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Tran LCD, Nguyen TQ, Dadam MN, Nguyen TD, Le DT, Dang VQ, Pham PH, Phan NP, Vo TQ, Cucè F, Abdallfatah A, Huy NT. Portal vein embolization and subsequent major hepatectomy for hepatocellular carcinoma with insufficient residual liver volume: experience of a tertiary center. Updates Surg 2025:10.1007/s13304-025-02190-5. [PMID: 40261573 DOI: 10.1007/s13304-025-02190-5] [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: 07/31/2024] [Accepted: 03/27/2025] [Indexed: 04/24/2025]
Abstract
Portal vein embolization (PVE) allows for liver regeneration to enhance reduced residual liver volume before resection in hepatocellular carcinoma (HCC) patients with systemic liver disease. A retrospective review of medical records was conducted, including patients who underwent PVE and subsequent major hepatectomy to treat resectable non-metastatic HCC at the University Medical Center in Ho Chi Minh City between 01/2016 and 6/2023. Patient demographics, timing of procedures, surgical interventions, intra- and postoperative complications, pattern of recurrence, and survival were analyzed. A total of 58 patients with HCC were included, and the median length of stay after surgery was 8 days (range 5-24). Post-hepatectomy liver failure (PHLF) occurred with an overall incidence of 31% (18/58 cases). Severe PHLF occurred in 6 cases: grade B in 5 cases (8.6%) and grade C in 1 case (1.7%), resulting in patient death. Postoperative bleeding and bile leak each occurred in 1 case (1.7%). Univariable and multivariable analyses identified portal vein pressure (PVP) after PVE as the only significant preoperative parameter associated with outcomes, correlating with PHLF occurrence (OR 1.27, p = 0.009) at a cut-off of 15 mmHg (p = 0.018). The overall survival at 3, 6, and 12 months was 96%, 94%, and 94%, respectively, with disease-free survival rates of 94%, 90%, and 87%, respectively. Major hepatectomy can be performed safely and effectively in HCC patients who have PVE-induced liver hypertrophy (sFLR ≥ 40%) and preserved liver function (Child-Pugh A) maintaining low morbidity. Multivariate analysis revealed that a post-PVE PVP cutoff of 15 mmHg significantly correlated with perioperative parameters, including operating time, blood loss, and PHLF occurrence.
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Affiliation(s)
- Long Cong Duy Tran
- Department of Hepatobiliary and Pancreatic Surgery, University Medical Center at Ho Chi Minh City, Ho Chi Minh City, Vietnam
- Department of Surgery, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Thanh Quoc Nguyen
- Department of Hepatobiliary and Pancreatic Surgery, University Medical Center at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Mohammad Najm Dadam
- Online Research Club, Nagasaki, Japan
- Department of Orthopedics and Trauma Surgery, Helios Klinikum Schwelm, Schwelm, Germany
| | - Thuan Duc Nguyen
- Department of Hepatobiliary and Pancreatic Surgery, University Medical Center at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Dat Tien Le
- Department of Hepatobiliary and Pancreatic Surgery, University Medical Center at Ho Chi Minh City, Ho Chi Minh City, Vietnam
- Department of Surgery, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Viet Quoc Dang
- Department of Hepatobiliary and Pancreatic Surgery, University Medical Center at Ho Chi Minh City, Ho Chi Minh City, Vietnam
- Department of Surgery, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Phu Hong Pham
- Department of Hepatobiliary and Pancreatic Surgery, University Medical Center at Ho Chi Minh City, Ho Chi Minh City, Vietnam
- Department of Surgery, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Nghia Phuoc Phan
- Department of Hepatobiliary and Pancreatic Surgery, University Medical Center at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Thinh Quan Vo
- Department of Hepatobiliary and Pancreatic Surgery, University Medical Center at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Federica Cucè
- General and Upper G.I. Surgery Division, Surgery, Dentistry, Maternity and Infant Department, University of Verona, Verona, Italy
| | | | - Nguyen Tien Huy
- Institute of Research and Development, Duy Tan University, Da Nang, Vietnam.
- School of Medicine and Pharmacy, Duy Tan University, Da Nang, Vietnam.
- Graduate School of Tropical Medicine and Global Health (TMGH), Nagasaki University, Nagasaki, 852-8523, Japan.
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Can E, Elkilany A, Paparoditis S, Gebauer B, Geisel D, Krenzien F, Pohrt A, Uller W, Doppler M, Ebel S, Gößmann H, Fehrenbach U. Future liver remnant hypertrophy and postoperative outcomes: a retrospective comparison between segmental and main right portal vein embolization. CVIR Endovasc 2025; 8:27. [PMID: 40148703 PMCID: PMC11950456 DOI: 10.1186/s42155-025-00537-y] [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: 01/30/2025] [Accepted: 03/10/2025] [Indexed: 03/29/2025] Open
Abstract
OBJECTIVE To assess the efficacy of segmental right portal vein embolization (SRPVE) versus main right portal vein embolization (MRPVE) in preoperative preparation for major hepatectomy. METHODS This retrospective single-center study included 220 consecutive patients who underwent portal vein embolization (PVE) before (extended) right hemihepatectomy between January 2014 and June 2021. Seventy-one patients underwent selective segmental embolization (SRPVE) and 149 patients underwent MRPVE. Volumetric analysis was conducted before PVE and before surgery. Key endpoints included evaluation of future liver remnant (FLR) hypertrophy, intraoperative complexity, and postoperative complications, technical success, clinical success, complications (Clavien-Dindo and CIRSE classifications), as well as evaluation of different factors which may influence hypertrophy of the FLR. RESULTS Technical success rate was 100% in the SRPVE group and 99.3% in the MRPVE group (p = 0.15). Clinical success rate was comparable between both techniques, measuring 95.8% in the SRPVE group and 95.3% in the MRPVE group (p = 0.18). Absolute hypertrophy (FLRabh) of the FLR was comparable between both techniques, measuring 47.15% in the SRPVE group and 40.78% in the MRPVE group (p = 0.54). Complication rates did not differ significantly (p = 0.12). Partial thrombosis involving the left portal vein, main portal vein, or mesentericosplenic region was observed in 2.8% of the patients in the SRPVE group vs 3.4% in the MRPVE group (p = 0.95). CIRSE Class II-VI complications were slightly higher in the MRPVE group (10.7% vs 9.8%, p = 0.82). Postoperative complications with Clavien-Dindo class ≥ IIIa occurred in 10.1% % in the MRPVE group vs 9.9% the SRPVE group (p = 0.92). Liver cirrhosis had a significant negative correlation with sFLR % increase following PVE (r = -0.54; p = 0.027). Neoadjuvant chemotherapy was also associated with reduced FLR hypertrophy following PVE, with a median sFLR% change of 63.8% (IQR: 60.8% - 75.2%) in patients who received neoadjuvant chemotherapy (n = 66 patients, 30%) compared to 82.6% (IQR: 77.4% - 84.2%) in those without chemotherapy (n = 154 patients, 70%). CONCLUSION Selective segmental right portal vein embolization, sparing the main right portal vein, offers a safe and effective alternative to MRPVE, achieving comparable FLR hypertrophy while potentially simplifying intraoperative procedures and reducing postprocedural complications. Future research should focus on conducting large, prospective, multicenter trials to further compare the long-term outcomes of this technique, particularly with regard to liver regeneration, postoperative liver function, complications and overall survival.
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Affiliation(s)
- Elif Can
- Department of Diagnostic and Interventional Radiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Aboelyazid Elkilany
- Department of Diagnostic and Interventional Radiology, University Hospital Leipzig, Leipzig, Germany.
| | - Sophia Paparoditis
- Department of Diagnostic and Interventional Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Bernhard Gebauer
- Department of Diagnostic and Interventional Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Dominik Geisel
- Department of Diagnostic and Interventional Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Felix Krenzien
- Department of General, Visceral and Transplantation Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, Berlin Institute of Health, Berlin, Germany
- Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Straße 2, 10178, Berlin, Germany
| | - Anne Pohrt
- Institute of Biometry and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Wibke Uller
- Department of Diagnostic and Interventional Radiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Michael Doppler
- Department of Diagnostic and Interventional Radiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Sebastian Ebel
- Department of Diagnostic and Interventional Radiology, University Hospital Leipzig, Leipzig, Germany
| | - Holger Gößmann
- Department of Diagnostic and Interventional Radiology, University Hospital Leipzig, Leipzig, Germany
| | - Uli Fehrenbach
- Department of Diagnostic and Interventional Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, Berlin Institute of Health, Berlin, Germany
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Kuhn TN, Engelhardt WD, Kahl VH, Alkukhun A, Gross M, Iseke S, Onofrey J, Covey A, Camacho JC, Kawaguchi Y, Hasegawa K, Odisio BC, Vauthey JN, Antoch G, Chapiro J, Madoff DC. Artificial Intelligence-Driven Patient Selection for Preoperative Portal Vein Embolization for Patients with Colorectal Cancer Liver Metastases. J Vasc Interv Radiol 2025; 36:477-488. [PMID: 39638087 DOI: 10.1016/j.jvir.2024.11.025] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 10/24/2024] [Accepted: 11/22/2024] [Indexed: 12/07/2024] Open
Abstract
PURPOSE To develop a machine learning algorithm to improve hepatic resection selection for patients with metastatic colorectal cancer (CRC) by predicting post-portal vein embolization (PVE) outcomes. MATERIALS AND METHODS This multicenter retrospective study (2000-2020) included 200 consecutive patients with CRC liver metastases planned for PVE before surgery. Data on radiomic features and laboratory values were collected. Patient-specific eigenvalues for each liver shape were calculated using a statistical shape model approach. After semiautomatic segmentation and review by a board-certified radiologist, the data were split 70%/30% for training and testing. Three machine learning algorithms predicting the total liver volume (TLV) after PVE, sufficient future liver remnant (FLR%), and kinetic growth rate (KGR%) were trained, with performance assessed using accuracy, sensitivity, specificity, area under the curve (AUC), or root mean squared error. Significance between the internal and external test sets was assessed by the Student t-test. One institution was kept separate as an external testing set. RESULTS A total of 114 (76 men; mean age, 56 years [SD± 12]) and 37 (19 men; mean age, 50 years ± [SD± 11]) patients met the inclusion criteria for the internal validation and external validation, respectively. Prediction accuracy and AUC for sufficient FLR% or liver growth potential (KGR%> 0%) were high in the internal testing set-85.81% (SD ± 1.01) and 0.91 (SD ± 0.01) or 87.44% (SD ± 0.10) and 0.66 (SD ± 0.03), respectively. Similar results occurred in the external testing set-79.66% (SD ± 0.60) and 0.88 (SD ± 0.00) or 72.06% (SD ± 0.30) and 0.69 (SD ± 0.01), respectively. TLV prediction showed discrepancy rates of 12.56% (SD ±4.20%; P = .86) internally and 13.57% (SD ± 3.76%; P = .91) externally. CONCLUSIONS Machine learning-based models incorporating radiomics and laboratory test results may help predict the FLR%, KGR%, and TLV as metrics for successful PVE.
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Affiliation(s)
- Tom N Kuhn
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut; Department of Diagnostic and Interventional Radiology, University Düsseldorf, Medical Faculty, Düsseldorf, Germany
| | - William D Engelhardt
- Department of Biomedical Engineering, James McKlevey School of Engineering, Washington University, St. Louis, Missouri
| | - Vinzent H Kahl
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut; Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Berlin, Germany
| | - Abedalrazaq Alkukhun
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
| | - Moritz Gross
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut; Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Berlin, Germany
| | - Simon Iseke
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut; Department of Diagnostic and Interventional Radiology, Pediatric Radiology and Neuroradiology, Rostock University Medical Center, Rostock, Germany
| | - John Onofrey
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut; Department of Biomedical Engineering, Yale University, New Haven, Connecticut; Department of Urology, Yale School of Medicine, New Haven, Connecticut
| | - Anne Covey
- Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Juan C Camacho
- Department of Clinical Sciences, Florida State University College of Medicine, Tallahassee, Florida
| | - Yoshikuni Kawaguchi
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Bruno C Odisio
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Gerald Antoch
- Department of Diagnostic and Interventional Radiology, University Düsseldorf, Medical Faculty, Düsseldorf, Germany
| | - Julius Chapiro
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut; Department of Biomedical Engineering, Yale University, New Haven, Connecticut; Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut
| | - David C Madoff
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut; Department of Internal Medicine, Section of Medical Oncology, Yale School of Medicine, New Haven, Connecticut; Department of Surgery, Section of Surgical Oncology, Yale School of Medicine, New Haven, Connecticut.
