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Welsh F, Sundaravadanan S, Sethi P, Kazeroun M, Fichera A, Nadziruddin I, Larkin SJ, Ansari-Pour N, Maughan T, Brady M, Banerjee R, Gooding S, Rees M. Quantitative liver function imaging and whole genome sequencing - Effective modalities for a new era in personalised decision-making for operable colorectal liver metastases? HPB (Oxford) 2025; 27:553-561. [PMID: 39827007 DOI: 10.1016/j.hpb.2024.12.023] [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: 10/17/2024] [Revised: 12/15/2024] [Accepted: 12/30/2024] [Indexed: 01/22/2025]
Abstract
BACKGROUND The optimal strategy for patients with colorectal liver metastases (CRLM) is unclear. The Precision1 prospective, observational trial assessed whether pre-operative functional imaging and whole genome sequencing (WGS), could enhance individualized decision-making. METHODS Patients with CRLM considered for hepatectomy were recruited. In addition to standard staging, patients underwent a quantitative multiparametric MRI (mpMRI) scan, to assess liver function. Use of mpMRI to aid surgical decision-making, was prospectively recorded, as were short-term clinical outcomes in patients who underwent hepatectomy. In the first 45 patients, WGS was performed on blood and liver tumour samples collected per-operatively. RESULTS 95 mpMRI scans were performed in 84 patients, who underwent 87 resections. The mpMRI scan affected surgical decision-making in 41 % (39/95) of scans, with 11 undergoing dual-vein embolization, 16 undergoing more conservative parenchymal-sparing surgery, 11 having more extensive surgery, and one patient following a low calorie diet pre-operatively. There were significant (Clavien-Dindo grades 3/4) complications in 5 % of patients, no Grade C post-hepatectomy liver failure, and zero 90-day mortality. WGS suggested additional therapeutic options and prognostic factors for 22 of 35 (63 %) evaluable patients. CONCLUSION Precision1 shows mpMRI can aid surgical decision-making, and optimise clinical outcomes. WGS provides additional information, to further enhance personalised decision-making.
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Affiliation(s)
- Fenella Welsh
- Hampshire Hospitals NHS Foundation Trust, Basingstoke, United Kingdom.
| | | | - Pulkit Sethi
- Hampshire Hospitals NHS Foundation Trust, Basingstoke, United Kingdom
| | - Mohammad Kazeroun
- Oxford Translational Myeloma Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom
| | | | | | | | - Naser Ansari-Pour
- Oxford Translational Myeloma Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom
| | - Tim Maughan
- Department of Oncology, University of Oxford, Oxford, United Kingdom
| | | | | | - Sarah Gooding
- MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
| | - Myrddin Rees
- Hampshire Hospitals NHS Foundation Trust, Basingstoke, United Kingdom
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Okuno T, Morizane C, Mizusawa J, Yanagimoto H, Kobayashi S, Imaoka H, Terashima T, Kawakami H, Sano Y, Okusaka T, Ikeda M, Ozaka M, Miwa H, Todaka A, Shimizu S, Mizuno N, Sekimoto M, Sano K, Tobimatsu K, Katanuma A, Gotoh K, Yamaguchi H, Ishii H, Furuse J, Ueno M. Influence of major hepatectomy on gemcitabine-based chemotherapy for recurrent biliary tract cancer after surgery: a subgroup analysis of JCOG1113. Int J Clin Oncol 2025; 30:83-91. [PMID: 39441453 DOI: 10.1007/s10147-024-02642-9] [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: 04/21/2024] [Accepted: 10/05/2024] [Indexed: 10/25/2024]
Abstract
BACKGROUND Major hepatectomy (MH) can increase the risk of adverse events (AEs) owing to impaired drug metabolism due to decreased liver volume and surgical injury. Thus, we performed this subgroup analysis using data from JCOG1113, a phase III trial comparing gemcitabine plus S-1 (GS) and gemcitabine plus cisplatin (GC) in patients with advanced and recurrent biliary tract cancer (BTC), to evaluate the effect of MH on the safety and efficacy of GC and GS regimens in patients with recurrent BTC. METHODS Of the 354 patients with advanced BTC enrolled in JCOG1113, 76 patients with postoperative recurrence (30 in the MH group and 46 in the non-MH group) were analyzed. RESULTS Grade ≥ 3 platelet count decreased in both arms was more frequent in the MH group than in non-MH group (GC, 0.0 vs. 17.6%; GS, 3.9 vs. 15.4%). However, in the MH group, the white blood cell decreased (GC, 55.0 vs. 38.5%; GS, 23.1 vs. 7.7%) and anemia (GC, 15.0 vs. 11.8%; GS, 23.1 vs. 7.7%) were less common than in the non-MH group. The MH and non-MH groups showed no significant difference in overall survival (OS) in both GC [median OS, 23.0 in MH vs. 16.9 months in non-MH (hazard ratio, 0.857; 95% CI 0.387-1.899)], and GS [median OS, 21.5 vs. 14.9 months (hazard ratio, 0.670; 95% CI 0.310-1.447)] arms. CONCLUSIONS The safety and efficacy of gemcitabine-based chemotherapy were comparable between patients who underwent MH and those who underwent other surgeries.
