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Andel D, van den Bent L, Ernest Hendrik Lam MG, Johannes Smits ML, Molenaar IQ, de Bruijne J, Laclé MM, Kranenburg O, Max Borel Rinkes IH, Hagendoorn J. 90Y-/ 166Ho- 'Radiation lobectomy' for liver tumors induces abnormal morphology and impaired drainage of peritumor lymphatics. JHEP Rep 2024; 6:100981. [PMID: 38298739 PMCID: PMC10827593 DOI: 10.1016/j.jhepr.2023.100981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 10/26/2023] [Accepted: 11/21/2023] [Indexed: 02/02/2024] Open
Abstract
Background & Aims High-dose unilobar radioembolization, or 'radiation lobectomy' (RL), is an induction therapy that achieves contralateral future liver remnant hypertrophy while simultaneously irradiating the tumor. As such, it may prevent further growth, but it is unknown whether RL affects intrahepatic lymphatics, a major route via which liver tumors disseminate. Methods This was a case-control study conducted at University Medical Center Utrecht. The study compared lymph vessels in livers that had undergone RL (cases) with those in livers that had not undergone RL (controls). Histological samples were acquired from patients diagnosed with hepatocellular carcinoma (HCC) or colorectal liver metastases (CRLM) between 2017 and 2022. Lymph vessel morphology was analyzed by two researchers using podoplanin, a protein that is expressed in lymphatic endothelium. In vivo liver lymph drainage of radioembolized livers was assessed using intraoperative liver lymphangiography (ILL): during liver surgery, patent blue dye was injected into the liver parenchyma, followed by inspection for staining of perihepatic lymph structures. ILL results were compared to a previously published cohort. Results Immunohistochemical analysis on post-RL tumor tissues from ten patients with CRLM and nine patients with HCC revealed aberrant morphology of irradiated liver lymphatics when compared to controls (n = 3 per group). Irradiated lymphatics were tortuous (p <0.05), thickened (p <0.05) and discontinuous (p <0.05). Moreover, post-RL lymphatics had larger lumens (1.5-1.7x, p <0.0001), indicating lymph stasis. ILL revealed diminished lymphatic drainage to perihepatic lymph nodes and vessels in irradiated livers when compared to non-radioembolized controls (p = 1.0x10-4). Conclusions Radioembolization impairs peritumoral lymph vessel function. Further research is needed to evaluate if radioembolization impairs tumor dissemination via this route. Impact and implications Unilobar radioembolization can serve as an alternative to portal venous embolization for patients who are considered unresectable due to an insufficient future liver remnant. This research suggests that radioembolization impairs the function of peritumoral liver lymph vessels, potentially hindering dissemination via this route. These findings provide support for considering unilobar radioembolization over standard portal venous embolization.
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Affiliation(s)
- Daan Andel
- Department of Surgical Oncology, University Medical Center Utrecht, Cancer Center, Utrecht, The Netherlands
- Laboratory for Translational Oncology, University Medical Center Utrecht, Cancer Center, Utrecht, The Netherlands
| | - Lotte van den Bent
- Department of Surgical Oncology, University Medical Center Utrecht, Cancer Center, Utrecht, The Netherlands
- Laboratory for Translational Oncology, University Medical Center Utrecht, Cancer Center, Utrecht, The Netherlands
| | | | - Maarten Leonard Johannes Smits
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Cancer Center, Utrecht, The Netherlands
| | - Isaac Quintus Molenaar
- Department of Surgical Oncology, University Medical Center Utrecht, Cancer Center, Utrecht, The Netherlands
| | - Joep de Bruijne
- Department Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Miangela Marie Laclé
- Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Onno Kranenburg
- Department of Surgical Oncology, University Medical Center Utrecht, Cancer Center, Utrecht, The Netherlands
- Laboratory for Translational Oncology, University Medical Center Utrecht, Cancer Center, Utrecht, The Netherlands
| | - Inne Hildbrand Max Borel Rinkes
- Department of Surgical Oncology, University Medical Center Utrecht, Cancer Center, Utrecht, The Netherlands
- Laboratory for Translational Oncology, University Medical Center Utrecht, Cancer Center, Utrecht, The Netherlands
| | - Jeroen Hagendoorn
- Department of Surgical Oncology, University Medical Center Utrecht, Cancer Center, Utrecht, The Netherlands
- Laboratory for Translational Oncology, University Medical Center Utrecht, Cancer Center, Utrecht, The Netherlands
