 01/26/2025] [Indexed: 04/02/2025]
Abstract
Robotic surgical approaches have demonstrated improved outcomes in primary hepatectomies. However, data on their effectiveness in redo hepatectomies (subsequent liver resections) are limited. This study aims to compare the outcomes of patients undergoing primary and redo robotic hepatectomies, with additional analysis comparing outcomes of robotic versus open redo hepatectomies. With IRB approval, we prospectively followed 101 patients from a parent population of 465, who were classified as either primary (non-redo) or redo robotic hepatectomy patients between 2013 and 2023. A Propensity Score Matched (PSM) analysis was conducted to compare perioperative variables between the two cohorts, using age, sex, BMI, IWATE score, tumor size, and tumor type as matching variables. Data are presented as median (mean ± standard deviation). Significance was accepted at p ≤ 0.05. After 3:1 PSM analysis (3 primary patients to 1 robotic redo patient), no significant differences were observed in pre-, intra-, or postoperative variables, except for the Model for End-Stage Liver Disease (MELD) score (p = 0.022). Additional analysis comparing robotic and open redo hepatectomies showed similar perioperative outcomes, with the robotic approach demonstrating comparable safety and feasibility. Length of stay, blood loss, operative duration, morbidity, and mortality showed no significant differences between the two groups. Major complications (Clavien-Dindo score ≥ III) occurred in 4% of non-redo patients, with none observed in the redo group. The findings suggest that patients undergoing redo robotic hepatectomies achieve outcomes comparable to those of primary hepatectomy patients. This indicates the potential of robotic platforms to mitigate the added complexities and risks associated with redo hepatectomies. Further multi-center collaboration is necessary to validate these findings.
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Affiliation(s)
- Bhavya Bansal
- AdventHealth Tampa, Digestive Health Institute, Tampa, FL, USA
- Case Western Reserve University, Cleveland, OH, USA
| | | | - Sharona Ross
- AdventHealth Tampa, Digestive Health Institute, Tampa, FL, USA
| | | | - Iswanto Sucandy
- AdventHealth Tampa, Digestive Health Institute, Tampa, FL, USA.
- Hepatopancreatobiliary and Gastrointestinal Surgery, Codirector of Advanced Gastrointestinal and Hepatopancreatobiliary Fellowship, Director of Robotic Liver and Biliary Surgery Program, Digestive Health Institute Tampa, University of Central Florida, 3000 Medical Park Drive, Suite #500, Tampa, FL, 33613, USA.
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4
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Bolinas DKM, Barcena AJR, Mishra A, Bernardino MR, Lin V, Heralde FM, Chintalapani G, Fowlkes NW, Huang SY, Melancon MP. Mesenchymal Stem Cells Loaded in Injectable Alginate Hydrogels Promote Liver Growth and Attenuate Liver Fibrosis in Cirrhotic Rats. Gels 2025; 11:250. [PMID: 40277686 PMCID: PMC12027234 DOI: 10.3390/gels11040250] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 03/23/2025] [Accepted: 03/24/2025] [Indexed: 04/26/2025] Open
Abstract
Cirrhosis, a marker of severe liver diseases, limits future liver remnant (FLR) growth, preventing many cancer patients from undergoing surgery. While portal vein blockade (PVB) techniques are used to stimulate liver regeneration, 20-30% of patients still fail to achieve the required growth. Although mesenchymal stem cell (MSC) therapy improves PVB, its efficacy is limited by poor cell retention. To address this, we utilized alginate hydrogels to deliver MSCs and improve their retention. MSCs were loaded in the hydrogel and injected intraportally in cirrhotic rats. Liver volume, weights, enzyme levels, and histology were monitored. Results showed that the hydrogel maintained 89.0 ± 3.0% cell viability and gradually released MSCs for over two weeks. Furthermore, the rats injected with the MSC-loaded hydrogel demonstrated higher liver volumes (FLR ratio of 0.57 ± 0.32) and weights (FLR ratio of 0.84 ± 0.05). The treated rats exhibited more improved liver enzymes (AST: 72.75 ± 14.17 U/L, ALP: 135.67 ± 41.20 U/L, ALT: 46.00 ± 2.94 U/L) and decreased fibrotic areas in the liver (4.52 ± 0.22%) compared to the control group. Histology revealed increased retention when MSCs were delivered with the hydrogel (37.30 ± 16.10 MSCs/mm2) compared to cells alone (21.70 ± 22.10 MSCs/mm2). Overall, the MSC-loaded hydrogels enhanced the growth and reduced the fibrosis of the liver by promoting cell retention and efficacy in cirrhotic rats. This approach holds significant potential for improving outcomes among cancer patients, offering a promising therapeutic strategy for liver regeneration and treatment of liver diseases.
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Affiliation(s)
- Dominic Karl M. Bolinas
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (D.K.M.B.); (A.J.R.B.); (A.M.); (M.R.B.); (V.L.); (G.C.); (S.Y.H.)
- College of Medicine, University of the Philippines Manila, Manila 1000, Philippines;
| | - Allan John R. Barcena
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (D.K.M.B.); (A.J.R.B.); (A.M.); (M.R.B.); (V.L.); (G.C.); (S.Y.H.)
| | - Archana Mishra
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (D.K.M.B.); (A.J.R.B.); (A.M.); (M.R.B.); (V.L.); (G.C.); (S.Y.H.)
| | - Marvin R. Bernardino
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (D.K.M.B.); (A.J.R.B.); (A.M.); (M.R.B.); (V.L.); (G.C.); (S.Y.H.)
| | - Vincent Lin
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (D.K.M.B.); (A.J.R.B.); (A.M.); (M.R.B.); (V.L.); (G.C.); (S.Y.H.)
| | - Francisco M. Heralde
- College of Medicine, University of the Philippines Manila, Manila 1000, Philippines;
| | - Gouthami Chintalapani
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (D.K.M.B.); (A.J.R.B.); (A.M.); (M.R.B.); (V.L.); (G.C.); (S.Y.H.)
| | - Natalie W. Fowlkes
- Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Steven Y. Huang
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (D.K.M.B.); (A.J.R.B.); (A.M.); (M.R.B.); (V.L.); (G.C.); (S.Y.H.)
| | - Marites P. Melancon
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (D.K.M.B.); (A.J.R.B.); (A.M.); (M.R.B.); (V.L.); (G.C.); (S.Y.H.)
- The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX 77030, USA
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Ghahramani E, Grimm PD, Weiss BE, Schoenleb NS, Knapp AJ, Wang J, Ahmad SA, Shah SA, Quillin Iii RC, Patel SH, Mast TD. Real-time control of radiofrequency ablation using three-dimensional ultrasound echo decorrelation imaging in normal and diseased ex vivohuman liver. Phys Med Biol 2025; 70:045007. [PMID: 39813814 DOI: 10.1088/1361-6560/adaacb] [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: 03/22/2024] [Accepted: 01/15/2025] [Indexed: 01/18/2025]
Abstract
Objective. Ultrasound echo decorrelation imaging can successfully monitor and control thermal ablation of animal liver and tumor tissueex vivoandin vivo. However, normal and diseased human liver has substantially different physical properties that affect echo decorrelation. Here, effects of human liver tissue condition on ablation guidance by three-dimensional echo decorrelation imaging are elucidated in experiments testing closed-loop control of radiofrequency ablation (RFA) in normal and diseased human liver tissueex vivo. Approach. Samples of normal, steatotic, and cirrhotic human liver tissue underwent RFA, targeting a 20 mm-diameter spherical ablation zone. For each tissue condition, RFA was controlled by echo decorrelation inN> 14 trials, automatically ceasing if average cumulative decorrelation within the targeted ablation zone surpassed a predetermined threshold (successfully controlled trials), or otherwise completing a standard ablation cycle of the RFA generator (unsuccessfully controlled). For comparison,N= 14 RFA trials for each tissue condition followed the RFA generator's standard algorithm without echo decorrelation feedback (uncontrolled). Receiver operating characteristic (ROC) and precision-recall curve analyses compared 3D echo decorrelation maps to segmented ablation zones. To assess effects of closed-loop control and liver condition on treatment reliability, ablation volumes, rates, and Dice coefficients for measured vs. targeted ablation zones were statistically compared among control conditions and liver types.Results. ROC curves showed effective prediction of local ablation by echo decorrelation across all liver types and control conditions (0.876 ⩽AUROC ⩽ 0.953). Successful control was significantly more frequent, ablated volumes were generally larger, and optimal echo decorrelation thresholds were smaller for normal compared to diseased liver.Significance. This study validates three-dimensional echo decorrelation imaging for monitoring and control of RFA in healthy and diseased human liver while elucidating the dependence of RFA and echo decorrelation outcomes on liver condition and resulting implications for clinical applications.
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Affiliation(s)
- Elmira Ghahramani
- Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States of America
| | - Peter D Grimm
- Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States of America
| | - Benjamin E Weiss
- Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States of America
| | - Nicholas S Schoenleb
- Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States of America
| | - Alexander J Knapp
- Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States of America
| | - Jiang Wang
- Department of Pathology, University of Cincinnati, Cincinnati, OH, United States of America
| | - Syed A Ahmad
- Department of Surgery, University of Cincinnati, Cincinnati, OH, United States of America
| | - Shimul A Shah
- Department of Surgery, University of Cincinnati, Cincinnati, OH, United States of America
| | - Ralph C Quillin Iii
- Department of Surgery, University of Cincinnati, Cincinnati, OH, United States of America
| | - Sameer H Patel
- Department of Surgery, University of Cincinnati, Cincinnati, OH, United States of America
| | - T Douglas Mast
- Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States of America
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Sigdel M, Fang Y, Sun Z, Sigdel M, Jiao D. Robotic navigation-assisted percutaneous liver puncture: a pilot study. Quant Imaging Med Surg 2025; 15:1543-1554. [PMID: 39995746 PMCID: PMC11847208 DOI: 10.21037/qims-24-1584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Accepted: 12/24/2024] [Indexed: 02/26/2025]
Abstract
Background Liver cancer is often diagnosed at an advanced stage, rendering many cases unresectable and necessitating minimally invasive treatments such as ablation, for which accurate puncture is essential. Manual techniques are limited by steep learning curves, frequent needle adjustments, and increased radiation exposure. Robotic navigation-assisted puncture (RNAP) offers improved precision, efficiency, and safety, but its efficacy compared to that of manual puncture (MP) remains unclear. This study aimed to assess the safety and efficacy of RNAP in the treatment of liver tumors. Methods From October 2023 to February 2024, 65 patients with liver tumors underwent percutaneous puncture procedures (ablation, iodine-125 implantation, and biopsy) at department of interventional radiology. They were divided into two groups: the RNAP group (n=29) and the MP group (n=36). Two techniques were compared in terms of technical success (TS), clinical success (CS), puncture scoring (PS), number of computed tomography (CT) scans, total procedure time (TPT), puncture time (PT), irradiation dose (ID), and puncture-related complications. Results There were significant differences between patients in the RNAP group and those in the MP group in terms of PS (3.02±0.68 vs. 2.24±0.73; P=0.01), PT (8.86±1.91 vs. 13.44±3.66 min; P=0.01), number of CT scans (7.03±2.30 vs. 11.58±4.25; P=0.01), and ID (160.76±40.60 vs. 230.06±86.46 mGy·cm; P=0.01); meanwhile, TS (100% vs. 100%; P>0.99), CS (91.50% vs. 91.40%; P=0.81), TPT (33.22±7.80 vs. 32.13±5.50 min; P=0.52), and complications (10.30% vs. 5.56%; P=0.47) showed no differences. Conclusions RNAP is a useful tool for performing puncture procedures on liver tumors, which can decrease PT, CT scan times, and ID.
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Affiliation(s)
- Milan Sigdel
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yi Fang
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhanguo Sun
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Madan Sigdel
- School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA, USA
| | - Dechao Jiao
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Saraswat I, Goel A, Gupta J. An In-depth Review on Argemone mexicana in the Management of Liver Health and Liver Cancer. Anticancer Agents Med Chem 2025; 25:24-34. [PMID: 39225208 DOI: 10.2174/0118715206307964240821051756] [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: 03/11/2024] [Revised: 05/25/2024] [Accepted: 07/23/2024] [Indexed: 09/04/2024]
Abstract
INTRODUCTION Argemone mexicana, commonly known as the Mexican prickly poppy, has been historically employed in traditional medicine for various ailments, including liver disorders. Given the rising prevalence of liver diseases, including cancer, investigating the potential efficacy of Argemone mexicana in promoting liver health is of paramount importance. This review aims to provide a comprehensive analysis of the existing literature on the hepatoprotective and anticancer properties of Argemone mexicana. METHODOLOGY A systematic literature search was conducted across PubMed, Google Scholar, and relevant botanical and pharmacological databases. Studies from various sources, including in vitro experiments, animal models, and clinical trials, were included in the review. The search focused on articles published up to 2010-2023, encompassing research that explored the botanical characteristics, chemical composition, traditional uses, and pharmacological properties of Argemone mexicana, specifically emphasizing its impact on liver health and cancer. RESULTS The review revealed a wealth of studies highlighting the diverse pharmacological properties of Argemone mexicana. The botanical composition includes compounds with antioxidant and anti-inflammatory potential, suggesting hepatoprotective effects. Studies using in vitro and in vivo models demonstrated promising outcomes regarding liver function improvement and inhibition of liver cancer cell proliferation. While some clinical studies supported the traditional uses of Argemone mexicana, further well-designed trials are warranted to establish its clinical efficacy. CONCLUSION In conclusion, Argemone mexicana shows promise as a natural agent for promoting liver health and combating liver cancer. Bioactive compounds with antioxidant and anti-inflammatory properties suggest potential hepatoprotective effects. However, translating these findings into clinical practice requires further rigorous investigation, including well-designed clinical trials. This review provides a foundation for future research efforts aimed at elucidating the full therapeutic potential of Argemone mexicana in liver health and cancer management.
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Affiliation(s)
- Istuti Saraswat
- Department of Biotechnology, GLA University, 17km Stone, NH-2 Mathura-Delhi Road Mathura, Chaumuhan, Mathura, Uttar Pradesh, India
| | - Anjana Goel
- Department of Biotechnology, GLA University, 17km Stone, NH-2 Mathura-Delhi Road Mathura, Chaumuhan, Mathura, Uttar Pradesh, India
| | - Jyoti Gupta
- Department of Biotechnology, GLA University, 17km Stone, NH-2 Mathura-Delhi Road Mathura, Chaumuhan, Mathura, Uttar Pradesh, India
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Dajti E, Serenari M, Malvi D, Dajti G, Ravaioli F, Colecchia L, Marasco G, Caputo F, Renzulli M, Vasuri F, Vestito A, Azzaroli F, Barbara G, Ravaioli M, Festi D, D'Errico A, Cescon M, Colecchia A. Porto-sinusoidal vascular disorder in surgical candidates for liver metastases: Prevalence, noninvasive diagnosis, and burden on surgical outcomes. Liver Transpl 2025; 31:58-69. [PMID: 39311847 DOI: 10.1097/lvt.0000000000000489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Accepted: 08/27/2024] [Indexed: 12/13/2024]
Abstract
Chemotherapy can cause vascular and metabolic liver injury in patients with liver metastases, but scarce data are available. We aimed to (i) describe the prevalence of porto-sinusoidal vascular disorder (PSVD) among patients undergoing resection for liver metastases; and (ii) assess whether liver (LSM) and spleen stiffness measurements could diagnose PSVD and predict postoperative complications. This is a prospective single-center study enrolling consecutive patients undergoing hepatic resection for metastases at a tertiary center. For each patient, we evaluated previous exposure to chemotherapy, comorbidities, elastography, type of surgery, histological features at the resection specimen, morbidity (post-hepatectomy liver failure and major complications according to Clavien-Dindo), and 90-day survival. Sixty-eight patients were included, of whom 60 (88%) had received chemotherapy. Twenty-nine (44%) patients had PSVD. Spleen stiffness measurements <21 kPa (negative predictive value 87%) and >40 kPa (positive predictive value 100%) could accurately diagnose PSVD. PSVD significantly increased the risk of post-hepatectomy liver failure (22% vs. 45%) and major complications (11% vs. 31%). Preoperative LSM was associated with postoperative morbidity. The cutoff LSMs <4.5 and >8 kPa predicted the risk of clinically significant post-hepatectomy liver failure (0%, 11%, and 33% in LSM <4.5, 4.5-8, and >8 kPa, respectively) and major complications (0%, 25%, 44% in LSM <4.5, 4.5-8, and >8 kPa, respectively). PSVD is very common among patients undergoing liver surgery for metastases, and it is associated with increased morbidity. LSM and spleen stiffness measurements can correctly identify patients with PSVD and those at risk of clinically relevant postoperative complications.