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Affiliation(s)
- Tatsuya Okuno
- Department of Medical Oncology, Faculty of Medicine, Kindai University, Osakasayama City, 377-2, Ohno-Higashi, Osaka, 589-8511, Japan.
| | - Chigusa Morizane
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Junki Mizusawa
- JCOG Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan
| | - Hiroaki Yanagimoto
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Satoshi Kobayashi
- Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan
| | - Hiroshi Imaoka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Takeshi Terashima
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan
| | - Hisato Kawakami
- Department of Medical Oncology, Faculty of Medicine, Kindai University, Osakasayama City, 377-2, Ohno-Higashi, Osaka, 589-8511, Japan
| | - Yusuke Sano
- JCOG Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan
| | - Takuji Okusaka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Masafumi Ikeda
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Masato Ozaka
- Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Haruo Miwa
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Akiko Todaka
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Satoshi Shimizu
- Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan
| | - Nobumasa Mizuno
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Mitsugu Sekimoto
- Department of Surgery, Kansai Medical University Hospital, Osaka, Japan
| | - Keiji Sano
- Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
| | - Kazutoshi Tobimatsu
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Akio Katanuma
- Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Kunihito Gotoh
- Department of Surgery, NHO Osaka National Hospital, Osaka, Japan
| | - Hironori Yamaguchi
- Department of Clinical Oncology, Jichi Medical University, Tochigi, Japan
| | - Hiroshi Ishii
- Clinical Research Center, Chiba Cancer Center, Chiba, Japan
| | - Junji Furuse
- Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan
| | - Makoto Ueno
- Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan
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Brewster F, Middleton Z, McWilliam A, Brocklehurst A, Radhakrishna G, Chuter R. Feasibility of using contrast-free quantitative magnetic resonance imaging for liver sparing stereotactic ablative body radiotherapy. Clin Transl Radiat Oncol 2024; 49:100859. [PMID: 39376618 PMCID: PMC11456905 DOI: 10.1016/j.ctro.2024.100859] [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: 07/15/2024] [Revised: 09/06/2024] [Accepted: 09/10/2024] [Indexed: 10/09/2024] Open
Abstract
Background and purpose Tumours in the liver often develop on a background of liver cirrhosis and impaired liver function. As a result, radiotherapy treatments are limited by radiation-induced liver disease, parameterised by the liver mean dose (LMD). Liver function is highly heterogeneous, especially in liver cancer, but the use of LMD does not take this into account. One possible way to improve liver treatments is to use quantitative imaging techniques to assess liver health and prioritise the sparing of healthy liver tissue. Materials and methods Anatomical T2 and quantitative iron-corrected T1 (cT1) images were made available for 10 patients with liver metastases. Functional liver volumes were automatically segmented on the quantitative images using a threshold. Liver stereotactic ablative body radiotherapy (SABR) plans were made using a departmental protocol. Liver-sparing plans were then made by reducing the dose to the functional sub-volume. Results The sparing plans achieved a statistically significant ( p = 0.002 ) reduction in the functional liver mean dose, with a mean reduction of 1.4 Gy. The LMD was also significantly different ( p = 0.002 ) but had a smaller magnitude with a mean reduction of 0.7 Gy. There were some differences in the planning target volume D99% ( p = 0.04 ) but the sparing plans remained within the optimal tolerance and the D95% was not significantly different ( p = 0.2 ). Conclusions This study has, for the first time, demonstrated the use of cT1 maps in radiotherapy showing significant reductions in dose to the healthy liver. Further work is needed to validate this in liver cancer patients, who would likely benefit most.
