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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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Kuhlmann KF, Tufo A, Kok NF, Gordon-Weeks A, Poston GJ, Diaz Nieto R, Jones R, Fenwick SW, Malik HZ. Disappearing colorectal liver metastases in the era of state-of-the-art triple-modality diagnostic imaging. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:1016-1022. [PMID: 36702715 DOI: 10.1016/j.ejso.2023.01.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 12/19/2022] [Accepted: 01/11/2023] [Indexed: 01/13/2023]
Abstract
INTRODUCTION Systemic therapy can result in disappearance of colorectal liver metastases in up to 40% of patients. This might be an overestimation caused by suboptimal imaging modalities. The aim of this study was to investigate the use of imaging modalities and the incidence, management and outcome of patients with disappearing liver metastases (DLMs). METHODS This was a retrospective study of consecutive patients treated for colorectal liver metastases at a high volume hepatobiliary centre between January 2013 and January 2015 after receiving induction or neoadjuvant systemic therapy. Main outcomes were use of imaging modalities, incidence, management and longterm outcome of patients with DLMs. RESULTS Of 158 patients included, 32 (20%) had 110 DLMs. Most patients (88%) had initial diagnostic imaging with contrast enhanced-CT, primovist-MR and FDG-PET and 94% of patients with DLMs were restaged using primovist-MR. Patients with DLMs had significantly smaller metastases and the median initial size of DLMs was 10 mm (range 5-61). In the per lesion analysis, recurrence after "watch & wait" for DLMs occurred in 36%, while in 19 of 20 resected DLMs no viable tumour cells were found. Median overall (51 vs. 28 months, p < 0.05) and progression free survival (10 vs. 3 months, p = 0.003) were significantly longer for patients with DLMs. CONCLUSION Even state-of-the-art imaging and restaging cannot solve problems associated with DLMs. Regrowth of these lesions occurs in approximately a third of the lesions. Patients with DLMs have better survival.
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Affiliation(s)
- K F Kuhlmann
- Department of Surgical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, the Netherlands; Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
| | - A Tufo
- Department of General Surgery, Ospedale del Mare, Via Enrico Russo, 80147, Naples, Italy; Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
| | - N F Kok
- Department of Surgical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, the Netherlands
| | - A Gordon-Weeks
- Nuffield Department of Surgical Sciences, University of Oxford, Old Road, OX3 7BN, United Kingdom
| | - G J Poston
- Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
| | - R Diaz Nieto
- Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
| | - R Jones
- Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
| | - S W Fenwick
- Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
| | - H Z Malik
- Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom.
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Missing colorectal liver metastases: the surgical challenge. Langenbecks Arch Surg 2021; 406:2163-2175. [PMID: 34590190 DOI: 10.1007/s00423-021-02297-4] [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: 02/08/2021] [Accepted: 08/04/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND New chemotherapy schemes have allowed for a better radiological response of unresectable colorectal liver metastases, leading to an interesting scenario known as a complete radiological response. The aim of this study was to review the current management of missing liver metastases (MLM) from the liver surgeon's point of view. METHODS A systematic search was conducted on all publications of PubMed and Embase between 2003 and 2018. Meta-analysis was performed on MLM resected/unresected. Residual tumor or regrowth and relapse-free survival were used as evaluation indices. RESULTS After literature search, 18 original articles were included for analysis. The predictive factors for MLM are type and duration of chemotherapy and size and number of lesions. Magnetic resonance is the most sensitive preoperative technique. Regarding clinical management, liver surgery is deemed the fundamental pillar in the therapeutic strategy of these patients. Meta-analysis due to data heterogeneity was inconclusive. CONCLUSIONS Depending on the clinical context, MLM monitoring appears to be a valid therapeutic alternative. Nevertheless, prospective randomized clinical studies are needed.
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Araujo RLC, Milani JM, Armentano DP, Moreira RB, Pinto GSF, de Castro LA, Lucchesi FR. Disappearing colorectal liver metastases: Strategies for the management of patients achieving a radiographic complete response after systemic chemotherapy. J Surg Oncol 2019; 121:848-856. [PMID: 31773747 DOI: 10.1002/jso.25784] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Accepted: 11/14/2019] [Indexed: 12/12/2022]
Abstract
The mainstays of treatment for colorectal liver metastases (CRLMs) are surgery and chemotherapy. Chemotherapeutic benefits of tumor shrinkage and systemic control of micrometastases are in part counterbalanced by chemotoxicity that can modify the liver parenchyma, jeopardizing the detection of CRLM. This review addresses the clinical decision-making process in the context of radiographic and pathologic responses, the preoperative imaging workup, and the approaches to the liver for CRLM, which disappear after systemic chemotherapy.
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Affiliation(s)
- Raphael L C Araujo
- Department of Digestive Surgery, Escola Paulista de Medicina - UNIFESP, São Paulo, Brazil.,Department of Oncology, Americas Medical Service/Brazil, United Health Group, São Paulo, Brazil.,Hospital Israelita Albert Einstein, São Paulo, Brazil.,Post-Graduation Program, Barretos Cancer Hospital, Barretos, Brazil
| | - Jean Michel Milani
- Department of Digestive Surgery, Escola Paulista de Medicina - UNIFESP, São Paulo, Brazil
| | | | - Raphael Brandão Moreira
- Department of Oncology, Americas Medical Service/Brazil, United Health Group, São Paulo, Brazil
| | - Gustavo S F Pinto
- Department of Clinical Oncology, Barretos Cancer Hospital, Barretos, Brazil
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Tsilimigras DI, Ntanasis-Stathopoulos I, Paredes AZ, Moris D, Gavriatopoulou M, Cloyd JM, Pawlik TM. Disappearing liver metastases: A systematic review of the current evidence. Surg Oncol 2019; 29:7-13. [PMID: 31196496 DOI: 10.1016/j.suronc.2019.02.005] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Accepted: 02/10/2019] [Indexed: 12/14/2022]
Abstract
Advances in systemic chemotherapy have resulted in a significant increase in the reported response rates of colorectal liver metastases (CRLM) over time. Although radiologic response is usually prognostic of favorable outcomes, complete shrinkage of CRLM after chemotherapy, namely "disappearing liver metastases" (DLMs) poses significant therapeutic dilemmas. A systematic review of the literature was conducted to evaluate the existing evidence on the imaging and management of patients with DLMs using the PubMed (Medline), Embase and Cochrane library through December 21st, 2018. The following algorithm was used: "(disappearing OR vanishing OR missing OR (residual tiny)) AND ((liver OR hepatic) AND (metastasis OR metastases OR metastatic OR secondary))." From the 225 records retrieved, 15 studies were finally deemed eligible. A total of 479 patients with DLMs with a median age of 59.5 years (range, 30-83) were identified. Median number of DLM per patient ranged from 1 to 8.8. Median size of LMs prior to chemotherapy was 1.07 cm (range 0.3-3.5). The systemic treatment used to achieve DLMs included systemic chemotherapy alone (only 2 studies) or in combination with targeted agents (11 studies). The median number of chemotherapy cycles in the included studies was 7.8 (range 6-12). Identified factors predisposing to the development of DLM were small size (<2 cm), increased number of treatment cycles, oxaliplatin-based therapy, increased number of CRLM (≥3) and synchronous CRLM. Baseline and preoperative MRI with iv contrast showed the highest sensitivity for DLM detection. Fiducial placement facilitated pre- and intra-operative identification of DLM. Although resection of DLM decreased the local recurrence risk, there was no clearly demonstrated survival benefit after resecting all sites of disappearing lesions. Future randomized clinical trials are highly encouraged to provide strict, evidence-based recommendations for the treatment of patients with DLM.
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Affiliation(s)
- Diamantis I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Ioannis Ntanasis-Stathopoulos
- Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece
| | - Anghela Z Paredes
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Dimitrios Moris
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Maria Gavriatopoulou
- Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece
| | - Jordan M Cloyd
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA.
