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Padmanabhan C, Nussbaum DP, D'Angelica M. Surgical Management of Colorectal Cancer Liver Metastases. Hematol Oncol Clin North Am 2025; 39:1-24. [PMID: 39510667 DOI: 10.1016/j.hoc.2024.08.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2024]
Abstract
Approximately 50% of colorectal cancer patients develop liver metastases. Hepatic metastases represent the most common cause of colorectal cancer-related mortality. Metastasectomy, if possible, represents the most effective treatment strategy; 20% of patients will be cured and more than 50% survive at least 5 years. Nuances to treatment planning hinge on whether patients present with resectable disease upfront, whether the future liver remnant is adequate, and whether the primary tumor, if present, is colon versus rectal in origin. This article discusses considerations impacting our approach to patients with colorectal liver metastases and the role for various multimodal treatment options.
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Affiliation(s)
- Chandrasekhar Padmanabhan
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-1272, New York, NY 10065, USA
| | - Daniel P Nussbaum
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-1272, New York, NY 10065, USA
| | - Michael D'Angelica
- Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-898, New York, NY 10065, USA.
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Sourrouille I, Pastier C, Gelli M, Benhaïm L, Cattan P, Ducreux M, Aparicio T, Goéré D. Results of complete cytoreductive strategy in patients with peritoneal metastases of colorectal origin with or without extraperitoneal metastases: A bicentric analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:108788. [PMID: 39531916 DOI: 10.1016/j.ejso.2024.108788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 10/03/2024] [Accepted: 10/24/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Increased survival can be achieved in patients with colorectal cancer peritoneal metastases (CRPM) treated with cytoreductive surgery. The benefit of this strategy remains uncertain when CRPM are associated with extraperitoneal metastases (EPM). The aim of this study was to compare short- and long-term outcomes of patients treated with CRS for CRPM, with or without EPM. METHODS This study included 413 consecutive patients who underwent CRS for CRPM: 120 with EPM (EPM+) and 293 without (EPM-). Patients with isolated ovarian metastases were included in EPM-group (n = 83). RESULTS EPM were mainly located to the liver (66 %,n = 79), retroperitoneal lymph nodes (33 %,n = 40); less frequently to the spleen (9 %,n = 12), lung (9 %,n = 10) or pleura (1 %,n = 1). Ovarian metastases were present in 126 patients (83 in EMP-, 43 in EPM+). Peritoneal carcinomatosis index (PCI) was similar in EPM- (8 [4-14]) and EPM+ (8 [3-13],p = 0.335) groups, as postoperative mortality (3 % vs 3 %,p = 1) and major morbidity rates (28 % vs 35 %,p = 0.223). Median overall survival (mOS) and disease-free survival were significantly higher in the EPM-group (58m vs 39m, and 16m vs 10m,p = 0.003). We highlighted 3 prognostic groups 1) EPM-with PCI<10 (mOS 93m), 2) EPM+ with PCI<10 (mOS 57m), 3) EPM-with 10 15 regardless EPM (mOS 26m, p < 0.001). CONCLUSION Complete cytoreductive surgery seems to be feasible in patients with EPM, without increase in postoperative morbidity and mortality compared to patients without EPM. This strategy provides prolonged survival in selected patients with limited peritoneal metastases from colorectal cancer.
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Affiliation(s)
| | - Clément Pastier
- Department of Surgical Oncology, Hopital Saint Louis, Paris, France
| | | | - Léonor Benhaïm
- Department of Surgical Oncology, Gustave Roussy, Villejuif, France
| | - Pierre Cattan
- Department of Surgical Oncology, Hopital Saint Louis, Paris, France
| | - Michel Ducreux
- Department of Medical Oncology, Gustave Roussy, Villejuif, France
| | - Thomas Aparicio
- Department of Medical Oncology, Hopital Saint Louis, Paris, France
| | - Diane Goéré
- Department of Surgical Oncology, Hopital Saint Louis, Paris, France.