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Dempsey PJ, Farrelly C, Cronin CG, Fenlon HM. Preoperative imaging of colorectal liver metastases: what the radiologist and the multidisciplinary team need to know. Br J Radiol 2024; 97:1602-1618. [PMID: 39078288 PMCID: PMC11417391 DOI: 10.1093/bjr/tqae133] [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: 12/14/2023] [Revised: 03/13/2024] [Accepted: 07/29/2024] [Indexed: 07/31/2024] Open
Abstract
The management of patients with colorectal liver metastases (CRLM) has transformed over the past 2 decades. Advances in surgical techniques, systemic therapies, and local treatments have resulted in a paradigm shift. Disease that would once have been considered terminal is now frequently treated aggressively with both a disease-free and overall survival benefit. In line with the expanding range of treatment options, there has been an increase in the volume and complexity of imaging required in the management of these patients to ensure optimal patient selection and outcome. The radiologist plays a pivotal role in interpreting these studies, conveying the relevant information and informing the discussion at multidisciplinary team meetings. The purpose of this review is to provide an update for radiologists on the current surgical management of patients with CRLM highlighting specific imaging information that is required by the multidisciplinary team when assessing resectability and/or the need for additional liver-directed therapies.
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Affiliation(s)
- Philip J Dempsey
- Department of Radiology, Mater Misericordiae University Hospital, Dublin D07, Ireland
| | - Cormac Farrelly
- Department of Radiology, Mater Misericordiae University Hospital, Dublin D07, Ireland
| | - Carmel G Cronin
- Department of Radiology, Mater Misericordiae University Hospital, Dublin D07, Ireland
| | - Helen M Fenlon
- Department of Radiology, Mater Misericordiae University Hospital, Dublin D07, Ireland
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Bilhim T, Böning G, Guiu B, Luz JH, Denys A. CIRSE Standards of Practice on Portal Vein Embolization and Double Vein Embolization/Liver Venous Deprivation. Cardiovasc Intervent Radiol 2024; 47:1025-1036. [PMID: 38884781 PMCID: PMC11303578 DOI: 10.1007/s00270-024-03743-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 04/20/2024] [Indexed: 06/18/2024]
Abstract
This CIRSE Standards of Practice document is aimed at interventional radiologists and provides best practices for performing liver regeneration therapies prior to major hepatectomies, including portal vein embolization, double vein embolization and liver venous deprivation. It has been developed by an expert writing group under the guidance of the CIRSE Standards of Practice Committee. It encompasses all clinical and technical details required to perform liver regeneration therapies, revising the indications, contra-indications, outcome measures assessed, technique and expected outcomes.
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Affiliation(s)
- Tiago Bilhim
- Interventional Radiology Unit, Curry Cabral Hospital, Unidade Local de Saúde São José; Centro Clínico Académico de Lisboa, SAMS Hospital, Lisbon, Portugal.
| | - Georg Böning
- Department of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Boris Guiu
- Department of Radiology, St-Eloi University Hospital, Montpellier, France
| | - José Hugo Luz
- Department of Interventional Radiology, Brazilian National Cancer Institute (INCA), Rio de Janeiro, Brazil
| | - Alban Denys
- Department of Radiology and Interventional Radiology, Centre Hospitalier Universitaire Vaudois CHUV, University of Lausanne, Lausanne, Switzerland
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Dar FS, Abbas Z, Ahmed I, Atique M, Aujla UI, Azeemuddin M, Aziz Z, Bhatti ABH, Bangash TA, Butt AS, Butt OT, Dogar AW, Farooqi JI, Hanif F, Haider J, Haider S, Hassan SM, Jabbar AA, Khan AN, Khan MS, Khan MY, Latif A, Luck NH, Malik AK, Rashid K, Rashid S, Salih M, Saeed A, Salamat A, Tayyab GUN, Yusuf A, Zia HH, Naveed A. National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma. World J Gastroenterol 2024; 30:1018-1042. [PMID: 38577184 PMCID: PMC10989497 DOI: 10.3748/wjg.v30.i9.1018] [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: 11/13/2023] [Revised: 01/03/2024] [Accepted: 01/29/2024] [Indexed: 03/06/2024] Open
Abstract
A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.
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Affiliation(s)
- Faisal Saud Dar
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Zaigham Abbas
- Department of Hepatogastroenterology and Liver Transplantation, Dr. Ziauddin University Hospital, Karachi 75600, Sindh, Pakistan
| | - Irfan Ahmed
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
- University of Aberdeen, Aberdeen B24 3FX, United Kingdom
| | - Muhammad Atique
- Department of Pathology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Usman Iqbal Aujla
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | | | - Zeba Aziz
- Department of Oncology, Hameed Latif Hospital, Lahore 54000, Pakistan
| | - Abu Bakar Hafeez Bhatti
- Division of Hepatopancreatic Biliary Surgery & Liver Transplantation, Shifa International Hospital, Islamabad 44000, Pakistan
| | - Tariq Ali Bangash
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Shaikh Zayed Hospital and Post Graduate Medical Institute, Lahore 54000, Pakistan
| | - Amna Subhan Butt
- Department of Medicine, Aga Khan University Hospital, Karachi 74800, Pakistan
| | - Osama Tariq Butt
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Abdul Wahab Dogar
- Department of Liver Transplant, Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences, Gambat 66020, Pakistan
| | - Javed Iqbal Farooqi
- Department of Medicine & Gastroenterology, Lifecare Hospital and Research Centre, Peshawar 25000, Khyber Pakhtunkhwa, Pakistan
| | - Faisal Hanif
- Department of Hepatopancreatobiliary & Liver Transplant, Bahria International Hospital, Lahore 54000, Pakistan
| | - Jahanzaib Haider
- Department of Surgery, Hepatopancreatobiliary & Liver Transplant, Dow University of Health Sciences, Karachi 74800, Pakistan
| | - Siraj Haider
- Department of Surgery, Hepatopancreatobiliary & Liver Transplant, Dow University of Health Sciences, Karachi 74800, Pakistan
| | - Syed Mujahid Hassan
- Department of Gastroenterology, Hepatology & Nutrition, Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences, Gambat 66020, Pakistan
| | | | - Aman Nawaz Khan
- Department of Radiology, Rehman Medical Institute, Peshawar 25000, Pakistan
| | - Muhammad Shoaib Khan
- Army Liver Transplant Unit, Pak Emirates Military Hospital, Rawalpindi 46000, Pakistan
| | - Muhammad Yasir Khan
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Amer Latif
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Shaikh Zayed Hospital and Post Graduate Medical Institute, Lahore 54000, Pakistan
| | - Nasir Hassan Luck
- Department of Gastroenterology, Sindh Institute of Urology and Transplantation, Karachi 75500, Pakistan
| | - Ahmad Karim Malik
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Kamran Rashid
- Rashid Nursing Home and Cancer Clinic, Rashid Nursing Home and Cancer Clinic, Rawalpindi 46000, Pakistan
| | - Sohail Rashid
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Mohammad Salih
- Department of Gastroenterology and Hepatology, Shifa International Hospital, Islamabad 44000, Pakistan
| | - Abdullah Saeed
- Department of Radiology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Amjad Salamat
- Department of Gastroenterology and Hepatology, Quaid-e-Azam International Hospital, Rawalpindi 44000, Pakistan
| | - Ghias-un-Nabi Tayyab
- Department of Gastroenterology and Hepatology, Post Graduate Medical Institute, Lahore 54000, Pakistan
| | - Aasim Yusuf
- Department of Internal Medicine, Division of Gastroenterology, Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore 54000, Pakistan
| | - Haseeb Haider Zia
- Division of Hepatopancreatic Biliary Surgery & Liver Transplantation, Shifa International Hospital, Islamabad 44000, Pakistan
| | - Ammara Naveed
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
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Butensky SD, Billingsley KG, Khan SA. Reasonable expansion of surgical candidates for HCC treatment. Clin Liver Dis (Hoboken) 2024; 23:e0153. [PMID: 38720794 PMCID: PMC11078523 DOI: 10.1097/cld.0000000000000153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Accepted: 02/12/2024] [Indexed: 05/12/2024] Open
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Maspero M, Yilmaz S, Cazzaniga B, Raj R, Ali K, Mazzaferro V, Schlegel A. The role of ischaemia-reperfusion injury and liver regeneration in hepatic tumour recurrence. JHEP Rep 2023; 5:100846. [PMID: 37771368 PMCID: PMC10523008 DOI: 10.1016/j.jhepr.2023.100846] [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: 02/17/2023] [Revised: 06/20/2023] [Accepted: 07/01/2023] [Indexed: 09/30/2023] Open
Abstract
The risk of cancer recurrence after liver surgery mainly depends on tumour biology, but preclinical and clinical evidence suggests that the degree of perioperative liver injury plays a role in creating a favourable microenvironment for tumour cell engraftment or proliferation of dormant micro-metastases. Understanding the contribution of perioperative liver injury to tumour recurrence is imperative, as these pathways are potentially actionable. In this review, we examine the key mechanisms of perioperative liver injury, which comprise mechanical handling and surgical stress, ischaemia-reperfusion injury, and parenchymal loss leading to liver regeneration. We explore how these processes can trigger downstream cascades leading to the activation of the immune system and the pro-inflammatory response, cellular proliferation, angiogenesis, anti-apoptotic signals, and release of circulating tumour cells. Finally, we discuss the novel therapies under investigation to decrease ischaemia-reperfusion injury and increase regeneration after liver surgery, including pharmaceutical agents, inflow modulation, and machine perfusion.
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Affiliation(s)
- Marianna Maspero
- Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
- General Surgery and Liver Transplantation Unit, IRCCS Istituto Tumori, Milan, Italy
| | - Sumeyye Yilmaz
- Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Beatrice Cazzaniga
- Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Roma Raj
- Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Khaled Ali
- Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Vincenzo Mazzaferro
- General Surgery and Liver Transplantation Unit, IRCCS Istituto Tumori, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Italy
| | - Andrea Schlegel
- Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
- Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
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9
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Vulasala SSR, Sutphin PD, Kethu S, Onteddu NK, Kalva SP. Interventional radiological therapies in colorectal hepatic metastases. Front Oncol 2023; 13:963966. [PMID: 37324012 PMCID: PMC10266282 DOI: 10.3389/fonc.2023.963966] [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: 06/08/2022] [Accepted: 05/19/2023] [Indexed: 06/17/2023] Open
Abstract
Colorectal malignancy is the third most common cancer and one of the prevalent causes of death globally. Around 20-25% of patients present with metastases at the time of diagnosis, and 50-60% of patients develop metastases in due course of the disease. Liver, followed by lung and lymph nodes, are the most common sites of colorectal cancer metastases. In such patients, the 5-year survival rate is approximately 19.2%. Although surgical resection is the primary mode of managing colorectal cancer metastases, only 10-25% of patients are competent for curative therapy. Hepatic insufficiency may be the aftermath of extensive surgical hepatectomy. Hence formal assessment of future liver remnant volume (FLR) is imperative prior to surgery to prevent hepatic failure. The evolution of minimally invasive interventional radiological techniques has enhanced the treatment algorithm of patients with colorectal cancer metastases. Studies have demonstrated that these techniques may address the limitations of curative resection, such as insufficient FLR, bi-lobar disease, and patients at higher risk for surgery. This review focuses on curative and palliative role through procedures including portal vein embolization, radioembolization, and ablation. Alongside, we deliberate various studies on conventional chemoembolization and chemoembolization with irinotecan-loaded drug-eluting beads. The radioembolization with Yttrium-90 microspheres has evolved as salvage therapy in surgically unresectable and chemo-resistant metastases.
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Affiliation(s)
- Sai Swarupa R. Vulasala
- Department of Radiology, University of Florida College of Medicine, Jacksonville, FL, United States
| | - Patrick D. Sutphin
- Division of Interventional Radiology, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
| | - Samira Kethu
- Department of Microbiology and Immunology, College of Arts and Sciences, University of Miami, Coral Gables, FL, United States
| | - Nirmal K. Onteddu
- Department of Hospital Medicine, Flowers Hospital, Dothan, AL, United States
| | - Sanjeeva P. Kalva
- Division of Interventional Radiology, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
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10
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Imaoka Y, Sato K, Ohira M, Imaoka K, Yano T, Nakano R, Tanaka Y, Ohdan H. Acute portal hypertension using portal vein ligation abrogates TRAIL expression of liver-resident NK cells. Hepatol Commun 2022; 6:2551-2564. [PMID: 35726345 PMCID: PMC9426399 DOI: 10.1002/hep4.2017] [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] [Received: 12/20/2021] [Revised: 03/16/2022] [Accepted: 05/09/2022] [Indexed: 11/29/2022] Open
Abstract
The effects of acute portal hypertension (PHT), which is reported as poor prognostic factors in patients with hepatocellular carcinoma, are not well known on the liver immune system, including natural killer (NK) cells. The aim of this study, therefore, was to investigate how acute PHT influences the functions and characteristics of liver-resident NK (lr-NK) cells using an acute PHT mouse model. Acute PHT decreased the number of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL+ ) lr-NK cells by about 20% and attenuated cytotoxic activity against the Hepa1-6 cell line by about 40%. Among various cytokine, only interleukin-33 (IL-33), which inhibits NK activity, significantly increased after portal vein ligation (PVL). Because lr-NK cells highly expressed ST2/IL-33R, IL-33 co-culture significantly suppressed TRAIL expression on lr-NK cells by about 50%, and IL-33 administration markedly decreased TRAIL expression and cytotoxic activity of lr-NK cells. Furthermore, the TRAIL+ NK cells population was maintained by anti-IL33 antibody or following portosystemic shunt procedure even after PVL. Finally, we demonstrated that IL-33 decreased TRAIL expression in lr-NK cells via AKT-forkhead box O (FoxO) and mitogen-activated protein kinase (MAPK) signaling. Conclusion: This work demonstrates that PHT suppresses the TRAIL+ lr-NK cell population and antitumor activities in the liver. Additionally, Akt-FoxO and MAPK signaling pathways attenuate the TRAIL expression in lt-NK cells via IL-33 receptor in mice.
