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Papakonstantinou M, Fantakis A, Torzilli G, Donadon M, Chatzikomnitsa P, Giakoustidis D, Papadopoulos VN, Giakoustidis A. A Systematic Review of Disappearing Colorectal Liver Metastases: Resection or No Resection? J Clin Med 2025; 14:1147. [PMID: 40004679 PMCID: PMC11856073 DOI: 10.3390/jcm14041147] [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: 01/05/2025] [Revised: 01/29/2025] [Accepted: 02/07/2025] [Indexed: 02/27/2025] Open
Abstract
Background: Colorectal cancer is the second most common type of cancer and a leading cause of cancer-related deaths worldwide. Approximately 15% of the patients with colorectal cancer will already have liver metastases (CRLMs) at diagnosis. Luckily, the advances in chemotherapy regimens during the past few decades have led to increased rates of disease regression that could even render an originally unresectable disease resectable. In certain patients with CRLMs, the hepatic lesions are missing on preoperative imaging after neoadjuvant chemotherapy. These patients can undergo surgery with or without resection of the sites of the disappearing liver metastases (DLMs). In this systematic review, we assess the recurrence rate of the DLMs that were left unresected as well as the complete pathologic response of those resected. Methods: A literature search was conducted in PubMed for studies including patients with CRLMs who received neoadjuvant chemotherapy and had DLMs in preoperative imaging. Two independent reviewers completed the search according to the PRISMA checklist. Results: Three hundred and twenty-six patients with 1134 DLMs were included in our review. A total of 47 out of 480 DLMs (72.29%) that were removed had viable tumor cells in postoperative histology. One hundred and forty-five tumors could not be identified intraoperatively and were removed based on previous imaging, with thirty (20.69%) of them presenting viable cancer cells. Four hundred and sixty-five lesions could not be identified and were left in place. Of them, 152 (32.69%) developed local recurrence within 5 years. Of note, 34 DLMs could not be categorized as viable or non-viable tumors. Finally, DLMs that were identifiable intraoperatively had a higher possibility of viable tumors compared to non-identifiable ones (72.29% vs. 20.69%, respectively). Conclusions: Disappearing liver metastases that are left unresected have an increased possibility of recurrence. Patients receiving neoadjuvant treatment for CRLMs may have better survival chances after resecting all the DLM sites, either identifiable intraoperatively or not.
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Affiliation(s)
- Menelaos Papakonstantinou
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
| | - Antonios Fantakis
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
| | - Guido Torzilli
- Department of Surgery, Division of Hepatobiliary Surgery & General Surgery, Humanitas Research Hospital, 20089 Rozzano, Italy;
| | - Matteo Donadon
- Surgical Oncology Program, University Maggiore Hospital, University of Piemonte Orientale, 28100 Novara, Italy;
| | - Paraskevi Chatzikomnitsa
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
| | - Dimitrios Giakoustidis
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
| | - Vasileios N. Papadopoulos
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
| | - Alexandros Giakoustidis
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
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Takei D, Kuroda S, Kobayashi T, Mashima H, Tahara H, Ohira M, Aikata H, Chosa K, Baba Y, Ohdan H. Prospective Exploratory Phase I Clinical Trial Assessing the Safety of Preoperative Marking for Small Liver Tumors. Cureus 2023; 15:e50603. [PMID: 38226110 PMCID: PMC10788183 DOI: 10.7759/cureus.50603] [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] [Accepted: 12/15/2023] [Indexed: 01/17/2024] Open
Abstract
Background Small tumors in liver cirrhosis are difficult to distinguish using intraoperative ultrasonography. In addition, preoperative chemotherapy for metastatic liver cancer may diminish tumor size, thus making tumors difficult to identify intraoperatively. To address such difficulties, we devised a method to mark liver tumors preoperatively to facilitate intraoperative identification. This study aimed to investigate the safety of a preoperative liver tumor marking method. Methodology This exploratory prospective clinical trial included patients with liver tumors measuring ≤20 mm requiring resection. Preoperative marking was performed by placing a coil for embolization of blood vessels near the tumor using either the transcatheter or percutaneous approach. The tumor was identified and resected by intraoperative ultrasonography based on the marker. The study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000028608). Results Overall, 19 patients (9 with primary liver cancer and 10 with metastatic tumors) were recruited. The transcatheter and percutaneous methods were used in 13 and 6 patients, respectively. Marking was not possible in two patients in the transcatheter group because the catheter could not be guided to the vicinity of the tumor. There were no marking-related complications. Hepatectomy was performed in all but one patient who was not fit for hepatectomy owing to the development of a metastatic liver tumor. The markers were adequately identified during hepatectomy. Additionally, there were no difficulties in the surgical procedure or postoperative complications. Conclusions Preoperative marking with embolization coils can be performed safely for intraoperative identification of liver nodules.