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Kepenekian V, Muller A, Valette PJ, Rousset P, Chauvenet M, Phelip G, Walter T, Adham M, Glehen O, Passot G. Evaluation of a strategy using pretherapeutic fiducial marker placement to avoid missing liver metastases. BJS Open 2019; 3:344-353. [PMID: 31183451 PMCID: PMC6551408 DOI: 10.1002/bjs5.50140] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Accepted: 12/06/2018] [Indexed: 12/19/2022] Open
Abstract
Background Hepatic surgery is appropriate for selected patients with colorectal liver metastases (CRLM). Advances in chemotherapy have led to modification of management, particularly when metastases disappear. Treatment should address all initial CRLM sites based on pretherapeutic cross-sectional imaging. This study aimed to evaluate pretherapeutic fiducial marker placement to optimize CRLM treatment. Methods This pilot investigation included patients with CRLM who were considered for potentially curative treatment between 2009 and 2016. According to a multidisciplinary team decision, lesions smaller than 25 mm in diameter that were more than 10 mm deep in the hepatic parenchyma and located outside the field of a planned resection were marked. Complication rates and clinicopathological data were analysed. Results Some 76 metastases were marked in 43 patients among 217 patients with CRLM treated with curative intent. Of these, 23 marked CRLM (30 per cent), with a mean(s.d.) size of 11·0(3·4) mm, disappeared with preoperative chemotherapy. There were four complications associated with marking: two intrahepatic haematomas, one fiducial migration and one misplacement. After a median follow-up of 47·7 (range 18·1-144·9) months, no needle-track seeding was noted. Of four disappearing CRLM that were marked and resected, two presented with persistent active disease. Other missing lesions were treated with thermoablation. Conclusion Pretherapeutic fiducial marker placement appears useful for the curative management of CRLM.
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Affiliation(s)
- V Kepenekian
- Department of Digestive Surgery Hospices Civils de Lyon, Centre Hospitalier Lyon Sud Lyon France
| | - A Muller
- Department of Radiology Hospices Civils de Lyon, Centre Hospitalier Lyon Sud Lyon France
| | - P J Valette
- Department of Radiology Hospices Civils de Lyon, Centre Hospitalier Lyon Sud Lyon France
| | - P Rousset
- Department of Radiology Hospices Civils de Lyon, Centre Hospitalier Lyon Sud Lyon France
| | - M Chauvenet
- Department of Digestive Oncology Hospices Civils de Lyon, Centre Hospitalier Lyon Sud Lyon France
| | - G Phelip
- Department of Digestive Oncology Hospices Civils de Lyon, Centre Hospitalier Lyon Sud Lyon France
| | - T Walter
- Department of Medical Oncology Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon 1 University Lyon France
| | - M Adham
- Department of Digestive Surgery Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon 1 University Lyon France
| | - O Glehen
- Department of Digestive Surgery Hospices Civils de Lyon, Centre Hospitalier Lyon Sud Lyon France
| | - G Passot
- Department of Digestive Surgery Hospices Civils de Lyon, Centre Hospitalier Lyon Sud Lyon France
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Brudvik KW, Jones RP, Giuliante F, Shindoh J, Passot G, Chung MH, Song J, Li L, Dagenborg VJ, Fretland ÅA, Røsok B, De Rose AM, Ardito F, Edwin B, Panettieri E, Larocca LM, Yamashita S, Conrad C, Aloia TA, Poston GJ, Bjørnbeth BA, Vauthey JN. RAS Mutation Clinical Risk Score to Predict Survival After Resection of Colorectal Liver Metastases. Ann Surg 2019; 269:120-126. [PMID: 28549012 DOI: 10.1097/sla.0000000000002319] [Citation(s) in RCA: 174] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE To determine the impact of RAS mutation status on the traditional clinical score (t-CS) to predict survival after resection of colorectal liver metastases (CLM). BACKGROUND The t-CS relies on the following factors: primary tumor nodal status, disease-free interval, number and size of CLM, and carcinoembryonic antigen level. We hypothesized that the addition of RAS mutation status could create a modified clinical score (m-CS) that would outperform the t-CS. METHODS Patients who underwent resection of CLM from 2005 through 2013 and had RAS mutation status and t-CS factors available were included. Multivariate analysis was used to identify prognostic factors to include in the m-CS. Log-rank survival analyses were used to compare the t-CS and the m-CS. The m-CS was validated in an international multicenter cohort of 608 patients. RESULTS A total of 564 patients were eligible for analysis. RAS mutation was detected in 205 (36.3%) of patients. On multivariate analysis, RAS mutation was associated with poor overall survival, as were positive primary tumor lymph node status and diameter of the largest liver metastasis >50 mm. Each factor was assigned 1 point to produce a m-CS. The m-CS accurately stratified patients by overall and recurrence-free survival in both the initial patient series and validation cohort, whereas the t-CS did not. CONCLUSIONS Modifying the t-CS by replacing disease-free interval, number of metastases, and CEA level with RAS mutation status produced an m-CS that outperformed the t-CS. The m-CS is therefore a simple validated tool that predicts survival after resection of CLM.
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Affiliation(s)
- Kristoffer W Brudvik
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway
| | - Robert P Jones
- Liverpool Hepatobiliary Unit, Aintree University Hospital, Liverpool, United Kingdom
| | - Felice Giuliante
- Hepatobiliary Surgery Unit, A. Gemelli Medical School, Rome, Italy
| | - Junichi Shindoh
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
- Hepatobiliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Guillaume Passot
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Michael H Chung
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Juhee Song
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Liang Li
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Vegar J Dagenborg
- Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway
| | - Åsmund A Fretland
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway
| | - Bård Røsok
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway
| | | | - Francesco Ardito
- Hepatobiliary Surgery Unit, A. Gemelli Medical School, Rome, Italy
| | - Bjørn Edwin
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway
| | - Elena Panettieri
- Hepatobiliary Surgery Unit, A. Gemelli Medical School, Rome, Italy
| | | | - Suguru Yamashita
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Claudius Conrad
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Thomas A Aloia
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Graeme J Poston
- Liverpool Hepatobiliary Unit, Aintree University Hospital, Liverpool, United Kingdom
| | - Bjørn A Bjørnbeth
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
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Oba A, Mise Y, Ito H, Hiratsuka M, Inoue Y, Ishizawa T, Arita J, Matsueda K, Takahashi Y, Saiura A. Clinical implications of disappearing colorectal liver metastases have changed in the era of hepatocyte-specific MRI and contrast-enhanced intraoperative ultrasonography. HPB (Oxford) 2018. [PMID: 29534862 DOI: 10.1016/j.hpb.2018.02.377] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Clinical implication of disappearing liver metastases (DLMs) from colorectal cancer after chemotherapy needs to be reviewed in the era of modern imaging studies. METHODS Between 2010 and 2015, 184 patients underwent curative hepatectomy for colorectal liver metastases following preoperative chemotherapy. The sites of metastases detected on pre-chemotherapy CE-CT were examined post-chemotherapy using CE-CT, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI), and contrast-enhanced intraoperative ultrasonography (CE-IOUS). DLMs were defined as tumors that disappeared on CE-CT post chemotherapy. The detection rate of DLMs with EOB-MRI and CE-IOUS were assessed, and the outcome of DLMs resected and those left in place were reviewed. RESULTS A total of 275 DLMs were noted in 59 patients. On EOB-MRI, 71 lesions (26%) were visible and were resected, 92% (65/71) of which contained viable disease. Using CE-IOUS, an additional 94 lesions were identified. A total of 165 DLMs (60%) were identified and resected by sequential use of EOB-MRI and CE-IOUS, 77% (127/165) of which contained viable disease. Of 110 DLMs not identified, 68 were resected, 4% (3/68) of which contained viable disease. Among 42 lesions left in place, 6 (14%) recurred during the median follow-up period of 27 (9-72) months. DISCUSSION EOB-MRI and CE-IOUS exploration identified clinically relevant DLMs containing viable disease with a high level of accuracy.
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Affiliation(s)
- Atsushi Oba
- Department of Hepatobiliary Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Japan
| | - Yoshihiro Mise
- Department of Hepatobiliary Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Japan
| | - Hiromichi Ito
- Department of Hepatobiliary Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Japan
| | - Makiko Hiratsuka
- Department of Diagnostic Imaging, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Japan
| | - Yosuke Inoue
- Department of Hepatobiliary Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Japan
| | - Takeaki Ishizawa
- Department of Hepatobiliary Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Japan
| | - Junichi Arita
- Department of Hepatobiliary Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Japan
| | - Kiyoshi Matsueda
- Department of Diagnostic Imaging, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Japan
| | - Yu Takahashi
- Department of Hepatobiliary Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Japan
| | - Akio Saiura
- Department of Hepatobiliary Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Japan.