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Affiliation(s)
- Yuki Imaoka
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical and Health SciencesHiroshima University 1‐2‐3HiroshimaJapan
| | - Koki Sato
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical and Health SciencesHiroshima University 1‐2‐3HiroshimaJapan
| | - Masahiro Ohira
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical and Health SciencesHiroshima University 1‐2‐3HiroshimaJapan
- Medical Center for Translational and Clinical Research Hiroshima University HospitalHiroshimaJapan
| | - Kouki Imaoka
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical and Health SciencesHiroshima University 1‐2‐3HiroshimaJapan
| | - Takuya Yano
- Department of SurgeryHiroshima City Hiroshima Citizens HospitalHiroshimaJapan
| | - Ryosuke Nakano
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical and Health SciencesHiroshima University 1‐2‐3HiroshimaJapan
| | - Yuka Tanaka
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical and Health SciencesHiroshima University 1‐2‐3HiroshimaJapan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant SurgeryGraduate School of Biomedical and Health SciencesHiroshima University 1‐2‐3HiroshimaJapan
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11
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Abstract
Selective internal radiation therapy represents an endovascular treatment option for patients with primary liver malignancies, in different clinical stages. Potential applications of this treatment are in early-stage hepatocellular carcinoma, as a curative option, or in combination with systemic treatments in intermediate and advanced-stages. This review, based on existing literature and ongoing trials, will focus on the future of this treatment in patients with hepatocellular carcinoma, in combination with systemic treatments, or with the use of new devices and technological developments; it will also describe new potential future indications and structural and organizational perspectives.
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12
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Makary MS, Ramsell S, Miller E, Beal EW, Dowell JD. Hepatocellular carcinoma locoregional therapies: Outcomes and future horizons. World J Gastroenterol 2021; 27:7462-7479. [PMID: 34887643 PMCID: PMC8613749 DOI: 10.3748/wjg.v27.i43.7462] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 07/09/2021] [Accepted: 10/27/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and has an overall five-year survival rate of less than twenty percent. For patients with unresectable disease, evolving liver-directed locoregional therapies provide efficacious treatment across the spectrum of disease stages and via a variety of catheter-directed and percutaneous techniques. Goals of locoregional therapies in HCC may include curative intent in early-stage disease, bridging or downstaging to surgical resection or transplantation for early or intermediate-stage disease, and local disease control and palliation in advanced-stage disease. This review explores the outcomes of chemoembolization, bland embolization, radioembolization, and percutaneous ablative therapies. Attention is also given to prognostic factors related to each of the respective techniques, as well as future directions of locoregional therapies for HCC.
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Affiliation(s)
- Mina S Makary
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Stuart Ramsell
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Eric Miller
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Eliza W Beal
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Joshua D Dowell
- Department of Radiology, Northwest Radiology, St. Vincent Health, Indianapolis, IN 46260, United States
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13
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Miller FH, Lopes Vendrami C, Gabr A, Horowitz JM, Kelahan LC, Riaz A, Salem R, Lewandowski RJ. Evolution of Radioembolization in Treatment of Hepatocellular Carcinoma: A Pictorial Review. Radiographics 2021; 41:1802-1818. [PMID: 34559587 DOI: 10.1148/rg.2021210014] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Transarterial radioembolization (TARE) with yttrium 90 has increasingly been performed to treat hepatocellular carcinoma (HCC). TARE was historically used as a palliative lobar therapy for patients with advanced HCC beyond surgical options, ablation, or transarterial chemoembolization, but recent advancements have led to its application across the Barcelona Clinic Liver Cancer staging paradigm. Newer techniques, termed radiation lobectomy and radiation segmentectomy, are being performed before liver resection to facilitate hypertrophy of the future liver remnant, before liver transplant to bridge or downstage to transplant, or as a definite curative treatment. Imaging assessment of therapeutic response to TARE is challenging as the intent of TARE is to deliver local high-dose radiation to tumors through microembolic microspheres, preserving blood flow to promote radiation injury to the tumor. Because of the microembolic nature, early imaging assessment after TARE cannot rely solely on changes in size. Knowledge of the evolving methods of TARE along with the tools to assess posttreatment imaging and response is essential to optimize TARE as a therapeutic option for patients with HCC. ©RSNA, 2021.
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Affiliation(s)
- Frank H Miller
- From the Department of Radiology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, 676 N St. Clair St, Ste 800, Chicago, IL 60611
| | - Camila Lopes Vendrami
- From the Department of Radiology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, 676 N St. Clair St, Ste 800, Chicago, IL 60611
| | - Ahmed Gabr
- From the Department of Radiology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, 676 N St. Clair St, Ste 800, Chicago, IL 60611
| | - Jeanne M Horowitz
- From the Department of Radiology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, 676 N St. Clair St, Ste 800, Chicago, IL 60611
| | - Linda C Kelahan
- From the Department of Radiology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, 676 N St. Clair St, Ste 800, Chicago, IL 60611
| | - Ahsun Riaz
- From the Department of Radiology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, 676 N St. Clair St, Ste 800, Chicago, IL 60611
| | - Riad Salem
- From the Department of Radiology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, 676 N St. Clair St, Ste 800, Chicago, IL 60611
| | - Robert J Lewandowski
- From the Department of Radiology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, 676 N St. Clair St, Ste 800, Chicago, IL 60611
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14
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Park C, Gwon DI, Chu HH, Kim JW, Kim JH, Ko GY. Correlation of tumor response on CT with pathologically proven necrosis in hepatocellular carcinoma treated by conventional transcatheter arterial chemoembolization: threshold value of intratumoral Lipiodol accumulation predicting tumor necrosis. Abdom Radiol (NY) 2021; 46:3729-3737. [PMID: 33141259 DOI: 10.1007/s00261-020-02845-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 10/24/2020] [Accepted: 10/29/2020] [Indexed: 12/12/2022]
Abstract
PURPOSE To evaluate associations between pathology and CT assessments made according to the mRECIST in HCC treated by conventional TACE (cTACE), and to identify predictors of complete tumor necrosis. METHODS From March 2016 to July 2018, 83 patients with a total of 100 masses were retrospectively included. Patients underwent sequential cTACE and portal vein embolization, and later hepatic surgery. Evaluation of treatment response and measurement of baseline lipiodol accumulation as mean HU was performed on CT at the time point closest to the time of operation (mean, 54.5 days after cTACE). Significant predictors associated with complete necrosis were identified by multivariate analysis. The optimal cut-off HU value of lipiodol accumulation for prediction of complete necrosis was determined using a ROC analysis. RESULTS According to mRECIST, complete response (CR, n = 70) and partial response (n = 30) were classified. 34.3% (24/70) masses classified as CR according to mRECIST were found to have viable lesions on pathology. On multivariate analysis, mean HU of lipiodol accumulation was the only significant predictor of complete necrosis (p = .003, odds ratio 1.746, 95% CI 1.201-2.539). On ROC analysis, 460 HU as a cut-off value was significantly associated with complete necrosis (67.4% sensitivity, 75.0% specificity). CONCLUSIONS A threshold value for lipiodol accumulation > 460 HU was highly sensitive and specific for complete necrosis, even in complete response according to mRECIST. Therefore, if lipiodol accumulation is insufficient in post-TACE CT, recurrence should be monitored more sensitively.
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Affiliation(s)
- Chan Park
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, South Korea
| | - Dong Il Gwon
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, South Korea.
| | - Hee Ho Chu
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, South Korea
| | - Jong Woo Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, South Korea
| | - Jin Hyoung Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, South Korea
| | - Gi-Young Ko
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-Gu, Seoul, 05505, South Korea
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15
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The evolution of surgery for colorectal liver metastases: A persistent challenge to improve survival. Surgery 2021; 170:1732-1740. [PMID: 34304889 DOI: 10.1016/j.surg.2021.06.033] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 06/01/2021] [Accepted: 06/21/2021] [Indexed: 02/07/2023]
Abstract
Only a few decades ago, the opinion that colorectal liver metastases were a palliative diagnosis changed. In fact, previously, the prevailing view was strongly resistant against resecting colorectal liver metastases. Constant technical improvement of liver surgery and, much later, effective chemotherapy allowed for a successful wider application of surgery. The clinical use of portal vein embolization was the starting signal of regenerative liver surgery, where insufficient liver volume can be expanded to an extent where safe resection is possible. Today, a number of these techniques including portal vein ligation, associating liver partition and portal vein ligation for staged hepatectomy, and bi-embolization (portal and hepatic vein) can be successfully used to address an insufficient future liver remnant in staged resections. It turned out that the road to success is embedding surgery in a well-orchestrated oncological concept of controlling systemic disease. This concept was the prerequisite that meant liver transplantation could enter the treatment strategy for colorectal liver metastases, ending up with a 5-year overall survival of 80% in highly selected cases. In particular, techniques combining principles of 2-stage hepatectomy and liver transplantation, such as "resection and partial liver segment 2-3 transplantation with delayed total hepatectomy" (RAPID) are on the rise. These techniques enable the use of partial liver grafts with primarily insufficient liver volume. All this progress also prompted a number of innovative local therapies to address recurrences ultimately transferring colorectal liver metastases from instantly deadly into a chronic disease in some cases.
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16
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Riddiough GE, Jalal Q, Perini MV, Majeed AW. Liver regeneration and liver metastasis. Semin Cancer Biol 2021; 71:86-97. [PMID: 32532594 DOI: 10.1016/j.semcancer.2020.05.012] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 05/18/2020] [Accepted: 05/18/2020] [Indexed: 12/12/2022]
Abstract
Surgical resection for primary and secondary hepatic neoplasms provides the best chance of cure. Advanced surgical techniques such as portal vein embolisation, two-staged hepatectomy and associated liver partition and portal vein ligation for staged-hepatectomy (ALPPS) have facilitated hepatic resection in patients with previously unresectable, bi-lobar disease. These techniques are frequently employed to ensure favourable clinical outcomes and avoid potentially fatal post-operative complications such as small for size syndrome and post-hepatectomy liver failure. However, they rely on the innate ability of the liver to regenerate. As our knowledge of liver organogenesis, liver regeneration and hepatocarcinogenesis has expanded in recent decades it has come to light that liver regeneration may also drive tumour recurrence. Clinical studies in patients undergoing portal vein embolisation indicate that tumours may progress following the procedure in concordance with liver regeneration and hypertrophy, however overall survival in these patients has not been shown to be worse. In this article, we delve into the mechanisms underlying liver regeneration to better understand the complex ways in which this may affect tumour behaviour and ultimately inform clinical decisions.
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Affiliation(s)
- Georgina E Riddiough
- Department of Surgery at Austin Health, The University of Melbourne, Level 8, Lance Townsend Building, 145 Studley Road, Heidelberg, VIC 3084, Australia.
| | - Qaiser Jalal
- Sheffield Teaching Hospitals, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF, United Kingdom.
| | - Marcos V Perini
- Department of Surgery at Austin Health, The University of Melbourne, Level 8, Lance Townsend Building, 145 Studley Road, Heidelberg, VIC 3084, Australia.
| | - Ali W Majeed
- Sheffield Teaching Hospitals, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF, United Kingdom.
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17
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Beppu T, Yamamura K, Okabe H, Imai K, Hayashi H. Oncological benefits of portal vein embolization for patients with hepatocellular carcinoma. Ann Gastroenterol Surg 2021; 5:287-295. [PMID: 34095718 PMCID: PMC8164464 DOI: 10.1002/ags3.12414] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 10/29/2020] [Accepted: 11/18/2020] [Indexed: 12/28/2022] Open
Abstract
Portal vein embolization (PVE) for hepatocellular carcinoma (HCC) was first introduced in 1986 and has been continuously developed throughout the years. Basically, PVE has been applied to expand the indication of liver resection for HCC patients of insufficient future liver remnant. Importantly, PVE can result in tumor progression in both embolized and non-embolized livers; however, long-term survival after liver resection following PVE is at least not inferior compared with liver resection alone despite the smaller future liver remnant volume. Five-year disease-free survival and 5-year overall survival were 17% to 49% and 12% to 53% in non-PVE patients, and 21% to 78% and 44% to 72% in PVE patients, respectively. At present, it has proven that PVE has multiple oncological advantages for both surgical and nonsurgical treatments. PVE can also enhance the anticancer effects of transarterial chemoembolization and can avoid intraportal tumor cell dissemination. Additional interventional transarterial chemoembolization and hepatic vein embolization as well as surgical two-stage hepatectomy and associated liver partition and portal vein ligation for staged hepatectomy can enhance the oncological benefit of PVE monotherapy. Taken together, PVE is an important treatment which we recommend for listing in the guidelines for HCC treatment strategies.