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Affiliation(s)
- Daisuke Takei
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, JPN
| | - Shintaro Kuroda
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, JPN
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, JPN
| | - Hiroaki Mashima
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, JPN
| | - Hiroyuki Tahara
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, JPN
| | - Masahiro Ohira
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, JPN
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, JPN
| | - Keigo Chosa
- Department of Diagnostic Radiology, Hiroshima University, Hiroshima, JPN
| | - Yasutaka Baba
- Department of Diagnostic Radiology, Saitama Medical University International Medical Center, Hidaka, JPN
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, JPN
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Ghazanfar MA, Abdelhamid A, Aldrighetti L, Sturesson C, Takemura N, Truant S, Fiorentini G, Teh C, Alikhanov R, Ahmed I, Hammond J, Ferrero A, Silva M, Pawlik T, Jones R, Bekheit M. The dilemma of the disappearing colorectal liver metastases: defining international trends in management. HPB (Oxford) 2023; 25:446-453. [PMID: 36775699 DOI: 10.1016/j.hpb.2023.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 12/18/2022] [Accepted: 01/10/2023] [Indexed: 02/14/2023]
Abstract
OBJECTIVE This survey sought to appraise the degree of consistency in the management of disappeared colorectal liver metastases (dCRLM) among liver surgeons in different countries. BACKGROUND Colorectal liver metastases (CRLM) account for half of the deaths secondary to colorectal cancer. Due to the high utilization of chemotherapy before surgery, some or all CRLM can disappear (dCRLM) but management of dCRLMs remains unclear. METHODS Seven simulated scenarios of dCRLM were presented to experienced liver surgeons using an online platform. Treatment decisions were submitted and analysed using the multi-rater kappa method. The effect of the experience, complexity of scenarios, and location and number of dCRLM on treatment decision were analysed. RESULTS Sixty-seven liver surgeons from 25 countries completed the survey. There was no agreement about the therapeutic strategies of dCRLM in all scenarios (kappa 0.12, IQR 0.20-0.32). In scenarios with lower difficulty scores, surgeons tended to offer surgical resection for dCRLM alongside the visible CRLM (vCRLM), however, with poor agreement (kappa 0.32, IQR 0.19-0.51). No agreement was seen for clinical scenario in which all CRLM lesions disappeared (kappa 0.20). CONCLUSION There are clear inconsistencies in the management decisions of dCRLM. Better evidence is required to define optimal management strategies.
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Affiliation(s)
- Mudassar A Ghazanfar
- Institute of Medical Sciences, University of Aberdeen, Scotland, UK; Department of HPB Surgery, NHS Grampian, Scotland, Aberdeen, UK
| | - Amir Abdelhamid
- Institute of Medical Sciences, University of Aberdeen, Scotland, UK; Department of HPB Surgery, NHS Grampian, Scotland, Aberdeen, UK
| | - Luca Aldrighetti
- Hepatobiliary Surgery Division, San Raffaele Hospital, Milan, Italy
| | - Christian Sturesson
- Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Nobuyuki Takemura
- Department of Surgery, National Center for Global Health and Medicine (NCGM), Tokyo, Japan
| | - Stephanie Truant
- Department of Surgery, Centre Hospitalier Régional Universitaire de Lille: Lille, Nord-Pas-de-Calais, Lille, France
| | - Guido Fiorentini
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic Rochester, Rochester, USA
| | - Catherine Teh
- Department of Surgery, Makati Medical Center, Makati Metro Manila, Philippines; Department of Surgery, National Kidney & Transplant Institute, Quezon, Philippines; Department of Surgery, St Luke's Medical Center, Quezon, Philippines
| | - Ruslan Alikhanov
- Moscow Clinical Scientific Center, Department of Liver and Pancreatic Surgery and Transplantation, Russia
| | - Irfan Ahmed
- Institute of Medical Sciences, University of Aberdeen, Scotland, UK; Department of HPB Surgery, NHS Grampian, Scotland, Aberdeen, UK
| | - John Hammond
- Department of HPB and Transplantation, Freeman Hospital, Newcastle Upon Tyne, Newcastle, UK
| | | | - Michael Silva
- Department of Surgery, Oxford University Hospital, Oxford, UK
| | - Timothy Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Ohio, USA
| | - Robert Jones
- Northwest Hepatobiliary Unit, Department of Surgery, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Mohamed Bekheit
- Institute of Medical Sciences, University of Aberdeen, Scotland, UK; Department of HPB Surgery, NHS Grampian, Scotland, Aberdeen, UK; HPB Integrated Center of Care, Elite Integrated Centers of Excellence, Alexandria, Egypt.