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Odisio BC, Yamashita S, Frota L, Huang SY, Kopetz SE, Ahrar K, Chun YS, Aloia TA, Hicks ME, Gupta S, Vauthey JN. Planned Treatment of Advanced Metastatic Disease with Completion Ablation After Hepatic Resection. J Gastrointest Surg 2017; 21:628-635. [PMID: 27882510 DOI: 10.1007/s11605-016-3324-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Accepted: 11/09/2016] [Indexed: 01/31/2023]
Abstract
PURPOSE The aim of this study is to describe a modified treatment strategy with image-guided percutaneous ablation after hepatic resection as a completion method to surgical eradication of liver metastases ("completion ablation [CA]"). METHODS We conducted a retrospective analyses of patients who underwent CA within 180 days from the liver surgical resection to eradicate liver metastases present on the pre-surgical cross-sectional imaging or identified during intraoperative ultrasound that were not resected due to various reasons. Lesions treated with CA were evaluated for local tumor progression (LTP). Patients were evaluated for hepatic- and overall-recurrence-free survivals (hepatic-RFS and overall-RFS, respectively) and overall survival (OS). RESULTS Sixteen patients (10 females; median age 55 years, range 28-69) underwent CA of 21 lesions (median size 8 mm, range 6 to 22). Indications for the use of CA were small future liver remnant in 10 (63%), inability to identify the lesion during surgical exploration in 3 (19%), and technical difficulty of resection in 3 (19%) patients. No liver-related complications were recorded following the surgical resection or the CA procedures. Primary and secondary CA efficacy rates were 95 and 100%, respectively. LTP was 0% at a median clinical follow-up of 27 months (range 4.0-108 months). Five-year hepatic-RFS, overall-RFS, and OS were 36, 16, and 51%, respectively. CONCLUSION The use of CA as a complement to surgical resection is safe and effective. Such approach could potentially expand the surgical candidacy for patients with limited liver functional reserve and reduce postoperative morbidity and mortality in this selected patient population with more advanced disease.
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Affiliation(s)
- Bruno C Odisio
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1471, Houston, TX, 77030, USA.
| | - Suguru Yamashita
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Livia Frota
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1471, Houston, TX, 77030, USA
| | - Steven Y Huang
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1471, Houston, TX, 77030, USA
| | - Scott E Kopetz
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Kamran Ahrar
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1471, Houston, TX, 77030, USA
| | - Yun Shin Chun
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Thomas A Aloia
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Marshall E Hicks
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1471, Houston, TX, 77030, USA
| | - Sanjay Gupta
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1471, Houston, TX, 77030, USA
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Aigner F, Pratschke J, Schmelzle M. Oligometastatic Disease in Colorectal Cancer - How to Proceed? Visc Med 2017; 33:23-28. [PMID: 28612013 DOI: 10.1159/000454688] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Oligometastatic disease in colorectal cancer may affect the liver, lung, and peritoneum. This review mainly focuses on colorectal liver metastases (CRLM) and highlights recommendations and therapeutic strategies drawn from the current literature and consensus conferences. The following data address a paradigm shift in surgical approaches to CRLM, pushing the limits of multimodal treatment concepts. METHODS A systematic review of the relevant literature on multimodal treatment strategies for synchronous and metachronous CRLM is presented. RESULTS The choice of treatment strategy depends on the clinical scenario; however, perioperative chemotherapy and the liver-first concept in synchronous CRLM are favored with subsequent partial extended liver resection with or without various augmentation techniques for liver surgery. CONCLUSION Surgical strategies should be strongly defined with regard to an adequate liver remnant. All patients with synchronous CRLM should be evaluated by a multidisciplinary team.
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Affiliation(s)
- Felix Aigner
- Department of Surgery, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Campus Virchow-Klinikum, Berlin, Germany
| | - Johann Pratschke
- Department of Surgery, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Campus Virchow-Klinikum, Berlin, Germany
| | - Moritz Schmelzle
- Department of Surgery, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Campus Virchow-Klinikum, Berlin, Germany
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11
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Dervenis C, Xynos E, Sotiropoulos G, Gouvas N, Boukovinas I, Agalianos C, Androulakis N, Athanasiadis A, Christodoulou C, Chrysou E, Emmanouilidis C, Georgiou P, Karachaliou N, Katopodi O, Kountourakis P, Kyriazanos I, Makatsoris T, Papakostas P, Papamichael D, Pechlivanides G, Pentheroudakis G, Pilpilidis I, Sgouros J, Tekkis P, Triantopoulou C, Tzardi M, Vassiliou V, Vini L, Xynogalos S, Ziras N, Souglakos J. Clinical practice guidelines for the management of metastatic colorectal cancer: a consensus statement of the Hellenic Society of Medical Oncologists (HeSMO). Ann Gastroenterol 2016; 29:390-416. [PMID: 27708505 PMCID: PMC5049546 DOI: 10.20524/aog.2016.0050] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Accepted: 03/10/2016] [Indexed: 12/12/2022] Open
Abstract
There is discrepancy and failure to adhere to current international guidelines for the management of metastatic colorectal cancer (CRC) in hospitals in Greece and Cyprus. The aim of the present document is to provide a consensus on the multidisciplinary management of metastastic CRC, considering both special characteristics of our Healthcare System and international guidelines. Following discussion and online communication among the members of an executive team chosen by the Hellenic Society of Medical Oncology (HeSMO), a consensus for metastastic CRC disease was developed. Statements were subjected to the Delphi methodology on two voting rounds by invited multidisciplinary international experts on CRC. Statements reaching level of agreement by ≥80% were considered as having achieved large consensus, whereas statements reaching 60-80% moderate consensus. One hundred and nine statements were developed. Ninety experts voted for those statements. The median rate of abstain per statement was 18.5% (range: 0-54%). In the end of the process, all statements achieved a large consensus. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and personalization is emphasized. R0 resection is the only intervention that may offer substantial improvement in the oncological outcomes.
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Affiliation(s)
- Christos Dervenis
- General Surgery, "Konstantopouleio" Hospital of Athens, Greece (Christos Dervenis)
| | - Evaghelos Xynos
- General Surgery, "InterClinic" Hospital of Heraklion, Greece (Evangelos Xynos)
| | | | - Nikolaos Gouvas
- General Surgery, "METROPOLITAN" Hospital of Piraeus, Greece (Nikolaos Gouvas)
| | - Ioannis Boukovinas
- Medical Oncology, "Bioclinic" of Thessaloniki, Greece (Ioannis Boukovinas)
| | - Christos Agalianos
- General Surgery, Athens Naval & Veterans Hospital, Greece (Christos Agalianos, Ioannis Kyriazanos, George Pechlivanides)
| | - Nikolaos Androulakis
- Medical Oncology, "Venizeleion" Hospital of Heraklion, Greece (Nikolaos Androulakis)
| | | | | | - Evangelia Chrysou
- Radiology, University Hospital of Heraklion, Greece (Evangelia Chrysou)
| | - Christos Emmanouilidis
- Medical Oncology, "Interbalkan" Medical Center, Thessaloniki, Greece (Christos Emmanoulidis)
| | - Panagiotis Georgiou
- Colorectal Surgery, Chelsea and Westminster NHS Foundation Trust, London, UK (Panagiotis Georgiou, Paris Tekkis)
| | - Niki Karachaliou
- Medical Oncology, Dexeus University Institut, Barcelona, Spain (Niki Carachaliou)
| | - Ourania Katopodi
- Medical Oncology, "Iaso" General Hospital, Athens, Greece (Ourania Katopoidi)
| | - Panteleimon Kountourakis
- Medical Oncology, Oncology Center of Bank of Cyprus, Nicosia, Cyprus (Pandelis Kountourakis, Demetris Papamichael)
| | - Ioannis Kyriazanos
- General Surgery, Athens Naval & Veterans Hospital, Greece (Christos Agalianos, Ioannis Kyriazanos, George Pechlivanides)
| | - Thomas Makatsoris
- Medical Oncology, University Hospital of Patras, Greece (Thomas Makatsoris)
| | - Pavlos Papakostas
- Medical Oncology, "Ippokrateion" Hospital of Athens, Greece (Pavlos Papakostas)
| | - Demetris Papamichael
- Medical Oncology, Oncology Center of Bank of Cyprus, Nicosia, Cyprus (Pandelis Kountourakis, Demetris Papamichael)
| | - George Pechlivanides
- General Surgery, Athens Naval & Veterans Hospital, Greece (Christos Agalianos, Ioannis Kyriazanos, George Pechlivanides)
| | | | - Ioannis Pilpilidis
- Gastroenterology, "Theageneion" Cancer Hospital, Thessaloniki, Greece (Ioannis Pilpilidis)
| | - Joseph Sgouros
- Medical Oncology, "Agioi Anargyroi" Hospital of Athens, Greece (Joseph Sgouros)
| | - Paris Tekkis
- Colorectal Surgery, Chelsea and Westminster NHS Foundation Trust, London, UK (Panagiotis Georgiou, Paris Tekkis)
| | | | - Maria Tzardi
- Pathology, University Hospital of Heraklion, Greece (Maria Tzardi)