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Affiliation(s)
- Elton Dajti
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Matteo Serenari
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- General Surgery and Transplant Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Deborah Malvi
- Pathology Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gerti Dajti
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Federico Ravaioli
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Luigi Colecchia
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Giovanni Marasco
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Francesca Caputo
- General Surgery and Transplant Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Matteo Renzulli
- Department of Radiology, IRCSS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
| | - Francesco Vasuri
- Pathology Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Amanda Vestito
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Francesco Azzaroli
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Giovanni Barbara
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Matteo Ravaioli
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- General Surgery and Transplant Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Davide Festi
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Antonietta D'Errico
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- Pathology Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Matteo Cescon
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- General Surgery and Transplant Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Antonio Colecchia
- Department of Medical Specialities, University Hospital of Modena, University of Modena & Reggio Emilia, Modena, Italy
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9
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Hsieh CL, Peng CM, Chen CW, Liu CH, Teng CT, Liu YJ. Benefits and drawbacks of radiofrequency ablation via percutaneous or minimally invasive surgery for treating hepatocellular carcinoma. World J Gastrointest Surg 2024; 16:3400-3407. [PMID: 39649197 PMCID: PMC11622093 DOI: 10.4240/wjgs.v16.i11.3400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 06/29/2024] [Accepted: 07/18/2024] [Indexed: 10/30/2024] Open
Abstract
The management of early stage hepatocellular carcinoma (HCC) presents significant challenges. While radiofrequency ablation (RFA) has shown safety and effectiveness in treating HCC, with lower mortality rates and shorter hospital stays, its high recurrence rate remains a significant impediment. Consequently, achieving improved survival solely through RFA is challenging, particularly in retrospective studies with inherent biases. Ultrasound is commonly used for guiding percutaneous RFA, but its low contrast can lead to missed tumors and the risk of HCC recurrence. To enhance the efficiency of ultrasound-guided percutaneous RFA, various techniques such as artificial ascites and contrast-enhanced ultrasound have been developed to facilitate complete tumor ablation. Minimally invasive surgery (MIS) offers advantages over open surgery and has gained traction in various surgical fields. Recent studies suggest that laparoscopic intraoperative RFA (IORFA) may be more effective than percutaneous RFA in terms of survival for HCC patients unsuitable for surgery, highlighting its significance. Therefore, combining MIS-IORFA with these enhanced percutaneous RFA techniques may hold greater significance for HCC treatment using the MIS-IORFA approach. This article reviews liver resection and RFA in HCC treatment, comparing their merits and proposing a trajectory involving their combination in future therapy.
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Affiliation(s)
- Ching-Lung Hsieh
- Department of Computer Science and Information Engineering, Feng Chia University, Taichung 40724, Taiwan
- Department of Surgery, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
| | - Cheng-Ming Peng
- Department of Surgery, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
| | - Chun-Wen Chen
- Department of Radiology, Taichung Armed Forces General Hospital, Taichung 406, Taiwan
- Department of Medical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology, Taichung 406, Taiwan
- Department of Radiology, School of Medicine, National Defense Medical Center, Taipei 11490, Taiwan
| | - Chang-Hsien Liu
- Department of Medical Imaging, China Medical University Hsinchu Hospital and China Medical University, Hsinchu 302, Taiwan
- Institute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu 300, Taiwan
| | - Chih-Tao Teng
- Department of Radiology, Nantou Hospital of the Ministry of Health and Welfare, Nantou 540, Taiwan
- Master’s Program of Biomedical Informatics and Biomedical Engineering, Feng Chia University, Taichung 407, Taiwan
| | - Yi-Jui Liu
- Department of Automatic Control Engineering, Feng Chia University, Taichung 407, Taiwan
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10
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Yu ZN, Xu LL, Li L, Zhang H, Ma YY, Wang L, Jiang JT, Zhang M. Comparison of the outcomes between ultrasonic devices and clamping in hepatectomy: a meta-analysis. World J Surg Oncol 2024; 22:304. [PMID: 39548479 PMCID: PMC11568570 DOI: 10.1186/s12957-024-03575-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Accepted: 10/26/2024] [Indexed: 11/18/2024] Open
Abstract
BACKGROUND Recent advances in ultrasound technology have led to widespread adoption of ultrasonic energy devices in liver resections. While various studies have assessed the comparative advantages of ultrasonic devices and traditional clamp-crushing, their findings vary. Moreover, a specific systematic review on this topic has not yet been conducted. OBJECTIVES This study aims to present a comprehensive, up-to-date analysis comparing outcomes between ultrasonic devices and conventional clamp-crushing methods in liver resection, based on currently available literature. PATIENTS AND METHODS We conducted a systematic literature search in databases such as PubMed, Embase, Web of Science, and CNKI up to November 2023. Studies that compared the efficacy or safety of ultrasonic devices against traditional clamp-crushing methods in hepatectomy were included. The analysis covered intraoperative outcomes like operating time, blood loss, and transfusion rate, as well as postoperative outcomes such as complication rate, mortality, postoperative bleeding, and bile leakage. Review Manager version 5.3 (Cochrane Collaboration, Oxford, UK) and Stata 17.0 (Stata Corp, College Station, TX, USA) were used for data analysis. RESULTS Thirteen studies, involving a total of 1,417 patients (630 using ultrasonic devices and 787 using clamp-crushing methods), were included. The clamp-crush method resulted in a shorter operation time. Contrarily, the ultrasonic device group experienced reduced blood loss and lower transfusion rates. Postoperatively, there was no significant difference in mortality or postoperative bleeding between the groups. However, the ultrasonic group had a lower overall complication rate, particularly a reduced incidence of bile leakage. Overall, the ultrasonic devices were associated with improved perioperative outcomes. CONCLUSIONS The findings suggest that ultrasonic devices provide better outcomes in hepatectomy compared to traditional clamp-crushing techniques. Nonetheless, large-scale randomized controlled trials are needed to confirm these results due to potential heterogeneity and biases. The choice of using ultrasonic devices should consider the surgeon's experience and individual patient circumstances.
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Affiliation(s)
- Zhang-Neng Yu
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Liang-Liang Xu
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Lian Li
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Hua Zhang
- Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Key Laboratory of Chronobiology, Sichuan University), National Health Commission of China, Chengdu, 610041, China
| | - Yong-Yuan Ma
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Liang Wang
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Jin-Ting Jiang
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Ming Zhang
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China.
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Tabrizian P, Marino R, Chow PK. Liver resection and transplantation in the era of checkpoint inhibitors. JHEP Rep 2024; 6:101181. [PMID: 39741696 PMCID: PMC11686060 DOI: 10.1016/j.jhepr.2024.101181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 06/24/2024] [Accepted: 07/26/2024] [Indexed: 01/03/2025] Open
Abstract
Immune checkpoint inhibitors (ICIs) have revolutionised the treatment landscape for advanced hepatocellular carcinoma (HCC). The combination of atezolizumab and bevacizumab has demonstrated efficacy, establishing a new standard of care for advanced HCC. Neoadjuvant studies have shown promising results with high response rates, increasing research into ICIs' role. In the peri-operative setting, in addition to adjuvant and neo-adjuvant therapies, strategies for "downstaging" and "bridging" patients to liver transplantation (LT) are being investigated, broadening the eligible candidate pool. Furthermore, therapeutic advances have reshaped conversion strategies for hepatic resection, with emerging evidence indicating a role for adjuvant immunotherapy in patients at high risk of postoperative recurrence. In LT, concerns have arisen over the potential conflict between immunosuppression needs and the immune-enhancing effects of ICIs, with reports of severe rejection. However, liver-specific factors may lessen rejection risks, prompting exploration into the safety of pre-transplant ICI administration. Moreover, ongoing trials must prioritise patient selection and vigilant management protocols. Despite the remarkable progress in immunotherapy, the intricate molecular interactions within the tumour microenvironment and their implications on oncogenic pathways remain incompletely understood. This highlights the need for specialised expertise to effectively integrate immunotherapy into the surgical management of HCC. Key challenges include ensuring safety, optimising oncological outcomes, managing the risk of graft rejection in transplant recipients, and refining patient selection criteria. In this review, we aim to provide a comprehensive overview of the evolving role of immunotherapy in the surgical management of HCC, discussing the rationale for its application in both pre- and post-surgical contexts, leveraging current clinical experience, identifying potential limitations, and envisioning future applications. By integrating existing knowledge and highlighting areas for further investigation, this review seeks to inform clinical practice and guide future research endeavours.
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Affiliation(s)
- Parissa Tabrizian
- Liver Transplant and Hepatobiliary Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, USA
| | - Rebecca Marino
- Liver Transplant and Hepatobiliary Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, USA
| | - Pierce K.H. Chow
- Department of Hepato-pancreato-Biliary and Transplant Surgery, National Cancer Center Singapore and Singapore General Hospital, Singapore
- Surgery Academic-Clinical Program, Duke-NUS Medical School Singapore, Singapore
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12
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Zhang H, Pei S, Li J, Zhu J, Li H, Wu G, Weng R, Chen R, Fang Z, Sun J, Chen K. Insights about exosomal circular RNAs as novel biomarkers and therapeutic targets for hepatocellular carcinoma. Front Pharmacol 2024; 15:1466424. [PMID: 39444611 PMCID: PMC11496148 DOI: 10.3389/fphar.2024.1466424] [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: 07/18/2024] [Accepted: 09/30/2024] [Indexed: 10/25/2024] Open
Abstract
One of the most prevalent pathological types of Primary Liver Cancer (PLC) is the Hepatocellular Carcinoma (HCC) poses a global health issue. The high recurrence and metastasis rate of HCC, coupled with a low 5-year survival rate, result in a bleak prognosis. Exosomes, small extracellular vesicles released by various cells, contain diverse non-coding RNA molecules, including circular RNAs (circRNAs), which play a significant role in intercellular communication and can impact HCC progression. Studies have revealed the potential clinical applications of exosomal circRNAs as biomarkers and therapeutic targets for HCC. These circRNAs can be transferred via exosomes to nearby non-cancerous cells, thereby regulating HCC progression and influencing malignant phenotypes, such as cell proliferation, invasion, metastasis, and drug resistance. This review provides a comprehensive overview of the identified exosomal circRNAs, highlighting their potential as non-invasive biomarkers for HCC, and suggesting new perspectives for HCC diagnosis and treatment. The circRNA from exosomal organelles promotes metastasis and immune scape because of their unique chirality which is different from the Biomolecular Homochirality.
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Affiliation(s)
- Haiyan Zhang
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
- Zhejiang Chinese Medical University, Shuren College, Hangzhou, China
| | - Shanshan Pei
- School of Pharmacy, Beihua University, Jilin, China
| | - Jiaxuan Li
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Jiajie Zhu
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Hongyu Li
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Guangshang Wu
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Ruiqi Weng
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Ruyi Chen
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Zhongbiao Fang
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
| | - Jingbo Sun
- School of Pharmacy, Beihua University, Jilin, China
| | - Keda Chen
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
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13
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Kornberg A. Risk of early hepatocellular carcinoma recurrence following liver resection: arbitrary specification or possible target to improve outcome? Hepatobiliary Surg Nutr 2024; 13:745-748. [PMID: 39175728 PMCID: PMC11336542 DOI: 10.21037/hbsn-24-202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 05/25/2024] [Indexed: 08/24/2024]
Affiliation(s)
- Arno Kornberg
- Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
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14
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Qiao W, Sheng S, Xiong Y, Han M, Jin R, Hu C. Nomogram for predicting post-therapy recurrence in BCLC A/B hepatocellular carcinoma with Child-Pugh B cirrhosis. Front Immunol 2024; 15:1369988. [PMID: 38799452 PMCID: PMC11116566 DOI: 10.3389/fimmu.2024.1369988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Accepted: 04/26/2024] [Indexed: 05/29/2024] Open
Abstract
Introduction This study conducts a retrospective analysis on patients with BCLC stage A/B hepatocellular carcinoma (HCC) accompanied by Child-Pugh B cirrhosis, who underwent transarterial chemoembolization (TACE) in combination with local ablation therapy. Our goal was to uncover risk factors contributing to post-treatment recurrence and to develop and validate an innovative 1-, 3-, and 5-year recurrence free survival (RFS) nomogram. Methods Data from 255 BCLC A/B HCC patients with Child-Pugh B cirrhosis treated at Beijing You'an Hospital (January 2014 - January 2020) were analyzed using random survival forest (RSF), LASSO regression, and multivariate Cox regression to identify independent risk factors for RFS. The prognostic nomogram was then constructed and validated, categorizing patients into low, intermediate, and high-risk groups, with RFS assessed using Kaplan-Meier curves. Results The nomogram, integrating the albumin/globulin ratio, gender, tumor number, and size, showcased robust predictive performance. Harrell's concordance index (C-index) values for the training and validation cohorts were 0.744 (95% CI: 0.703-0.785) and 0.724 (95% CI: 0.644-0.804), respectively. The area under the curve (AUC) values for 1-, 3-, and 5-year RFS in the two cohorts were also promising. Calibration curves highlighted the nomogram's reliability and decision curve analysis (DCA) confirmed its practical clinical benefits. Through meticulous patient stratification, we also revealed the nomogram's efficacy in distinguishing varying recurrence risks. Conclusion This study advances recurrence prediction in BCLC A/B HCC patients with Child-Pugh B cirrhosis following TACE combined with ablation. The established nomogram accurately predicts 1-, 3-, and 5-year RFS, facilitating timely identification of high-risk populations.
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Affiliation(s)
- Wenying Qiao
- Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Infectious Diseases, Beijing, China
- National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Changping Laboratory, Beijing, China
| | - Shugui Sheng
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Infectious Diseases, Beijing, China
- National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yiqi Xiong
- Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, China
| | - Ming Han
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Infectious Diseases, Beijing, China
- National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ronghua Jin
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Infectious Diseases, Beijing, China
- National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Changping Laboratory, Beijing, China
| | - Caixia Hu
- Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, China
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15
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Schrecker C, Schulze F, Trojan J, Bechstein WO, Zeuzem S, Koch C. Diagnostic performance of non-invasive liver fibrosis scores in patients with early-intermediate hepatocellular carcinoma. J Cancer Res Clin Oncol 2024; 150:187. [PMID: 38602548 PMCID: PMC11008064 DOI: 10.1007/s00432-024-05708-3] [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: 02/10/2024] [Accepted: 03/16/2024] [Indexed: 04/12/2024]
Abstract
PURPOSE Hepatocellular carcinoma (HCC) arises in individuals with underlying liver disease. Diagnosing the degree of hepatic fibrosis helps to determine the severity of the underlying liver disease and may influence therapeutic decisions in HCC patients. Non-invasive fibrosis scores can be used to estimate the degree of fibrosis in liver disease patients, but most of these scores were developed in patients with viral hepatitis and without HCC. This study explored the ability of the Fibrosis-4 Index (FIB-4), the AST/Platelet Ratio Index (APRI), and the AST/ALT ratio to diagnose or exclude advanced fibrosis (METAVIR F3/4 versus F0-2) in patients with early-intermediate, potentially resectable HCC. METHODS We retrospectively reviewed 119 patients who underwent hepatic resection for HCC at a tertiary centre (2007-2019), 75 of whom had advanced fibrosis (prevalence 63%). Histological assessment of the surgical liver specimen was used as a reference standard for the degree of fibrosis. RESULTS Overall diagnostic performance was highest for the FIB-4 Index, with an area under the receiver operating characteristic curve (AUROC) of 0.82, compared with 0.78 for APRI, and 0.56 for the AST/ALT ratio. Using established cut-off values, FIB-4 achieved a 90% positive predictive value at the higher cut-off (3.25) and a 90% negative predictive value at the lower cut-off (1.45). CONCLUSION The FIB-4 Index could reliably diagnose or exclude advanced fibrosis in patients with early-intermediate HCC, and may thus have a role in guiding therapeutic decisions in these patients.