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Affiliation(s)
- Frank Brewster
- Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester, UK
| | | | - Alan McWilliam
- Department of Radiotherapy Related Research, Division of Clinical Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, UK
| | - Andrew Brocklehurst
- Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK
| | - Ganesh Radhakrishna
- Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK
| | - Robert Chuter
- Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester, UK
- Department of Radiotherapy Related Research, Division of Clinical Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, UK
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Kendall T, Overi D, Guido M, Braconi C, Banales J, Cardinale V, Gaudio E, Groot Koerkamp B, Carpino G. Recommendations on maximising the clinical value of tissue in the management of patients with intrahepatic cholangiocarcinoma. JHEP Rep 2024; 6:101067. [PMID: 38699072 PMCID: PMC11060959 DOI: 10.1016/j.jhepr.2024.101067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Revised: 03/04/2024] [Accepted: 03/08/2024] [Indexed: 05/05/2024] Open
Abstract
Background & Aims Patients with intrahepatic cholangiocarcinoma can now be managed with targeted therapies directed against specific molecular alterations. Consequently, tissue samples submitted to the pathology department must produce molecular information in addition to a diagnosis or, for resection specimens, staging information. The pathologist's role when evaluating these specimens has therefore changed to accommodate such personalised approaches. Methods We developed recommendations and guidance for pathologists by conducting a systematic review of existing guidance to generate candidate statements followed by an international Delphi process. Fifty-nine pathologists from 28 countries in six continents rated statements mapped to all elements of the specimen pathway from receipt in the pathology department to authorisation of the final written report. A separate survey of 'end-users' of the report including surgeons, oncologists, and gastroenterologists was undertaken to evaluate what information should be included in the written report to enable appropriate patient management. Results Forty-eight statements reached consensus for inclusion in the guidance including 10 statements about the content of the written report that also reached consensus by end-user participants. A reporting proforma to allow easy inclusion of the recommended data points was developed. Conclusions These guiding principles and recommendations provide a framework to allow pathologists reporting on patients with intrahepatic cholangiocarcinoma to maximise the informational yield of specimens required for personalised patient management. Impact and Implications Biopsy or resection lesional tissue from intrahepatic cholangiocarcinoma must yield information about the molecular abnormalities within the tumour that define suitability for personalised therapies in addition to a diagnosis and staging information. Here, we have developed international consensus guidance for pathologists that report such cases using a Delphi process that sought the views of both pathologists and 'end-users of pathology reports. The guide highlights the need to report cases in a way that preserves tissue for molecular testing and emphasises that reporting requires interpretation of histological characteristics within the broader clinical and radiological context. The guide will allow pathologists to report cases of intrahepatic cholangiocarcinoma in a uniform manner that maximises the value of the tissue received to facilitate optimal multidisciplinary patient management.
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Affiliation(s)
- Timothy Kendall
- University of Edinburgh Centre for Inflammation Research and Edinburgh Pathology, University of Edinburgh, Edinburgh, UK
| | - Diletta Overi
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
| | - Maria Guido
- Department of Medicine, DIMED, University of Padua, Padua, Italy
| | - Chiara Braconi
- School of Cancer Sciences, University of Glasgow, CRUK Scotland Cancer Centre, Beatson West of Scotland Cancer Centre, Glasgow, UK
| | - Jesus Banales
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, CIBERehd and University of the Basque Country (UPV/EHU), San Sebastian, Spain
- Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain
| | - Vincenzo Cardinale
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Eugenio Gaudio
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Guido Carpino
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
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Sundaravadanan S, Welsh FK, Sethi P, Noorani S, Cresswell BA, Connell JJ, Knapp SK, Núñez L, Brady JM, Banerjee R, Rees M. Novel multiparametric MRI detects improved future liver remnant quality post-dual vein embolization. HPB (Oxford) 2024; 26:764-771. [PMID: 38480098 DOI: 10.1016/j.hpb.2024.02.008] [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: 06/06/2023] [Accepted: 02/11/2024] [Indexed: 06/02/2024]
Abstract
BACKGROUND Optimisation of the future liver remnant (FLR) is crucial to outcomes of extended liver resections. This study aimed to assess the quality of the FLR before and after dual vein embolization (DVE) by quantitative multiparametric MRI. METHODS Of 100 patients with liver metastases recruited in a clinical trial (Precision1:NCT04597710), ten consecutive patients with insufficient FLR underwent quantitative multiparametric MRI pre- and post-DVE (right portal and hepatic vein). FLR volume, liver fibro-inflammation (corrected T1) scores and fat percentage (proton density fat fraction, PDFF) were determined. Patient metrics were compared by Wilcoxon signed-rank test and statistical analysis done using R software. RESULTS All patients underwent uncomplicated DVE with improvement in liver remnant health, median 37 days after DVE: cT1 scores reduced from median (interquartile range) 790 ms (753-833 ms) to 741 ms (708-760 ms) p = 0.014 [healthy range <795 ms], as did PDFF from 11% (4-21%), to 3% (2-12%) p = 0.017 [healthy range <5.6%]. There was a significant increase in median (interquartile range) FLR volume from 33% (30-37%)% to 49% (44-52%), p = 0.002. CONCLUSION This non-invasive and reproducible MRI technique showed improvement in volume and quality of the FLR after DVE. This is a significant advance in our understanding of how to prevent liver failure in patients undergoing major liver surgery.