| | - Vassilis Vassiliou
- Radiation Oncology, Oncology Center of Bank of Cyprus, Nicosia, Cyprus (Vassilis Vassiliou)
| | - Louiza Vini
- Radiation Oncology, "Iatriko" Center of Athens, Greece (Lousa Vini)
| | - Spyridon Xynogalos
- Medical Oncology, "George Gennimatas" General Hospital, Athens, Greece (Spyridon Xynogalos)
| | - Nikolaos Ziras
- Medical Oncology, "Metaxas" Cancer Hospital, Piraeus, Greece (Nikolaos Ziras)
| | - John Souglakos
- Medical Oncology, University Hospital of Heraklion, Greece (John Souglakos)
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12
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Eradication of Missing Liver Metastases After Fiducial Placement. J Gastrointest Surg 2016; 20:1173-8. [PMID: 26791387 DOI: 10.1007/s11605-016-3079-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Accepted: 01/11/2016] [Indexed: 01/31/2023]
Abstract
BACKGROUND The risk of colorectal liver metastases (CLM) disappearing on cross-sectional imaging has increased with advances in preoperative chemotherapy, but <50 % of disappearing CLM demonstrate complete pathological response. OBJECTIVE The aim of this study was to evaluate the role of fiducial marker placement before potentially curative treatment of CLM at risk of disappearing with chemotherapy. METHODS All consecutive patients who underwent fiducial placement for tracking of CLM at a tertiary center were reviewed. RESULTS Among 1377 patients undergoing CLM resection between 2005 and 2015, 35 patients underwent fiducial placement. Three patients were excluded due to disease progression. The study population comprised 32 patients who underwent fiducial placement in 41 CLM. Among the 41 marked CLM, 34 (83 %) were located >10 mm deep in the liver parenchyma, 25 (61 %) were in the right liver, and median size was 12 mm (range, 6-20 mm). No complication occurred after fiducial placement. After chemotherapy, 19 (46 %) of the 41 marked metastases disappeared on cross-sectional imaging. All fiducial-tracked CLM were treated with resection (n = 31) or ablation (n = 10). After median follow-up of 14 months (range, 0-64 months), no local recurrences were observed. CONCLUSION Fiducial placement represents a safe procedure that facilitates accurate localization for resection or ablation of small CLM at risk of disappearing with chemotherapy.
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Kuhlmann K, van Hilst J, Fisher S, Poston G. Management of disappearing colorectal liver metastases. Eur J Surg Oncol 2016; 42:1798-1805. [PMID: 27260846 DOI: 10.1016/j.ejso.2016.05.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Revised: 04/17/2016] [Accepted: 05/05/2016] [Indexed: 01/18/2023] Open
Abstract
The development of new potent systemic treatment modalities has led to a significant increase in survival of patients with colorectal liver metastases. In the neo-adjuvant setting, these modalities can be used for patient selection, down staging, and conversion from non-resectable to resectable liver metastases. In addition, complete radiological disappearance of metastases can occur, the phenomenon of disappearing liver metastases. Because only a small percentage of these patients (0-8%) have a complete radiological response of all liver metastases, most patients will undergo surgery. At laparotomy, local residual disease at the site of the disappeared metastasis is still found in 11-67%, which highlights the influence of the imaging modalities used at (re)staging. When the region of the disappeared liver metastasis was resected, microscopically residual disease was found in up to 80% of the specimens. Alternatively, conservative management of radiologically disappeared liver metastases resulted in 19-74% local recurrence, mostly within two years. Obviously, these studies are highly dependent on the quality of the imaging modalities utilised. Most studies employed CT as the modality of choice, while MRI and PET was only used in selective series. Overall, the phenomenon of disappearing liver metastases seems to be a radiological rather than an actual biological occurrence, because the rates of macroscopic and microscopic residual disease are high as well as the local recurrence rates. Therefore, the disappeared metastases still require an aggressive surgical approach and standard (re)staging imaging modalities should include at least CT and MRI.
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Affiliation(s)
- K Kuhlmann
- Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom.
| | - J van Hilst
- Department of Surgery, Academic Medical Center, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands
| | - S Fisher
- Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
| | - G Poston
- Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
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14
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Ntourakis D, Memeo R, Soler L, Marescaux J, Mutter D, Pessaux P. Augmented Reality Guidance for the Resection of Missing Colorectal Liver Metastases: An Initial Experience. World J Surg 2016; 40:419-426. [PMID: 26316112 DOI: 10.1007/s00268-015-3229-8] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Modern chemotherapy achieves the shrinking of colorectal cancer liver metastases (CRLM) to such extent that they may disappear from radiological imaging. Disappearing CRLM rarely represents a complete pathological remission and have an important risk of recurrence. Augmented reality (AR) consists in the fusion of real-time patient images with a computer-generated 3D virtual patient model created from pre-operative medical imaging. The aim of this prospective pilot study is to investigate the potential of AR navigation as a tool to help locate and surgically resect missing CRLM. METHODS A 3D virtual anatomical model was created from thoracoabdominal CT-scans using customary software (VR RENDER(®), IRCAD). The virtual model was superimposed to the operative field using an Exoscope (VITOM(®), Karl Storz, Tüttlingen, Germany). Virtual and real images were manually registered in real-time using a video mixer, based on external anatomical landmarks with an estimated accuracy of 5 mm. This modality was tested in three patients, with four missing CRLM that had sizes from 12 to 24 mm, undergoing laparotomy after receiving pre-operative oxaliplatin-based chemotherapy. RESULTS AR display and fine registration was performed within 6 min. AR helped detect all four missing CRLM, and guided their resection. In all cases the planned security margin of 1 cm was clear and resections were confirmed to be R0 by pathology. There was no postoperative major morbidity or mortality. No local recurrence occurred in the follow-up period of 6-22 months. CONCLUSIONS This initial experience suggests that AR may be a helpful navigation tool for the resection of missing CRLM.
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Affiliation(s)
- Dimitrios Ntourakis
- IRCAD-IHU, University of Strasbourg, 1 place de l'Hôpital, 67091, Strasbourg, France.
| | - Ricardo Memeo
- IRCAD-IHU, University of Strasbourg, 1 place de l'Hôpital, 67091, Strasbourg, France
| | - Luc Soler
- IRCAD-IHU, University of Strasbourg, 1 place de l'Hôpital, 67091, Strasbourg, France
| | - Jacques Marescaux
- IRCAD-IHU, University of Strasbourg, 1 place de l'Hôpital, 67091, Strasbourg, France
| | - Didier Mutter
- IRCAD-IHU, University of Strasbourg, 1 place de l'Hôpital, 67091, Strasbourg, France
| | - Patrick Pessaux
- IRCAD-IHU, University of Strasbourg, 1 place de l'Hôpital, 67091, Strasbourg, France.
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15
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Ntourakis D, Memeo R, Soler L, Marescaux J, Mutter D, Pessaux P. Augmented Reality Guidance for the Resection of Missing Colorectal Liver Metastases: An Initial Experience. World J Surg 2016; 40:419-426. [PMID: 26316112 DOI: 10.1007/-s00268-015-3229-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Modern chemotherapy achieves the shrinking of colorectal cancer liver metastases (CRLM) to such extent that they may disappear from radiological imaging. Disappearing CRLM rarely represents a complete pathological remission and have an important risk of recurrence. Augmented reality (AR) consists in the fusion of real-time patient images with a computer-generated 3D virtual patient model created from pre-operative medical imaging. The aim of this prospective pilot study is to investigate the potential of AR navigation as a tool to help locate and surgically resect missing CRLM. METHODS A 3D virtual anatomical model was created from thoracoabdominal CT-scans using customary software (VR RENDER(®), IRCAD). The virtual model was superimposed to the operative field using an Exoscope (VITOM(®), Karl Storz, Tüttlingen, Germany). Virtual and real images were manually registered in real-time using a video mixer, based on external anatomical landmarks with an estimated accuracy of 5 mm. This modality was tested in three patients, with four missing CRLM that had sizes from 12 to 24 mm, undergoing laparotomy after receiving pre-operative oxaliplatin-based chemotherapy. RESULTS AR display and fine registration was performed within 6 min. AR helped detect all four missing CRLM, and guided their resection. In all cases the planned security margin of 1 cm was clear and resections were confirmed to be R0 by pathology. There was no postoperative major morbidity or mortality. No local recurrence occurred in the follow-up period of 6-22 months. CONCLUSIONS This initial experience suggests that AR may be a helpful navigation tool for the resection of missing CRLM.