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Affiliation(s)
- Christopher Schrecker
- Department of Medicine, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany.
| | - Falko Schulze
- Dr. Senckenberg Institute of Pathology, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany
| | - Jörg Trojan
- Department of Medicine, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany
| | - Wolf Otto Bechstein
- Department of Surgery, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany
| | - Stefan Zeuzem
- Department of Medicine, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany
| | - Christine Koch
- Department of Medicine, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany.
- Frankfurt Institute of Clinical Cancer Research, Krankenhaus Nordwest, Frankfurt am Main, Germany.
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Jo E, Savsani K, Alfonso A, Park A, Lee SD, Sakar D, Kinsey N, Sambommatsu Y, Imaid D, Khan A, Sharma A, Saeed M, Kumaran V, Cotterell A, Levy M, Bruno D. Photodynamic effect of indocyanine green and its application to hepatocellular carcinoma treatment. JOURNAL OF CANCER METASTASIS AND TREATMENT 2024. [DOI: 10.20517/2394-4722.2024.18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Hepatocellular carcinoma (HCC) stands as the primary cause of liver cancers, with limited treatment options outside of surgical resection or transplant. Photodynamic therapy (PDT) using indocyanine green (ICG) as a photosensitizer offers a promising therapeutic option for HCC. ICG PDT has demonstrated efficacy in vitro and in vivo , providing a safe treatment option for patients ineligible for resection or transplant. Challenges in PDT optimization include limited light delivery, poor photosensitizer optimization, and low oxygen generation. Innovative solutions, such as ICG incorporation into nanostructures and direct administration for HCC cases, show promise. Combining ICG PDT with Lentinula edodes mycelia (LEM) and hydrogen gas inhalation may address oxygen production limitations. Utilizing a combination of therapeutic approaches and therapies may increase the efficacy of ICG PDT, making it the safer and more effective treatment option for patients. ICG’s proven clinical safety may expedite potential approval for its use in PDT. Advancements in photosensitizer technology, such as aggregation-induced emission photosensitizers (AIE-PSs), and combination therapies will enhance PDT efficacy shortly, as developments show promise for improved outcomes. For HCC patients, ICG PDT presents a valuable therapeutic option. This work is novel because it explores new combination therapy approaches, leveraging the benefits of PDT with ICG and the developments in photosensitizer technology, nanotechnology, and the combination of other treatments such as LEM and hydrogen gas, which could potentially revolutionize the treatment of HCC and offer a better prognosis for patients.
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17
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Ursu CP, Ciocan A, Ursu Ș, Ciocan RA, Gherman CD, Cordoș AA, Vălean D, Pop RS, Furcea LE, Procopeț B, Ștefănescu H, Moiș EI, Al Hajjar N, Graur F. Prognostic Indicators of Overall Survival in Hepatocellular Carcinoma Patients Undergoing Liver Resection. Cancers (Basel) 2024; 16:1427. [PMID: 38611104 PMCID: PMC11010842 DOI: 10.3390/cancers16071427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 03/27/2024] [Accepted: 04/05/2024] [Indexed: 04/14/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer and the third contributor to malignancy-related deaths worldwide. The hepatic venous pressure gradient (HVPG), transient elastography-liver stiffness measurement (TE-LSM), and the association between TBS (tumor burden score), alpha-fetoprotein levels, and the Child-Pugh classification (TAC score) can serve as valuable prognostic indicators for these patients. Therefore, the main objective of our research was to analyze the prognostic value of the HVPG, TE-LSM, TBS, and TAC scores. An observational and survival study was conducted on 144 subjects. Our findings indicated that HVPG greater than 10 mmHg, AFP surpassing 400 ng/mL, an advanced C-P class, and low TAC score are independent predictors of overall survival. During the multivariate analysis, AFP serum levels and C-P class proved statistically significant. The present study revealed significant differences in overall survival between the two groups divided upon HVPG values and settled by the cutoff of 10 mmHg (p = 0.02). Moreover, by dividing the cohort into three groups based on the TAC score (very low, low, and moderate), statistically significant differences in overall survival were observed across the groups (p = 0.004).
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Affiliation(s)
- Cristina-Paula Ursu
- Department of Surgery, “Iuliu Hațieganu” University of Medicine and Pharmacy, Croitorilor Street, No. 19–21, 400162 Cluj-Napoca, Romania; (C.-P.U.); (Ș.U.); (D.V.); (L.E.F.); (E.I.M.); (N.A.H.); (F.G.)
- “Prof. Dr. Octavian Fodor” Regional Institute of Gastroenterology and Hepatology, Croitorilor Street, No. 19–21, 400162 Cluj-Napoca, Romania; (B.P.)
| | - Andra Ciocan
- Department of Surgery, “Iuliu Hațieganu” University of Medicine and Pharmacy, Croitorilor Street, No. 19–21, 400162 Cluj-Napoca, Romania; (C.-P.U.); (Ș.U.); (D.V.); (L.E.F.); (E.I.M.); (N.A.H.); (F.G.)
- “Prof. Dr. Octavian Fodor” Regional Institute of Gastroenterology and Hepatology, Croitorilor Street, No. 19–21, 400162 Cluj-Napoca, Romania; (B.P.)
| | - Ștefan Ursu
- Department of Surgery, “Iuliu Hațieganu” University of Medicine and Pharmacy, Croitorilor Street, No. 19–21, 400162 Cluj-Napoca, Romania; (C.-P.U.); (Ș.U.); (D.V.); (L.E.F.); (E.I.M.); (N.A.H.); (F.G.)
- “Prof. Dr. Octavian Fodor” Regional Institute of Gastroenterology and Hepatology, Croitorilor Street, No. 19–21, 400162 Cluj-Napoca, Romania; (B.P.)
| | - Răzvan Alexandru Ciocan
- Department of Surgery-Practical Abilities, “Iuliu Hațieganu” University of Medicine and Pharmacy, Marinescu Street, No. 23, 400337 Cluj-Napoca, Romania; (R.A.C.); (C.D.G.); (A.-A.C.)
| | - Claudia Diana Gherman
- Department of Surgery-Practical Abilities, “Iuliu Hațieganu” University of Medicine and Pharmacy, Marinescu Street, No. 23, 400337 Cluj-Napoca, Romania; (R.A.C.); (C.D.G.); (A.-A.C.)
| | - Ariana-Anamaria Cordoș
- Department of Surgery-Practical Abilities, “Iuliu Hațieganu” University of Medicine and Pharmacy, Marinescu Street, No. 23, 400337 Cluj-Napoca, Romania; (R.A.C.); (C.D.G.); (A.-A.C.)
- Romanian Society of Medical Informatics, 300041 Timișoara, Romania
| | - Dan Vălean
- Department of Surgery, “Iuliu Hațieganu” University of Medicine and Pharmacy, Croitorilor Street, No. 19–21, 400162 Cluj-Napoca, Romania; (C.-P.U.); (Ș.U.); (D.V.); (L.E.F.); (E.I.M.); (N.A.H.); (F.G.)
- “Prof. Dr. Octavian Fodor” Regional Institute of Gastroenterology and Hepatology, Croitorilor Street, No. 19–21, 400162 Cluj-Napoca, Romania; (B.P.)
| | - Rodica Sorina Pop
- Department of Community Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, Avram Iancu Street, No. 31, 400347 Cluj-Napoca, Romania;
| | - Luminița Elena Furcea
- Department of Surgery, “Iuliu Hațieganu” University of Medicine and Pharmacy, Croitorilor Street, No. 19–21, 400162 Cluj-Napoca, Romania; (C.-P.U.); (Ș.U.); (D.V.); (L.E.F.); (E.I.M.); (N.A.H.); (F.G.)
- “Prof. Dr. Octavian Fodor” Regional Institute of Gastroenterology and Hepatology, Croitorilor Street, No. 19–21, 400162 Cluj-Napoca, Romania; (B.P.)
| | - Bogdan Procopeț
- “Prof. Dr. Octavian Fodor” Regional Institute of Gastroenterology and Hepatology, Croitorilor Street, No. 19–21, 400162 Cluj-Napoca, Romania; (B.P.)
- Department of Internal Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, Croitorilor Street, No. 19–21, 400162 Cluj-Napoca, Romania
| | - Horia Ștefănescu
- “Prof. Dr. Octavian Fodor” Regional Institute of Gastroenterology and Hepatology, Croitorilor Street, No. 19–21, 400162 Cluj-Napoca, Romania; (B.P.)
| | - Emil Ioan Moiș
- Department of Surgery, “Iuliu Hațieganu” University of Medicine and Pharmacy, Croitorilor Street, No. 19–21, 400162 Cluj-Napoca, Romania; (C.-P.U.); (Ș.U.); (D.V.); (L.E.F.); (E.I.M.); (N.A.H.); (F.G.)
- “Prof. Dr. Octavian Fodor” Regional Institute of Gastroenterology and Hepatology, Croitorilor Street, No. 19–21, 400162 Cluj-Napoca, Romania; (B.P.)
| | - Nadim Al Hajjar
- Department of Surgery, “Iuliu Hațieganu” University of Medicine and Pharmacy, Croitorilor Street, No. 19–21, 400162 Cluj-Napoca, Romania; (C.-P.U.); (Ș.U.); (D.V.); (L.E.F.); (E.I.M.); (N.A.H.); (F.G.)
- “Prof. Dr. Octavian Fodor” Regional Institute of Gastroenterology and Hepatology, Croitorilor Street, No. 19–21, 400162 Cluj-Napoca, Romania; (B.P.)
| | - Florin Graur
- Department of Surgery, “Iuliu Hațieganu” University of Medicine and Pharmacy, Croitorilor Street, No. 19–21, 400162 Cluj-Napoca, Romania; (C.-P.U.); (Ș.U.); (D.V.); (L.E.F.); (E.I.M.); (N.A.H.); (F.G.)
- “Prof. Dr. Octavian Fodor” Regional Institute of Gastroenterology and Hepatology, Croitorilor Street, No. 19–21, 400162 Cluj-Napoca, Romania; (B.P.)
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Zhang ZH, Du Y, Wei S, Pei W. Multilayered insights: a machine learning approach for personalized prognostic assessment in hepatocellular carcinoma. Front Oncol 2024; 13:1327147. [PMID: 38486931 PMCID: PMC10937467 DOI: 10.3389/fonc.2023.1327147] [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: 10/24/2023] [Accepted: 12/08/2023] [Indexed: 03/17/2024] Open
Abstract
Background Hepatocellular carcinoma (HCC) is a complex malignancy, and precise prognosis assessment is vital for personalized treatment decisions. Objective This study aimed to develop a multi-level prognostic risk model for HCC, offering individualized prognosis assessment and treatment guidance. Methods By utilizing data from The Cancer Genome Atlas (TCGA) and the Surveillance, Epidemiology, and End Results (SEER) database, we performed differential gene expression analysis to identify genes associated with survival in HCC patients. The HCC Differential Gene Prognostic Model (HCC-DGPM) was developed through multivariate Cox regression. Clinical indicators were incorporated into the HCC-DGPM using Cox regression, leading to the creation of the HCC Multilevel Prognostic Model (HCC-MLPM). Immune function was evaluated using single-sample Gene Set Enrichment Analysis (ssGSEA), and immune cell infiltration was assessed. Patient responsiveness to immunotherapy was evaluated using the Immunophenoscore (IPS). Clinical drug responsiveness was investigated using drug-related information from the TCGA database. Cox regression, Kaplan-Meier analysis, and trend association tests were conducted. Results Seven differentially expressed genes from the TCGA database were used to construct the HCC-DGPM. Additionally, four clinical indicators associated with survival were identified from the SEER database for model adjustment. The adjusted HCC-MLPM showed significantly improved discriminative capacity (AUC=0.819 vs. 0.724). External validation involving 153 HCC patients from the International Cancer Genome Consortium (ICGC) database verified the performance of the HCC-MLPM (AUC=0.776). Significantly, the HCC-MLPM exhibited predictive capacity for patient response to immunotherapy and clinical drug efficacy (P < 0.05). Conclusion This study offers comprehensive insights into HCC prognosis and develops predictive models to enhance patient outcomes. The evaluation of immune function, immune cell infiltration, and clinical drug responsiveness enhances our comprehension and management of HCC.
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Affiliation(s)
| | - Yunxiang Du
- Department of Oncology, Huai’an 82 Hospital, China RongTong Medical Healthcare Group Co., Ltd., Chengdu, China
| | - Shuzhen Wei
- Department of Oncology, Huai’an 82 Hospital, China RongTong Medical Healthcare Group Co., Ltd., Chengdu, China
| | - Weidong Pei
- Department of Discipline Development, China RongTong Medical Healthcare Group Co., Ltd., Chengdu, China
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Vitale A, Angelico R, Sensi B, Lai Q, Kauffmann E, Scalera I, Serenari M, Ginesini M, Romano P, Furlanetto A, D’Amico F. What Is the Role of Minimally Invasive Liver Surgery in Treating Patients with Hepatocellular Carcinoma on Cirrhosis? Cancers (Basel) 2024; 16:966. [PMID: 38473327 PMCID: PMC10930835 DOI: 10.3390/cancers16050966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Revised: 02/24/2024] [Accepted: 02/25/2024] [Indexed: 03/14/2024] Open
Abstract
Minimally invasive liver surgery (MILS) has been slowly introduced in the past two decades and today represents a major weapon in the fight against HCC, for several reasons. This narrative review conveys the major emerging concepts in the field. The rise in metabolic-associated steatotic liver disease (MASLD)-related HCC means that patients with significant cardiovascular risk will benefit more profoundly from MILS. The advent of efficacious therapy is leading to conversion from non-resectable to resectable cases, and therefore more patients will be able to undergo MILS. In fact, resection outcomes with MILS are superior compared to open surgery both in the short and long term. Furthermore, indications to surgery may be further expanded by its use in Child B7 patients and by the use of laparoscopic ablation, a curative technique, instead of trans-arterial approaches in cases not amenable to radiofrequency. Therefore, in a promising new approach, multi-parametric treatment hierarchy, MILS is hierarchically superior to open surgery and comes second only to liver transplantation.
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Affiliation(s)
- Alessandro Vitale
- Department of Surgical Oncological and Gastroenterological Sciences, Padua University, 35122 Padua, Italy; (A.V.); (P.R.); (A.F.)
| | - Roberta Angelico
- Transplant and HPB Unit, Department of Surgical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Bruno Sensi
- Transplant and HPB Unit, Department of Surgical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, AUO Policlinico I of Rome, Sapienza University of Rome, 00185 Rome, Italy;
| | - Emanuele Kauffmann
- Division of General and Transplant Surgery, Pisa University, 56126 Pisa, Italy; (E.K.); (M.G.)
| | - Irene Scalera
- Unità di Chirurgia Epatobiliare e Trapianti di Fegato, Azienda Ospedaliero—Universitaria Consorziale Policlinico di Bari, 70124 Bari, Italy; (I.S.); (F.D.)
| | - Matteo Serenari
- General Surgery and Transplant Unit, IRCCS Azienda Ospedaliero—Universitaria di Bologna, Sant’Orsola-Malpighi Hospital, 40138 Bologna, Italy;
- Department of Medical and Surgical Sciences—DIMEC, Alma Mater Studiorum—University of Bologna, 40126 Bologna, Italy
| | - Michael Ginesini
- Division of General and Transplant Surgery, Pisa University, 56126 Pisa, Italy; (E.K.); (M.G.)
| | - Pierluigi Romano
- Department of Surgical Oncological and Gastroenterological Sciences, Padua University, 35122 Padua, Italy; (A.V.); (P.R.); (A.F.)
| | - Alessandro Furlanetto
- Department of Surgical Oncological and Gastroenterological Sciences, Padua University, 35122 Padua, Italy; (A.V.); (P.R.); (A.F.)
| | - Francesco D’Amico
- Unità di Chirurgia Epatobiliare e Trapianti di Fegato, Azienda Ospedaliero—Universitaria Consorziale Policlinico di Bari, 70124 Bari, Italy; (I.S.); (F.D.)