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Affiliation(s)
- Senthil Sundaravadanan
- Department of Hepatobiliary Surgery, Basingstoke and North Hampshire Hospital, Basingstoke, Hampshire, United Kingdom.
| | - Fenella Ks Welsh
- Department of Hepatobiliary Surgery, Basingstoke and North Hampshire Hospital, Basingstoke, Hampshire, United Kingdom
| | - Pulkit Sethi
- Department of Hepatobiliary Surgery, Basingstoke and North Hampshire Hospital, Basingstoke, Hampshire, United Kingdom
| | - Shaheen Noorani
- Department of Interventional Radiology, Basingstoke and North Hampshire Hospital, Basingstoke, Hampshire, United Kingdom
| | - Ben A Cresswell
- Department of Hepatobiliary Surgery, Basingstoke and North Hampshire Hospital, Basingstoke, Hampshire, United Kingdom
| | | | | | - Luis Núñez
- Perspectum, Gemini One, Oxford, United Kingdom
| | | | | | - Myrddin Rees
- Department of Hepatobiliary Surgery, Basingstoke and North Hampshire Hospital, Basingstoke, Hampshire, United Kingdom
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Jimenez Ramos M, Kendall TJ, Drozdov I, Fallowfield JA. A data-driven approach to decode metabolic dysfunction-associated steatotic liver disease. Ann Hepatol 2024; 29:101278. [PMID: 38135251 PMCID: PMC10907333 DOI: 10.1016/j.aohep.2023.101278] [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: 11/30/2023] [Accepted: 12/04/2023] [Indexed: 12/24/2023]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), defined by the presence of liver steatosis together with at least one out of five cardiometabolic factors, is the most common cause of chronic liver disease worldwide, affecting around one in three people. Yet the clinical presentation of MASLD and the risk of progression to cirrhosis and adverse clinical outcomes is highly variable. It, therefore, represents both a global public health threat and a precision medicine challenge. Artificial intelligence (AI) is being investigated in MASLD to develop reproducible, quantitative, and automated methods to enhance patient stratification and to discover new biomarkers and therapeutic targets in MASLD. This review details the different applications of AI and machine learning algorithms in MASLD, particularly in analyzing electronic health record, digital pathology, and imaging data. Additionally, it also describes how specific MASLD consortia are leveraging multimodal data sources to spark research breakthroughs in the field. Using a new national-level 'data commons' (SteatoSITE) as an exemplar, the opportunities, as well as the technical challenges of large-scale databases in MASLD research, are highlighted.
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Affiliation(s)
- Maria Jimenez Ramos
- Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh BioQuarter, 4-5 Little France Drive, Edinburgh EH16 4UU, UK
| | - Timothy J Kendall
- Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh BioQuarter, 4-5 Little France Drive, Edinburgh EH16 4UU, UK; Edinburgh Pathology, University of Edinburgh, 51 Little France Crescent, Old Dalkeith Rd, Edinburgh EH16 4SA, UK
| | - Ignat Drozdov
- Bering Limited, 54 Portland Place, London, W1B 1DY, UK
| | - Jonathan A Fallowfield
- Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh BioQuarter, 4-5 Little France Drive, Edinburgh EH16 4UU, UK.