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Affiliation(s)
- Dimitrios Ntourakis
- IRCAD-IHU, University of Strasbourg, 1 place de l'Hôpital, 67091, Strasbourg, France.
| | - Ricardo Memeo
- IRCAD-IHU, University of Strasbourg, 1 place de l'Hôpital, 67091, Strasbourg, France
| | - Luc Soler
- IRCAD-IHU, University of Strasbourg, 1 place de l'Hôpital, 67091, Strasbourg, France
| | - Jacques Marescaux
- IRCAD-IHU, University of Strasbourg, 1 place de l'Hôpital, 67091, Strasbourg, France
| | - Didier Mutter
- IRCAD-IHU, University of Strasbourg, 1 place de l'Hôpital, 67091, Strasbourg, France
| | - Patrick Pessaux
- IRCAD-IHU, University of Strasbourg, 1 place de l'Hôpital, 67091, Strasbourg, France.
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16
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Tyng CJ, Schiavon LHO, Coimbra FJF, Barbosa PNV, Bitencourt AGV, Almeida MFA, Schiavon ACSA, Diniz AL, Guimaraes MD, Chojniak R. Modified preoperative computed tomographic-guided localization of colorectal liver metastases with metallic clips--technical note. Clin Colorectal Cancer 2015; 14:123-7. [PMID: 25600447 DOI: 10.1016/j.clcc.2014.12.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2014] [Revised: 12/17/2014] [Accepted: 12/19/2014] [Indexed: 11/19/2022]
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17
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Zendel A, Lahat E, Dreznik Y, Zakai BB, Eshkenazy R, Ariche A. "Vanishing liver metastases"-A real challenge for liver surgeons. Hepatobiliary Surg Nutr 2014; 3:295-302. [PMID: 25392841 DOI: 10.3978/j.issn.2304-3881.2014.09.13] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2014] [Accepted: 09/16/2014] [Indexed: 12/21/2022]
Abstract
Expanded surgical intervention in colorectal liver metastasis (LM) and improved chemotherapy led to increasing problem of disappearing liver metastases (DLM). Treatment of those continues to evolve and poses a real challenge for HPB surgeons. This review discusses a clinical approach to DLM, emphasizing crucial steps in clinical algorithm. Particular issues such as imaging, intraoperative detection and surgical techniques are addressed. A step-by-step algorithm is suggested.
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Affiliation(s)
- Alex Zendel
- 1 Department of Surgery C, 2 Department of Surgery B, 3 Department of HPB Surgery, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Eylon Lahat
- 1 Department of Surgery C, 2 Department of Surgery B, 3 Department of HPB Surgery, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Yael Dreznik
- 1 Department of Surgery C, 2 Department of Surgery B, 3 Department of HPB Surgery, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Barak Bar Zakai
- 1 Department of Surgery C, 2 Department of Surgery B, 3 Department of HPB Surgery, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Rony Eshkenazy
- 1 Department of Surgery C, 2 Department of Surgery B, 3 Department of HPB Surgery, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Arie Ariche
- 1 Department of Surgery C, 2 Department of Surgery B, 3 Department of HPB Surgery, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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18
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Brouquet A, Nordlinger B. Adjuvant Therapy in Combination with Resection of Colorectal Cancer Metastasis to the Liver or Lungs. CURRENT COLORECTAL CANCER REPORTS 2014. [DOI: 10.1007/s11888-014-0239-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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Macedo FIB, Makarawo T. Colorectal hepatic metastasis: Evolving therapies. World J Hepatol 2014; 6:453-463. [PMID: 25067997 PMCID: PMC4110537 DOI: 10.4254/wjh.v6.i7.453] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2013] [Revised: 02/23/2014] [Accepted: 06/03/2014] [Indexed: 02/06/2023] Open
Abstract
The approach for colorectal hepatic metastasis has advanced tremendously over the past decade. Multidrug chemotherapy regimens have been successfully introduced with improved outcomes. Concurrently, adjunct multimodal therapies have improved survival rates, and increased the number of patients eligible for curative liver resection. Herein, we described major advancements of surgical and oncologic management of such lesions, thereby discussing modern chemotherapeutic regimens, adjunct therapies and surgical aspects of liver resection.
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20
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Cooper A, Aloia TA. Managing Disappearing Liver Metastases Following Chemotherapy. CURRENT COLORECTAL CANCER REPORTS 2014. [DOI: 10.1007/s11888-014-0215-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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21
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Bischof DA, Clary BM, Maithel SK, Pawlik TM. Surgical management of disappearing colorectal liver metastases. Br J Surg 2013; 100:1414-20. [PMID: 24037559 DOI: 10.1002/bjs.9213] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/22/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND Owing to expanded surgical indications for colorectal liver metastasis (CRLM) and improved systemic therapy, hepatic surgeons are increasingly faced with the problem of disappearing (no longer visible on imaging) liver metastasis (DLM). METHODS A review of relevant studies was performed. Studies that reported on DLM associated with preoperative chemotherapy for CRLM were identified, and data were synthesized and tabulated. The PubMed database was searched for relevant articles published between January 2000 and December 2012. RESULTS A complete response on imaging does not necessarily equate with a complete clinical or pathological response. Rather, residual macroscopic disease is found in about 25-45 per cent of patients at the time of operation. Even among patients with a complete pathological response, long-term remission occurs in only 20-50 per cent of those treated with systemic therapy. A durable response of DLM is more common following the use of hepatic artery infusion therapy. CONCLUSION Liver resection should include all original sites of disease if possible.
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Affiliation(s)
- D A Bischof
- Departments of Surgery, Johns Hopkins Hospital, Baltimore, Maryland
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22
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Abdalla EK, Bauer TW, Chun YS, D'Angelica M, Kooby DA, Jarnagin WR. Locoregional surgical and interventional therapies for advanced colorectal cancer liver metastases: expert consensus statements. HPB (Oxford) 2013; 15:119-30. [PMID: 23297723 PMCID: PMC3719918 DOI: 10.1111/j.1477-2574.2012.00597.x] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2012] [Accepted: 08/20/2012] [Indexed: 12/12/2022]
Abstract
Selection of the optimal surgical and interventional therapies for advanced colorectal cancer liver metastases (CRLM) requires multidisciplinary discussion of treatment strategies early in the trajectory of the individual patient's care. This paper reports on expert consensus on locoregional and interventional therapies for the treatment of advanced CRLM. Resection remains the reference treatment for patients with bilateral CRLM and synchronous presentation of primary and metastatic cancer. Patients with oligonodular bilateral CRLM may be candidates for one-stage multiple segmentectomies; two-stage resection with or without portal vein embolization may allow complete resection in patients with more advanced disease. After downsizing with preoperative systemic and/or regional therapy, curative-intent hepatectomy requires resection of all initial and currently known sites of disease; debulking procedures are not recommended. Many patients with synchronous primary disease and CRLM can safely undergo simultaneous resection of all disease. Staged resections should be considered for patients in whom the volume of the future liver remnant is anticipated to be marginal or inadequate, who have significant medical comorbid condition(s), or in whom extensive resections are required for the primary cancer and/or CRLM. Priority for liver-first or primary-first resection should depend on primary tumour-related symptoms or concern for the progression of marginally resectable CRLM during treatment of the primary disease. Chemotherapy delivered by hepatic arterial infusion represents a valid option in patients with liver-only disease, although it is best delivered in experienced centres. Ablation strategies are not recommended as first-line treatments for resectable CRLM alone or in combination with resection because of high local failure rates and limitations related to tumour size, multiplicity and intrahepatic location.