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Andel D, Lam MGEH, de Bruijne J, Smits MLJ, Braat AJAT, Moelker A, Vegt E, Ruiter SJS, Noordzij W, Grazi G, Vallati GE, Bennink RJ, van Delden OM, Kranenburg OW, Ijzermans JNM, Nijkamp MW, Erdmann JI, Sciuto R, Hagendoorn J, Borel Rinkes IHM. Dose finding study for unilobar radioembolization using holmium-166 microspheres to improve resectability in patients with HCC: the RALLY protocol. BMC Cancer 2023; 23:771. [PMID: 37596578 PMCID: PMC10436405 DOI: 10.1186/s12885-023-11280-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 08/08/2023] [Indexed: 08/20/2023] Open
Abstract
BACKGROUND High dose unilobar radioembolization (also termed 'radiation lobectomy')-the transarterial unilobar infusion of radioactive microspheres as a means of controlling tumour growth while concomitantly inducing future liver remnant hypertrophy-has recently gained interest as induction strategy for surgical resection. Prospective studies on the safety and efficacy of the unilobar radioembolization-surgery treatment algorithm are lacking. The RALLY study aims to assess the safety and toxicity profile of holmium-166 unilobar radioembolization in patients with hepatocellular carcinoma ineligible for surgery due to insufficiency of the future liver remnant. METHODS The RALLY study is a multicenter, interventional, non-randomized, open-label, non-comparative safety study. Patients with hepatocellular carcinoma who are considered ineligible for surgery due to insufficiency of the future liver remnant (< 2.7%/min/m2 on hepatobiliary iminodiacetic acid scan will be included. A classical 3 + 3 dose escalation model will be used, enrolling three to six patients in each cohort. The primary objective is to determine the maximum tolerated treated non-tumourous liver-absorbed dose (cohorts of 50, 60, 70 and 80 Gy). Secondary objectives are to evaluate dose-response relationships, to establish the safety and feasibility of surgical resection following unilobar radioembolization, to assess quality of life, and to generate a biobank. DISCUSSION This will be the first clinical study to assess the unilobar radioembolization-surgery treatment algorithm and may serve as a stepping stone towards its implementation in routine clinical practice. TRIAL REGISTRATION Netherlands Trial Register NL8902 , registered on 2020-09-15.
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Affiliation(s)
- Daan Andel
- Department of Surgical Oncology, University Medical Center Utrecht, Cancer Center, PO BOX 85500, 3508 GA, Utrecht, The Netherlands.
| | - Marnix G E H Lam
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Cancer Center, Utrecht, The Netherlands
| | - Joep de Bruijne
- Department Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Maarten L J Smits
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Cancer Center, Utrecht, The Netherlands
| | - Arthur J A T Braat
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Cancer Center, Utrecht, The Netherlands
| | - Adriaan Moelker
- Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Erik Vegt
- Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Simeon J S Ruiter
- Department of HPB & Liver Transplantation, University Medical Center Groningen, Groningen, The Netherlands
| | - Walter Noordzij
- Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands
| | - Gianluca Grazi
- Hepatopancreatobiliary Surgery, IRCCS - Regina Elena National Cancer Institute, Rome, Italy
| | - Giulio E Vallati
- Interventional Radiology, IRCCS - Regina Elena National Cancer Institute, Rome, Italy
| | - Roel J Bennink
- Department of Radiology and Nuclear Medicine, Cancer Center, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands
| | - Otto M van Delden
- Department of Radiology and Nuclear Medicine, Cancer Center, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands
| | - Onno W Kranenburg
- Department of Surgical Oncology, University Medical Center Utrecht, Cancer Center, PO BOX 85500, 3508 GA, Utrecht, The Netherlands
| | - Jan N M Ijzermans
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Maarten W Nijkamp
- Department of HPB & Liver Transplantation, University Medical Center Groningen, Groningen, The Netherlands
| | - Joris I Erdmann
- Department of Surgery, Cancer Center, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Rosa Sciuto
- Nuclear Medicine, IRCCS - Regina Elena National Cancer Institute, Rome, Italy
| | - Jeroen Hagendoorn
- Department of Surgical Oncology, University Medical Center Utrecht, Cancer Center, PO BOX 85500, 3508 GA, Utrecht, The Netherlands
| | - Inne H M Borel Rinkes
- Department of Surgical Oncology, University Medical Center Utrecht, Cancer Center, PO BOX 85500, 3508 GA, Utrecht, The Netherlands.