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Xu D, He Y, Liao C, Tan J. Identifying risk and prognostic factors for synchronous liver metastasis in small bowel adenocarcinoma: a predictive analysis using the SEER database. Front Surg 2024; 11:1437124. [PMID: 39136035 PMCID: PMC11317383 DOI: 10.3389/fsurg.2024.1437124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 07/19/2024] [Indexed: 08/15/2024] Open
Abstract
Background Small bowel adenocarcinoma (SBA) is a rare gastrointestinal malignancy with an increasing incidence and a high propensity for liver metastasis (LM). This study aimed to investigate the risk factors for synchronous LM and prognostic factors in patients with LM. Methods Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, this study analyzed data from 2,064 patients diagnosed with SBA between 2010 and 2020. Logistic regression was used to determine risk factors for synchronous LM. A nomogram was developed to predict the risk of LM in SBA patients, and its predictive performance was assessed through receiver operating characteristic (ROC) curves and calibration curves. Kaplan-Meier and Cox regression analyses were conducted to evaluate survival outcomes for SBA patients with LM. Results Synchronous LM was present in 13.4% of SBA patients (n = 276). Six independent predictive factors for LM were identified, including tumor location, T stage, N stage, surgical intervention, retrieval of regional lymph nodes (RORLN), and chemotherapy. The nomogram demonstrated good discriminative ability, with an area under the curve (AUC) of 83.8%. Patients with LM had significantly lower survival rates than those without LM (P < 0.001). Survival analysis revealed that advanced age, tumor location in the duodenum, surgery, RORLN and chemotherapy were associated with cancer-specific survival (CSS) in patients with LM originating from SBA. Conclusions This study highlights the significant impact of LM on the survival of SBA patients and identifies key risk factors for its occurrence. The developed nomogram aids in targeted screening and personalized treatment planning.
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Affiliation(s)
- Duogang Xu
- Department of General Surgery, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, China
- Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Kunming, China
| | - Yulei He
- The First School of Clinical Medicine, Yunnan University of Chinese Medicine, Kunming, China
| | - Changkang Liao
- Department of General Surgery, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, China
- Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Kunming, China
| | - Jing Tan
- Department of General Surgery, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, China
- Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Kunming, China
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Yokoi R, Tajima JY, Fukada M, Hayashi H, Kuno M, Asai R, Sato Y, Yasufuku I, Kiyama S, Tanaka Y, Murase K, Matsuhashi N. Optimizing Treatment Strategy for Oligometastases/Oligo-Recurrence of Colorectal Cancer. Cancers (Basel) 2023; 16:142. [PMID: 38201569 PMCID: PMC10777959 DOI: 10.3390/cancers16010142] [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: 11/28/2023] [Revised: 12/25/2023] [Accepted: 12/26/2023] [Indexed: 01/12/2024] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer, and nearly half of CRC patients experience metastases. Oligometastatic CRC represents a distinct clinical state characterized by limited metastatic involvement, demonstrating a less aggressive nature and potentially improved survival with multidisciplinary treatment. However, the varied clinical scenarios giving rise to oligometastases necessitate a precise definition, considering primary tumor status and oncological factors, to optimize treatment strategies. This review delineates the concepts of oligometastatic CRC, encompassing oligo-recurrence, where the primary tumor is under control, resulting in a more favorable prognosis. A comprehensive examination of multidisciplinary treatment with local treatments and systemic therapy is provided. The overarching objective in managing oligometastatic CRC is the complete eradication of metastases, offering prospects of a cure. Essential to this management approach are local treatments, with surgical resection serving as the standard of care. Percutaneous ablation and stereotactic body radiotherapy present less invasive alternatives for lesions unsuitable for surgery, demonstrating efficacy in select cases. Perioperative systemic therapy, aiming to control micrometastatic disease and enhance local treatment effectiveness, has shown improvements in progression-free survival through clinical trials. However, the extension of overall survival remains variable. The review emphasizes the need for further prospective trials to establish a cohesive definition and an optimized treatment strategy for oligometastatic CRC.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Nobuhisa Matsuhashi
- Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Gifu, Japan; (R.Y.); (K.M.)