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Chouari T, Merali N, La Costa F, Santol J, Chapman S, Horton A, Aroori S, Connell J, Rockall TA, Mole D, Starlinger P, Welsh F, Rees M, Frampton AE. The Role of the Multiparametric MRI LiverMultiScan TM in the Quantitative Assessment of the Liver and Its Predicted Clinical Applications in Patients Undergoing Major Hepatic Resection for Colorectal Liver Metastasis. Cancers (Basel) 2023; 15:4863. [PMID: 37835557 PMCID: PMC10571783 DOI: 10.3390/cancers15194863] [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: 04/11/2023] [Revised: 08/05/2023] [Accepted: 10/02/2023] [Indexed: 10/15/2023] Open
Abstract
Liver biopsy remains the gold standard for the histological assessment of the liver. With clear disadvantages and the rise in the incidences of liver disease, the role of neoadjuvant chemotherapy in colorectal liver metastasis (CRLM) and an explosion of surgical management options available, non-invasive serological and imaging markers of liver histopathology have never been more pertinent in order to assess liver health and stratify patients considered for surgical intervention. Liver MRI is a leading modality in the assessment of hepatic malignancy. Recent technological advancements in multiparametric MRI software such as the LiverMultiScanTM offers an attractive non-invasive assay of anatomy and histopathology in the pre-operative setting, especially in the context of CRLM. This narrative review examines the evidence for the LiverMultiScanTM in the assessment of hepatic fibrosis, steatosis/steatohepatitis, and potential applications for chemotherapy-associated hepatic changes. We postulate its future role and the hurdles it must surpass in order to be implemented in the pre-operative management of patients undergoing hepatic resection for colorectal liver metastasis. Such a role likely extends to other hepatic malignancies planned for resection.
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Affiliation(s)
- Tarak Chouari
- MATTU, The Leggett Building, Daphne Jackson Road, Guildford GU2 7WG, UK; (T.C.)
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
- Oncology Section, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK
| | - Nabeel Merali
- MATTU, The Leggett Building, Daphne Jackson Road, Guildford GU2 7WG, UK; (T.C.)
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
- Oncology Section, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK
| | - Francesca La Costa
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
| | - Jonas Santol
- Department of Surgery, HPB Center, Vienna Health Network, Clinic Favoriten and Sigmund Freud Private University, 1090 Vienna, Austria
- Institute of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria
| | - Shelley Chapman
- Department of Radiology, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
| | - Alex Horton
- Department of Radiology, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
| | - Somaiah Aroori
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery and Transplant Surgery, Derriford Hospital, Plymouth PL6 8DH, UK
| | | | - Timothy A. Rockall
- MATTU, The Leggett Building, Daphne Jackson Road, Guildford GU2 7WG, UK; (T.C.)
- Oncology Section, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK
| | - Damian Mole
- Clinical Surgery, Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh EH10 5HF, UK
- Centre for Inflammation Research, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh EH105HF, UK
| | - Patrick Starlinger
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN 55902, USA
- Center of Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria
- Department of Surgery, Medical University of Vienna, General Hospital, 1090 Vienna, Austria
| | - Fenella Welsh
- Hepato-Biliary Unit, Hampshire Hospitals Foundation Trust, Basingstoke, Hampshire RG24 9NA, UK
| | - Myrddin Rees
- Hepato-Biliary Unit, Hampshire Hospitals Foundation Trust, Basingstoke, Hampshire RG24 9NA, UK
| | - Adam E. Frampton
- MATTU, The Leggett Building, Daphne Jackson Road, Guildford GU2 7WG, UK; (T.C.)