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Wei Z, Xie K, Xu F, Dai C. The tumor burden score may be a discriminator in microwave ablation versus liver resection for hepatocellular carcinoma within the Milan criteria: a propensity score matching and inverse probability of treatment weighting study. Front Oncol 2024; 14:1330851. [PMID: 38434686 PMCID: PMC10905383 DOI: 10.3389/fonc.2024.1330851] [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: 10/31/2023] [Accepted: 01/30/2024] [Indexed: 03/05/2024] Open
Abstract
PURPOSE This study aims to compare the prognostic outcome of resection (RES) and microwave ablation (MWA) in different tumor burden score (TBS) cohorts. PATIENTS AND METHODS We retrospectively analyzed 479 patients with primary hepatocellular carcinoma (HCC) who underwent RES (n = 329) or MWA (n = 150) with curative intent at our institution. We assessed their overall survival (OS) and progression-free survival (PFS) using the Kaplan-Meier curve. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to minimize selection and confounding biases. Multivariate Cox regression was used to define the association between surgical modalities and outcomes. RESULTS Following PSM, in the TBS ≤3 cohort, the cumulative 1-, 3-, 5- year OS in the RES and MWA groups were 92.5% vs. 98.8%, 82.7% vs. 90.0%, and 82.7% vs. 83.2% (P = 0.366), respectively. The corresponding PFS rates in the RES and MWA groups were 82.7% vs. 88.0%, 63.6% vs. 68.3% and 55.2% vs. 56.3, respectively (P = 0.218). In the TBS >3 cohort, the cumulative 1-, 3-, 5- year OS between the RES and MWA groups were 92.5% vs. 95.0%, 82.8% vs. 73.2% and 76.3% vs. 55.1%, (P = 0.034), respectively. The corresponding PFS rates in the RES and MWA groups were 78.0% vs. 67.5%, 63.6% vs. 37.5% and 55.2% vs. 37.1%, respectively (P = 0.044). The IPTW analysis showed similar results as shown in PSM analysis. The multivariate Cox regression indicated that the type of surgical modality was not associated with a poorer prognostic outcome in the TBS ≤3 cohort, unlike in the TBS >3 cohort. CONCLUSION TBS, as a discriminator, might help guide treatment decision-making for HCC within the Milan criteria.
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Affiliation(s)
- Zeyuan Wei
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital of China Medical University, Shenyang, China
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Kailing Xie
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital of China Medical University, Shenyang, China
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Feng Xu
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital of China Medical University, Shenyang, China
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Chaoliu Dai
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital of China Medical University, Shenyang, China
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
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Wang A, Li J, Li C, Zhang H, Fan Y, Ma K, Wang Q. Impact of body composition on the prognosis of hepatocellular carcinoma patients treated with transarterial chemoembolization: A systematic review and meta-analysis. Heliyon 2024; 10:e25237. [PMID: 38352764 PMCID: PMC10862505 DOI: 10.1016/j.heliyon.2024.e25237] [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: 10/18/2023] [Revised: 01/22/2024] [Accepted: 01/23/2024] [Indexed: 02/16/2024] Open
Abstract
Objectives To summarize current evidence about the influence of body composition on the prognosis of patients with hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) treatment. Methods Public databases were systematically searched to identify relevant studies published from the inception of the database up to May 2023. Studies that evaluated the association between body composition and clinical outcomes in HCC patients who underwent TACE were included. A pre-designed table was applied to summarize relevant information. Meta-analysis was performed to estimate the association of body composition with overall survival. Results Fourteen studies were included in this review, including 3631 patients (sample size range: 56-908, median 186). All body composition measurements (including skeletal muscle area, visceral and subcutaneous adipose area, and bone mineral density) were based on computer tomography. The commonly used parameter was skeletal muscle index at 3rd lumbar vertebra level (8/14). Three studies evaluated the correlations of body composition changes with the prognosis after TACE. Most studies (12/14) identified body composition parameters as an independent indicator for overall survival, progression-free survival, and treatment response rate. The hazard ratio of different body composition parameters ranged from 1.01 to 2.88, and hazard ratio of body composition changes ranged from 1.88 to 5.93. The pooled hazard ratio of sarcopenia for overall survival was 1.38 (95 %CI: 1.20-1.58). Conclusions Body composition seems to be an important prognostic factor for a poorer clinical outcome after TACE treatment in patients with hepatocellular carcinoma. Future prospective studies with a larger sample size are required to confirm these findings. Registration study This study has been prospectively registered at the PROSPERO platform (https://www.crd.york.ac.uk/prospero/) with the registration No. CRD42022345602.
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Affiliation(s)
- Anrong Wang
- Department of Vascular Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Department of Interventional Therapy, People's Hospital of Dianjiang County, Chongqing, China
| | - Junfeng Li
- Department of Oncology, People's Hospital of Dianjiang County, Chongqing, China
| | - Changfeng Li
- Institution of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China
| | - Hui Zhang
- Institution of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China
| | - Yingfang Fan
- Department of Hepatobiliary Surgery, Third Affiliated Hospital, Southern Medical University, Guangzhou, China
| | - Kuansheng Ma
- Institution of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China
| | - Qiang Wang
- Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
- Department of Radiology, Karolinska University Hospital Huddinge, Stockholm, Sweden
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Zhang WQ, Zhang Q, Tan L, Guan ZF, Tian F, Tang HT, He K, Chen WQ. Postoperative adjuvant immunotherapy for high-risk hepatocellular carcinoma patients. Front Oncol 2023; 13:1289916. [PMID: 38179173 PMCID: PMC10766105 DOI: 10.3389/fonc.2023.1289916] [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: 09/06/2023] [Accepted: 11/29/2023] [Indexed: 01/06/2024] Open
Abstract
Background and aim Standardized approach to postoperative adjuvant therapy for hepatocellular carcinoma (HCC) remains elusive. This study endeavors to examine the effects of postoperative PD-1 adjuvant therapy on the short-term and long-term prognosis of patients at a heightened risk of post-surgical recurrence. Methods The data of HCC patients who underwent hepatectomy at our center from June 2018 to March 2023 were collected from the hospital database. Propensity score matching (PSM) was employed to perform a 1:1 match between the postoperative anti-PD-1 antibody group and the postoperative non-anti-PD-1 antibody group. Kaplan-Meier method was utilized to compare the overall survival (OS) and recurrence-free survival (RFS) between the two groups. Cox regression analysis was conducted to identify the prognostic factors affecting patient outcomes. Subgroup analyses were performed for different high-risk factors. Results Among the 446 patients included in the study, 122 patients received adjuvant therapy with postoperative anti-PD-1 antibodies. After PSM, the PD-1 group had postoperative 1-year, 2-year, 3-year, and 4-year OS rates of 93.1%, 86.8%, 78.2%, and 51.1%, respectively, while the non-PD-1 group had rates of 85.3%, 70.2%, 47.7%, and 30.0%. The PD-1 group had postoperative 1-year, 2-year, 3-year, and 4-year RFS rates of 81.7%, 77.0%, 52.3%, and 23.1%, respectively, whereas the non-PD-1 group had rates of 68.4%, 47.7%, and 25.8% in 1-year, 2-year, 3-year. A multifactorial Cox regression analysis revealed that postoperative PD-1 use was a prognostic protective factor associated with OS and RFS. Subgroup analysis results indicated that HCC patients with high recurrence risks significantly benefited from postoperative anti-PD-1 antibody treatment in terms of OS and RFS. Conclusion For HCC patients with high-risk recurrence factors and undergoing hepatectomy, postoperative adjuvant therapy with anti-PD-1 antibodies can effectively improve their survival prognosis.
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Affiliation(s)
| | - Qiao Zhang
- Department of Emergency, Zhongshan Hospital, Zhongshan, China
| | - Li Tan
- Department of General Surgery, Zhongshan Hospital, Zhongshan, China
| | - Zhi-Feng Guan
- Department of General Surgery, Zhongshan Hospital, Zhongshan, China
| | - Feng Tian
- Guangdong Medical College, Zhanjiang, China
| | | | - Kun He
- Department of General Surgery, Zhongshan Hospital, Zhongshan, China
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Liu S, Feng J, Ren Q, Qin H, Yang W, Cheng H, Yao X, Xu J, Han J, Chang S, Yang S, Mou J, Lin Y, He L, Wang H. Evaluating the clinical efficacy and limitations of indocyanine green fluorescence-guided surgery in childhood hepatoblastoma: A retrospective study. Photodiagnosis Photodyn Ther 2023; 44:103790. [PMID: 37696318 DOI: 10.1016/j.pdpdt.2023.103790] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Revised: 08/20/2023] [Accepted: 09/06/2023] [Indexed: 09/13/2023]
Abstract
BACKGROUND Indocyanine green (ICG) fluorescence guided surgery has been used to treat childhood hepatoblastoma (HB), but the advantages and disadvantages of this technique have not been fully discussed. The purpose of this study is to summarize the experience and to explore the clinical value of this technique for children with HB. METHODS 45 children with HB who underwent ICG fluorescence guided surgery (n = 22) and general surgery (n = 23) in our center from January 2020 to December 2022 were enrolled retrospectively. RESULTS All the liver tumors in the ICG group showed hyperfluorescence, including total and partial fluorescent types. With the help of ICG navigation, minimally invasive surgery was performed in 3 cases. 18.2 % of cases with tumors could not be accurately identified under white light, but could be identified by fluorescence imaging. The fluorescent cutting lines of 59.1 % of cases were consistent with the safe cutting lines. In 36.4 % of cases, the fluorescence boundary was not clear because of tumor necrosis. In 36.4 % of cases, the fluorescence could not be detected on the inner edge of the tumors because of the depth. A total of 29 ICG (+) suspicious lesions were found during the operations, of which 5 were true positive lesions. CONCLUSION ICG fluorescence guided surgery is safe and feasible in children with HB. This technique is helpful for locating tumors, determining margin and finding small lesions with negative imaging, especially in minimally invasive surgery. However, preoperative chemotherapy, tumor necrosis, tumor depth, and ICG administration impact the effect of fluorescence imaging.
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Affiliation(s)
- Shan Liu
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 56 NanLishi Road Xicheng District, Beijing 100045, China
| | - Jun Feng
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 56 NanLishi Road Xicheng District, Beijing 100045, China
| | - Qinghua Ren
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 56 NanLishi Road Xicheng District, Beijing 100045, China
| | - Hong Qin
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 56 NanLishi Road Xicheng District, Beijing 100045, China.
| | - Wei Yang
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 56 NanLishi Road Xicheng District, Beijing 100045, China.
| | - Haiyan Cheng
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 56 NanLishi Road Xicheng District, Beijing 100045, China
| | - Xingfeng Yao
- Department of Pathology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China
| | - Jiatong Xu
- Department of Pathology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China
| | - Jianyu Han
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 56 NanLishi Road Xicheng District, Beijing 100045, China
| | - Saishuo Chang
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 56 NanLishi Road Xicheng District, Beijing 100045, China
| | - Shen Yang
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 56 NanLishi Road Xicheng District, Beijing 100045, China
| | - Jianing Mou
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 56 NanLishi Road Xicheng District, Beijing 100045, China
| | - Yu Lin
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 56 NanLishi Road Xicheng District, Beijing 100045, China
| | - Lejian He
- Department of Pathology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China
| | - Huanmin Wang
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 56 NanLishi Road Xicheng District, Beijing 100045, China.
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Giudicelli H, Andraud M, Wagner M, Bourdais R, Goumard C, Scatton O, Thabut D, Simon J, Allaire M. Portal-hypertension features are associated with ascites occurrence and survival in patients with hepatocellular carcinoma treated by external radiotherapy. United European Gastroenterol J 2023; 11:985-997. [PMID: 38018771 PMCID: PMC10720686 DOI: 10.1002/ueg2.12488] [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: 06/12/2023] [Accepted: 09/19/2023] [Indexed: 11/30/2023] Open
Abstract
BACKGROUND AND AIMS We studied the impact of Portal hypertension (PHT) on ascites occurrence and on radiotherapy outcome in cirrhotic patients with hepatocellular carcinoma (HCC). METHOD All cirrhotic patients that received radiotherapy for HCC between 2012 and 2022 were included. Portal hypertension-Score was built using univariate analysis with the presence of esophageal varices (EV), platelet count, history of acute variceal bleeding (AVB) and spleen size. Time-to-events data were estimated using Kaplan-Meier method with log-rank and Cox-models. RESULTS 60 patients were included (female 27%, age 67 years-old, Child-Pugh A 82%, alcoholic/non-alcoholic steatohepatitis/hepatitis C virus 55/40/32%). 38% and 15% presented history of ascites and AVB respectively, 25% had large EV, 53.5% presented PHT score ≥ 5. 92% were BCLC-0/A, median tumor size was 30 mm. At 6 months, ascites incidence was 19% and precluded access to further HCC treatment for all patients with HCC recurrence. All PHT parameters included in the score and PHT score ≥ 5 (hazard ratio (HR) = 14.07, p = 0.01) were associated with ascites occurrence. Transplantation free survival and recurrence free survival at 1 year were 56% and 47% respectively. Albi grade 3 (HR = 3.01; p = 0.04) was independently associated with Transplantation free survival. CONCLUSION Radiotherapy should be cautiously performed in patients with PHT score ≥ 5 because of ascites occurrence risk precluding access to further HCC treatments.
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Affiliation(s)
- Héloïse Giudicelli
- AP‐HP Sorbonne UniversitéHôpital Universitaire Pitié‐SalpêtrièreService d’Hépato‐gastroentérologieParisFrance
| | - Mickaël Andraud
- AP‐HP Sorbonne UniversitéHôpital Universitaire Pitié‐SalpêtrièreService de radiothérapieParisFrance
| | - Mathilde Wagner
- AP‐HP, Sorbonne UniversitéHôpital Universitaire Pitié‐SalpêtrièreService d’imagerieParisFrance
- Sorbonne UniversitéLaboratoire d’Imagerie biomédicaleUMR 7371 ‐ U1146ParisFrance
| | - Rémi Bourdais
- AP‐HP Sorbonne UniversitéHôpital Universitaire Pitié‐SalpêtrièreService de radiothérapieParisFrance
| | - Claire Goumard
- AP‐HP Sorbonne UniversitéHôpital Universitaire Pitié‐SalpêtrièreService de chirurgie digestiveParisFrance
- Sorbonne UniversitéINSERMCentre de recherche Saint‐Antoine (CRSA)Institute of Cardiometabolism and Nutrition (ICAN)ParisFrance
| | - Olivier Scatton
- AP‐HP Sorbonne UniversitéHôpital Universitaire Pitié‐SalpêtrièreService de chirurgie digestiveParisFrance
- Sorbonne UniversitéINSERMCentre de recherche Saint‐Antoine (CRSA)Institute of Cardiometabolism and Nutrition (ICAN)ParisFrance
| | - Dominique Thabut
- AP‐HP Sorbonne UniversitéHôpital Universitaire Pitié‐SalpêtrièreService d’Hépato‐gastroentérologieParisFrance
- Sorbonne UniversitéINSERMCentre de recherche Saint‐Antoine (CRSA)Institute of Cardiometabolism and Nutrition (ICAN)ParisFrance
| | - Jean‐Marc Simon
- AP‐HP Sorbonne UniversitéHôpital Universitaire Pitié‐SalpêtrièreService de radiothérapieParisFrance
| | - Manon Allaire
- AP‐HP Sorbonne UniversitéHôpital Universitaire Pitié‐SalpêtrièreService d’Hépato‐gastroentérologieParisFrance
- INSERM UMR 1138Centre de recherche des CordeliersParisFrance
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Yue ZQ, Zhang P, Yan S, Ju LL, Wang HX, Yuan LX, Chen L, Wu JZ, Cao YL. Clinical study of standard residual liver volume and transient elastography in predicting poor prognosis of patients after hemihepatectomy. World J Clin Oncol 2023; 14:459-470. [PMID: 38059184 PMCID: PMC10696215 DOI: 10.5306/wjco.v14.i11.459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 09/28/2023] [Accepted: 10/16/2023] [Indexed: 11/22/2023] Open
Abstract
BACKGROUND Liver cancer resection, especially in patients with hemihepatectomy or extended hemihepatectomy, often leads to poor prognosis, such as liver insufficiency and even liver failure and death, because the standard residual liver volume (SRLV) cannot be fully compensated after surgery. AIM To explore the risk factors of poor prognosis after hemihepatectomy for hepatocellular carcinoma and evaluate the application value of related prognostic approaches. METHODS The clinical data of 35 patients with primary liver cancer in Nantong Third People's Hospital from February 2016 to July 2020 were retrospectively analyzed. The receiver operating characteristic curve was created using medcac19.0.4 to compare the critical values of the SRLV in different stages of liver fibrosis after hemihepatectomy with those of liver dysfunction after hemihepatectomy. It was constructed by combining the Child-Pugh score to evaluate its application value in predicting liver function compensation. RESULTS The liver stiffness measure (LSM) value and SRLV were associated with liver dysfunction after hemihepatectomy. Logistic regression analysis showed that an LSM value ≥ 25 kPa [odds ratio (OR) = 6.254, P < 0.05] and SRLV ≤ 0.290 L/m2 (OR = 5.686, P < 0.05) were independent risk factors for postoperative liver dysfunction. The accuracy of the new liver reserve evaluation model for predicting postoperative liver function was higher than that of the Child-Pugh score (P < 0.05). CONCLUSION SRLV and LSM values can be used to evaluate the safety of hemihepatectomy. The new liver reserve evaluation model has good application potential in the evaluation of liver reserve function after hemihepatectomy.