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Zlotnik O, Krzywon L, Bloom J, Kalil J, Altubi I, Lazaris A, Metrakos P. Targeting Liver Metastases to Potentiate Immunotherapy in MS-Stable Colorectal Cancer-A Review of the Literature. Cancers (Basel) 2023; 15:5210. [PMID: 37958384 PMCID: PMC10649257 DOI: 10.3390/cancers15215210] [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: 10/05/2023] [Revised: 10/26/2023] [Accepted: 10/26/2023] [Indexed: 11/15/2023] Open
Abstract
Immunotherapy has revolutionized the treatment of several cancers, including melanoma and lung cancer. However, for colorectal cancer, it is ineffective for 95% of patients with microsatellite-stable disease. Recent evidence suggests that the liver's immune microenvironment plays a pivotal role in limiting the effectiveness of immunotherapy. There is also evidence to show that targeting liver metastases with locoregional therapies, such as surgery or irradiation, could potentiate immunotherapy for these patients. This review presents evidence from preclinical studies regarding the underlying mechanisms and from clinical studies that support this approach. Furthermore, we outline potential directions for future clinical trials. This innovative strategy could potentially establish immunotherapy as an effective treatment for MS-stable colorectal cancer patients, which are currently considered resistant.
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Affiliation(s)
- Oran Zlotnik
- Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (O.Z.); (L.K.); (J.B.); (J.K.); (A.L.)
- Division of General Surgery, McGill University, Montreal, QC H4A 3J1, Canada;
| | - Lucyna Krzywon
- Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (O.Z.); (L.K.); (J.B.); (J.K.); (A.L.)
| | - Jessica Bloom
- Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (O.Z.); (L.K.); (J.B.); (J.K.); (A.L.)
| | - Jennifer Kalil
- Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (O.Z.); (L.K.); (J.B.); (J.K.); (A.L.)
- Division of General Surgery, McGill University, Montreal, QC H4A 3J1, Canada;
| | - Ikhtiyar Altubi
- Division of General Surgery, McGill University, Montreal, QC H4A 3J1, Canada;
| | - Anthoula Lazaris
- Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (O.Z.); (L.K.); (J.B.); (J.K.); (A.L.)
| | - Peter Metrakos
- Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; (O.Z.); (L.K.); (J.B.); (J.K.); (A.L.)
- Division of General Surgery, McGill University, Montreal, QC H4A 3J1, Canada;
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Zhu L, Gong P, Liu Y, Shi Y, Wang W, Zhang W, Hu Z, Li X. A retrospective case-series of influence of chronic hepatitis B on synchronous liver metastasis of colorectal cancer. Front Oncol 2023; 13:1109464. [PMID: 36910607 PMCID: PMC9995980 DOI: 10.3389/fonc.2023.1109464] [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: 12/13/2022] [Accepted: 02/14/2023] [Indexed: 02/25/2023] Open
Abstract
Main point Our retrospective analysis of a large number of cases found in patients with primary colorectal cancer (CRC) carrying positive HBsAg inhibited the occurrence of synchronous liver metastases (SLM). However, liver cirrhosis caused by non-HBV factors promoted the occurrence of SLM. Objectives This study aimed to investigate the effect of HBV on the occurrence of synchronous liver metastases (SLM) of colorectal cancer (CRC). Methods Univariate and multivariate analyses were used to analyze the influence of clinical parameters on the occurrence of SLM. Results A total of 6, 020 patients with primary CRC were included in our study, of which 449 patients carrying HBsAg(+) accounted for 7.46%. 44 cases of SLM occurred in the HBsAg(+) group, accounting for 9.80%, which was much lower than 13.6% (758/5571) in the HBsAg(-) group (X=5.214, P=0.022). Among CRC patients with HBsAg(-), the incidence of SLM was 24.9% and 14.9% in the group with high APRI and FIB-4 levels, respectively, which were significantly higher than that in the compared groups (12.3% and 12.5%, all P<0.05). Compared with the control group, female patients, late-onset patients, and HBV-infective patients had lower risks of SLM (HR=0.737, 95%CI: 0.614-0.883, P<0.001; HR=0.752, 95%CI: 0.603-0.943, P=0.013; HR=0.682, 95%CI: 0.473-0.961, P=0.034). Conclusions The carriage of HBsAg(+) status inhibited the occurrence of SLM from CRC. HBV-causing liver cirrhosis did not further influence the occurrence of SLM, whereas non-HBV-factor cirrhosis promoted the occurrence of SLM. Nevertheless, this still required prospective data validation.