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Affiliation(s)
- Eddie K Abdalla
- Department of Surgery, Lebanese American UniversityBeirut, Lebanon
| | - Todd W Bauer
- Department of Surgery, University of Virginia Health SystemCharlottesville, VA, USA
| | - Yun S Chun
- Department of Surgical Oncology, Fox Chase Cancer CenterPhiladelphia, PA, USA
| | - Michael D'Angelica
- Department of Surgery, Memorial Sloan–Kettering Cancer CenterNew York, NY, USA
| | - David A Kooby
- Department of Surgery, Emory University School of MedicineAtlanta, GA, USA
| | - William R Jarnagin
- Department of Surgery, Memorial Sloan–Kettering Cancer CenterNew York, NY, USA
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23
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Adams RB, Aloia TA, Loyer E, Pawlik TM, Taouli B, Vauthey JN. Selection for hepatic resection of colorectal liver metastases: expert consensus statement. HPB (Oxford) 2013; 15:91-103. [PMID: 23297719 PMCID: PMC3719914 DOI: 10.1111/j.1477-2574.2012.00557.x] [Citation(s) in RCA: 223] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2012] [Accepted: 07/29/2012] [Indexed: 02/06/2023]
Abstract
Hepatic resection offers a chance of a cure in selected patients with colorectal liver metastases (CLM). To achieve adequate patient selection and curative surgery, (i) precise assessment of the extent of disease, (ii) sensitive criteria for chemotherapy effect, (iii) adequate decision making in surgical indication and (iv) an optimal surgical approach for pre-treated tumours are required. For assessment of the extent of the disease, contrast-enhanced computed tomography (CT) and/or magnetic resonance imaging (MRI) with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) is recommended depending on the local expertise and availability. Positron emission tomography (PET) and PET/CT may offer additive information in detecting extrahepatic disease. The RECIST criteria are a reasonable method to evaluate the effect of chemotherapy. However, they are imperfect in predicting a pathological response in the era of modern systemic therapy with biological agents. The assessment of radiographical morphological changes is a better surrogate of the pathological response and survival especially in the patients treated with bevacizumab. Resectability of CLM is dependent on both anatomic and oncological factors. To decrease the surgical risk, a sufficient volume of liver remnant with adequate blood perfusion and biliary drainage is required according to the degree of histopathological injury of the underlying liver. Portal vein embolization is sometimes required to decrease the surgical risk in a patient with small future liver remnant volume. As a complete radiological response does not signify a complete pathological response, liver resection should include all the site of a tumour detected prior to systemic treatment.
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Affiliation(s)
- Reid B Adams
- Division of General Surgery, University of Virginia School of MedicineCharlottesville, VA, USA
| | - Thomas A Aloia
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer CenterHouston, TX, USA
| | - Evelyne Loyer
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer CenterHouston, TX, USA
| | - Timothy M Pawlik
- Department of Surgery, Johns Hopkins UniversityBaltimore, MD, USA
| | - Bachir Taouli
- Department of Radiology, Mount Sinai Medical CenterNew York, NY, USA
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer CenterHouston, TX, USA
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Alonso Casado O, González Moreno S, Encinas García S, Rojo Sebastián A, Olavarría Delgado A. [Hepatic metastasis marking before neoadjuvant chemotherapy for their subsequent location and resection using non-anatomical hepatectomy]. Cir Esp 2012; 91:687-9. [PMID: 23041103 DOI: 10.1016/j.ciresp.2012.07.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2012] [Accepted: 07/07/2012] [Indexed: 10/27/2022]
Affiliation(s)
- Oscar Alonso Casado
- Unidad de Oncología Quirúrgica Digestiva, MD Anderson Cancer Center, Madrid, España.
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25
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Nanji S, Cleary S, Ryan P, Guindi M, Selvarajah S, Al-Ali H, Grieg P, McGilvary I, Taylor B, Wei A, Moulton CA, Gallinger S. Up-front hepatic resection for metastatic colorectal cancer results in favorable long-term survival. Ann Surg Oncol 2012; 20:295-304. [PMID: 23054102 DOI: 10.1245/s10434-012-2424-1] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2011] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatic metastasis from colorectal cancer (CRC) is best managed with a multimodal approach; however, the optimal timing of liver resection in relation to administration of perioperative chemotherapy remains unclear. Our strategy has been to offer up-front liver resection for patients with resectable hepatic metastases, followed by post-liver resection chemotherapy. We report the outcomes of patients based on this surgical approach. METHODS A retrospective review of all patients undergoing liver resection for CRC metastases over a 5-year period (2002-2007) was performed. Associations between clinicopathologic factors and survival were evaluated by the Cox proportional hazard method. RESULTS A total of 320 patients underwent 336 liver resections. Median follow-up was 40 (range 8-80) months. The majority (n=195, 60.9%) had metachronous disease, and most patients (n=286, 85%) had a major hepatectomy (>3 segments). Thirty-six patients (11%) received preoperative chemotherapy, predominantly for downstaging unresectable disease. Ninety-day mortality was 2.1%, and perioperative morbidity occurred in 68 patients (20.2%). Actual disease-free survival at 3 and 5 years was 46.2% and 42%, respectively. Actual overall survival (OS) at 3 and 5 years was 63.7% and 55%, respectively. Multivariate analysis identified four factors that were independently associated with differences in OS (hazard ratio; 95% confidence interval): size of metastasis>6 cm (2.2; 1.3-3.5), positive lymph node status of the primary CRC (N1 (2.0; 1.0-3.8), N2 (2.4; 1.2-4.9)), synchronous disease (2.1; 1.3-3.5), and treatment with chemotherapy after liver resection (0.42; 0.23-0.75). CONCLUSIONS Up-front surgery for patients with resectable CRC liver metastases, followed by chemotherapy, can lead to favorable OS.
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Affiliation(s)
- Sulaiman Nanji
- Department of Surgery, Queen's University, Kingston, ON, Canada
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26
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Adam R, De Gramont A, Figueras J, Guthrie A, Kokudo N, Kunstlinger F, Loyer E, Poston G, Rougier P, Rubbia-Brandt L, Sobrero A, Tabernero J, Teh C, Van Cutsem E. The oncosurgery approach to managing liver metastases from colorectal cancer: a multidisciplinary international consensus. Oncologist 2012; 17:1225-39. [PMID: 22962059 DOI: 10.1634/theoncologist.2012-0121] [Citation(s) in RCA: 410] [Impact Index Per Article: 31.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
An international panel of multidisciplinary experts convened to develop recommendations for the management of patients with liver metastases from colorectal cancer (CRC). The aim was to address the main issues facing the CRC hepatobiliary multidisciplinary team (MDT) when managing such patients and to standardize the treatment patients receive in different centers. Based on current evidence, the group agreed on a number of issues including the following: (a) the primary aim of treatment is achieving a long disease-free survival (DFS) interval following resection; (b) assessment of resectability should be performed with high-quality cross-sectional imaging, staging the liver with magnetic resonance imaging and/or abdominal computed tomography (CT), depending on local expertise, staging extrahepatic disease with thoracic and pelvic CT, and, in selected cases, fluorodeoxyglucose positron emission tomography with ultrasound (preferably contrast-enhanced ultrasound) for intraoperative staging; (c) optimal first-line chemotherapy-doublet or triplet chemotherapy regimens combined with targeted therapy-is advisable in potentially resectable patients; (d) in this situation, at least four courses of first-line chemotherapy should be given, with assessment of tumor response every 2 months; (e) response assessed by the Response Evaluation Criteria in Solid Tumors (conventional chemotherapy) or nonsize-based morphological changes (antiangiogenic agents) is clearly correlated with outcome; no imaging technique is currently able to accurately diagnose complete pathological response but high-quality imaging is crucial for patient management; (f) the duration of chemotherapy should be as short as possible and resection achieved as soon as technically possible in the absence of tumor progression; (g) the number of metastases or patient age should not be an absolute contraindication to surgery combined with chemotherapy; (h) for synchronous metastases, it is not advisable to undertake major hepatic surgery during surgery for removal of the primary CRC; the reverse surgical approach (liver first) produces as good an outcome as the conventional approach in selected cases; (i) for patients with resectable liver metastases from CRC, perioperative chemotherapy may be associated with a modestly better DFS outcome; and (j) whether initially resectable or unresectable, cure or at least a long survival duration is possible after complete resection of the metastases, and MDT treatment is essential for improving clinical and survival outcomes. The group proposed a new system to classify initial unresectability based on technical and oncological contraindications.
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Affiliation(s)
- René Adam
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Sud, UMR-S 776, Villejuf, France.