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Affiliation(s)
- Zhi-Qiang Yue
- Medical School of Nantong University, Nantong Third People’s Hospital, Affiliated Nantong Hospital 3 of Nantong University, Nantong 226000, Jiangsu Province, China
| | - Peng Zhang
- Department of Hepatobiliary Surgery, Nantong Third People’s Hospital, Affiliated Nantong Hospital 3 of Nantong University, Nantong 226000, Jiangsu Province, China
| | - Shuai Yan
- Medical School of Nantong University, Nantong Third People’s Hospital, Affiliated Nantong Hospital 3 of Nantong University, Nantong 226000, Jiangsu Province, China
| | - Lin-Ling Ju
- Nantong Institute of Liver Disease, Nantong Third People’s Hospital, Affiliated Nantong Hospital 3 of Nantong University, Nantong 226000, Jiangsu Province, China
| | - Hui-Xuan Wang
- Nantong Institute of Liver Disease, Nantong Third People’s Hospital, Affiliated Nantong Hospital 3 of Nantong University, Nantong 226000, Jiangsu Province, China
| | - Liu-Xia Yuan
- Nantong Institute of Liver Disease, Nantong Third People’s Hospital, Affiliated Nantong Hospital 3 of Nantong University, Nantong 226000, Jiangsu Province, China
| | - Lin Chen
- Nantong Institute of Liver Disease, Nantong Third People’s Hospital, Affiliated Nantong Hospital 3 of Nantong University, Nantong 226000, Jiangsu Province, China
| | - Jin-Zhu Wu
- Department of Hepatobiliary Surgery, Nantong Third People’s Hospital, Affiliated Nantong Hospital 3 of Nantong University, Nantong 226000, Jiangsu Province, China
| | - Ya-Li Cao
- Preventive Health Department, Nantong Third People’s Hospital, Affiliated Nantong Hospital 3 of Nantong University, Nantong 226000, Jiangsu Province, China
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26
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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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27
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Nishio T, Taura K, Koyama Y, Ishii T, Hatano E. Current status of preoperative risk assessment for posthepatectomy liver failure in patients with hepatocellular carcinoma. Ann Gastroenterol Surg 2023; 7:871-886. [PMID: 37927928 PMCID: PMC10623981 DOI: 10.1002/ags3.12692] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 04/08/2023] [Accepted: 05/03/2023] [Indexed: 11/07/2023] Open
Abstract
Liver resection is an effective therapeutic option for patients with hepatocellular carcinoma. However, posthepatectomy liver failure (PHLF) remains a major cause of hepatectomy-related mortality, and the accurate prediction of PHLF based on preoperative assessment of liver functional reserve is a critical issue. The definition of PHLF proposed by the International Study Group for Liver Surgery has gained acceptance as a standard grading criterion. Liver function can be estimated using a variety of parameters, including routine blood biochemical examinations, clinical scoring systems, dynamic liver function tests, liver stiffness and fibrosis markers, and imaging studies. The Child-Pugh score and model for end-stage liver disease scores are conventionally used for estimating liver decompensation, although the alternatively developed albumin-bilirubin score shows superior performance for predicting hepatic dysfunction. Indocyanine green clearance, a dynamic liver function test mostly used in Japan and other Asian countries, serves as a quantitative estimation of liver function reserve and helps determine indications for surgical procedures according to the estimated risk of PHLF. In an attempt to improve predictive accuracy, specific evaluation of liver fibrosis and portal hypertension has gained popularity, including liver stiffness measurements using ultrasonography or magnetic resonance elastography, as well as noninvasive fibrosis markers. Imaging modalities, including Tc-99m-labeled galactosyl serum albumin scintigraphy and gadolinium-enhanced magnetic resonance imaging, are used for preoperative evaluation in combination with liver volume. This review aims to provide an overview of the usefulness of current options for the preoperative assessment of liver function in predicting PHLF.
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Affiliation(s)
- Takahiro Nishio
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Kojiro Taura
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
- Department of Gastroenterological Surgery and OncologyKitano HospitalOsakaJapan
| | - Yukinori Koyama
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Takamichi Ishii
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Etsuro Hatano
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
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28
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Waked I, Alsammany S, Tirmazy SH, Rasul K, Bani-Issa J, Abdel-Razek W, Omar A, Shafik A, Eid S, Abdelaal A, Hosni A, Esmat G. Multidisciplinary consensus recommendations for management of hepatocellular carcinoma in Middle East and North Africa region. Liver Int 2023; 43:2062-2077. [PMID: 37553777 DOI: 10.1111/liv.15685] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 06/30/2023] [Accepted: 07/20/2023] [Indexed: 08/10/2023]
Abstract
Hepatocellular carcinoma (HCC) is a growing health concern projected to cross over a million cases worldwide by 2025. HCC presents a significant burden of disease in Middle East and North African (MENA) countries due to a high prevalence of risk factors such as hepatitis C and B infections and rising incidence of non-alcoholic steatohepatitis and non-alcoholic fatty liver disease. In August 2022, an advisory meeting consisting of experts from 5 MENA countries was convened in an attempt to provide consensus recommendations on HCC screening, early diagnosis, current treatment modalities and unmet medical needs in the region. Data were collected from a pre-meeting survey questionnaire and responses analysed and presented during the advisory meeting. This review summarizes the evidence discussed at the meeting and provides expert recommendations on the management of HCC. The 2022 update of Barcelona clinic liver cancer (BCLC) staging and treatment strategy and its implementation in the MENA region was extensively discussed. A key consensus of the expert panel was that multidisciplinary care is crucial to effective patient management that results in better clinical outcomes and overall survival of the patient. The panel recommended the use of predictive and early response biomarkers to guide clinicians in arriving at more effective therapeutic decisions. The experts also emphasized the role of robust screening/surveillance systems, population-based registries, effective referral pathways and standardization of guidelines to ensure the successful management of HCC in the region.
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Affiliation(s)
- Imam Waked
- Department of Medicine, National Liver Institute, Menoufia University, Shebin El-Kom, Egypt
| | - Sherif Alsammany
- Department of Medical Oncology, King Abdullah Medical City, Mecca, KSA
| | | | - Kakil Rasul
- Department of Medical Oncology, GI Unit, National Centre for Cancer Care and Research, Doha, Qatar
| | - Jafar Bani-Issa
- Department of Interventional Radiology, King Hussein Cancer Center, Amman, Jordan
| | - Wael Abdel-Razek
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, Egypt
| | - Ashraf Omar
- Department of Endemic Medicine and Hepato-Gastroentrology, Cairo University, Cairo, Egypt
| | - Amr Shafik
- Department of Clinical Oncology, Ain Shams University, Cairo, Egypt
| | - Salem Eid
- Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt
| | - Amr Abdelaal
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Ain Shams University, Cairo, Egypt
| | - Ahmed Hosni
- Department of Diagnostic and Interventional Radiology, Cairo University, Cairo, Egypt
| | - Gamal Esmat
- Department of Endemic Medicine and Hepato-Gastroentrology, Cairo University, Cairo, Egypt
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29
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Omar A, Kaseb A, Elbaz T, El-Kassas M, El Fouly A, Hanno AF, El Dorry A, Hosni A, Helmy A, Saad AS, Alolayan A, Eysa BE, Hamada E, Azim H, Khattab H, Elghazaly H, Tawfik H, Ayoub H, Khaled H, Saadeldin I, Waked I, Barakat EMF, El Meteini M, Hamed Shaaban M, EzzElarab M, Fathy M, Shaker M, Sobhi M, Shaker MK, ElGharib M, Abdullah M, Mokhtar M, Elshazli M, Heikal OMK, Hetta O, ElWakil RM, Abdel Wahab S, Eid SS, Rostom Y, On behalf of the Egyptian Liver Cancer Committee Study Group. Egyptian Society of Liver Cancer Recommendation Guidelines for the Management of Hepatocellular Carcinoma. J Hepatocell Carcinoma 2023; 10:1547-1571. [PMID: 37744303 PMCID: PMC10516190 DOI: 10.2147/jhc.s404424] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 09/01/2023] [Indexed: 09/26/2023] Open
Abstract
Globally, hepatocellular carcinoma (HCC) is the fourth most common cause of death from cancer. The prevalence of this pathology, which has been on the rise in the last 30 years, has been predicted to continue increasing. HCC is the most common cause of cancer-related morbidity and mortality in Egypt and is also the most common cancer in males. Chronic liver diseases, including chronic hepatitis C, which is a primary health concern in Egypt, are considered major risk factors for HCC. However, HCC surveillance is recommended for patients with chronic hepatitis B virus (HBV) and liver cirrhosis; those above 40 with HBV but without cirrhosis; individuals with hepatitis D co-infection or a family history of HCC; and Nonalcoholic fatty liver disease (NAFLD) patients exhibiting significant fibrosis or cirrhosis. Several international guidelines aid physicians in the management of HCC. However, the availability and cost of diagnostic modalities and treatment options vary from one country to another. Therefore, the current guidelines aim to standardize the management of HCC in Egypt. The recommendations presented in this report represent the current management strategy at HCC treatment centers in Egypt. Recommendations were developed by an expert panel consisting of hepatologists, oncologists, gastroenterologists, surgeons, pathologists, and radiologists working under the umbrella of the Egyptian Society of Liver Cancer. The recommendations, which are based on the currently available local diagnostic aids and treatments in the country, include recommendations for future prospects.
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Affiliation(s)
- Ashraf Omar
- Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Kaseb
- Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Tamer Elbaz
- Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Amr El Fouly
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Abdel Fatah Hanno
- Department of Gastroenterology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Ahmed El Dorry
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ahmed Hosni
- Department of Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Amr Helmy
- Department of Surgery, National Liver Institute Menoufia University, Menoufia, Egypt
| | - Amr S Saad
- Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ashwaq Alolayan
- Department of Oncology, National Guard Hospital, Riyadh, Saudi Arabia
| | - Basem Elsayed Eysa
- Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Emad Hamada
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hamdy Azim
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hany Khattab
- Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hesham Elghazaly
- Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Hesham Tawfik
- Department of Oncology, Faculty of Medicine, Tanta University, TantaEgypt
| | - Hisham Ayoub
- Department of Gastroenterology, Military Medical Academy, Cairo, Egypt
| | - Hussein Khaled
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ibtessam Saadeldin
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Imam Waked
- Department of Gastroenterology, Menoufia Liver Institute, Menoufia, Egypt
| | - Eman M F Barakat
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mahmoud El Meteini
- Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Hamed Shaaban
- Department of Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed EzzElarab
- Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Mohamed Fathy
- Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Shaker
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Sobhi
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Kamal Shaker
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed ElGharib
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohammed Abdullah
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohesn Mokhtar
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mostafa Elshazli
- Department of Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt
| | | | - Osama Hetta
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Reda Mahmoud ElWakil
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Sameh Abdel Wahab
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Samir Shehata Eid
- Department of Oncology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Yousri Rostom
- Department of Oncology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - On behalf of the Egyptian Liver Cancer Committee Study Group
- Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
- Department of Gastroenterology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Surgery, National Liver Institute Menoufia University, Menoufia, Egypt
- Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Oncology, National Guard Hospital, Riyadh, Saudi Arabia
- Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Oncology, Faculty of Medicine, Tanta University, TantaEgypt
- Department of Gastroenterology, Military Medical Academy, Cairo, Egypt
- Department of Gastroenterology, Menoufia Liver Institute, Menoufia, Egypt
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Oncology, Faculty of Medicine, Assiut University, Assiut, Egypt
- Department of Oncology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
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Gorji L, Brown ZJ, Pawlik TM. Mutational Landscape and Precision Medicine in Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:4221. [PMID: 37686496 PMCID: PMC10487145 DOI: 10.3390/cancers15174221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 08/16/2023] [Accepted: 08/17/2023] [Indexed: 09/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fourth most common malignancy worldwide and exhibits a universal burden as the incidence of the disease continues to rise. In addition to curative-intent therapies such as liver resection and transplantation, locoregional and systemic therapy options also exist. However, existing treatments carry a dismal prognosis, often plagued with high recurrence and mortality. For this reason, understanding the tumor microenvironment and mutational pathophysiology has become the center of investigation for disease control. The use of precision medicine and genetic analysis can supplement current treatment modalities to promote individualized management of HCC. In the search for personalized medicine, tools such as next-generation sequencing have been used to identify unique tumor mutations and improve targeted therapies. Furthermore, investigations are underway for specific HCC biomarkers to augment the diagnosis of malignancy, the prediction of whether the tumor environment is amenable to available therapies, the surveillance of treatment response, the monitoring for disease recurrence, and even the identification of novel therapeutic opportunities. Understanding the mutational landscape and biomarkers of the disease is imperative for tailored management of the malignancy. In this review, we summarize the molecular targets of HCC and discuss the current role of precision medicine in the treatment of HCC.