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
- Oncology Section, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK
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Parmar KL, O'Reilly D, Valle J, Braun M, Malcomson L, Jones RP, Balaa F, Rees M, Welsh FKS, Filobbos R, Renehan AG. Protocol for the CoNoR Study: A prospective multi-step study of the potential added benefit of two novel assessment tools in colorectal liver metastases technical resectability decision-making. BMJ Open 2023; 13:e059369. [PMID: 36997247 PMCID: PMC10069542 DOI: 10.1136/bmjopen-2021-059369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/31/2023] Open
Abstract
INTRODUCTION Liver resection is the only curative treatment for colorectal liver metastases (CLM). Resectability decision-making is therefore a key determinant of outcomes. Wide variation has been demonstrated in resectability decision-making, despite the existence of criteria. This paper summarises a study protocol to evaluate the potential added value of two novel assessment tools in assessing CLM technical resectability: the Hepatica preoperative MR scan (MR-based volumetry, Couinaud segmentation, liver tissue characteristics and operative planning tool) and the LiMAx test (hepatic functional capacity). METHODS AND ANALYSIS This study uses a systematic multistep approach, whereby three preparatory workstreams aid the design of the final international case-based scenario survey:Workstream 1: systematic literature review of published resectability criteria.Workstream 2: international hepatopancreatobiliary (HPB) interviews.Workstream 3: international HPB questionnaire.Workstream 4: international HPB case-based scenario survey.The primary outcome measures are change in resectability decision-making and change in planned operative strategy, resulting from the novel test results. Secondary outcome measures are variability in CLM resectability decision-making and opinions on the role for novel tools. ETHICS AND DISSEMINATION The study protocol has been approved by a National Health Service Research Ethics Committee and registered with the Health Research Authority. Dissemination will be via international and national conferences. Manuscripts will be published. REGISTRATION DETAILS The CoNoR Study is registered with ClinicalTrials.gov (registration number NCT04270851). The systematic review is registered on the PROSPERO database (registration number CRD42019136748).
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Affiliation(s)
- Kat L Parmar
- Division of Cancer Sciences, The University of Manchester, Manchester, UK
- NIHR Manchester Biomedical Research Centre, Manchester Cancer Research Centre, Manchester, UK
| | - Derek O'Reilly
- Division of Cancer Sciences, The University of Manchester, Manchester, UK
- Department of Hepatobiliary Surgery, Manchester University NHS Foundation Trust, Manchester, UK
| | - Juan Valle
- Division of Cancer Sciences, The University of Manchester, Manchester, UK
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK
| | - Michael Braun
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK
| | - Lee Malcomson
- Division of Cancer Sciences, The University of Manchester, Manchester, UK
- NIHR Manchester Biomedical Research Centre, Manchester Cancer Research Centre, Manchester, UK
| | - Robert P Jones
- Department of Hepatobiliary Surgery, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
| | - Fady Balaa
- Department of Surgery, Ottawa Hospital, Ottawa, Ontario, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Myrddin Rees
- Department of Surgery, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | - Fenella K S Welsh
- Department of Surgery, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | - Rafik Filobbos
- Department of Radiology, Manchester University NHS Foundation Trust, Manchester, UK
| | - Andrew G Renehan
- Division of Cancer Sciences, The University of Manchester, Manchester, UK
- NIHR Manchester Biomedical Research Centre, Manchester Cancer Research Centre, Manchester, UK
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Welsh FK, Connell JJ, Kelly M, Gooding S, Banerjee R, Rees M. Precision medicine for liver tumours with quantitative MRI and whole genome sequencing (Precision1 trial): study protocol for observational cohort study. BMJ Open 2022; 12:e057163. [PMID: 35383076 PMCID: PMC8984042 DOI: 10.1136/bmjopen-2021-057163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
INTRODUCTION Radiogenomic analysis of patients being considered for liver resection is seldom performed in the clinic despite recent evidence indicating that quantitative MRI could improve posthepatectomy outcomes. Meanwhile, the increasingly accessible results from whole genome sequencing reporting on clinically actionable genetic biomarkers are yet to be fully integrated into the clinical care pathway. METHODS AND ANALYSIS A prospective observational cohort study of up to 200 participants is planned, recruiting adults with primary or secondary liver cancer being considered for liver resection at Hampshire Hospitals NHS Foundation Trust. The data will be evaluated to address the primary endpoint to calculate the proportion of participants in which the results from whole genome sequencing would have resulted in a change in clinical management. Participants will be offered an additional non-invasive quantitative MRI scan prior to the operation and the impact of the imaging results on treatment decision-making will be evaluated. ETHICS AND DISSEMINATION This study was reviewed by the NHS Health Research Authority and given favourable opinion by the Brighton and Sussex Research Ethics Committee (REC reference: 20/PR/0222). Research findings will be discussed with a patient and public involvement and engagement group, presented at relevant scientific conferences and published in open access journals. TRIAL REGISTRATION NUMBER NCT04597710.