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Anselmo A, Cascone C, Siragusa L, Sensi B, Materazzo M, Riccetti C, Bacchiocchi G, Ielpo B, Rosso E, Tisone G. Disappearing Colorectal Liver Metastases: Do We Really Need a Ghostbuster? Healthcare (Basel) 2022; 10:healthcare10101898. [PMID: 36292345 PMCID: PMC9602313 DOI: 10.3390/healthcare10101898] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 09/06/2022] [Accepted: 09/22/2022] [Indexed: 11/24/2022] Open
Abstract
The development of new systemic treatment strategies has resulted in a significant increase in the response rates of colorectal liver metastases (CRLM) in the last few years. Although the radiological response is a favorable prognostic factor, complete shrinkage of CRLM, known as disappearing liver metastases (DLM), presents a therapeutic dilemma, and proper management is still debated in the literature. In fact, DLM is not necessarily equal to cure, and when resected, pathological examination reveals in more than 80% of patients a variable percentage of the tumor as residual disease or early recurrence in situ. Moreover, while a higher incidence of intrahepatic recurrence is documented in small series when surgery is avoided, its clinical significance for long-term OS is still under investigation. In light of this, a multidisciplinary approach and, in particular, radiologists’ role is needed to assist the surgeon in the management of DLM, thanks to emerging technology and strategy. Therefore, the aim of this review is to provide an overview of the DLM phenomenon and current management.
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Affiliation(s)
- Alessandro Anselmo
- Department of Surgical Science, University of Rome “Tor Vergata”, 00133 Roma, Italy
| | - Chiara Cascone
- Department of Surgery, University Campus Bio-Medico di Roma, 00128 Roma, Italy
- Correspondence: ; Tel.: +39-348-445-7000
| | - Leandro Siragusa
- Department of Surgical Science, University of Rome “Tor Vergata”, 00133 Roma, Italy
| | - Bruno Sensi
- Department of Surgical Science, University of Rome “Tor Vergata”, 00133 Roma, Italy
| | - Marco Materazzo
- Department of Surgical Science, University of Rome “Tor Vergata”, 00133 Roma, Italy
| | - Camilla Riccetti
- Department of Surgical Science, University of Rome “Tor Vergata”, 00133 Roma, Italy
| | - Giulia Bacchiocchi
- Department of Surgical Science, University of Rome “Tor Vergata”, 00133 Roma, Italy
| | - Benedetto Ielpo
- Hepatobiliary and Pancreatic Surgery Unit, Hospital del Mar. Universitat Pompeu Fabra Barcelona, 08003 Barcelona, Spain
| | - Edoardo Rosso
- Unité des Maladies de l’Appareil Digestif et Endocrine, Centre Hospitalier de Luxembourg, 1210 Luxembourg, Luxembourg
| | - Giuseppe Tisone
- Department of Surgical Science, University of Rome “Tor Vergata”, 00133 Roma, Italy
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Guo M, Jin N, Pawlik T, Cloyd JM. Neoadjuvant chemotherapy for colorectal liver metastases: A contemporary review of the literature. World J Gastrointest Oncol 2021; 13:1043-1061. [PMID: 34616511 PMCID: PMC8465453 DOI: 10.4251/wjgo.v13.i9.1043] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/17/2021] [Accepted: 08/06/2021] [Indexed: 02/06/2023] Open
Abstract
Colorectal carcinoma (CRC) is one of the leading causes of cancer-related deaths worldwide, and up to 50% of patients with CRC develop colorectal liver metastases (CRLM). For these patients, surgical resection remains the only opportunity for cure and long-term survival. Over the past few decades, outcomes of patients with metastatic CRC have improved significantly due to advances in systemic therapy, as well as improvements in operative technique and perioperative care. Chemotherapy in the modern era of oxaliplatin- and irinotecan-containing regimens has been augmented by the introduction of targeted biologics and immunotherapeutic agents. The increasing efficacy of contemporary systemic therapies has led to an expansion in the proportion of patients eligible for curative-intent surgery. Consequently, the use of neoadjuvant strategies is becoming progressively more established. For patients with CRLM, the primary advantage of neoadjuvant chemotherapy (NCT) is the potential to down-stage metastatic disease in order to facilitate hepatic resection. On the other hand, the routine use of NCT for patients with resectable metastases remains controversial, especially given the potential risk of inducing chemotherapy-associated liver injury prior to hepatectomy. Current guidelines recommend upfront surgery in patients with initially resectable disease and low operative risk, reserving NCT for patients with borderline resectable or unresectable disease and high operative risk. Patients undergoing NCT require close monitoring for tumor response and conversion of CRLM to resectability. In light of the growing number of treatment options available to patients with metastatic CRC, it is generally agreed that these patients are best served at tertiary centers with an expert multidisciplinary team.
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Affiliation(s)
- Marissa Guo
- Department of Surgery, The Ohio State University Medical Center, Columbus, OH 43210, United States
| | - Ning Jin
- Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Medical Center, Columbus, OH 43210, United States
| | - Timothy Pawlik
- Department of Surgery, The Ohio State University, Columbus, OH 43210, United States
| | - Jordan M Cloyd
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Medical Center, Columbus, OH 43210, United States
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