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Affiliation(s)
- Leva Gorji
- Department of Surgery, Kettering Health Dayton, Dayton, OH 45405, USA;
| | - Zachary J. Brown
- Department of Surgery, Division of Surgical Oncology, New York University—Long Island, Mineola, NY 11501, USA;
| | - Timothy M. Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital, Columbus, OH 43210, USA
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Peri V, Lee E, Fink M, Starkey G, Nikfarjam M, Yoshino O, Furtado R, Sinclair M, Testro A, Majumdar A, Jones R, Muralidharan V, Perini MV. A Single Centre Experience with Pre-Operative Markers in the Prediction of Outcomes after Liver Resection for Hepatocellular Carcinoma. J Gastrointest Surg 2023; 27:1376-1386. [PMID: 37095335 DOI: 10.1007/s11605-023-05681-1] [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: 12/16/2022] [Accepted: 04/08/2023] [Indexed: 04/26/2023]
Abstract
BACKGROUND AND AIM The C-reactive protein to albumin ratio, albumin-bilirubin index and platelet-albumin-bilirubin index have emerged as prognostic scores in hepatocellular carcinoma, although their clinical utility remains unclear, with ongoing investigation in multiple patient populations. This study aims to report survival outcomes and evaluate these indices in a cohort of patients undergoing liver resection for hepatocellular carcinoma in a tertiary Australian centre. METHODS This retrospective study reviewed data from the Department of Surgery at Austin Health and electronic health records (Cerner corporation). The impact of pre, intra and post-operative parameters on post-operative complications, overall and recurrence free survival were analyzed. RESULTS 163 liver resections were performed in 157 patients between 2007 and 2020. Post-operative complications occurred in 58 patients (35.6%), with pre-operative albumin < 36.5 g/L (3.41(1.41-8.29),p = 0.007) and open liver resection (3.93(1.38-11.21),p = 0.011) demonstrating independent predictive significance. 1,3 and 5-year overall survival was 91.0%, 76.7% and 66.9% respectively, with a median survival time of 92.7 months (81.3-103.9). Hepatocellular carcinoma recurred in 95 patients (58.3%) with a median time to recurrence of 27.8 months (15.6-39.9). 1,3 and 5 year recurrence-free survival rates were 94.0%, 73.7% and 55.1% respectively. Pre-operative C-reactive protein-albumin ratio > 0.034 was significantly associated with reduced overall (4.39(1.19-16.16),p = 0.026) and recurrence-free (2.53(1.21-5.30),p = 0.014) survival. CONCLUSION C-reactive protein-albumin ratio > 0.034 is a strong predictor of poor prognosis following liver resection for hepatocellular carcinoma. In addition, pre-operative hypoalbuminemia was associated with post-operative complications, and future studies are required to assess the potential benefits of albumin replacement in reducing post-surgical morbidity.
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Affiliation(s)
- Varun Peri
- Department of Surgery (Austin Precinct), LVL 8, LTB, Austin Hospital, The University of Melbourne, 145 Studley Road, Heidelberg, 3084, Australia
| | - Eunice Lee
- Department of Surgery (Austin Precinct), LVL 8, LTB, Austin Hospital, The University of Melbourne, 145 Studley Road, Heidelberg, 3084, Australia
- HPB & Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Michael Fink
- Department of Surgery (Austin Precinct), LVL 8, LTB, Austin Hospital, The University of Melbourne, 145 Studley Road, Heidelberg, 3084, Australia
- HPB & Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Graham Starkey
- HPB & Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Mehrdad Nikfarjam
- Department of Surgery (Austin Precinct), LVL 8, LTB, Austin Hospital, The University of Melbourne, 145 Studley Road, Heidelberg, 3084, Australia
- HPB & Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Osamu Yoshino
- HPB & Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Ruelan Furtado
- HPB & Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Marie Sinclair
- Victorian Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Adam Testro
- Victorian Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Avik Majumdar
- Victorian Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Robert Jones
- Department of Surgery (Austin Precinct), LVL 8, LTB, Austin Hospital, The University of Melbourne, 145 Studley Road, Heidelberg, 3084, Australia
- HPB & Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Vijayaragavan Muralidharan
- Department of Surgery (Austin Precinct), LVL 8, LTB, Austin Hospital, The University of Melbourne, 145 Studley Road, Heidelberg, 3084, Australia
- HPB & Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia
| | - Marcos Vinicius Perini
- Department of Surgery (Austin Precinct), LVL 8, LTB, Austin Hospital, The University of Melbourne, 145 Studley Road, Heidelberg, 3084, Australia.
- HPB & Liver Transplant Unit, 145 Studley Road, Austin HealthHeidelberg, 3084, Australia.
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Li HL, Ning SL, Gao YJ, Zhou T, Chen YX. In situ subtotal spleen resection combined with selective pericardial devascularization for the treatment of portal hypertension. World J Gastrointest Surg 2023; 15:634-642. [PMID: 37206069 PMCID: PMC10190734 DOI: 10.4240/wjgs.v15.i4.634] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 01/24/2023] [Accepted: 03/23/2023] [Indexed: 04/22/2023] Open
Abstract
BACKGROUND Hypersplenism and esophageal varices bleeding are the major complications of portal hypertension (PHT). In recent years, increasing attention has been given to spleen preservation operations. The mode and long-term effects of subtotal splenectomy and selective pericardial devascularization for PHT remain controversial. AIM To investigate the clinical efficacy and safety of subtotal splenectomy combined with selective pericardial devascularization for the treatment of PHT. METHODS This was a retrospective study of 15 patients with PHT who underwent subtotal splenectomy not preserving the splenic artery or vein combined with selective pericardial devascularization in the Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University from February 2011 to April 2022. Fifteen propensity score-matched patients with PHT who underwent total splenectomy at the same time served as the control group. The patients were followed for up to 11 years after surgery. We compared the postoperative platelet levels, perioperative splenic vein thrombosis, and serum immunoglobulin levels between the two groups. Abdominal enhanced computed tomography was used to evaluate the blood supply and function of the residual spleen. The operation time, intraoperative blood loss, evacuation time, and hospital stay were compared between the two groups. RESULTS The postoperative platelet level of patients in the subtotal splenectomy group was significantly lower than that in the total splenectomy group (P < 0.05), and the postoperative portal system thrombosis rate in the subtotal splenectomy group was also much lower than that in the total splenectomy group. The levels of serum immunoglobulins (IgG, IgA, and IgM) showed no significant differences after surgery compared with before surgery in the subtotal splenectomy group (P > 0.05), but serum immunoglobulin IgG and IgM levels decreased dramatically after total splenectomy (P < 0.05). The operation time in the subtotal splenectomy group was longer than that in the total splenectomy group (P < 0.05), but there were no significant differences in the amount of intraoperative blood loss, evacuation time, or hospital stay between the two groups. CONCLUSION Subtotal splenectomy not preserving the splenic artery or vein combined with selective pericardial devascularization is a safe and effective surgical treatment for patients with PHT, not only correcting hypersplenism but also preserving splenic function, especially immunological function.
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Affiliation(s)
- Hai-Lin Li
- Department of Hepatobiliary Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Shang-Lei Ning
- Department of Hepatobiliary Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Yan-Jing Gao
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Tao Zhou
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Yu-Xin Chen
- Department of Hepatobiliary Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
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Koza A, Bhogal RH, Fotiadis N, Mavroeidis VK. The Role of Ablative Techniques in the Management of Hepatocellular Carcinoma: Indications and Outcomes. Biomedicines 2023; 11:1062. [PMID: 37189680 PMCID: PMC10135821 DOI: 10.3390/biomedicines11041062] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 03/18/2023] [Accepted: 03/27/2023] [Indexed: 04/03/2023] Open
Abstract
The management of hepatocellular carcinoma (HCC) remains complex and will continue to rely on the multidisciplinary input of hepatologists, surgeons, radiologists, oncologists and radiotherapists. With the appropriate staging of patients and selection of suitable treatments, the outcomes for HCC are improving. Surgical treatments encompassing both liver resection and orthotopic liver transplantation (OLT) are the definitive curative-intent options. However, patient suitability, as well as organ availability, pose essential limitations. Consequently, non-surgical options, such as ablative techniques, play an increasingly important role, especially in small HCCs, where overall and disease-free survival can be comparable to surgical resection. Ablative techniques are globally recommended in recognised classification systems, showing increasingly promising results. Recent technical refinements, as well as the emerging use of robotic assistance, may expand the treatment paradigm to achieve improved oncological results. At present, in very early stage and early stage unresectable disease, percutaneous thermal ablation is considered the treatment of choice. Owing to their different features, various ablative techniques, including radiofrequency ablation, microwave ablation, cryotherapy ablation and irreversible electroporation, have been shown to confer different comparative advantages and applicability. We herein review the role of available ablative techniques in the current complex multidisciplinary management of HCC, with a main focus on the indications and outcomes, and discuss future perspectives.
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Affiliation(s)
- Asanda Koza
- Department of Interventional Radiology, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK
| | - Ricky H. Bhogal
- Department of Academic Surgery, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK
| | - Nicos Fotiadis
- Department of Interventional Radiology, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK
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Fan Z, Zhou P, Jin B, Li G, Feng L, Zhuang C, Wang S. Recent therapeutics in hepatocellular carcinoma. Am J Cancer Res 2023; 13:261-275. [PMID: 36777510 PMCID: PMC9906068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 12/26/2022] [Indexed: 02/14/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a malignant tumor of hepatocytes. It is a common malignant tumor of the digestive system that often has initially hidden presentation followed by rapid progression. There are no obvious symptoms in the early stage of HCC. When diagnosed, most patients have locally advanced tumor or distant metastasis; therefore, HCC is difficult to treat and only supportive and symptomatic treatment is adopted. The prognosis is poor and survival time is short. How to effectively treat HCC is important clinically. In recent years, advances in medical technology have resulted in comprehensive treatment methods based on surgery.
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Affiliation(s)
- Zhe Fan
- Department of General Surgery & Department of Central Laboratory, The Third People’s Hospital of Dalian, Dalian Medical UniversityDalian, Liaoning, China
| | - Pengcheng Zhou
- School of Medicine, Southeast UniversityNanjing, Jiangsu, China
| | - Binghui Jin
- Department of General Surgery & Department of Central Laboratory, The Third People’s Hospital of Dalian, Dalian Medical UniversityDalian, Liaoning, China
| | - Guangyao Li
- Department of General Surgery & Department of Central Laboratory, The Third People’s Hospital of Dalian, Dalian Medical UniversityDalian, Liaoning, China
| | - Lu Feng
- Department of Pathology, The First Affiliated Hospital of Dalian Medical UniversityDalian, Liaoning, China
| | - Chengjun Zhuang
- Department of Critical Care Medicine, The Second Affiliated Hospital of Dalian Medical UniversityDalian, Liaoning, China
| | - Shuang Wang
- Department of Endocrinology, The Second Affiliated Hospital of Dalian Medical UniversityDalian, Liaoning, China
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Qu Z, Wu KJ, Feng JW, Shi DS, Chen YX, Sun DL, Duan YF, Chen J, He XZ. Treatment of hepatic venous system hemorrhage and carbon dioxide gas embolization during laparoscopic hepatectomy via hepatic vein approach. Front Oncol 2023; 12:1060823. [PMID: 36686784 PMCID: PMC9850092 DOI: 10.3389/fonc.2022.1060823] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Accepted: 12/12/2022] [Indexed: 01/07/2023] Open
Abstract
With the improvement of laparoscopic surgery, the feasibility and safety of laparoscopic hepatectomy have been affirmed, but intraoperative hepatic venous system hemorrhage and carbon dioxide gas embolism are the difficulties in laparoscopic hepatectomy. The incidence of preoperative hemorrhage and carbon dioxide gas embolism could be reduced through preoperative imaging evaluation, reasonable liver blood flow blocking method, appropriate liver-breaking device, controlled low-center venous pressure technology, and fine-precision precision operation. In the case of blood vessel rupture bleeding in the liver vein system, after controlling and reducing bleeding, confirm the type and severity of vascular damage in the liver and venous system, take appropriate measures to stop the bleeding quickly and effectively, and, if necessary, transfer the abdominal treatment in time. In addition, to strengthen the understanding, prevention and emergency treatment of severe CO2 gas embolism in laparoscopic hepatectomy is also the key to the success of surgery. This study aims to investigate the methods to deal with hepatic venous system hemorrhage and carbon dioxide gas embolization based on author's institutional experience and relevant literature. We retrospectively analyzed the data of 60 patients who received laparoscopic anatomical hepatectomy of hepatic vein approach for HCC. For patients with intraoperative complications, corresponding treatments were given to cope with different complications. After the operation, combined with clinical experience and literature, we summarized and discussed the good treatment methods in the face of such situations so that minimize the harm to patients as much as possible.
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Affiliation(s)
| | | | | | | | | | | | - Yun-Fei Duan
- *Correspondence: Yun-Fei Duan, ; Jing Chen, ; Xiao-zhou He,
| | - Jing Chen
- *Correspondence: Yun-Fei Duan, ; Jing Chen, ; Xiao-zhou He,
| | - Xiao-zhou He
- *Correspondence: Yun-Fei Duan, ; Jing Chen, ; Xiao-zhou He,
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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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Cassese G, Han HS, Cho JY, Lee HW, Lee B, Troisi RI. Selecting the Best Approach for the Treatment of Multiple Non-Metastatic Hepatocellular Carcinoma. Cancers (Basel) 2022; 14:5997. [PMID: 36497478 PMCID: PMC9737585 DOI: 10.3390/cancers14235997] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 11/29/2022] [Accepted: 12/03/2022] [Indexed: 12/12/2022] Open
Abstract
According to the Barcelona Clinic Liver Cancer (BCLC) staging system, the optimal strategy for patients with multiple HCC within the Milan Criteria is liver transplantation (LT). However, LT cannot be offered to all the patients due to organ shortages and long waiting lists, as well as because of the advanced disease carrying a high risk of poor outcomes. For early stages, liver resection (LR) or thermal ablation (TA) can be proposed, while trans-arterial chemoembolization (TACE) still remains the treatment of choice for intermediate stages (BCLC-B). Asian guidelines and the National Comprehensive Cancer Network suggest LR for resectable multinodular HCCs, even beyond Milan criteria. In this scenario, a growing body of evidence shows better outcomes after surgical resection when compared with TACE. Trans-arterial radioembolization (TARE) and stereotaxic body radiation therapy (SBRT) can also play an important role in this setting. Furthermore, the role of minimally invasive liver surgery (MILS) specifically for patients with multiple HCC is still not clear. This review aims to summarize current knowledge about the best therapeutical strategy for multiple HCC while focusing on the role of minimally invasive surgery and on the most attractive future perspectives.
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Affiliation(s)
- Gianluca Cassese
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 166 Gumi-ro, Bundang-gu, Seongnam-si 13620, Republic of Korea
- Department of Clinical Medicine and Surgery, Division of Minimally Invasive and Robotic HPB Surgery and Transplantation Service, Federico II University, 80138 Naples, Italy
| | - Ho-Seong Han
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 166 Gumi-ro, Bundang-gu, Seongnam-si 13620, Republic of Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 166 Gumi-ro, Bundang-gu, Seongnam-si 13620, Republic of Korea
| | - Hae-Won Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 166 Gumi-ro, Bundang-gu, Seongnam-si 13620, Republic of Korea
| | - Boram Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 166 Gumi-ro, Bundang-gu, Seongnam-si 13620, Republic of Korea
| | - Roberto Ivan Troisi
- Department of Clinical Medicine and Surgery, Division of Minimally Invasive and Robotic HPB Surgery and Transplantation Service, Federico II University, 80138 Naples, Italy
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Tseng TC, Yin WY. Minor hepatectomy for hepatocellular carcinoma in a patient with portal hypertension: A case report and review of the literature. Medicine (Baltimore) 2022; 101:e32176. [PMID: 36482633 PMCID: PMC9726341 DOI: 10.1097/md.0000000000032176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Curative modalities for early hepatocellular carcinoma (HCC) include liver resection (LR) and transplantation. For patients with portal hypertension (PH), liver transplantation (LT) is the preferred treatment but is oftentimes limited by organ shortage and can lead candidates to drop off due to disease progression, while hepatectomy has a higher risk of complications. This would pose a dilemma as to whether wait for donor organs or prioritize hepatectomy. PATIENT CONCERNS The patient was a 56-year-old male, a case of liver cirrhosis due to hepatitis C with sustained virological response following direct-acting antiviral agents. He was a liver transplant candidate, presented to the gastroenterology outpatient department for a recently-diagnosed liver tumor during a regular follow-up session. Pre-operative survey revealed PH manifested by thrombocytopenia, splenomegaly, huge splenorenal shunt and varices. The patient's Child-Pugh score was 7. INTERVENTIONS AND DIAGNOSIS Considering the patient's overall condition, tumor size and location, and a shortage of grafts, he underwent segment 5 and 6 partial hepatectomy. The pathological diagnosis was moderately differentiated HCC. OUTCOMES His postoperative course was complicated by refractory intraabdominal infection (IAI) and recovered under aggressive antibiotics treatment. He remained recurrence-free for over a year. CONCLUSION For patients with early resectable HCC, the approach of having a minor hepatectomy followed by salvage transplantation should serve as a compromising strategy. Tumor resection retards the progression of the disease. Comprehensive healthcare can expectantly improve clinical outcomes.