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Affiliation(s)
- Fenella K Welsh
- Department of Hepatobiliary Surgery, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | | | | | - Sarah Gooding
- Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
| | | | - Myrddin Rees
- Department of Hepatobiliary Surgery, Basingstoke and North Hampshire Hospital, Basingstoke, UK
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10
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Magnetic Resonance Imaging and Serum AFP-L3 and GP-73 in the Diagnosis of Primary Liver Cancer. JOURNAL OF ONCOLOGY 2022; 2022:1192368. [PMID: 35401747 PMCID: PMC8986367 DOI: 10.1155/2022/1192368] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 02/12/2022] [Accepted: 03/05/2022] [Indexed: 12/24/2022]
Abstract
Objective To investigate the combined application value of magnetic resonance imaging (MRI) combined with serum alpha-fetoprotein (AFP)-L3 and Golgi protein (GP)-73 in the diagnosis of primary liver cancer. Methods The data of 200 patients with suspected liver cancer admitted to our hospital from February 2020 to February 2021 were retrospectively analyzed, and they were randomly divided into an experimental group and a control group, with 100 cases in each group. The experimental group received a combined detection of MRI with serum AFP-L3 and GP-73, and the control group adopted traditional diagnostic methods (spiral computed tomography and serum AFP). The diagnostic yields of the two groups were compared. Surgical resection was performed after the diagnosis of primary liver cancer, and the correlation between the efficacy and combined detection of MRI with serum AFP-L3 and GP-73 levels was analyzed. Results The two groups presented comparable general information (P >0.05). The surgical results showed 160 cases of primary liver cancer, including 75 cases in the experimental group and 85 cases in the control group, and 40 cases of benign liver lesions. The diagnostic accuracy of the experimental group (73/75, 95%) was significantly higher than that of the control group (76/85, 86%) (P < 0.05). The serum levels of AFP-L3, GP-73, and AFP in patients with primary liver cancer were remarkably decreased after surgery (P < 0.001). The preoperative and postoperative AFP-L3, GP-73, and AFP levels of patients with primary liver cancer were significantly higher than those of patients with benign liver lesions. The AUC (95% CI) for the combined detection of MRI and serum AFP-L3 and GP-73 levels in patients with surgically confirmed primary liver cancer was 0.747 (0.619-0.874). Conclusion MRI combined with serum AFP-L3 and GP-73 presents favorable diagnostic efficiency in the diagnosis of primary liver cancer, which is worthy of clinical application.
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Hill CE, Biasiolli L, Robson MD, Grau V, Pavlides M. Emerging artificial intelligence applications in liver magnetic resonance imaging. World J Gastroenterol 2021; 27:6825-6843. [PMID: 34790009 PMCID: PMC8567471 DOI: 10.3748/wjg.v27.i40.6825] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 04/16/2021] [Accepted: 09/30/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic liver diseases (CLDs) are becoming increasingly more prevalent in modern society. The use of imaging techniques for early detection, such as magnetic resonance imaging (MRI), is crucial in reducing the impact of these diseases on healthcare systems. Artificial intelligence (AI) algorithms have been shown over the past decade to excel at image-based analysis tasks such as detection and segmentation. When applied to liver MRI, they have the potential to improve clinical decision making, and increase throughput by automating analyses. With Liver diseases becoming more prevalent in society, the need to implement these techniques to utilize liver MRI to its full potential, is paramount. In this review, we report on the current methods and applications of AI methods in liver MRI, with a focus on machine learning and deep learning methods. We assess four main themes of segmentation, classification, image synthesis and artefact detection, and their respective potential in liver MRI and the wider clinic. We provide a brief explanation of some of the algorithms used and explore the current challenges affecting the field. Though there are many hurdles to overcome in implementing AI methods in the clinic, we conclude that AI methods have the potential to positively aid healthcare professionals for years to come.