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Affiliation(s)
- Toru Beppu
- Department of SurgeryYamaga City Medical CenterKumamotoJapan
- Department of Gastroenterological SurgeryGraduate School of Life SciencesKumamoto UniversityKumamotoJapan
| | - Kensuke Yamamura
- Department of SurgeryYamaga City Medical CenterKumamotoJapan
- Department of Gastroenterological SurgeryGraduate School of Life SciencesKumamoto UniversityKumamotoJapan
| | - Hirohisa Okabe
- Department of Gastroenterological SurgeryGraduate School of Life SciencesKumamoto UniversityKumamotoJapan
| | - Katsunori Imai
- Department of Gastroenterological SurgeryGraduate School of Life SciencesKumamoto UniversityKumamotoJapan
| | - Hiromitsu Hayashi
- Department of Gastroenterological SurgeryGraduate School of Life SciencesKumamoto UniversityKumamotoJapan
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18
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Ahmed A, Stauffer JA, LeGout JD, Burns J, Croome K, Paz-Fumagalli R, Frey G, Toskich B. The use of neoadjuvant lobar radioembolization prior to major hepatic resection for malignancy results in a low rate of post hepatectomy liver failure. J Gastrointest Oncol 2021; 12:751-761. [PMID: 34012663 DOI: 10.21037/jgo-20-507] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background Neoadjuvant yttrium-90 transarterial radioembolization (TARE) is increasingly being used as a strategy to facilitate resection of otherwise unresectable tumors due to its ability to generate both tumor response and remnant liver hypertrophy. Perioperative outcomes after the use of neoadjuvant lobar TARE remain underinvestigated. Methods A single center retrospective review of patients who underwent lobar TARE prior to major hepatectomy for primary or metastatic liver cancer between 2007 and 2018 was conducted. Baseline demographics, radioembolization parameters, pre- and post-radioembolization volumetrics, intra-operative surgical data, adverse events, and post-operative outcomes were analyzed. Results Twenty-six patients underwent major hepatectomy after neoadjuvant lobar TARE. The mean age was 58.3 years (17-88 years). 62% of patients (n=16) had primary liver malignancies while the remainder had metastatic disease. Liver resection included right hepatectomy or trisegmentectomy, left or extended left hepatectomy, and sectorectomy/segmentectomy in 77% (n=20), 8% (n=2), and 15% (n=4) of patients, respectively. The mean length of stay was 8.3 days (range, 3-33 days) and there were no grade IV morbidities or 90-day mortalities. The incidence of post hepatectomy liver failure (PHLF) was 3.8% (n=1). The median time to progression after resection was 4.5 months (range, 3.3-10 months). Twenty-three percent (n=6) of patients had no recurrence. The median survival was 28.9 months (range, 16.9-46.8 months) from major hepatectomy and 37.6 months (range, 25.2-53.1 months) from TARE. Conclusions Major hepatectomy after neoadjuvant lobar radioembolization is safe with a low incidence of PHLF.
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Affiliation(s)
- Altan Ahmed
- Department of Radiology, Mayo Clinic, Jacksonville, FL, USA.,Department of Radiology, Moffitt Cancer Center, Tampa, FL, USA
| | | | | | - Justin Burns
- Department of Transplantation, Mayo Clinic, Jacksonville, FL, USA
| | | | | | - Gregory Frey
- Department of Radiology, Mayo Clinic, Jacksonville, FL, USA
| | - Beau Toskich
- Department of Radiology, Mayo Clinic, Jacksonville, FL, USA
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19
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Induction of liver hypertrophy for extended liver surgery and partial liver transplantation: State of the art of parenchyma augmentation-assisted liver surgery. Langenbecks Arch Surg 2021; 406:2201-2215. [PMID: 33740114 PMCID: PMC8578101 DOI: 10.1007/s00423-021-02148-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 03/03/2021] [Indexed: 12/17/2022]
Abstract
Background Liver surgery and transplantation currently represent the only curative treatment options for primary and secondary hepatic malignancies. Despite the ability of the liver to regenerate after tissue loss, 25–30% future liver remnant is considered the minimum requirement to prevent serious risk for post-hepatectomy liver failure. Purpose The aim of this review is to depict the various interventions for liver parenchyma augmentation–assisting surgery enabling extended liver resections. The article summarizes one- and two-stage procedures with a focus on hypertrophy- and corresponding resection rates. Conclusions To induce liver parenchymal augmentation prior to hepatectomy, most techniques rely on portal vein occlusion, but more recently inclusion of parenchymal splitting, hepatic vein occlusion, and partial liver transplantation has extended the technical armamentarium. Safely accomplishing major and ultimately total hepatectomy by these techniques requires integration into a meaningful oncological concept. The advent of highly effective chemotherapeutic regimen in the neo-adjuvant, interstage, and adjuvant setting has underlined an aggressive surgical approach in the given setting to convert formerly “palliative” disease into a curative and sometimes in a “chronic” disease.
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20
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Shehta A, Lee JM, Suh KS, Kim HC, Hong SK, Cho JH, Yi NJ, Lee KW. Bridging and downstaging role of trans-arterial radio-embolization for expected small remnant volume before liver resection for hepatocellular carcinoma. Ann Hepatobiliary Pancreat Surg 2020; 24:421-430. [PMID: 33234744 PMCID: PMC7691198 DOI: 10.14701/ahbps.2020.24.4.421] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 07/13/2020] [Accepted: 07/13/2020] [Indexed: 02/06/2023] Open
Abstract
Backgrounds/Aims To evaluate our initial experience of bridging role of trans-arterial radio-embolization (TARE) before major hepatectomy for hepatocellular carcinoma (HCC) in risky patients with small expected remnant liver volume (ERLV). Methods We reviewed the data of patients with HCC who underwent major hepatectomy after TARE during the period between March and December 2017. Patients included had uni-lobar large HCC (>5 cm) requiring major hepatectomy with small ERLV. Results Five patients were included in our study. All patients were Child Pugh class A. A single session of TARE was applied in all patients. None developed any adverse events related to irradiation. The mean tumor size at baseline was 8.4 cm and 6.1 cm after TARE (p=0.077). The mean % of tumor shrinkage was 24.5%. ERLV improved from 354.6 ml at baseline to 500.8 ml after TARE (p=0.012). ERLV percentage improved from 27.2% at baseline to 38.1% after TARE (p=0.004). The mean % of ERLV was 39.5%. The mean interval time between TARE and resection was 99.6 days. Four patients (80%) underwent right hemi-hepatectomy and one patient (20%) underwent extended right hemi-hepatectomy. The mean operation time was 151 minutes, and mean blood loss was 56 ml. The mean hospital stay was 13.8 days, and one patient (20%) developed postoperative morbidity. After a mean follow-up of 15 months, all patients were alive with no recurrence. Conclusions Yttrium-90 TARE can play a bridging role before major hepatectomy for borderline resectable HCC in risky patients with small ERLV.
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Affiliation(s)
- Ahmed Shehta
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.,Liver Transplantation Unit, Gastrointestinal Surgery Center, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Jeong-Moo Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hyo-Cheol Kim
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Suk Kyun Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jae-Hyung Cho
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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Burlaka AA, Paliichuk AV, Iatsyna OI, Kolesnik ОО. Colorectal cancer liver metastases within the central and peripheral segments: Parenchymal sparing surgery adaptation. Ann Med Surg (Lond) 2020; 58:8-13. [PMID: 32874570 PMCID: PMC7452121 DOI: 10.1016/j.amsu.2020.07.052] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 07/27/2020] [Accepted: 07/30/2020] [Indexed: 02/06/2023] Open
Abstract
Background The debate over the surgical strategy optimization in colorectal cancer patients with liver metastases (mCRC) has been ongoing in the last 20 years. However, parenchyma sparing surgery (PPS) in cases of hard to reach liver cites (HTRLC) remain to be controversial. Methods A prospective analysis of 185 mCRC patients performed who were devided in two groups depending by predominant liver cite localization. Peripherally localized metastases (PLM) (n = 107) (S2, S3, S6, S7, Spiegel lobe and subcapsular area 1-2 cm below the liver surface). Group 2 included those with metastases localized in HTRLC (n = 78) - metastatic lesions of the "right venous core", portal and caval hilum, paracaval part of S1, "deep" parenchyma cites of S5, S8 and S4. Results In 26 (33,3%) and 32 (29,9%) patients of HTRLC and PLM, respectively, performed one liver re-resection (0,62). In HTRLC group 2 and more re-resection were performed in 7 (8,9%) cases while in PLM in 11 (10,3%), p = 0,76. Postoperative major morbidity was 24,4%, 21,8% (p = 0,15) and mortality 8,9%, 4,6% for HTRLC and PLM groups, respectively. R1v principles were implemented in 24 (30,7%) cases with centrally located metastases and in only 6 cases (5.6%) with peripheral localized metastases (p = 0,001). Cumulative 3-year disease-free survival (DSF) for PLM and HTRLC groups was 63% and 41% (p = 0,008). DFS for R1v (n = 24) and R0 (54) cochorts in HTRLC group was 33% and 43%, respeсtively (p = 0,44). Conclusions Principles of the PPS tactic provides an adequate removal of metastatic lesions in hard to reach liver cites allowing to maintain organ functions and increases the feasibility of the repeated liver resections in case of the initial disease progression.
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Affiliation(s)
- A A Burlaka
- Colorectal Cancer Department of National Cancer Institute, Ukraine
| | | | - O I Iatsyna
- Medical Director of National Cancer Institute, Ukraine
| | - О О Kolesnik
- Main Researcher of Colorectal Cancer Department of National Cancer Institute, Ukraine
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Expression of MMP-2 in residual VX2 liver tumor after transcatheter arterial embolization combined with portal venous embolization in an animal model. J Interv Med 2020; 3:167-173. [PMID: 34805929 PMCID: PMC8562231 DOI: 10.1016/j.jimed.2020.08.006] [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: 04/08/2020] [Revised: 07/20/2020] [Accepted: 08/03/2020] [Indexed: 11/21/2022] Open
Abstract
Objective This study aimed to analyze the effects of transcatheter arterial embolization (TAE) combined with portal venous embolization (PVE) on the expression of MMP-2 in residual VX2 liver tumor tissues, liver function and non-embolic lobe regeneration. Methods A total of 72 rabbits were randomly divided into Sham, TAE, PVE and TAE + PVE groups (n = 18/group). The tissue samples from each group were taken at 6 h, 3 days and 7 days after interventional operation, respectively. MMP-2 expression was detected by immunohistochemistry, Real-time PCR, and Western-blotting. The main indicators (such as AST, ATL, and TBIL) of liver function and the volume of non-embolized hepatic lobes were measured in each group after operation. One-way ANOVA and Kruskal-wallis method were used for statistical analysis. Results The expression of MMP-2 mRNA and protein remained the highest in the Sham group, and the expression of MMP-2 mRNA and protein in TAE, PVE and TAE + PVE groups were successively increased, and the expression of MMP-2 in TAE + PVE group was always significantly higher than TAE group. The AST and ALT levels in each group on day 7 after operation showed a significant declination, and all groups have recovered to the preoperative baseline level and TBIL has a slight fluctuation in each group after operation with no statistical difference. On day 7 after operation, the increasing volume of non-embolized liver lobes in TAE + PVE group showed a more significant effect than those in PVE group, but there was no statistical significance (37.62 ± 1.54 ml VS 36.18 ± 1.15 ml, P = 0.881), and its volume was significantly higher than those in the sham group (27.03 ± 1.11 ml). Conclusion TAE + PVE is considered to be an efficient and safe approach for treating rabbit VX2 liver transplantation tumor, but the expression of MMP-2 increased fastest after TAE + PVE, which might promote tumor cell invasion and metastasis.
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Chan KS, Low JK, Shelat VG. Associated liver partition and portal vein ligation for staged hepatectomy: a review. Transl Gastroenterol Hepatol 2020; 5:37. [PMID: 32632388 PMCID: PMC7063517 DOI: 10.21037/tgh.2019.12.01] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Accepted: 11/30/2019] [Indexed: 02/05/2023] Open
Abstract
Outcomes of liver resection have improved with advances in surgical techniques, improvements in critical care and expansion of resectability criteria. However, morbidity and mortality following liver resection continue to plague surgeons. Post-hepatectomy liver failure (PHLF) due to inadequate future liver remnant (FLR) is an important cause of morbidity and mortality following liver resection. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel two-staged procedure described in 2012, which aims to induce rapid hypertrophy of the FLR unlike conventional two-stage hepatectomy, which require a longer time for FLR hypertrophy. Careful patient selection and modifications in surgical technique has improved morbidity and mortality rates in ALPPS. Colorectal liver metastases (CRLM) confers the best outcomes post-ALPPS. Patients <60 years old and low-grade fibrosis with underlying hepatocellular carcinoma (HCC) are also eligible for ALPPS. Evidence for other types of cancers is less promising. Current studies, though limited, demonstrate that ALPPS has comparable oncological outcomes with conventional two-stage hepatectomy. Modifications such as partial-ALPPS and mini-ALPPS have shown improved morbidity and mortality compared to classic ALPPS. ALPPS may be superior to conventional two-stage hepatectomy in carefully selected groups of patients and has a promising outlook in liver surgery.