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Affiliation(s)
| | - Wen-Yao Yin
- School of Medicine, Tzu Chi University, Hualien, Taiwan
- Department of Surgery, Dalin Tzu Chi General Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- * Correspondence: Wen-Yao Yin, Division of Transplant Surgery, Department of Surgery, Dalin Tzu Chi General Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Minsheng Road, Dalin Town, Chiayi County 622401, Taiwan (e-mail: )
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Vogel A, Meyer T, Sapisochin G, Salem R, Saborowski A. Hepatocellular carcinoma. Lancet 2022; 400:1345-1362. [PMID: 36084663 DOI: 10.1016/s0140-6736(22)01200-4] [Citation(s) in RCA: 1156] [Impact Index Per Article: 385.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 05/31/2022] [Accepted: 06/15/2022] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma is one of the most common cancers worldwide and represents a major global health-care challenge. Although viral hepatitis and alcohol remain important risk factors, non-alcoholic fatty liver disease is rapidly becoming a dominant cause of hepatocellular carcinoma. A broad range of treatment options are available for patients with hepatocellular carcinoma, including liver transplantation, surgical resection, percutaneous ablation, and radiation, as well as transarterial and systemic therapies. As such, clinical decision making requires a multidisciplinary team that longitudinally adapts the individual treatment strategy according to the patient's tumour stage, liver function, and performance status. With the approval of new first-line agents and second-line agents, as well as the establishment of immune checkpoint inhibitor-based therapies as standard of care, the treatment landscape of advanced hepatocellular carcinoma is more diversified than ever. Consequently, the outlook for patients with hepatocellular carcinoma has improved. However, the optimal sequencing of drugs remains to be defined, and predictive biomarkers are urgently needed to inform treatment selection. In this Seminar, we present an update on the causes, diagnosis, molecular classification, and treatment of hepatocellular carcinoma.
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Affiliation(s)
- Arndt Vogel
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
| | - Tim Meyer
- Research Department of Oncology, UCL Cancer Institute, University College London, Royal Free Hospital, London, UK
| | - Gonzalo Sapisochin
- Abdominal Transplant & HPB Surgical Oncology, University Health Network, University of Toronto, ON, Canada
| | - Riad Salem
- Department of Radiology, Northwestern University, Chicago, IL, USA
| | - Anna Saborowski
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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Li JX, Zhou P, Chang DH, Tong Y, Bao Y, Xiao YD, Zhou S, Cai WW. Ideal patients for liver resection in Barcelona Clinic Liver Cancer or Hong Kong Liver clinic systems for hepatocellular carcinoma: Conservative or aggressive? Front Med (Lausanne) 2022; 9:977135. [PMID: 36314035 PMCID: PMC9614110 DOI: 10.3389/fmed.2022.977135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 09/21/2022] [Indexed: 12/03/2022] Open
Abstract
Background Both the Barcelona Clinic Liver Cancer (BCLC) staging and the Hong Kong Liver Cancer (HKLC) staging have their own definitions of ideal patients for liver resection (IPLR) in hepatocellular carcinoma (HCC). This study aimed to compare the prognosis of IPLRs between the BCLC and HKLC staging systems, and to identify patients who may benefit from liver resection (LR) in the HKLC staging but beyond the BCLC staging. Methods This retrospective study evaluated 1,296 consecutive patients with HCC who underwent LR between August 2013 and April 2021 (457 patients and 1,046 patients were IPLR according to the BCLC and HKLC staging systems, respectively). Overall survival (OS) was compared between the two groups. To assess potential benefit of LR for IPLR in the HKLC staging but beyond the BCLC staging, univariate and multivariate Cox regression analysis was performed to determine prognostic factors of OS, and prognostic stratification was performed based on the selected prognostic factors. The IPLRs in the HKLC staging but beyond the BCLC staging were divided into subgroups according to the prognostic stratification and separately compared with the IPLRs in the BCLC staging. Results OS was different between the two staging systems (P = 0.011). All the 457 IPLRs in the BCLC staging were also the IPLRs in the HKLC staging. Diameter of the largest tumor5 cm (HR = 1.58; 95% CI: 1.18–2.10; P = 0.002) and liver cirrhosis (HR = 1.61; 95% CI: 1.19–2.20; P = 0.002) were risk factors for poor OS in IPLRs in the HKLC staging but beyond the BCLC staging; hence, patients were divided into the low-risk (n = 104), intermediate-risk (n = 369), and high-risk groups (n = 116) accordingly. There was no difference in OS between patients in the BCLC staging and patients in low-risk group (P = 0.996). However, OS was significantly different between patients in the BCLC staging and those in intermediate-risk (P = 0.003) and high-risk groups (P < 0.001). Conclusion IPLRs in the BCLC staging system have better prognosis. However, IPLRs in the HKLC staging system but beyond the BCLC staging may have equivalent prognosis to IPLRs in the BCLC staging if the tumor size is ≤ 5 cm and liver cirrhosis is absent.
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Affiliation(s)
- Jun-Xiang Li
- 1Department of Interventional Radiology, Guizhou Medical University Affiliated Cancer Hospital, Guiyang, China
| | - Peng Zhou
- 2Department of Pathology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - De-Hua Chang
- 3Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Yao Tong
- 4Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Yan Bao
- 5Department of Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Yu-Dong Xiao
- 4Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Shi Zhou
- 1Department of Interventional Radiology, Guizhou Medical University Affiliated Cancer Hospital, Guiyang, China,5Department of Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China,*Correspondence: Shi Zhou,
| | - Wen-Wu Cai
- 6Department of Liver Surgery, The Second Xiangya Hospital of Central South University, Changsha, China,Wen-Wu Cai,
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Wang H, Chu F, Zhijie L, Bi Q, Lixin L, Zhuang Y, Xiaofeng Z, Niu X, Zhang D, Xi H, Li BA. MTBP enhances the activation of transcription factor ETS-1 and promotes the proliferation of hepatocellular carcinoma cells. Front Oncol 2022; 12:985082. [PMID: 36106099 PMCID: PMC9464980 DOI: 10.3389/fonc.2022.985082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Accepted: 07/27/2022] [Indexed: 11/30/2022] Open
Abstract
Increasing evidence indicates that the oncoprotein murine double minute (MDM2) binding protein (MTBP) can be considered a pro-oncogene of human malignancies; however, its function and mechanisms in hepatocellular carcinoma (HCC) are still not clear. In the present work, our results demonstrate that MTBP could function as a co-activator of transcription factor E26 transformation-specific sequence (ETS-1), which plays an important role in HCC cell proliferation and/or metastasis and promotes proliferation of HCC cells. Using luciferase and real-time polymerase chain reaction (qPCR) assays, MTBP was found to enhance the transcription factor activation of ETS-1. The results from chromatin co-immunoprecipitation showed that MTBP enhanced the recruitment of ETS-1 to its downstream gene’s (mmp1’s) promoter region with ETS-1 binding sites. In cellular and nude mice models, overexpression of MTBP was shown to promote the proliferation of MHCC97-L cells with low endogenous MTBP levels, whereas the knockdown of MTBP led to inhibition of the proliferation of MHCC97-H cells that possessed high endogenous levels of MTBP. The effect of MTBP on ETS-1 was confirmed in the clinical specimens; the expression of MTBP was positively correlated with the downstream genes of ETS-1, mmp3, mmp9, and uPA. Therefore, by establishing the role of MTBP as a novel co-activator of ETS-1, this work expands our knowledge of MTBP or ETS-1 and helps to provide new ideas concerning HCC-related research.
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Affiliation(s)
- Hongbo Wang
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Fang Chu
- Department of Emergency, The Fifth Medical Center of Chinese People’s Liberation Army General Hospital, Beijing, China
| | - Li Zhijie
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Qian Bi
- Endoscopy Center, Department of Hepatology, The Fifth Medical Center of Chinese People’s Liberation Army General Hospital, Beijing, China
| | - Li Lixin
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Yunlong Zhuang
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Zhang Xiaofeng
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Xiaofeng Niu
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Dali Zhang
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - He Xi
- Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Bo-an Li
- Clinical Laboratory, The Fifth Medical Center of Chinese People’s Liberation Army General Hospital, Beijing, China
- *Correspondence: Bo-an Li,
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Wang J, Zhang Z, Shang D, Liao Y, Yu P, Li J, Chen S, Liu D, Miao H, Li S, Zhang B, Huang A, Liu H, Zhang Y, Qi X. A Novel Nomogram for Prediction of Post-Hepatectomy Liver Failure in Patients with Resectable Hepatocellular Carcinoma: A Multicenter Study. J Hepatocell Carcinoma 2022; 9:901-912. [PMID: 36061234 PMCID: PMC9432387 DOI: 10.2147/jhc.s366937] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 07/14/2022] [Indexed: 01/27/2023] Open
Abstract
Objective To develop a nomogram for predicting post-hepatectomy liver failure (PHLF) in patients with resectable hepatocellular carcinoma (HCC) based on portal hypertension, the extent of resection, ALT, total bilirubin, and platelet count. Methods Patients with HCC hospitalized from January 2015 to December 2020 were included in a retrospective cohort study. 595 HCC patients were divided into a training cohort (n=416) and a validation cohort (n=179) by random sampling. Univariate and multivariable analyses were performed to identify the independent variables to predict PHLF. The nomogram models for predicting the overall risk of PHLF and the risk of PHLF B+C were constructed based on the independent variables. Comparisons were made by using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) with traditional models, such as FIB-4 score, APRI score, CP class (Child-Pugh), MELD score (model of end-stage liver disease), and ALBI score (albumin-bilirubin) to analyze the accuracy and superiority of the nomogram. Results We discovered that portal hypertension (yes vs no) (OR=1.677,95% CI:1.817-4.083, p=0.002), the extent of liver resection (OR=1.872,95% CI:3.937-47.096, p=0.001), ALT (OR=1.003,95% CI:1.003-1.016, P=0.003), total bilirubin (OR=1.036,95% CI:1.031-1.184, p=0.005), and platelet count (OR= 1.004, 95% CI:0.982-0.998, p=0.020) were independent risk factors for PHLF using multifactorial analysis. The nomogram models were constructed using well-fit calibration curves for each of these five covariates. When compared to the FIB4, ALBI, MELD, and CP score, our nomogram models have a better predictive value for predicting the overall risk of PHLF or the risk of PHLF B+C. The validation cohort's results were consistent. DCA also confirmed the conclusion. Conclusion Our models, in the form of static nomogram or web application, were developed to predict PHLF overall risk and PHLF B+C risk in patients with HCC, with a high prediction sensitivity and specificity performance than other commonly used scoring systems.
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Affiliation(s)
- Jitao Wang
- Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China
- Xingtai Key Laboratory of Precision Medicine for Liver Cirrhosis and Portal Hypertension, Xingtai People’s Hospital of Hebei Medical University, Xingtai, People’s Republic of China
| | - Zhanguo Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Hospital Affiliated to Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Dong Shang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China
| | - Yong Liao
- Xingtai Key Laboratory of Precision Medicine for Liver Cirrhosis and Portal Hypertension, Xingtai People’s Hospital of Hebei Medical University, Xingtai, People’s Republic of China
| | - Peng Yu
- Department of Hepatobiliary Surgery, Fifth Medical Center of PLA General Hospital, Beijing, People’s Republic of China
| | - Jinling Li
- Xingtai Key Laboratory of Precision Medicine for Liver Cirrhosis and Portal Hypertension, Xingtai People’s Hospital of Hebei Medical University, Xingtai, People’s Republic of China
| | - Shubo Chen
- Xingtai Key Laboratory of Precision Medicine for Liver Cirrhosis and Portal Hypertension, Xingtai People’s Hospital of Hebei Medical University, Xingtai, People’s Republic of China
| | - Dengxiang Liu
- Xingtai Key Laboratory of Precision Medicine for Liver Cirrhosis and Portal Hypertension, Xingtai People’s Hospital of Hebei Medical University, Xingtai, People’s Republic of China
| | - Hongrui Miao
- Hepatic Surgery Center, Tongji Hospital, Tongji Hospital Affiliated to Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Shuang Li
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China
| | - Biao Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China
| | - Anliang Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China
| | - Hao Liu
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Yewei Zhang
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Xiaolong Qi
- Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China
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Zhang CH, Cheng Y, Zhang S, Fan J, Gao Q. Changing epidemiology of hepatocellular carcinoma in Asia. Liver Int 2022; 42:2029-2041. [PMID: 35319165 DOI: 10.1111/liv.15251] [Citation(s) in RCA: 180] [Impact Index Per Article: 60.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 12/06/2021] [Accepted: 03/19/2022] [Indexed: 12/24/2022]
Abstract
Liver cancer is the fifth most common cancer and the second leading cause of malignant death in Asia, and Asia reports 72.5% of the world's cases in 2020. As the most common histological type, hepatocellular carcinoma (HCC) accounts for the majority of incidence and mortality of liver cancer cases. This review presents the changing epidemiology of HCC in Asian countries in recent years. Globally, aged, male and Asian populations remain the group with the highest risk of HCC. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are still the leading risk factors of HCC with a slight decline in most Asian countries, which is mainly attributed to HBV vaccination of newborns, prevention of HCV horizontal transmission and treatment of chronic hepatitis. However, the prevalence of HCC caused by metabolic factors, including metabolic syndrome, obesity and non-alcoholic fatty liver diseases, is increasing rapidly in Asian countries, which may eventually become the major cause of HCC. Excessive alcohol consumption continues to be an important risk factor as the average consumption of alcohol is still growing. Hopefully, great effort has been made to better prevention and treatment of HCC in most Asian regions, which significantly prolongs the survival of HCC patients. Asian countries tend to use more aggressive intervention than European and American countries, but it remains unclear whether this preference is related to a better prognosis. In conclusion, HCC remains a major disease burden in Asia, and the management of HCC should be adjusted dynamically based on the changing epidemiology.
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Affiliation(s)
- Chen-Hao Zhang
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China
| | - Yifei Cheng
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China
| | - Shu Zhang
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China
| | - Jia Fan
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China
| | - Qiang Gao
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China.,Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.,State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China
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Faria LLD, Darce GF, Bordini AL, Herman P, Jeismann VB, de Oliveira IS, Ortega CD, Rocha MDS. Liver Surgery: Important Considerations for Pre- and Postoperative Imaging. Radiographics 2022; 42:722-740. [PMID: 35363553 DOI: 10.1148/rg.210124] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Liver surgery may be a curative treatment option not only for primary liver neoplasms but also for liver metastases in selected patients. The number of liver surgeries performed worldwide has increased, but surgical morbidity associated with these surgeries remains significant. Therefore, radiologists need to understand the terminology, surgical techniques, resectability and unresectability criteria, and possible postoperative complications as these are part of the decision-making process. Because vascular and biliary variations are common, an adequate preoperative anatomic evaluation determines the best surgical technique, helps identify patients in whom additional surgical steps will be required, and reduces the risk of inadvertent injury. The surgeon must ensure that the future liver remnant is sufficient to maintain adequate function, aided by the radiologist who can provide valuable information such as the presence of steatosis, biliary dilatation, signs of cirrhosis, and portal hypertension, in addition to the volume of the future liver remnant. Postoperative complications must also be understood and evaluated. The most common postoperative complications are vascular (bleeding, thrombosis, and ischemia), biliary (fistulas, bilomas, and strictures), infectious (incisional or deep), those related to liver failure, and even tumor recurrence. An invited commentary by Winslow is available online. Online supplemental material is available for this article. ©RSNA, 2022.