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Affiliation(s)
- Charles E Hill
- Department of Engineering Science, University of Oxford, Oxford OX3 7DQ, United Kingdom
| | - Luca Biasiolli
- Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, United Kingdom
| | | | - Vicente Grau
- Department of Engineering, University of Oxford, Oxford OX3 7DQ, United Kingdom
| | - Michael Pavlides
- Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, United Kingdom
- Translational Gastroenterology Unit, University of Oxford, Oxford OX3 9DU, United Kingdom
- Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford OX3 9DU, United Kingdom
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12
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Quantitative multiparametric MRI as a non-invasive stratification tool in children and adolescents with autoimmune liver disease. Sci Rep 2021; 11:15261. [PMID: 34315985 PMCID: PMC8316432 DOI: 10.1038/s41598-021-94754-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 07/08/2021] [Indexed: 12/12/2022] Open
Abstract
Autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC) are two very closely related autoimmune liver diseases with overlapping clinical features and similar management strategies. The purpose of this study was to assess the utility of quantitative imaging markers to distinguish ASC from AIH in paediatrics. 66 participants (N = 52 AIH, N = 14 ASC) aged 14.4 ± 3.3 years scheduled to undergo routine biopsy and baseline serum liver biochemistry testing were invited to undergo MRI (non-contrast abdominal MRI and 3D fast spin-echo MRCP). Multiparametric MRI was used to measure fibro-inflammation with corrected T1 (cT1), while the biliary tree was modelled using quantitative MRCP (MRCP +). Mann–Whitney U tests were performed to compare liver function tests with imaging markers between patient groups (ASC vs AIH). Receiver operating characteristic curves and stepwise logistic regressions were used to identify the best combination of markers to discriminate between ASC and AIH. Correlations between liver function tests and imaging markers were performed using Spearman’s rank correlation. cT1 was significantly correlated with liver function tests (range 0.33 ≤ R ≤ 56, p < 0.05), as well as with fibrosis, lobular and portal inflammation (range 0.31 ≤ R ≤ 42, p < 0.05). 19 MRCP + metrics correlated significantly with liver function tests (range 0.29 ≤ R ≤ 0.43, p < 0.05). GGT and MRCP + metrics were significantly higher in ASC compared to those with AIH. The best multivariable model for distinguishing ASC from AIH included total number of ducts and the sum of relative severity of both strictures and dilatations AUC: 0.91 (95% CI 0.78–1). Quantitative MRCP metrics are a good discriminator of ASC from AIH.
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Sethi P, Thavanesan N, Welsh FK, Connell J, Pickles E, Kelly M, Fallowfield JA, Kendall TJ, Mole DJ, Rees M. Quantitative multiparametric MRI allows safe surgical planning in patients undergoing liver resection for colorectal liver metastases: report of two patients. BJR Case Rep 2021; 7:20200172. [PMID: 34131498 PMCID: PMC8171142 DOI: 10.1259/bjrcr.20200172] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 12/16/2020] [Accepted: 12/26/2020] [Indexed: 01/11/2023] Open
Abstract
It is not uncommon for clinicians to encounter varying degrees of hepatic steatosis in patients undergoing resection for colorectal liver metastases (CRLM). Magnetic resonance imaging is currently the preferred investigation for identification and pre-operative planning of these patients. An objective assessment of liver quality and degree of steatosis is paramount for planning a safe resection, which is seldom provided by routine MRI sequences. We studied two patients who underwent an additional pre-operative multiparametric MRI scan (LiverMultiScanTM) as a part of an observational clinical trial (HepaT1ca, NCT03213314) to assess the quality of liver. Outcome was assessed in the form of post-hepatectomy liver failure. Both patients (Patient 1 and 2) had comparable pre-operative characteristics. Both patients were planned for an extended right hepatectomy with an estimated future liver remnant of approximately 30%. Conventional preoperative contrast MRI showed mild liver steatosis in both patients. Patient one developed post-hepatectomy liver failure leading to prolonged hospital stay compared to patient two who had uneventful post-operative course. Retrospective evaluation of multiparametric MRI scan revealed findings consistent with fibro-inflammatory disease and steatosis (cT1 829 ms, PDFF 14%) for patient 1 whereas patient two had normal parameters (cT1 735 ms, PDFF 2.4%). These findings corresponded with the resection specimen histology. Multiparametric MRI can objectively evaluate future liver health and volume which may help refine surgical decision-making and improve patient outcomes.
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Affiliation(s)
- Pulkit Sethi
- Department of Hepatobiliary Surgery, Basingstoke and North Hampshire Hospital, Basingstoke, Hampshire, United Kingdom
| | - Navamayooran Thavanesan
- Department of Hepatobiliary Surgery, Basingstoke and North Hampshire Hospital, Basingstoke, Hampshire, United Kingdom
| | - Fenella Ks Welsh
- Department of Hepatobiliary Surgery, Basingstoke and North Hampshire Hospital, Basingstoke, Hampshire, United Kingdom
| | | | | | - Matt Kelly
- Perspectum, Gemini One, Oxford, United Kingdom
| | - Jonathan A Fallowfield
- Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | - Timothy J Kendall
- Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | | | - Myrddin Rees
- Department of Hepatobiliary Surgery, Basingstoke and North Hampshire Hospital, Basingstoke, Hampshire, United Kingdom
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