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Affiliation(s)
- Kai Siang Chan
- Department of Medicine, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Jee Keem Low
- Department of General Surgery, Tan Tock Seng Hospital, Singapore
| | - Vishal G. Shelat
- Department of General Surgery, Tan Tock Seng Hospital, Singapore
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Primary Tumor Location Is a Prognostic Factor for Intrahepatic Progression-Free Survival in Patients with Colorectal Liver Metastases Undergoing Portal Vein Embolization as Preparation for Major Hepatic Surgery. Cancers (Basel) 2020; 12:cancers12061638. [PMID: 32575781 PMCID: PMC7352622 DOI: 10.3390/cancers12061638] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 05/29/2020] [Accepted: 06/17/2020] [Indexed: 11/17/2022] Open
Abstract
The aim of this study was to identify prognostic factors affecting intrahepatic progression-free survival (ihPFS) and overall survival (OS) in patients with colorectal cancer liver metastases (CRCLM) undergoing portal vein embolization (PVE) and subsequent (extended) right hemihepatectomy. A total of 59 patients (mean age: 60.8 ± 9.3 years) with CRCLM who underwent PVE in preparation for right hemihepatectomy were included. IhPFS and OS after PVE were calculated using the Kaplan–Meier method. Cox regression analyses were conducted to investigate the association between the following factors and survival: patient age, laterality of the colorectal cancer (right- versus left-sided), tumor location (colon versus rectal cancer), time of occurrence of hepatic metastases (synchronous versus metachronous), baseline number and size of hepatic metastases, presence or absence of metastases in the future liver remnant (FLR) before PVE, preoperative carcinoembryogenic antigen (CEA) levels, time between PVE and surgery, history of neoadjuvant or adjuvant chemotherapy, and the presence or absence of extrahepatic disease before PVE. Median follow up was 18 months. The median ihPFS was 8.2 months (95% confidence interval: 6.2–10.2 months), and median OS was 34.1 months (95% confidence interval: 27.3–40.9 months). Laterality of the primary colorectal cancer was the only statistically significant predictor of ihPFS after PVE (hazard ratio (HR) = 2.242; 95% confidence interval: 1.125, 4.465; p = 0.022), with patients with right-sided colorectal cancer having significantly shorter median ihPFS than patients with left-sided cancer (4.0 ± 1.9 months versus 10.2 ± 1.5 months; log rank test: p = 0.018). Other factors, in particular also the presence or absence of additional metastases in the FLR, were not associated with intrahepatic progression-free survival. The presence of extrahepatic disease was associated with worse OS (HR = 3.050, 95% confidence interval: 1.247, 7.459; p = 0.015).
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Rassam F, Olthof PB, van Lienden KP, Bennink RJ, Erdmann JI, Swijnenburg RJ, Busch OR, Besselink MG, van Gulik TM. Comparison of functional and volumetric increase of the future remnant liver and postoperative outcomes after portal vein embolization and complete or partial associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:436. [PMID: 32395480 PMCID: PMC7210209 DOI: 10.21037/atm.2020.03.191] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Background Portal vein embolization (PVE) is performed to induce hypertrophy of an insufficient future remnant liver (FRL) before major liver resection. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) aims to offer a more rapid and increased hypertrophy response. The first stage can be performed with complete or partial (laparoscopic) transection of the liver parenchyma. This study aimed to investigate the increase in FRL volume and function, as well as postoperative outcomes after PVE or complete- or partial-ALPPS1. Methods Patients with insufficient FRL undergoing either PVE or ALPPS underwent CT-volumetry and functional assessment using 99mTc-mebrofenin hepatobiliary scintigraphy (HBS). Severe complications and 90-day mortality were evaluated after liver resection. Results Seventy-two patients were included; 51 underwent PVE, 12 complete-ALPPS1 and 9 partial-ALPPS1 of which 7 laparoscopic. The median increase in FRL function was 1.5-, 1.7- and 1.3-fold higher, respectively, than the increase in volume; (P<0.01, P<0.01 and P=0.44). The target hypertrophy response did not differ between the groups, but was reached earlier in both ALPPS1 groups (8 and 10 days) compared to the PVE group (23 days). Of the resected patients, 18%, 30% and 17% had severe postoperative complications and the 90-day mortality was 2%, 25% and 0%, respectively. Conclusions Increase of FRL function exceeded increase of volume after both PVE and ALPPS1. The target hypertrophy response was reached earlier in ALPPS. Complete and partial-ALPPS1 showed comparable functional and volumetric hypertrophy responses. A (laparoscopic) partial-ALPPS1 is preferred considering lower morbidity and mortality rates after resection.
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Affiliation(s)
- Fadi Rassam
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Pim B Olthof
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Krijn P van Lienden
- Departments of Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Roel J Bennink
- Departments of Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Joris I Erdmann
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Rutger-Jan Swijnenburg
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Olivier R Busch
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Marc G Besselink
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Thomas M van Gulik
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, The Netherlands
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Kim D, Cornman-Homonoff J, Madoff DC. Preparing for liver surgery with "Alphabet Soup": PVE, ALPPS, TAE-PVE, LVD and RL. Hepatobiliary Surg Nutr 2020; 9:136-151. [PMID: 32355673 PMCID: PMC7188547 DOI: 10.21037/hbsn.2019.09.10] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 09/10/2019] [Indexed: 02/06/2023]
Abstract
Future liver remnant (FLR) size and function is a critical limiting factor for treatment eligibility and postoperative prognosis when considering surgical hepatectomy. Pre-operative portal vein embolization (PVE) has been proven effective in modulating FLR and now widely accepted as a standard of care. However, PVE is not always effective due to potentially inadequate augmentation of the FLR as well as tumor progression while awaiting liver growth. These concerns have prompted exploration of alternative techniques: associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), transarterial embolization-portal vein embolization (TAE-PVE), liver venous deprivation (LVD), and radiation lobectomy (RL). The article aims to review the principles and applications of PVE and these newer hepatic regenerative techniques.
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Affiliation(s)
- DaeHee Kim
- Department of Radiology, Division of Interventional Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Joshua Cornman-Homonoff
- Department of Radiology and Biomedical Imaging, Section of Interventional Radiology, Yale School of Medicine, New Haven, CT, USA
| | - David C. Madoff
- Department of Radiology and Biomedical Imaging, Section of Interventional Radiology, Yale School of Medicine, New Haven, CT, USA
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27
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Au KP, Chan ACY. Current status of associating liver partition with portal vein ligation for staged hepatectomy: Comparison with two-stage hepatectomy and strategies for better outcomes. World J Gastroenterol 2019; 25:6373-6385. [PMID: 31798275 PMCID: PMC6881507 DOI: 10.3748/wjg.v25.i43.6373] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Revised: 07/31/2019] [Accepted: 08/07/2019] [Indexed: 02/06/2023] Open
Abstract
Since its introduction in 2012, associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) has significantly expanded the pool of candidates for liver resection. It offers patients with insufficient liver function a chance of a cure. ALPPS is most controversial when its high morbidity and mortality is concerned. Operative mortality is usually a result of post-hepatectomy liver failure and can be minimized with careful patient selection. Elderly patients have limited reserve for tolerating the demanding operation. Patients with colorectal liver metastasis have normal liver and are ideal candidates. ALPPS for cholangiocarcinoma is technically challenging and associated with fair outcomes. Patients with hepatocellular carcinoma have chronic liver disease and limited parenchymal hypertrophy. However, in selected patients with limited hepatic fibrosis satisfactory outcomes have been produced. During the inter-stage period, serum bilirubin and creatinine level and presence of surgical complication predict mortality after stage II. Kinetic growth rate and hepatobiliary scintigraphy also guide the decision whether to postpone or omit stage II surgery. The outcomes of ALPPS have been improved by a combination of technical modifications. In patients with challenging anatomy, partial ALPPS potentially reduces morbidity, but remnant hypertrophy may compare unfavorably to a complete split. When compared to conventional two-stage hepatectomy with portal vein embolization or portal vein ligation, ALPPS offers a higher resection rate for colorectal liver metastasis without increased morbidity or mortality. While ALPPS has obvious theoretical oncological advantages over two-stage hepatectomy, the long-term outcomes are yet to be determined.
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Affiliation(s)
- Kin Pan Au
- Department of Surgery, Queen Mary Hospital, Hong Kong, China
| | - Albert Chi Yan Chan
- Department of Surgery and State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
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28
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Gabr A, Riaz A, Mouli S, Desai K, Thornburg B, Salem R, Lewandowski RJ. Modified Radiation Lobectomy: An Evolving Paradigm to Convert Patients to Liver Resection Candidacy. Semin Intervent Radiol 2019; 36:343-348. [PMID: 31680726 DOI: 10.1055/s-0039-1696648] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Affiliation(s)
- Ahmed Gabr
- Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois
| | - Ahsun Riaz
- Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois
| | - Samdeep Mouli
- Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois
| | - Kush Desai
- Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois
| | - Bartley Thornburg
- Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois
| | - Riad Salem
- Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois.,Division of Transplantation, Department of Surgery, Comprehensive Transplant Center, Northwestern University, Chicago, Illinois.,Division of Hematology and Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois
| | - Robert J Lewandowski
- Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois.,Division of Transplantation, Department of Surgery, Comprehensive Transplant Center, Northwestern University, Chicago, Illinois.,Division of Hematology and Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois
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Is disease progression a contraindication for the strategy of portal vein embolization followed by hepatectomy for hepatocellular carcinoma? Surgery 2018; 165:696-702. [PMID: 30467039 DOI: 10.1016/j.surg.2018.10.023] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 10/06/2018] [Accepted: 10/19/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Portal vein embolization has been used worldwide to induce hypertrophy of the future liver remnant and to reduce the risk of hepatic insufficiency and death after major hepatectomy. However, whether disease progression after portal vein embolization can affect long-term oncologic outcomes in patients with hepatocellular carcinoma is uncertain. METHODS From a total of 107 patients who underwent portal vein embolization and subsequent hepatectomy between 2000 and 2016, 57 patients with hepatocellular carcinoma were enrolled. We evaluated their long-term oncologic outcomes and investigated whether the disease progression between portal vein embolization and subsequent hepatectomy affected survival. RESULTS The 5-year overall survival and disease-free survival after hepatectomy were 74.5% and 31.7%, respectively. Multivariate analyses revealed that tumor number before hepatectomy ≥3 (hazard ratio 3.59, P = .019), des-γ-carboxy prothrombin >200 mAU/mL (hazard ratio 3.36, P = .045), and red blood cell transfusion (hazard ratio 11.03, P = .0008) were independent prognostic factors for overall survival. Male sex (hazard ratio 3.74, P = .029), bilobar tumor distribution (hazard ratio 3.65, P = .004), and red blood cell transfusion (hazard ratio 6.22, P = .0026) were independent prognostic factors for disease-free survival. Disease progressions after portal vein embolization, including increases in tumor size, tumor number, α-fetoprotein, lens culinaris agglutinin-reactive fraction of α-fetoprotein, and des-γ-carboxy prothrombin, were observed in 22.8%, 14.0%, 29.8%, 19.3%, and 47.4% of patients, respectively. Only an increase of tumor number significantly decreased the disease-free survival rate after hepatectomy in a univariate analysis, and none of the variables affected overall survival. CONCLUSION Disease progression after portal vein embolization did not affect long-term survival in patients with hepatocellular carcinoma if the planned subsequent hepatectomy could be completed.
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De Raffele E, Mirarchi M, Cuicchi D, Lecce F, Ricci C, Casadei R, Cola B, Minni F. Simultaneous curative resection of double colorectal carcinoma with synchronous bilobar liver metastases. World J Gastrointest Oncol 2018; 10:293-316. [PMID: 30364774 PMCID: PMC6198303 DOI: 10.4251/wjgo.v10.i10.293] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2018] [Revised: 07/28/2018] [Accepted: 08/21/2018] [Indexed: 02/05/2023] Open
Abstract
Synchronous colorectal carcinoma (SCRC) indicates more than one primary colorectal carcinoma (CRC) discovered at the time of initial presentation, accounts for 3.1%-3.9% of CRC, and may occur either in the same or in different colorectal segments. The accurate preoperative diagnosis of SCRC is difficult and diagnostic failures may lead to inappropriate treatment and poorer prognosis. SCRC requires colorectal resections tailored to individual patients, based on the number, location, and stage of the tumours, from conventional or extended hemicolectomies to total colectomy or proctocolectomy, when established predisposing conditions exist. The overall perioperative risks of surgery for SCRC seem to be higher than for solitary CRC. Simultaneous colorectal and liver resection represents an appealing surgical strategy in selected patients with CRC and synchronous liver metastases (CRLM), even though the cumulative risks of the two procedures need to be adequately evaluated. Simultaneous resections have the noticeable advantage of avoiding a second laparotomy, give the opportunity of an earlier initiation of adjuvant therapy, and may significantly reduce the hospital costs. Because an increasing number of recent studies have shown good results, with morbidity, perioperative hospitalization, and mortality rates comparable to staged resections, simultaneous procedures can be selectively proposed even in case of complex colorectal resections, including those for SCRC and rectal cancer. However, in patients with multiple bilobar CRLM, major hepatectomies performed simultaneously with colorectal resection have been associated with significant perioperative risks. Conservative or parenchymal-sparing hepatectomies reduce the extent of hepatectomy while preserving oncological radicality, and may represent the best option for selected patients with multiple CRLM involving both liver lobes. Parenchymal-sparing liver resection, instead of major or two-stage hepatectomy for bilobar disease, seemingly reduces the overall operative risk of candidates to simultaneous colorectal and liver resection, and may represent the most appropriate surgical strategy whenever possible, also for patients with advanced SCRC and multiple bilobar liver metastases.