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Del Basso C, Gaillard M, Lainas P, Zervaki S, Perlemuter G, Chagué P, Rocher L, Voican CS, Dagher I, Tranchart H. Current strategies to induce liver remnant hypertrophy before major liver resection. World J Hepatol 2021; 13:1629-1641. [PMID: 34904033 PMCID: PMC8637666 DOI: 10.4254/wjh.v13.i11.1629] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 06/08/2021] [Accepted: 10/11/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatic resection is the gold standard for patients affected by primary or metastatic liver tumors but is hampered by the risk of post-hepatectomy liver failure. Despite recent improvements, liver surgery still requires excellent clinical judgement in selecting patients for surgery and, above all, efficient pre-operative strategies to provide adequate future liver remnant. The aim of this article is to review the literature on the rational, the preliminary assessment, the advantages as well as the limits of each existing technique for preparing the liver for major hepatectomy.
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Affiliation(s)
- Celeste Del Basso
- Department of Minimally Invasive Digestive Surgery, Antoine Béclère Hospital, Clamart 92140, France
| | - Martin Gaillard
- Department of Minimally Invasive Digestive Surgery, Antoine Béclère Hospital, Clamart 92140, France
| | - Panagiotis Lainas
- Department of Minimally Invasive Digestive Surgery, Antoine Béclère Hospital, Clamart 92140, France
| | - Stella Zervaki
- Department of Minimally Invasive Digestive Surgery, Antoine Béclère Hospital, Clamart 92140, France
| | - Gabriel Perlemuter
- Department of Hepato-Gastroenterology and Nutrition, Antoine Béclère Hospital, Clamart 92140, France
| | - Pierre Chagué
- Department of Radiology, Antoine Béclère Hospital, Clamart 92140, France
| | - Laurence Rocher
- Department of Radiology, Antoine Béclère Hospital, Clamart 92140, France
| | - Cosmin Sebastian Voican
- Department of Hepato-Gastroenterology and Nutrition, Antoine Béclère Hospital, Clamart 92140, France
| | - Ibrahim Dagher
- Department of Minimally Invasive Digestive Surgery, Antoine Béclère Hospital, Clamart 92140, France
| | - Hadrien Tranchart
- Department of Minimally Invasive Digestive Surgery, Antoine Béclère Hospital, Clamart 92140, France
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Ho VL, Pham NH, Nguyen TX, Tran AP, Dang NT, Pham NH. Hepatectomy with Takasaki's Technique Using SonaStar Ultrasonic Aspiration System: An Experience from 58 Cases. Clin Exp Gastroenterol 2021; 14:297-302. [PMID: 34188512 PMCID: PMC8235924 DOI: 10.2147/ceg.s319434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Accepted: 06/11/2021] [Indexed: 11/23/2022] Open
Abstract
Objective This study aims to explore the short-term results of hepatectomy with Takasaki’s technique using Sonastar ultrasonic aspiration system. Materials and Methods We retrospectively examined data of 58 patients who underwent hepatectomy with Takasaki’s technique using Sonastar ultrasonic aspiration system at Hue Central Hospital from 01/2018 to 02/2021. Results The mean age was 60.7 ± 10.5 years (25–80) and the male/female ratio was 6:1. Patients with solitary tumor accounted for 79%; 68.4% had tumor size greater than 5 cm. Pringle maneuver was used in 57.9%, while selective right or left Glissonean pedicle occlusion was used in 69.0% and 32.8%, respectively. Final transection surface reinforcement was achieved by Surgicel and BioGlue in 78.9% and 21.5% of cases, respectively. Major liver resection accounted for 73.7%. The mean parenchymal transection time was 50 (45–110) minutes, while mean total operative time was 125 (90–280) minutes. Mean operative blood loss was 250 (150–650) mL. Mean post-operative hospital stay was 8 days (7–23). Post-operative complication rate was 15.9% and mortality rate was 1.7%. Conclusion Hepatectomy using Takasaki technique with Sonastar ultrasonic aspiration system is safe, effective, allowing an anatomical resection with sufficient safety margin and resulting in low complication rates (liver failure, biliary leakage) and good survival outcomes.
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Affiliation(s)
- Van Linh Ho
- Digestive Surgery Department, Hue Central Hospital, Hue City, Vietnam
| | - Nhu Hien Pham
- Department of Abdominal Emergency and Pediatric Surgery, Hue Central Hospital, Hue City, Vietnam
| | - Thanh Xuan Nguyen
- Department of Abdominal Emergency and Pediatric Surgery, Hue Central Hospital, Hue City, Vietnam
| | - An Phong Tran
- Digestive Surgery Department, Hue Central Hospital, Hue City, Vietnam
| | - Nhu Thanh Dang
- Surgery Department, Hue University of Medicine and Pharmacy, Hue City, Vietnam
| | - Nhu Hiep Pham
- Digestive Surgery Department, Hue Central Hospital, Hue City, Vietnam
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