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Affiliation(s)
- Lin Zhu
- Department of General Surgery, Tongji Hospital, Medical College of Tongji University, Shanghai, China
| | - Piqing Gong
- Department of Anorectal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, China
| | - Ye Liu
- Department of Blood Transfusion, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, China
| | - Yunjie Shi
- Department of Anorectal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, China
| | - Wenqiang Wang
- Department of General Surgery, Tongji Hospital, Medical College of Tongji University, Shanghai, China
| | - Wei Zhang
- Department of General Surgery, Tongji Hospital, Medical College of Tongji University, Shanghai, China
| | - Zhiqian Hu
- Department of General Surgery, Tongji Hospital, Medical College of Tongji University, Shanghai, China.,Department of Anorectal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, China
| | - Xinxing Li
- Department of General Surgery, Tongji Hospital, Medical College of Tongji University, Shanghai, China
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ADAM R, ACCARDO C, ALLARD MA. Cytoreductive surgery for colorectal liver metastases: is it worthwhile? Minerva Surg 2022; 77:433-440. [DOI: 10.23736/s2724-5691.22.09669-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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Literature review of imaging, pathological diagnosis, and outcomes of metachronous lung and pancreatic metastasis of cecal cancer. World J Surg Oncol 2022; 20:341. [PMID: 36253824 PMCID: PMC9575218 DOI: 10.1186/s12957-022-02797-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 09/18/2022] [Indexed: 11/10/2022] Open
Abstract
Background Pancreatic metastasis from colorectal cancer is extremely rare. Here, we report a case of colorectal cancer with lung and pancreatic metastasis and analyze the histopathology, immunohistochemistry, and next-generation sequencing (NGS) to generate a differential diagnosis and treatment of metastatic colon cancer. Case presentation AC1 A 78-year-old man was admitted because of a recently elevated carcinoembryonic antigen. This patient had undergone laparoscopic right hemicolectomy for cecal cancer IIA (T3N0M0) 5 years before admission, and thoracoscopic left upper lung wedge resection for primary colon cancer lung metastasis 2 years before admission. At that time, the patient was thought to have pancreatic metastasis from colon cancer. He underwent laparoscopic distal pancreatectomy (combined with splenectomy). Postoperative pathology revealed colon cancer metastasis. We performed NGS on tumor samples at three loci and found colon cancer's most common oncogenic driver genes (KRAS, APC, and TP53). One month after surgery, the patient was given capecitabine for six cycles of chemotherapy. At present, no high adverse reactions have been reported. Discussion For patients with pancreatic space-occupying, such as a previous history of colorectal cancer, and recent carcinoembryonic antigen elevation, we should highly suspect pancreatic metastatic colorectal cancer. NGS is an essential auxiliary for identifying metastatic tumors. Surgery combined with postoperative chemotherapy is an effective treatment.