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Affiliation(s)
- Emilio De Raffele
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Mariateresa Mirarchi
- U.O. di Chirurgia Generale, Dipartimento Strutturale Chirurgico, Ospedale “Antonio e Margherita, ” Tortona (AL) 15057, Italy
| | - Dajana Cuicchi
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Ferdinando Lecce
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Claudio Ricci
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Riccardo Casadei
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Bruno Cola
- Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Alma Mater Studiorum, Policlinico S.Orsola-Malpighi, University of Bologna, Bologna 40138, Italy
| | - Francesco Minni
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
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31
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Russolillo N, Langella S, Perotti S, Balbo Mussetto A, Lo Tesoriere R, Cirillo S, De Rosa G, Ferrero A. Alcohol injection into the portal vein prior to ligation increases liver regeneration rate. HPB (Oxford) 2018; 20:739-744. [PMID: 29571617 DOI: 10.1016/j.hpb.2018.02.637] [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: 06/28/2017] [Revised: 02/05/2018] [Accepted: 02/15/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Failure of portal vein ligation (PVL) to induce hypertrophy is not uncommon. The aim of the study was to evaluate the impact of intraportal alcohol injection prior to ligation on liver regeneration. METHOD Forty-two patients with colorectal liver metastases who underwent PVL between 01/2004 and 06/2014 were analyzed. Beginning in 09/2011, alcohol was injected prior to PVL. Patients treated with PVL alone (Alc- group) were compared with those treated with alcohol injection plus PVL (Alc+ group). Liver regeneration was assessed by volumetric increase (VI). RESULTS Alc+ (23 patients) and Alc- (19 patients) groups were similar in terms of age, sex and pre-PVL FLRV. Alc- group had a higher risk of recanalization (12 vs. 1, p < 0.001) and cavernous transformation (7 vs. 2, p = 0.055) of the occluded portal vein. Post-PVL FLRV (43.3 ± 14.3% vs. 34.6 ± 6.4%, p = 0.013) and VI (0.44 ± 0.24 vs. 0.28 ± 0.20, p = 0.029) were higher in Alc+ group. On multivariate analysis male sex (B = -0.149) and alcohol injection (B = 0.143) significantly predicted VI. CONCLUSIONS Alcohol injection prior to PVL may increase the regeneration of the FLRV by reducing the recanalization of the occluded portal vein.
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Affiliation(s)
- Nadia Russolillo
- Mauriziano Hospital, Department of General and Oncological Surgery, Turin, Italy.
| | - Serena Langella
- Mauriziano Hospital, Department of General and Oncological Surgery, Turin, Italy
| | - Serena Perotti
- Mauriziano Hospital, Department of General and Oncological Surgery, Turin, Italy
| | | | - Roberto Lo Tesoriere
- Mauriziano Hospital, Department of General and Oncological Surgery, Turin, Italy
| | | | | | - Alessandro Ferrero
- Mauriziano Hospital, Department of General and Oncological Surgery, Turin, Italy
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Marti J, Giacca M, Alshebeeb K, Bahl S, Hua C, Horn JC, BouAyache J, Patel R, Facciuto M, Schwartz M, Florman S, Kim E, Gunasekaran G. Analysis of Preoperative Portal Vein Embolization Outcomes in Patients with Hepatocellular Carcinoma: A Single-Center Experience. J Vasc Interv Radiol 2018; 29:920-926. [DOI: 10.1016/j.jvir.2018.01.780] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2017] [Revised: 01/22/2018] [Accepted: 01/24/2018] [Indexed: 12/11/2022] Open
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Kis B, El-Haddad G, Sheth RA, Parikh NS, Ganguli S, Shyn PB, Choi J, Brown KT. Liver-Directed Therapies for Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. Cancer Control 2018; 24:1073274817729244. [PMID: 28975829 PMCID: PMC5937250 DOI: 10.1177/1073274817729244] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC) are primary liver cancers where all or most of the tumor burden is usually confined to the liver. Therefore, locoregional liver-directed therapies can provide an opportunity to control intrahepatic disease with minimal systemic side effects. The English medical literature and clinical trials were reviewed to provide a synopsis on the available liver-directed percutaneous therapies for HCC and IHC. Locoregional liver-directed therapies provide survival benefit for patients with HCC and IHC compared to best medical treatment and have lower comorbid risks compared to surgical resection. These treatment options should be considered, especially in patients with unresectable disease.
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Affiliation(s)
- Bela Kis
- 1 Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Ghassan El-Haddad
- 1 Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Rahul A Sheth
- 2 Department of Interventional Radiology, MD Anderson Cancer Center, Houston, TX, USA
| | - Nainesh S Parikh
- 1 Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Suvranu Ganguli
- 3 Center for Image Guided Cancer Therapy, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Paul B Shyn
- 4 Department of Radiology, Abdominal Imaging and Intervention, Brigham and Women's, Boston, MA, USA
| | - Junsung Choi
- 1 Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Karen T Brown
- 5 Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Clinical validation of prospective liquid biopsy monitoring in patients with wild-type RAS metastatic colorectal cancer treated with FOLFIRI-cetuximab. Oncotarget 2018; 8:35289-35300. [PMID: 27852040 PMCID: PMC5471055 DOI: 10.18632/oncotarget.13311] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Accepted: 10/24/2016] [Indexed: 12/12/2022] Open
Abstract
Cancer genomics and translational medicine rely on the molecular profiling of patient's tumor obtained during surgery or biopsy. Alternatively, blood is a less invasive source of tumor DNA shed, amongst other ways, as cell-free DNA (cfDNA). Highly-sensitive assays capable to detect cancer genetic events from patient's blood plasma became popularly known as liquid biopsy (LqB). Importantly, retrospective studies including small number of selected patients with metastatic colorectal cancer (mCRC) patients treated with anti-EGFR therapy have shown LqB capable to detect the acquired clonal mutations in RAS genes leading to therapy resistance. However, the usefulness of LqB in the real-life clinical monitoring of these patients still lack additional validation on controlled studies. In this context, we designed a prospective LqB clinical trial to monitor newly diagnosed KRAS wild-type (wt) mCRC patients who received a standard FOLFIRI-cetuximab regimen. We used BEAMing technique for evaluate cfDNA mutations in KRAS, NRAS, BRAF, and PIK3CA in twenty-five patients during a 2-y period. A total of 2,178 cfDNA mutation analyses were performed and we observed that: a) continued wt circulating status was correlated with a prolonged response; b) smoldering increases in mutant cfDNA were correlated with acquired resistance; while c) mutation upsurge/explosion anticipated a remarkable clinical deterioration. The current study provides evidences, obtained for the first time in an unbiased and prospective manner, that reinforces the utility of LqB for monitoring mCRC patients.
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Kambakamba P, Linecker M, Schneider M, Reiner CS, Nguyen-Kim TDL, Limani P, Romic I, Figueras J, Petrowsky H, Clavien PA, Lesurtel M. Impact of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) on growth of colorectal liver metastases. Surgery 2018; 163:311-317. [PMID: 29248180 DOI: 10.1016/j.surg.2017.10.036] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Revised: 09/30/2017] [Accepted: 10/18/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy induces an unprecedented liver hypertrophy and enables resection of otherwise unresectable liver tumors. The effect of associating liver partition and portal vein ligation for staged hepatectomy on tumor proliferation, however, remains a concern. This study investigated the impact of associating liver partition and portal vein ligation for staged hepatectomy on growth of colorectal metastases in mice and in humans. METHODS The effect of associating liver partition and portal vein ligation for staged hepatectomy and 90% portal vein ligation on colorectal liver and lung metastases was investigated in mice. In vivo tumor progression was assessed by magnetic resonance imaging, histology, and survival experiments. The effects of associating liver partition and portal vein ligation for staged hepatectomy, portal vein ligation, and control sera on cultures of several colorectal cancer cell lines (MC38 and CT26) were tested in vitro. Additionally, the international associating liver partition and portal vein ligation for staged hepatectomy registry enabled us to identify patients with remaining tumor in the future liver remnant after associating liver partition and portal vein ligation for staged hepatectomy stage 1. RESULTS Two and 3 weeks after associating liver partition and portal vein ligation for staged hepatectomy stage 1, portal vein ligation, or sham surgery, liver magnetic resonance images showed similar numbers (P=.14/0.82), sizes (P=.45/0.98), and growth kinetics (P=.58/0.68) of intrahepatic tumor. Tumor growth was not different between the associating liver partition and portal vein ligation for staged hepatectomy and portal vein ligation groups after completion of stage 2. Median survival after tumor cell injection was similar after sham surgery (36 days; 95% confidence interval; 27-57 days), completion of associating liver partition and portal vein ligation for staged hepatectomy (42 days; 95% confidence interval; 35-49 days), and portal vein ligation (39 days; 95% confidence interval; 34-43 days, P=.237). Progression of pulmonary metastases and in vitro cell proliferation were comparable among groups. Observations in humans failed to identify any accelerated tumor growth in the future liver remnant within the regenerative phase after associating liver partition and portal vein ligation for staged hepatectomy stage 1. CONCLUSION The accelerated regeneration process associated with associating liver partition and portal vein ligation for staged hepatectomy does not appear to enhance growth of colorectal metastases.
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Affiliation(s)
- Patryk Kambakamba
- Department of Visceral and Transplant Surgery, University and University Hospital Zurich, Zürich, Switzerland
| | - Michael Linecker
- Department of Visceral and Transplant Surgery, University and University Hospital Zurich, Zürich, Switzerland
| | - Marcel Schneider
- Department of Visceral and Transplant Surgery, University and University Hospital Zurich, Zürich, Switzerland
| | - Cäcilia S Reiner
- Department of Radiology, University Hospital Zurich, Zürich, Switzerland
| | | | - Perparim Limani
- Department of Visceral and Transplant Surgery, University and University Hospital Zurich, Zürich, Switzerland
| | - Ivan Romic
- Department of Surgery, University Hospital Zagreb, Zagreb, Croatia
| | - Joan Figueras
- Department of Surgery, University Hospital Dr. Josep Trueta Girona, Girona, Spain
| | - Henrik Petrowsky
- Department of Visceral and Transplant Surgery, University and University Hospital Zurich, Zürich, Switzerland
| | - Pierre-Alain Clavien
- Department of Visceral and Transplant Surgery, University and University Hospital Zurich, Zürich, Switzerland
| | - Mickaël Lesurtel
- Department of Visceral and Transplant Surgery, University and University Hospital Zurich, Zürich, Switzerland; Department of General Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, University of Lyon I, Lyon, France.
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Kikuchi Y, Hiroshima Y, Matsuo K, Murakami T, Kawaguchi D, Kasahara K, Tanaka K. Impact of associating liver partition and portal vein occlusion for staged hepatectomy on tumor growth in a mouse model of liver metastasis. Eur J Surg Oncol 2018; 44:130-138. [DOI: 10.1016/j.ejso.2017.11.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Revised: 10/29/2017] [Accepted: 11/14/2017] [Indexed: 12/13/2022] Open
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Abstract
BACKGROUND The main limiting factor for major liver resections is the volume and function of the future remnant liver (FLR). Portal vein embolization (PVE) is now standard in most centers for preoperative hypertrophy of FLR. However, it has a failure rate of about 20-30 %. In these cases, the "Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy" (ALPPS) may represent a suitable and possibly the only alternative. METHODS We performed a retrospective analysis of nine patients who had ALPPS following an insufficient hypertrophy after PVE. Computed tomography volumetry were performed before and after PVE as well as the first step of ALPPS. Furthermore, complications, 30-day mortality and outcome were analyzed. RESULTS The FLR volume rose significantly by 77.7 ± 40.7 % (FLR/TLV: 34.9 ± 9.7 %) as early as 9 days after the first stage despite insufficient hypertrophy after preoperative portal vein embolization. Major complications (Grade > IIIb) occurred in 33 % of the patients, and 30-day mortality was 11.1 %. The OS at 1 and 2 years was 78 and 44 %. Four patients are presently still alive at a median of 33.4 (range 15-48) months (survival rate 44.4 %). CONCLUSION The ALPPS procedure could be a suitable alternative for patients following insufficient PVE or indeed the last chance of a potentially curative treatment in this situation. Nevertheless, the high morbidity and mortality rates and the lack of data on the long-term oncological outcome must also be taken into account.