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27
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Knowles B, Welsh FKS, Chandrakumaran K, John TG, Rees M. Detailed liver-specific imaging prior to pre-operative chemotherapy for colorectal liver metastases reduces intra-hepatic recurrence and the need for a repeat hepatectomy. HPB (Oxford) 2012; 14:298-309. [PMID: 22487067 PMCID: PMC3384849 DOI: 10.1111/j.1477-2574.2012.00447.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Neoadjuvant chemotherapy for colorectal liver metastases (CRLM) reduces the accuracy of liver imaging which may understage patients pre-operatively. Retrospective review of a prospective database to determine whether liver-specific magnetic resonance imaging (MRI) prior to pre-operative chemotherapy affects intra-hepatic recurrence and long-term outcome after hepatectomy. PATIENTS AND METHODS Between 2003 and 2009, 242 patients with CRLM underwent a hepatectomy after ≥3 cycles of oxaliplatin or irinotecan-based chemotherapy. All had a liver-specific MRI immediately pre-operatively. The outcome of patients who had a liver-specific MRI prior to chemotherapy (PCI group, n= 92) was compared with those who did not (non-PCI group, n= 150). RESULTS A liver-specific MRI pre-chemotherapy changed the staging in 56% of patients. At a median (range) follow-up of 55 (6-94) months, there was a higher incidence of intra-hepatic recurrence at a new site in the non-PCI group (65% vs. 48% in the PCI group, P= 0.041) and an increased rate of recurrence in patients with the same number of lesions pre- and post-chemotherapy [hazard ratio (HR) 2.02, 1:10-3.37, P= 0.024]. The non-PCI group underwent more repeat hepatectomies than the PCI group (24.7% vs. 13%, P= 0.034), achieving similar long-term survival. CONCLUSIONS A liver-specific MRI prior to chemotherapy reduces intra-hepatic recurrence and avoids a repeat hepatectomy.
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Affiliation(s)
- Brett Knowles
- Hepatobiliary Unit, Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK
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28
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Brouquet A, Nordlinger B. Neoadjuvant and adjuvant therapy in relation to surgery for colorectal liver metastases. Scand J Gastroenterol 2012; 47:286-95. [PMID: 22182353 DOI: 10.3109/00365521.2012.640826] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Liver resection is associated with prolonged survival in patients with colorectal liver metastases. At diagnosis, 15-20% of patients have resectable colorectal liver metastases whereas other patients have too advanced disease to enable surgical treatment and receive chemotherapy. In patients undergoing resection of colorectal liver metastases, disease relapse occurs in up to 70%. Therefore, a combined approach including preoperative or postoperative chemotherapy or both has been tested to improve outcome after surgery. In patients with unresectable colorectal liver metastases, chemotherapy is initially the sole treatment option. The considerable improvement of the efficacy of anticancer agents has contributed to increase the response rate in patients with advanced colorectal cancer. In case of major response to chemotherapy, surgery with curative intent can be offered to patients with initially unresectable liver metastases.
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Affiliation(s)
- Antoine Brouquet
- Department Digestive and Oncologic Surgery, AP-HP, Université Versailles Saint Quentin en Yvelines, Hôpital Ambroise Paré, Versailles, France
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29
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Brouquet A, Overman MJ, Kopetz S, Maru DM, Loyer EM, Andreou A, Cooper A, Curley SA, Garrett CR, Abdalla EK, Vauthey JN. Is resection of colorectal liver metastases after a second-line chemotherapy regimen justified? Cancer 2011; 117:4484-92. [PMID: 21446046 PMCID: PMC3128184 DOI: 10.1002/cncr.26036] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2010] [Revised: 11/22/2010] [Accepted: 01/03/2011] [Indexed: 12/29/2022]
Abstract
BACKGROUND Patient outcomes following resection of colorectal liver metastases (CLM) after second-line chemotherapy regimen is unknown. METHODS From August 1998 to June 2009, data from 1099 patients with CLM were collected prospectively. We retrospectively analyzed outcomes of patients who underwent resection of CLM after second-line (2 or more) chemotherapy regimens. RESULTS Sixty patients underwent resection of CLM after 2 or more chemotherapy regimens. Patients had advanced CLM (mean number of CLM ± standard deviation, 4 ± 3.5; mean maximum size of CLM, 5 ± 3.2 cm) and had received 17 ± 8 cycles of preoperative chemotherapy. In 54 (90%) patients, the switch from the first regimen to another regimen was motivated by tumor progression or suboptimal radiographic response. All patients received irinotecan or oxaliplatin, and the majority (42/60 [70%]) received a monoclonal antibody (bevacizumab or cetuximab) as part of the last preoperative regimen. Postoperative morbidity and mortality rates were 33% and 3%, respectively. At a median follow-up of 32 months, 1-year, 3-year, and 5-year overall survival rates were 83%, 41%, and 22%, respectively. Median chemotherapy-free survival after resection or completion of additional chemotherapy administered after resection was 9 months (95% confidence interval, 4-14 months). Synchronous (vs metachronous) CLM and minor (vs major) pathologic response were independently associated with worse survival. CONCLUSIONS Resection of CLM after a second-line chemotherapy regimen was found to be safe and was associated with a modest hope for definitive cure. This approach represents a viable option in patients with advanced CLM.
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Affiliation(s)
- Antoine Brouquet
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
| | - Michael J. Overman
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
| | - Scott Kopetz
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
| | - Dipen M. Maru
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
| | - Evelyne M. Loyer
- Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
| | - Andreas Andreou
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
| | - Amanda Cooper
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
| | - Steven A. Curley
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
| | - Christopher R. Garrett
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
| | - Eddie K. Abdalla
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
| | - Jean Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
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30
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Brouquet A, Andreou A, Vauthey JN. The management of solitary colorectal liver metastases. Surgeon 2011; 9:265-72. [PMID: 21843821 DOI: 10.1016/j.surge.2010.12.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2010] [Accepted: 12/16/2010] [Indexed: 02/07/2023]
Abstract
Surgical resection of solitary colorectal liver metastases is associated with long-term survival. Radiofrequency ablation used as the primary treatment option of solitary resectable colorectal liver metastases is associated with an increased risk of local recurrence that generally leads to worse survival compared to resection. In contrast with treatment of other hepatic malignancies, radiofrequency ablation is not equivalent to resection for colorectal liver metastases and should not be used as an alternative but limited to inoperable patients. Although overall survival rate after resection can be up to 71% at 5 years, the majority of patients develop recurrence. Preoperative chemotherapy contributes to decrease the risk of recurrence after resection of colorectal liver metastases. In patients with advanced solitary colorectal liver metastasis initially non suitable for resection, chemotherapy and portal vein embolization contribute to increase the number of surgical candidates whereas radiofrequency is rarely an option.
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Affiliation(s)
- Antoine Brouquet
- Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 444, Houston, TX 77030, United States
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31
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Patients operated on for initially unresectable colorectal liver metastases with missing metastases experience a favorable long-term outcome. Ann Surg 2011; 254:114-8. [PMID: 21516034 DOI: 10.1097/sla.0b013e31821ad704] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND After chemotherapy, complete clinical responses of colorectal liver metastases (CRLMs) increasingly occur, but these responses are rarely complete pathological responses. The management of patients with missing metastases, that is, CRLMs that disappear under chemotherapy are undetectable intraoperatively and finally left in place, continues to be controversial. The aim of this study was to assess the long-term outcome of patients with "missing CRLMs." PATIENTS Between 1999 and 2007, among 523 patients operated on for CRLMs, 96 missing CRLMs were observed and left in place in 27 originally unresectable patients. All of these patients received preoperative chemotherapy. Hepatic arterial infusion (HAI) of oxaliplatin combined with systemic 5-fluorouracil was administered in 23 patients, including 12 before hepatectomy and 11 after. Hepatic surgery was performed after a minimal interval of 3 months during which CRLMs had disappeared on imaging. RESULTS After a median follow-up of 55 months (24-137) after hepatic surgery, an intrahepatic recurrence was diagnosed in 14 (52%) patients, but the recurrence rate was significantly lower in patients who had received adjuvant HAI compared with the others (27% vs 83%, P = 0.006). Recurrences arose at the site of the missing CRLMs in 9 (33%) patients, but was associated in all cases with another recurrence in the liver. The 5-year overall survival rate of these 27 highly chemosensitive patients was 80%, and the 5-year disease-free survival rate was 23%. CONCLUSION Highly chemosensitive patients, whose initially unresectable CRLMs become resectable because of missing CRLMs left in place, have a favorable long-term outcome. Missing CRLMs should not be longer, a contraindication to hepatic surgery. Use of postoperative HAI of oxaliplatin can help to reduce the risk of hepatic relapse.