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Affiliation(s)
- Luisa Leitão de Faria
- From the Department of Radiology (L.L.d.F., A.L.B., I.S.d.O., C.D.O., M.d.S.R.) and Liver Surgery Unit, Discipline of Digestive Surgery, Department of Gastroenterology (G.F.D., P.H., V.B.J.), University of São Paulo School of Medicine, Ovídio Pires de Campos 75, São Paulo 05403-010, Brazil
| | - George Felipe Darce
- From the Department of Radiology (L.L.d.F., A.L.B., I.S.d.O., C.D.O., M.d.S.R.) and Liver Surgery Unit, Discipline of Digestive Surgery, Department of Gastroenterology (G.F.D., P.H., V.B.J.), University of São Paulo School of Medicine, Ovídio Pires de Campos 75, São Paulo 05403-010, Brazil
| | - André Leopoldino Bordini
- From the Department of Radiology (L.L.d.F., A.L.B., I.S.d.O., C.D.O., M.d.S.R.) and Liver Surgery Unit, Discipline of Digestive Surgery, Department of Gastroenterology (G.F.D., P.H., V.B.J.), University of São Paulo School of Medicine, Ovídio Pires de Campos 75, São Paulo 05403-010, Brazil
| | - Paulo Herman
- From the Department of Radiology (L.L.d.F., A.L.B., I.S.d.O., C.D.O., M.d.S.R.) and Liver Surgery Unit, Discipline of Digestive Surgery, Department of Gastroenterology (G.F.D., P.H., V.B.J.), University of São Paulo School of Medicine, Ovídio Pires de Campos 75, São Paulo 05403-010, Brazil
| | - Vagner Birk Jeismann
- From the Department of Radiology (L.L.d.F., A.L.B., I.S.d.O., C.D.O., M.d.S.R.) and Liver Surgery Unit, Discipline of Digestive Surgery, Department of Gastroenterology (G.F.D., P.H., V.B.J.), University of São Paulo School of Medicine, Ovídio Pires de Campos 75, São Paulo 05403-010, Brazil
| | - Iraí Santana de Oliveira
- From the Department of Radiology (L.L.d.F., A.L.B., I.S.d.O., C.D.O., M.d.S.R.) and Liver Surgery Unit, Discipline of Digestive Surgery, Department of Gastroenterology (G.F.D., P.H., V.B.J.), University of São Paulo School of Medicine, Ovídio Pires de Campos 75, São Paulo 05403-010, Brazil
| | - Cinthia D Ortega
- From the Department of Radiology (L.L.d.F., A.L.B., I.S.d.O., C.D.O., M.d.S.R.) and Liver Surgery Unit, Discipline of Digestive Surgery, Department of Gastroenterology (G.F.D., P.H., V.B.J.), University of São Paulo School of Medicine, Ovídio Pires de Campos 75, São Paulo 05403-010, Brazil
| | - Manoel de Souza Rocha
- From the Department of Radiology (L.L.d.F., A.L.B., I.S.d.O., C.D.O., M.d.S.R.) and Liver Surgery Unit, Discipline of Digestive Surgery, Department of Gastroenterology (G.F.D., P.H., V.B.J.), University of São Paulo School of Medicine, Ovídio Pires de Campos 75, São Paulo 05403-010, Brazil
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Zhang Y, Li M, Qiu Y, Wu Y, Chen S, Ni B, Tang D, Deng Z, Hu Z. MiR-139-5p/ENAH Affects Progression of Hepatocellular Carcinoma Cells. Biochem Genet 2022; 60:2106-2119. [PMID: 35254597 DOI: 10.1007/s10528-022-10204-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 02/09/2022] [Indexed: 12/17/2022]
Abstract
This study aims to investigate the specific mechanism of miR-139-5p regulating hepatocellular carcinoma (HCC). Bioinformatic approaches was utilized to observe miR-139-5p level in HCC and unearth its target mRNA. Next, miR-139-5p and enabled homolog (ENAH) levels in HCC cell lines and normal liver cell line were evaluated with qRT-PCR. ENAH protein level was assessed by Western blot. The cell viability, migratory and invasive capacities of HepG2 cells was observed by cell functional assays. The binding of these two genes was proved through dual-luciferase method. Xenograft nude mouse model was prepared to identify the role of miR-139-5p in vivo. Poorly expressed miR-139-5p in HCC hindered the phenotypes of cancer cells. ENAH was at high level in HCC and it is a downstream target of miR-139-5p. Additionally, ENAH could reverse the suppressive impacts of miR-139-5p on HCC cell behaviors. Likewise, miR-139-5p was determined to perform tumor-suppressing function in vivo. MiR-139-5p hampered HCC cell processes by mediating ENAH, and miR-139-5p/ENAH is hopefully to be the possible target for HCC patients.
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Affiliation(s)
- Yueming Zhang
- Department of General Surgery, The Third Hospital of Changsha, 176 Laodong West Road, Changsha City, 410015, Hunan Province, China
| | - Meng Li
- Department of General Surgery, The Third Hospital of Changsha, 176 Laodong West Road, Changsha City, 410015, Hunan Province, China
| | - Yinghuan Qiu
- Department of General Surgery, The Third Hospital of Changsha, 176 Laodong West Road, Changsha City, 410015, Hunan Province, China
| | - Yuhua Wu
- Department of General Surgery, The Third Hospital of Changsha, 176 Laodong West Road, Changsha City, 410015, Hunan Province, China
| | - Shan Chen
- Department of General Surgery, The Third Hospital of Changsha, 176 Laodong West Road, Changsha City, 410015, Hunan Province, China
| | - Bin Ni
- Department of General Surgery, The Third Hospital of Changsha, 176 Laodong West Road, Changsha City, 410015, Hunan Province, China
| | - Ding Tang
- Department of General Surgery, The Third Hospital of Changsha, 176 Laodong West Road, Changsha City, 410015, Hunan Province, China
| | - Zhouzi Deng
- Department of General Surgery, The Third Hospital of Changsha, 176 Laodong West Road, Changsha City, 410015, Hunan Province, China
| | - Zhiqiang Hu
- Department of General Surgery, The Third Hospital of Changsha, 176 Laodong West Road, Changsha City, 410015, Hunan Province, China.
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Li S, Chen S, Dong Z, Song X, Li X, Huang Z, Li H, Huang L, Zhuang G, Lan R, Guo M, Li W, Saw PE, Zhang L. Concurrent silencing of TBCE and drug delivery to overcome platinum-based resistance in liver cancer. Acta Pharm Sin B 2022; 13:967-981. [PMID: 36970197 PMCID: PMC10031151 DOI: 10.1016/j.apsb.2022.03.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Revised: 01/05/2022] [Accepted: 02/15/2022] [Indexed: 12/24/2022] Open
Abstract
Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.
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Ye D, Liu Y, Li G, Sun B, Peng J, Xu Q. A New Risk Score Based on Eight Hepatocellular Carcinoma- Immune Gene Expression Can Predict the Prognosis of the Patients. Front Oncol 2021; 11:766072. [PMID: 34868990 PMCID: PMC8639602 DOI: 10.3389/fonc.2021.766072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Accepted: 11/01/2021] [Indexed: 11/16/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) is one of the malignant tumors with high morbidity and mortality worldwide. Immunotherapy has emerged as an increasingly important cancer treatment modality. However, the potential relationship between immune genes and HCC still needs to be explored. The purpose of this study is to construct a new prognostic risk signature to predict the prognosis of HCC patients based on the expression of immune-related genes (IRGs) and explore its potential mechanism. Methods We analyzed the gene expression data of 332 HCC patient samples and 46 adjacent normal tissues samples (Solid Tissue Normal including cirrhotic tissue) in The Cancer Genome Atlas (TCGA) database and clinical characteristics. We analyzed the gene expression data, identified differentially expressed IRGs in HCC tissues, filtered IRGs with prognostic value to construct an IRG signature, and classified patients into high and low gene expression groups based on the expression of IRGs in their tumor tissues. We also investigated the potential molecular mechanisms of IRGs through a bioinformatics approach using Protein-Protein Interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG) database analysis and Gene Ontology (GO) database analysis. Differentially expressed IRGs associated with significant clinical outcomes (SIRGs) were identified by univariate Cox regression analysis. An immune-related risk score model (IRRSM) was established based on Lasso Cox regression analysis and multivariate Cox regression analysis. Based on the IRRSM, the immune score of the patients was calculated, and the patients were divided into high-risk and low-risk patients according to the median score, and the differences in survival between the two groups were compared. Then, the correlation analysis between the IRRSM and clinical characteristics was performed, and the IRRSM was validated using the International Cancer Genome Consortium (ICGC) database. Results The IRRSM was eventually constructed and confirmed to be an independent prognostic model for HCC patients. The IRRSM was shown to be positively correlated with the infiltration of four types of immune cells. Conclusion Our results showed that some SIRGs have potential value for predicting the prognosis and clinical outcomes of HCC patients. IRGs affect the prognosis of HCC patients by regulating the tumor immune microenvironment (TIME). This study provides a new insight for immune research and treatment strategies in HCC patients.
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Affiliation(s)
- Dingde Ye
- Nanjing Drum Tower Hospital, Medicine School of Southeast University, Nanjing, China
| | - Yaping Liu
- School of Life Science and Technology, Southeast University, Nanjing, China
| | - Guoqiang Li
- Department of General Surgery, Affiliated Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
| | - Beicheng Sun
- Department of General Surgery, Affiliated Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
| | - Jin Peng
- Department of General Surgery, Affiliated Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
| | - Qingxiang Xu
- Nanjing Drum Tower Hospital, Medicine School of Southeast University, Nanjing, China.,Department of General Surgery, Affiliated Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
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48
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Desert R, Ge X, Song Z, Han H, Lantvit D, Chen W, Das S, Athavale D, Abraham-Enachescu I, Blajszczak C, Chen Y, Musso O, Guzman G, Hoshida Y, Nieto N. Role of Hepatocyte-Derived Osteopontin in Liver Carcinogenesis. Hepatol Commun 2021; 6:692-709. [PMID: 34730871 PMCID: PMC8948552 DOI: 10.1002/hep4.1845] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 09/13/2021] [Accepted: 10/02/2021] [Indexed: 12/24/2022] Open
Abstract
Osteopontin (OPN) expression correlates with tumor progression in many cancers, including hepatocellular carcinoma (HCC); however, its role in the onset of HCC remains unclear. We hypothesized that increased hepatocyte‐derived OPN is a driver of hepatocarcinogenesis. Analysis of a tissue microarray of 366 human samples revealed a continuous increase in OPN expression during hepatocarcinogenesis. In patients with cirrhosis, a transcriptome‐based OPN correlation network was associated with HCC incidence along 10 years of follow‐up, together with messenger RNA (mRNA) signatures of carcinogenesis. After diethylnitrosamine (DEN) injection, mice with conditional overexpression of Opn in hepatocytes (OpnHep transgenic [Tg]) showed increased tumor burden. Surprisingly, mice with conditional ablation of Opn in hepatocytes (OpnΔHep) expressed a similar phenotype. The acute response to DEN was reduced in OpnΔHep, which also showed more cancer stem/progenitor cells (CSCs, CD44+AFP+) at 5 months. CSCs from OpnHep Tg mice expressed several mRNA signatures known to promote carcinogenesis, and mRNA signatures from OpnHep Tg mice were associated with poor outcome in human HCC patients. Treatment with rOPN had little effect on CSCs, and their progression to HCC was similar in Opn−/− compared with wild‐type mice. Finally, ablation of Cd44, an OPN receptor, did not reduce tumor burden in Cd44−/−OpnHep Tg mice. Conclusions: Hepatocyte‐derived OPN acts as a tumor suppressor at physiological levels by controlling the acute response to DEN and the presence of CSCs, while induction of OPN is pro‐tumorigenic. This is primarily due to intracellular events rather that by the secretion of the protein and receptor activation.
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Affiliation(s)
- Romain Desert
- Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA
| | - Xiaodong Ge
- Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA.,Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Zhuolun Song
- Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA
| | - Hui Han
- Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA
| | - Daniel Lantvit
- Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA
| | - Wei Chen
- Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA
| | - Sukanta Das
- Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA
| | - Dipti Athavale
- Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA
| | - Ioana Abraham-Enachescu
- Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Chuck Blajszczak
- Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA
| | - Yu Chen
- Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA
| | - Orlando Musso
- INSERM, University of Rennes, INRA, Institut NuMeCAN (Nutrition Metabolisms and Cancer), Rennes, France
| | - Grace Guzman
- Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA
| | - Yujin Hoshida
- Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Liver Tumor Translational Research Program, Harold C. Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Natalia Nieto
- Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA.,Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA
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49
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De la Pinta C. Toward Personalized Medicine in Radiotherapy of Hepatocellular Carcinoma: Emerging Radiomic Biomarker Candidates of Response and Toxicity. OMICS : A JOURNAL OF INTEGRATIVE BIOLOGY 2021; 25:537-544. [PMID: 34448625 DOI: 10.1089/omi.2021.0065] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Radiology and radiotherapy are currently undergoing radical transformation with use of biomarkers and digital technologies such as artificial intelligence. These current and upcoming changes in radiology speak of an overarching new vision for personalized medicine. This is particularly evident in the case of radiotherapy of cancers, and of liver cancer in particular. The development of modern radiotherapy with stereotactic body radiotherapy allows targeted treatments to be delivered to the tumor site, limiting the dose to surrounding healthy organs, thus becoming a new therapeutic alternative for hepatocellular carcinoma and other liver tumors. However, not all patients have the same response to radiotherapy or display the same side-effect profile. Biomarkers of response and toxicity in liver radiotherapy would facilitate the vision and practice of personalized medicine. This expert review examines the available molecular, radiomic, and radiogenomic biomarker candidates for acute liver toxicity with potential use for prediction of radiotherapy-induced liver toxicity. To this end, I highlight for oncologists and life scientists that radiomics allows diagnostic images to be analyzed using computer algorithms to extract information imperceptible to the human eye and of relevance to forecasting clinical outcomes. This article underscores particularly (1) the microRNA-based biomarker candidates as among the most promising predictors of radiation-induced liver toxicity and (2) the texture features in radiomic analyses for response prediction. Radiotherapy of hepatocellular carcinoma is edging toward personalized medicine with emerging radiomic biomarker candidates. Future large-scale biomarker studies are called for to enable personalized medicine in liver cancers.
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Affiliation(s)
- Carolina De la Pinta
- Radiation Oncology Department, Ramon y Cajal University Hospital, IRYCIS, Madrid, Spain
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50
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Allaire M, Rudler M, Thabut D. Portal hypertension and hepatocellular carcinoma: Des liaisons dangereuses…. Liver Int 2021; 41:1734-1743. [PMID: 34051060 DOI: 10.1111/liv.14977] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 05/17/2021] [Accepted: 05/24/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIMS Portal hypertension (PHT) and hepatocellular carcinoma (HCC) are major complication of cirrhosis which significantly contribute to morbidity and mortality. In this review, we aim to describe the consequences of both angiogenesis and inflammation in the pathogenesis of PHT and HCC, but also the difficulty to propose adapted treatment when PHT and HCC coexist in the same patients. METHODS Studies for review in this article were retrieved from the PubMed database using literature published in English until March 2021. RESULTS Portal hypertension occurs secondary to an increase of intrahepatic vascular resistances, the opening of portosystemic collateral vessels and the formation of neovessels, related to vascular endothelial growth factor (VEGF). Recently, bacterial translocation-mediated inflammation was also identified as a major contributor to PHT. Interestingly, VEGF and chronic inflammation also contribute to HCC occurrence. As PHT and HCC often coexist in the same patient, management of PHT and its related complications as well as HCC treatment appear more complex. Indeed, PHT-related complications such as significant ascites may hamper the access to HCC treatment and the presence of HCC is also independently associated with poor prognosis in patients with acute variceal bleeding related to PHT. Due to their respective mechanism of action, the combination of Atezolizumab and Bevacizumab for advanced HCC may impact the level of PHT and its related complications and to date, no real-life data are available. CONSLUSIONS Appropriate evaluation and treatment of PHT remains a major issue in order to improve the outcome of HCC patients.
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Affiliation(s)
- Manon Allaire
- Service d'Hépatolo-gastroentérologie, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Sorbonne Université, Paris, France.,Inserm U1149, Centre de Recherche sur l'Inflammation, France Faculté de Médecine Xavier Bichat, Université Paris Diderot, Paris, France
| | - Marika Rudler
- Service d'Hépatolo-gastroentérologie, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Sorbonne Université, Paris, France.,INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, Paris, France
| | - Dominique Thabut
- Service d'Hépatolo-gastroentérologie, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Sorbonne Université, Paris, France.,INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, Paris, France
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