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Remnant Liver Tumor Growth Activity During Treatment Associating Liver Partition and Portal Vein Occlusion for Staged Hepatectomy (ALPPS). J Gastrointest Surg 2017; 21:1851-1858. [PMID: 28785935 DOI: 10.1007/s11605-017-3523-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2017] [Accepted: 07/27/2017] [Indexed: 01/31/2023]
Abstract
BACKGROUND We compared tumor growth activity during treatment associating liver partition and portal vein occlusion for staged hepatectomy (ALPPS) with that in classical 2-stage hepatectomy. METHODS Short-term outcomes, serial changes in volume of the future liver remnant (FLR), and tumor growth activity during the treatment period were compared between 12 patients treated with ALPPS and 20 patients treated with 2-stage hepatectomy for colorectal liver metastases. This study was registered in UMIN Clinical Trials Registry (registration number, UMIN000018622). RESULTS The FLR hypertrophy ratio at 1 week after the first operation was greater in the ALPPS group (1.43 ± 0.24) than the 2-stage group (1.21 ± 0.28, P = 0.043). The mean kinetic growth rate (mKGR) of tumors in the ALPPS group (0.548 ± 7.29 mL/day) did not differ significantly from that in the 2-stage group (-3.53 ± 7.02 mL/day) in the first week after the initial procedure (P = 0.210). However, mKGR between 1 and 3 weeks after the first procedure (1.29 ± 2.34 mL/day) was significantly greater than that in first week after the procedure in the 2-stage group (P = 0.034). CONCLUSIONS ALPPS induces a rapid FLR volume increase while avoiding remnant tumor progression.
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Mouli SK, Goff LW. Local Arterial Therapies in the Management of Unresectable Hepatocellular Carcinoma. Curr Treat Options Oncol 2017; 18:67. [DOI: 10.1007/s11864-017-0509-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Hong YM, Cho M, Yoon KT, Chu CW, Yang KH, Park YM, Rhu JH. Risk factors of early recurrence after curative hepatectomy in hepatocellular carcinoma. Tumour Biol 2017; 39:1010428317720863. [PMID: 29034775 DOI: 10.1177/1010428317720863] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Early recurrence is common after curative hepatectomy for hepatocellular carcinoma and is associated with poor prognosis. This study aimed to identify risk factors of early recurrence after curative hepatectomy in hepatocellular carcinoma. Overall, 63 patients who underwent curative hepatectomy for hepatocellular carcinoma were enrolled. Patients were divided into the early recurrence group, who developed recurrence within 12 months after hepatectomy (n = 10), and the non-early recurrence group (n = 53). Clinicopathological factors of early recurrence were retrospectively analyzed. Among the 63 patients, 10 (15.9%) patients experienced early recurrence. Univariate analysis showed tumor necrosis (p = 0.012), level of PIVKA-II (prothrombin induced by vitamin K absence or antagonist-II; p = 0.002), and microvascular invasion (p = 0.029) to be associated with early recurrence. By multivariate analysis, there were significant differences in high PIVKA-II (p < 0.001) and tumor necrosis (p = 0.012) in patients with early recurrence. The optimal cutoff values of PIVKA-II and tumor necrosis were 46 mAU/mL and 3% of total tumor volume, respectively. Patients with a high preoperative PIVKA-II level and extent of tumor necrosis, which are independent risk factors for early recurrence, should be actively treated and monitored closely after hepatectomy.
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Affiliation(s)
- Young Mi Hong
- 1 Department of Internal Medicine, College of Medicine Pusan National University, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
| | - Mong Cho
- 1 Department of Internal Medicine, College of Medicine Pusan National University, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
| | - Ki Tae Yoon
- 1 Department of Internal Medicine, College of Medicine Pusan National University, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
| | - Chong Woo Chu
- 2 Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, College of Medicine Pusan National University, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
| | - Kwang Ho Yang
- 2 Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, College of Medicine Pusan National University, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
| | - Yong Mok Park
- 2 Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, College of Medicine Pusan National University, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
| | - Je Ho Rhu
- 2 Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, College of Medicine Pusan National University, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
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Transcriptome Analysis Uncovers a Growth-Promoting Activity of Orosomucoid-1 on Hepatocytes. EBioMedicine 2017; 24:257-266. [PMID: 28927749 PMCID: PMC5652006 DOI: 10.1016/j.ebiom.2017.09.008] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2017] [Revised: 09/06/2017] [Accepted: 09/08/2017] [Indexed: 02/08/2023] Open
Abstract
The acute phase protein orosomucoid-1 (Orm1) is mainly expressed by hepatocytes (HPCs) under stress conditions. However, its specific function is not fully understood. Here, we report a role of Orm1 as an executer of HPC proliferation. Increases in serum levels of Orm1 were observed in patients after surgical resection for liver cancer and in mice undergone partial hepatectomy (PH). Transcriptome study showed that Orm1 became the most abundant in HPCs isolated from regenerating mouse liver tissues after PH. Both in vitro and in vivo siRNA-induced knockdown of Orm1 suppressed proliferation of mouse regenerating HPCs and human hepatic cells. Microarray analysis in regenerating mouse livers revealed that the signaling pathways controlling chromatin replication, especially the minichromosome maintenance protein complex genes were uniformly down-regulated following Orm1 knockdown. These data suggest that Orm1 is induced in response to hepatic injury and executes liver regeneration by activating cell cycle progression in HPCs.
Serum Orm1 levels increased approximately 1.3- to 2.5-folds in both humans and mice after partial hepatectomy. Transcriptome analysis revealed that Orm1 mostly induced in hepatocytes as a regulator of mouse liver regeneration. Orm1 knockdown in mice impaired liver regeneration with poor hepatocyte growth and suppressed cell cycle signaling. Orosomucoid-1 (Orm1) is an acute phase protein mainly expressed by hepatocytes under stress conditions. Beginning from the finding that Orm1 was induced after partial hepatectomy in humans and mice, we showed enrichment of Orm1 in regenerating hepatocytes of hepatectomized mice by transcriptome analysis and following culture and animal experiments. Knockdown of Orm1 in mice resulted in decreases in hepatocyte growth accompanying suppressed signaling in controlling chromatin replication. Therefore, Orm1 would be a potential therapeutic and prognostic biomarker for liver diseases, especially after surgical resection of cancer-bearing liver, through its newly found ability to stimulate the cell cycle in regenerating hepatocytes.
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Xiao N, Yu K, Yu S, Wu J, Wang J, Shan S, Zheng S, Wang L, Wang J, Peng S. The paradigm of tumor shrinkage and rapid liver remnant hypertrophy for conversion of initially unresectable colorectal liver metastasis: a case report and literature review. World J Surg Oncol 2017; 15:148. [PMID: 28774330 PMCID: PMC5543586 DOI: 10.1186/s12957-017-1212-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2017] [Accepted: 07/22/2017] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND For colorectal liver metastasis (CRLM) patients, hepatic resection is currently the sole cure offering the chance of long-term survival. Tumor shrinkage and planned liver remnant hypertrophy are the two key strategies for conversion of initially unresectable CRLM. First conducted in 2012, associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) allows rapid liver growth. As a means to induce hypertrophy, portal vein embolization (PVE) has been widely applied before extending hepatectomy. Recently, Peng et al. present a new approach of terminal branches portal vein embolization (TBPVE), offering an efficient way to amplify FLR and making chances for surgery in 2 weeks. CASE PRESENTATION We reported a 61-year-old woman with synchronous hepatic metastasized carcinoma of the colon sigmoideum underwent TBPVE after 6 cycles of neoadjuvant therapy in order to perform a planned right trisectionectomy. Rapid liver remnant hypertrophy and remarkable tumor shrinkage were achieved, and laparoscopic sigmoidectomy and right trisectionectomy were successfully performed. The postsurgical course was uneventful and 7 months of recurrence-free survival have been witnessed. CONCLUSIONS The dual tactics of tumor shrinkage and planned rapid liver remnant hypertrophy will make concerted efforts to further increase the clinical candidacy for curative resection, which are valuable for further investigation.
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Affiliation(s)
- Nan Xiao
- Department of Surgical Oncology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Kailin Yu
- Department of Surgical Oncology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Shaojun Yu
- Department of Surgical Oncology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Jianjun Wu
- Department of Radiology and Intervention, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Jian Wang
- Department of Surgical Oncology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Siyang Shan
- Department of Surgical Oncology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Shuchun Zheng
- Department of Surgical Oncology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Liuhong Wang
- Department of Radiology and Intervention, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Jianwei Wang
- Department of Surgical Oncology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China.
| | - Shuyou Peng
- Department of General Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
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Ironside N, Bell R, Bartlett A, McCall J, Powell J, Pandanaboyana S. Systematic review of perioperative and survival outcomes of liver resections with and without preoperative portal vein embolization for colorectal metastases. HPB (Oxford) 2017; 19:559-566. [PMID: 28438427 DOI: 10.1016/j.hpb.2017.03.003] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2016] [Revised: 02/14/2017] [Accepted: 03/01/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND The aim of this systematic review was to evaluate perioperative and long term outcomes in patients who underwent PVE prior to liver resection for colorectal liver metastases. METHODS A systematic search of PubMed, MEDLINE, Embase and the Cochrane library was performed in accordance with PRISMA guidelines. Studies including patients who underwent liver resection with and without PVE (N-PVE) were included. RESULTS Thirteen studies including 1345 were included of which 539 patients had PVE and 806 had N-PVE. Eight studies reported that from a total of 450 patients who underwent PVE, 136 (30%) did not proceed to liver resection. In 114 (84%) patients this was due to disease progression. The postoperative morbidity was 42% (n = 151) after PVE and 10% (n = 35) developed postoperative liver failure after liver resection. Median overall survival, reported in all studies, was 38.9 months and 45.6 months respectively, following resection with PVE and N-PVE. The median disease free survival, reported in eight studies, was 15.7 (PVE) and 21.4 (N-PVE) months respectively. CONCLUSION Following PVE 70% of patients proceed to liver resection, with a 10% risk of postoperative liver failure. Tumour progression after PVE was the predominant reason for not proceeding to liver resection.
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Affiliation(s)
- Natasha Ironside
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Richard Bell
- Department of Hepatobiliary Surgery, St James Hospital, Leeds, UK
| | - Adam Bartlett
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; Department of Hepatobiliary Surgery, Auckland City Hospital, Auckland, New Zealand
| | - John McCall
- Department of Hepatobiliary Surgery, Auckland City Hospital, Auckland, New Zealand
| | - James Powell
- Department of Hepatobiliary Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Sanjay Pandanaboyana
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; Department of Hepatobiliary Surgery, Auckland City Hospital, Auckland, New Zealand.
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Cieslak KP, Huisman F, Bais T, Bennink RJ, van Lienden KP, Verheij J, Besselink MG, Busch ORC, van Gulik TM. Future remnant liver function as predictive factor for the hypertrophy response after portal vein embolization. Surgery 2017; 162:37-47. [PMID: 28365007 DOI: 10.1016/j.surg.2016.12.031] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2016] [Revised: 12/12/2016] [Accepted: 12/30/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Preoperative portal vein embolization is widely used to increase the future remnant liver. Identification of nonresponders to portal vein embolization is essential because these patients may benefit from associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), which induces a more powerful hypertrophy response. 99mTc-mebrofenin hepatobiliary scintigraphy is a quantitative method for assessment of future remnant liver function with a calculated cutoff value for the prediction of postoperative liver failure. The aim of this study was to analyze future remnant liver function before portal vein embolization to predict sufficient functional hypertrophy response after portal vein embolization. METHODS Sixty-three patients who underwent preoperative portal vein embolization and computed tomography imaging were included. Hepatobiliary scintigraphy was performed to determine pre-portal vein embolization and post-portal vein embolization future remnant liver function. Receiver operator characteristic analysis of pre-portal vein embolization future remnant liver function was performed to identify patients who would meet the post-portal vein embolization cutoff value for sufficient function (ie, 2.7%/min/m2). RESULTS Mean pre-portal vein embolization future remnant liver function was 1.80% ± 0.45%/min/m2 and increased to 2.89% ± 0.97%/min/m2 post-portal vein embolization. Receiver operator characteristic analysis in 33 patients who did not receive chemotherapy revealed that a pre-portal vein embolization future remnant liver function of ≥1.72%/min/m2 was able to identify patients who would meet the safe future remnant liver function cutoff value 3 weeks after portal vein embolization (area under the curve = 0.820). The predictive value was less pronounced in 30 patients treated with neoadjuvant chemotherapy (area under the curve = 0.618). A total of 45 of 63 patients underwent liver resection, of whom 5 of 45 developed postoperative liver failure; 4 of 5 patients had a post-portal vein embolization future remnant liver function below the cutoff value for safe resection. CONCLUSION When selecting patients for portal vein embolization, future remnant liver function assessed with hepatobiliary scintigraphy can be used as a predictor of insufficient functional hypertrophy after portal vein embolization, especially in nonchemotherapy patients. These patients are potential candidates for ALPPS.
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Affiliation(s)
- Kasia P Cieslak
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Floor Huisman
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Thomas Bais
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Roelof J Bennink
- Department of Radiology and Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands
| | - Krijn P van Lienden
- Department of Radiology and Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands
| | - Joanne Verheij
- Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
| | - Marc G Besselink
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Olivier R C Busch
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Thomas M van Gulik
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands.