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32
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[Hepatectomy for colorectal liver metastases after neoadjuvant chemotherapy]. Bull Cancer 2011; 98:11-8. [PMID: 21300602 DOI: 10.1684/bdc.2010.1284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The majority of patients with colorectal liver metastases receive systemic chemotherapy. In the context of unresectable liver metastases, the objective of chemotherapy based on new and more effective regimens is not only to prolong survival, but also to induce enough response and shrinkage of the tumor to render resectable patients initially not deemed to be surgical candidates. In patients with resectable liver metastases, the goal of chemotherapy is to improve the outcome after surgery and especially to decrease the risk of recurrence. Although the principles of combined modality treatment become widely accepted, this therapeutic strategy is also associated with potential risks related to the preoperative use of chemotherapy.
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33
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Brouquet A, Nordlinger B. Neoadjuvant therapy of colorectal liver metastases: Lessons learned from clinical trials. J Surg Oncol 2010; 102:932-6. [PMID: 21165995 DOI: 10.1002/jso.21657] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Antoine Brouquet
- Department of Digestive and Oncologic Surgery, AP-HP, Hôpital Ambroise Paré, Université Versailles Saint Quentin en Yvelines, Versailles, France
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34
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van Vledder MG, de Jong MC, Pawlik TM, Schulick RD, Diaz LA, Choti MA. Disappearing colorectal liver metastases after chemotherapy: should we be concerned? J Gastrointest Surg 2010; 14:1691-700. [PMID: 20839072 DOI: 10.1007/s11605-010-1348-y] [Citation(s) in RCA: 96] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2010] [Accepted: 08/23/2010] [Indexed: 01/31/2023]
Abstract
BACKGROUND With increasing efficacy of preoperative chemotherapy for colorectal cancer, more patients will present with one or more disappearing liver metastases (DLM) on preoperative cross-sectional imaging. PATIENTS AND METHODS A retrospective review was conducted evaluating the radiological response to preoperative chemotherapy for 168 patients undergoing surgical therapy for colorectal liver metastases at Johns Hopkins Hospital between 2000 and 2008. RESULTS Forty patients (23.8%) had one or more DLM, accounting for a total of 127 lesions. In 22 patients (55%), all DLM sites were treated during surgery. Of the 17 patients with unidentified, untreated DLM, ten patients (59%) developed a local recurrence at the initial site, half of which also developed recurrences in other sites. While the intrahepatic recurrence rate was higher for patients with DLM left in situ (p = 0.04), the 1-, 3-, and 5-year overall survival rate was not significantly different for patients with DLM left in situ (93.8%, 63.5%, and 63.5%, respectively) when compared to patients with a radiological chemotherapy response in whom all original disease sites were surgically treated (92.3%, 70.8%, and 46.2%, respectively; p = 0.66). CONCLUSIONS DLM were frequently observed in patients undergoing preoperative chemotherapy for liver metastases. Survival was comparable in patients with untreated DLM, in spite of high intrahepatic recurrence rates seen in these patients. Therefore, aggressive surgical therapy should be considered in patients with marked response to chemotherapy, even when all DLM sites cannot be identified.
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Affiliation(s)
- Mark G van Vledder
- Department of Surgery and Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
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35
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Auer RC, White RR, Kemeny NE, Schwartz LH, Shia J, Blumgart LH, Dematteo RP, Fong Y, Jarnagin WR, D'Angelica MI. Predictors of a true complete response among disappearing liver metastases from colorectal cancer after chemotherapy. Cancer 2010; 116:1502-9. [PMID: 20120032 DOI: 10.1002/cncr.24912] [Citation(s) in RCA: 136] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND During chemotherapy, some colorectal liver metastases (LMs) disappear on serial imaging. This disappearance may represent a complete response (CR) or a reduction in the sensitivity of imaging during chemotherapy. The objective of the current study was to determine the fate of disappearing LMs (DLMs) and the factors that predict a true CR. METHODS Between 2000 and 2003, 435 patients who were evaluated by hepatobiliary surgeons received chemotherapy before they were considered for resection. Inclusion criteria were <12 LMs before chemotherapy, at least 1 DLM on a computed tomography (CT) scan, and either surgical resection or 1 year of clinical follow-up after the disappearance of LMs. A true CR was defined as either a pathologic CR (no tumor detected in the resection specimen) or a durable clinical CR (did not reappear on follow-up imaging). Clinical and pathologic factors were analyzed to identify those associated with a true CR. RESULTS During chemotherapy, 39 patients (9%) had a total of 118 DLMs on follow-up CT scans. Sixty-eight DLMs were resected, and 50 were followed clinically. Overall, 75 DLMs (64%) were true CRs, including 44 pathologic CRs and 31 durable clinical CRs. On multivariate analysis, the use of hepatic arterial infusion (HAI) chemotherapy (odds ratio [OR], 6.2; P = .02), the inability to observe the DLM on a magnetic resonance image (OR, 4.7; P = .005), and normalization of serum carcinoembryonic antigen levels (OR, 4.6; P = .006) were associated independently with a true CR. CONCLUSIONS Approximately 66% of DLMs represented a true CR according to assessment by resection or radiologic follow-up. Predictive factors may help to stratify patients who are likely to harbor residual disease.
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Affiliation(s)
- Rebecca C Auer
- Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada.
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36
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Vauthey JN, Nordlinger B, Kopetz S, Poston G. Sequenced chemotherapy and surgery for potentially resectable colorectal liver metastases: a debate over goals of research and an approach while the jury remains out. Ann Surg Oncol 2010; 17:1983-6. [PMID: 20232164 DOI: 10.1245/s10434-010-1007-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2009] [Indexed: 02/06/2023]
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Brouquet A, Mitry E, Benoist S. [The role of perioperative chemotherapy in patients with resectable colorectal liver metastases]. ACTA ACUST UNITED AC 2010; 147 Suppl 1:S1-6. [PMID: 20172199 DOI: 10.1016/s0021-7697(10)70001-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Surgical resection remains the only treatment of colorectal liver metastases that can ensure long-term survival and cure in some patients, but only a minority of patients with liver metastases is directly amenable to surgery. Cancer relapse is observed in the majority of patients after resection of liver metastases despite progress in surgical technique and improved surgical skills. In order to decrease the risk of cancer relapse, it has been proposed to combine surgery and chemotherapy, which could be administered before, after or before and after surgery. It has been demonstrated that perioperative chemotherapy can reduce the risk of cancer relapse and should be considered as the standard of care for most patients with resectable colorectal liver metastases. However perioperative chemotherapy has also potential disadvantages. This review will summarize the current data on the rationale, benefits and potential disadvantages of perioperative chemotherapy in patients with resectable colorectal liver metastases.
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Affiliation(s)
- A Brouquet
- Service de Chirurgie Digestive et Oncologique AP-HP, Hôpital Ambroise Paré, 9, avenue Charles-de-Gaulle, 92104 Boulogne cedex, France; Université de Versailles - Saint-Quentin-en-Yvelines, 23, rue du Refuge, 78000 Versailles, France
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Abstract
Surgery is the only curative option for patients with liver metastases of colorectal cancer, but few patients present with resectable hepatic lesions. Chemotherapy is increasingly used to downstage initially unresectable disease and allow for potentially curative surgery. Standard chemotherapy regimens convert 10%-20% of cases to resectable disease in unselected populations and 30%-40% of those with disease confined to the liver. One strategy to further increase the number of candidates eligible for surgery is the addition of active targeted agents such as cetuximab and bevacizumab to standard chemotherapy. Data from a phase III trial indicate that cetuximab increases the number of patients eligible for secondary hepatic resection, as well as the rate of complete resection when combined with first-line treatment with the FOLFIRI regimen. The safety profiles of preoperative cetuximab or bevacizumab have not been thoroughly assessed, but preliminary evidence indicates that these agents do not increase surgical mortality or exacerbate chemotherapy-related hepatotoxicity, such as steatosis (5-fluorouracil), steatohepatitis (irinotecan), and sinusoidal obstruction (oxaliplatin). Secondary resection is a valid treatment goal for certain patients with initially unresectable liver metastases and an important end point for future clinical trials.
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