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Song D, Hu M, Guo W. Liver Injury and Tumor-Inhibiting Effect of Sequential Transcatheter Arterial Chemoembolization and Portal Venous Embolization on Rabbit VX2 Liver Carcinoma. Med Sci Monit 2017; 23:1471-1476. [PMID: 28344313 PMCID: PMC5381340 DOI: 10.12659/msm.899941] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND The concepts of sequential transcatheter arterial chemoembolization (TACE) and portal venous embolization (PVE) were proposed to prevent the detrimental tumor growth-inducing effect of PVE and to facilitate growth of further future liver remnant (FLR). This study aimed to investigate the effect of sequential TACE and PVE on liver damage and the therapeutic effect in a rabbit VX2 liver tumor model. MATERIAL AND METHODS Rabbits bearing VX2 liver tumors were randomly divided into TACE+PVE, TACE, PVE, and Sham groups. Plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), and alkaline phosphatase (ALP) at 6 h, 24 h, 3 days, and 7 days were measured by ELISA assay. Tumor diameter on day 7 was measured and the tumor sections with cleaved caspase-3 was stained and observed. RESULTS Plasma ALT, AST, and ALP levels were significantly increased at the first hours after the interventions. The TACE group had higher increases than the TACE+PVE and PVE alone groups. ALT, AST, and ALP levels decreased on day 7 and presented a trend to return to the baseline level. The TACE+PVE group showed stronger tumor-inhibiting effect than the TACE and PVE alone groups and also induced the highest level of tumor cell apoptosis. CONCLUSIONS The liver damage caused by TACE+PVE is mild and recoverable. TACE+PVE showed stronger tumor-inhibiting effect than in the TACE and PVE group and also induced the highest level of tumor cell apoptosis.
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Affiliation(s)
- Dongda Song
- Department of Surgical Oncology, Chinese PLA General Hospital, Beijing, China (mainland)
| | - Minggen Hu
- Department of Surgical Oncology, Chinese PLA General Hospital, Beijing, China (mainland)
| | - Weichang Guo
- Department of Interventional Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (mainland)
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Al Bandar MH, Kim NK. Current status and future perspectives on treatment of liver metastasis in colorectal cancer (Review). Oncol Rep 2017; 37:2553-2564. [PMID: 28350137 DOI: 10.3892/or.2017.5531] [Citation(s) in RCA: 96] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2016] [Accepted: 03/13/2017] [Indexed: 12/29/2022] Open
Abstract
Liver metastasis is the most common site of colorectal cancer (CRC) metastasis. Approximately half of all colorectal cancer patients will develop liver metastases. Although radical surgery is the standard treatment modality, only 10-20% of patients are deemed eligible for resection. Despite advances in survival with chemotherapy, surgical resection is still considered the only curative option for patients with liver metastases. Much effort has been expended to address patients with metastatic liver disease. The majority of evidence stated a significant survival benefit with surgical resection to reach an overall 5-year survival rate of 35-55% after hepatic resection. However, still majority of patients will experience disease recurrence even after a successful resection. In this review, we describe current status and controversies related to treatment options for CRC liver metastases and its potential for enhancing oncologic outcomes and improving quality of life.
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Affiliation(s)
- Mahdi Hussain Al Bandar
- Department of Surgery, Yonsei University, College of Medicine, Seoul 120-752, Republic of Korea
| | - Nam Kyu Kim
- Department of Surgery, Yonsei University, College of Medicine, Seoul 120-752, Republic of Korea
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Joechle K, Moser C, Ruemmele P, Schmidt KM, Werner JM, Geissler EK, Schlitt HJ, Lang SA. ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) does not affect proliferation, apoptosis, or angiogenesis as compared to standard liver resection for colorectal liver metastases. World J Surg Oncol 2017; 15:57. [PMID: 28270160 PMCID: PMC5341393 DOI: 10.1186/s12957-017-1121-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Accepted: 02/14/2017] [Indexed: 01/27/2023] Open
Abstract
Background ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) is a novel two-stage strategy to induce rapid hypertrophy of the future liver remnant (FLR) when patients are in danger of postoperative liver failure due to insufficient FLR. However, the effects of ALPPS on colorectal liver metastases (CRLM) are not clear so far. The aim of our study was to determine whether ALPPS induces proliferation, apoptosis, or vascularization compared to standard (one-stage) liver resection. Methods Six patients who underwent ALPPS were matched with 12 patients undergoing standard liver resection regarding characteristics of the metastases (size, number), time of appearance (syn-/metachronous), preoperative chemotherapy, primary tumor (localization, TNM stage, grading), and patient variables (gender, age). The largest resected metastasis was used for the analyses. Tissue was stained for tumor cell proliferation (Ki67), apoptosis (TUNEL, caspase-3), vascularization (CD31), and pericytes (αSMA). Results Vascularization (CD31; p = 0.149), proliferation (Mib-1; p = 0.244), and αSMA expression (p = 0.205) did not significantly differ between the two groups, although a trend towards less proliferation and αSMA expression was observed in patients undergoing ALPPS. Concerning apoptosis, caspase-3 staining showed significantly fewer apoptotic cells upon ALPPS (p < 0.0001), but this was not confirmed by TUNEL staining (p = 0.7344). Conclusions ALPPS does not induce proliferation, apoptosis, or vascularization of CRLM when compared to standard liver resection.
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Affiliation(s)
- Katharina Joechle
- Department of Surgery, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053, Regensburg, Germany
| | - Christian Moser
- Department of Surgery, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053, Regensburg, Germany
| | - Petra Ruemmele
- Department of Pathology, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053, Regensburg, Germany
| | - Katharina M Schmidt
- Department of Surgery, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053, Regensburg, Germany
| | - Jens M Werner
- Department of Surgery, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053, Regensburg, Germany
| | - Edward K Geissler
- Department of Surgery, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053, Regensburg, Germany
| | - Hans J Schlitt
- Department of Surgery, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053, Regensburg, Germany
| | - Sven A Lang
- Department of Surgery, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053, Regensburg, Germany.
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Deipolyi AR, Zhang YS, Khademhosseini A, Naidu S, Borad M, Sahin B, Mathur AK, Oklu R. Portal Vein Embolization: Impact of Chemotherapy and Genetic Mutations. J Clin Med 2017; 6:jcm6030026. [PMID: 28257031 PMCID: PMC5372995 DOI: 10.3390/jcm6030026] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Revised: 02/12/2017] [Accepted: 02/21/2017] [Indexed: 12/12/2022] Open
Abstract
We characterized the effect of systemic therapy given after portal vein embolization (PVE) and before hepatectomy on hepatic tumor and functional liver remnant (FLR) volumes. All 76 patients who underwent right PVE from 2002–2016 were retrospectively studied. Etiologies included colorectal cancer (n = 44), hepatocellular carcinoma (n = 17), cholangiocarcinoma (n = 10), and other metastases (n = 5). Imaging before and after PVE was assessed. Chart review revealed systemic therapy administration, SNaPshot genetic profiling, and comorbidities. Nine patients received systemic therapy; 67 did not. Tumor volume increased 28% in patients who did not receive and decreased −24% in patients who did receive systemic therapy (p = 0.026), with no difference in FLR growth (28% vs. 34%; p = 0.645). Among 30 patients with genetic profiling, 15 were wild type and 15 had mutations. Mutations were an independent predictor of tumor growth (p = 0.049), but did not impact FLR growth (32% vs. 28%; p = 0.93). Neither cirrhosis, hepatic steatosis, nor diabetes impacted changes in tumor or FLR volume (p > 0.20). Systemic therapy administered after PVE before hepatic lobectomy had no effect on FLR growth; however, it was associated with decreasing tumor volumes. Continuing systemic therapy until hepatectomy may be warranted, particularly in patients with genetic mutations.
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Affiliation(s)
- Amy R Deipolyi
- Interventional Radiology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
| | - Yu Shrike Zhang
- Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
- Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA.
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
| | - Ali Khademhosseini
- Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
- Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA.
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
| | - Sailendra Naidu
- Division of Vascular and Interventional Radiology, Mayo Clinic, Phoenix, AZ 85054, USA.
| | - Mitesh Borad
- Division of Oncology, Mayo Clinic, Phoenix, AZ 85054, USA.
| | - Burcu Sahin
- Department of Radiology, Ankara Oncology Training and Research Hospital, Ankara, Turkey.
| | - Amit K Mathur
- Division of Transplant Surgery, Mayo Clinic, Phoenix, AZ 85054, USA.
| | - Rahmi Oklu
- Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
- Division of Vascular and Interventional Radiology, Mayo Clinic, Phoenix, AZ 85054, USA.
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Lee EC, Park SJ, Han SS, Park HM, Lee SD, Kim SH, Lee IJ, Kim HB. Mortality after portal vein embolization: Two case reports. Medicine (Baltimore) 2017; 96:e5446. [PMID: 28178122 PMCID: PMC5312979 DOI: 10.1097/md.0000000000005446] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Portal vein embolization (PVE) is increasingly performed worldwide to reduce the possibility of liver failure after extended hepatectomy, by inducing future liver remnant (FLR) hypertrophy and atrophy of the liver planned for resection. The procedure is known to be very safe and to have few procedure-related complications.In this study, we described 2 elderly patients with Bismuth-Corlette type IV Klatskin tumor who underwent right trisectional PVE involving the embolization of the right portal vein, the left medial sectional portal branch, and caudate portal vein. Within 1 week after PVE, patients went into sepsis combined with bile leak and died within 1 month.Sepsis can cause acute liver failure in patients with chronic liver disease. In this study, the common patient characteristics other than sepsis, that is, trisectional PVE; chronic alcoholism; aged >65 years; heart-related comorbidity; and elevated serum total bilirubin (TB) level (7.0 mg/dL) at the time of the PVE procedure in 1 patient, and concurrent biliary procedure, that is, percutaneous transhepatic biliary drainage in the other patient might have affected the outcomes of PVE.These cases highlight that PVE is not a safe procedure. Care should be taken to minimize the occurrence of infectious events because sepsis following PVE can cause acute liver failure. Additionally, prior to performing PVE, the extent of PVE, chronic alcohol consumption, age, comorbidity, long-lasting jaundice, concurrent biliary procedure, etc. should be considered for patient safety.
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Chapelle T, Op de Beeck B, Roeyen G, Bracke B, Hartman V, De Greef K, Huyghe I, Van der Zijden T, Morrison S, Francque S, Ysebaert D. Measuring future liver remnant function prior to hepatectomy may guide the indication for portal vein occlusion and avoid posthepatectomy liver failure: a prospective interventional study. HPB (Oxford) 2017; 19:108-117. [PMID: 27956027 DOI: 10.1016/j.hpb.2016.11.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Revised: 11/07/2016] [Accepted: 11/15/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Estimation of the future liver remnant function (eFLRF) can avoid post-hepatectomy liver failure (PHLF). In a previous study, a cutoff value of 2.3%/min/m2 for eFLRF was a better predictor of PHLF than future liver remnant volume (FLRV%). In this prospective interventional study, investigating a management strategy aimed at avoiding PHLF, this cutoff value was the sole criterion assessing eligibility for hepatectomy, with or without portal vein occlusion (PVO). METHODS In 100 consecutive patients, eFLRF was determined using the formula: eFLRF = FLRV% × total liver function (TLF). Group 1 (eFLRF >2.3%/min/m2) underwent hepatectomy without preoperative intervention. Group 2 (eFLRF <2.3%/min/m2) underwent PVO and re-evaluation of eFLRF at 4-6 weeks. Hepatectomy was performed if eFLRF had increased to >2.3%/min/m2, but was considered contraindicated if the value remained lower. RESULTS In group 1 (n = 93), 1 patient developed grade B PHLF. In group 2 (n = 7) no PHLF was recorded. Postoperative recovery of TLF in patients with preoperative eFLRF <2.3%/min/m2 occurred more rapidly when PVO had been performed. CONCLUSION A predefined cutoff for preoperatively calculated eFLRF can be used as a tool for selecting patients prior to hepatectomy, with or without PVO, thus avoiding PHLF and PHLF-related mortality.
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Affiliation(s)
- Thiery Chapelle
- Hepatobiliary, Endocrine and Transplantation Surgery, Antwerp University Hospital, Edegem, Belgium.
| | | | - Geert Roeyen
- Hepatobiliary, Endocrine and Transplantation Surgery, Antwerp University Hospital, Edegem, Belgium
| | - Bart Bracke
- Hepatobiliary, Endocrine and Transplantation Surgery, Antwerp University Hospital, Edegem, Belgium
| | - Vera Hartman
- Hepatobiliary, Endocrine and Transplantation Surgery, Antwerp University Hospital, Edegem, Belgium
| | - Kathleen De Greef
- Hepatobiliary, Endocrine and Transplantation Surgery, Antwerp University Hospital, Edegem, Belgium
| | - Ivan Huyghe
- Nuclear Medicine, Antwerp University Hospital, Edegem, Belgium
| | | | - Stuart Morrison
- Anaesthesiology, Antwerp University Hospital, Edegem, Belgium
| | - Sven Francque
- Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium
| | - Dirk Ysebaert
- Hepatobiliary, Endocrine and Transplantation Surgery, Antwerp University Hospital, Edegem, Belgium
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