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Lillemoe HA, Passot G, Kawaguchi Y, DeBellis M, Glehen O, Chun YS, Tzeng CWD, Aloia TA, Lopez J, Vauthey JN. RAS/TP53 Co-mutation is Associated With Worse Survival After Concurrent Resection of Colorectal Liver Metastases and Extrahepatic Disease. Ann Surg 2022; 276:357-362. [PMID: 33351476 PMCID: PMC11992627 DOI: 10.1097/sla.0000000000004672] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To determine if tumor genetics are associated with overall survival (OS) after concurrent resection of colorectal liver metastases (CLM) and extrahepatic disease (EHD). SUMMARY BACKGROUND DATA The prognosis for patients who undergo concurrent resection of CLM/EHD is unclear and the impact of somatic mutations has not been reported. METHODS Patients undergoing concurrent resection of CLM and EHD from 2007 to 2017 were identified from 2 academic centers. From 1 center, patients were selected from a pre-existing database of patients undergoing cytore-ductive surgery with hyperthermic intraperitoneal chemotherapy. The Kaplan-Meier method was used to construct survival curves, compared using the log-rank test. Multivariable Cox analysis for OS was performed. RESULTS One hundred nine patients were included. Most common EHD sites included lung (33 patients), peritoneum (32), and portal lymph nodes (14). TP53 mutation was the most common mutation, identified in 75 patients (69%), and RAS/TP53 co-mutation was identified in 31 patients (28%). The median OS was 49 months (interquartile range, 24-125), and 3- and 5-year OS rates were 66% and 44%, respectively. Compared to patients without RAS/ TP53 co-mutation, patients with RAS/TP53 co-mutation had lower median OS: 39 vs. 51 months ( P = 0.02). On multivariable analysis, lung EHD [hazard ratio (HR), 0.7; 95% confidence intervals (CI), 0.3-1.4], peritoneal EHD (HR, 2.2; 95% CI, 1.1-4.2) and RAS/TP53 co-mutation (HR, 2.8; 95% CI, 1.1-7.2) were independently associated with OS. CONCLUSIONS RAS/TP53 co-mutation is associated with worse OS after concurrent CLM/EHD resection. Mutational status and site of EHD should be included in the evaluation of patients considered for concurrent resection.
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Affiliation(s)
- Heather A. Lillemoe
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Guillaume Passot
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France
- EMR 3738, CICLY, Université Claude Bernard Lyon 1, Lyon, France
| | - Yoshikuni Kawaguchi
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Mario DeBellis
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Olivier Glehen
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France
- EMR 3738, CICLY, Université Claude Bernard Lyon 1, Lyon, France
| | - Yun Shin Chun
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Thomas A. Aloia
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Jonathan Lopez
- Cancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France / Department of Biochemistry and Molecular Biology, Lyon University Hospital, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Lyon, France
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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Is Surgical Treatment Effective or Contraindicated in Patients with Colorectal Cancer Liver Metastases Exhibiting Extrahepatic Metastasis? J Gastrointest Surg 2022; 26:594-601. [PMID: 34506021 DOI: 10.1007/s11605-021-05122-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 08/07/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND Surgical resection for patients with hepatic and extrahepatic colorectal metastases remains controversial. This study aimed to determine the efficacy of curative resection of distant extrahepatic metastatic lesions in patients with colorectal liver metastases (CRLM). METHODS From 2007 to 2019, 377 patients with CRLM were treated; of these, 323 patients underwent hepatectomy, and 54 patients with extrahepatic metastases (EHM) had received only chemotherapy. Survival and recurrence were compared between patients with and without EHM. Variables potentially associated with survival were analyzed in univariate and multivariate analyses. RESULTS Among patients who underwent hepatectomy, the median, 3-, and 5-year overall survival rates for patients with EHM (n = 60) were 32 months, 47%, and 28%, respectively, while those for patients without EHM (n = 263) were 115 months, 79%, and 66%, respectively (p < 0.001). Furthermore, outcomes were similar in R2 patients with EHM and those with unresectable tumors. However, outcomes were significantly better in the R0/1 group than in the R2 and unresectable groups (p < 0.001). Among patients with EHM, multivariate analysis revealed that higher clinical risk score, incomplete resection of all EHM, extrahepatic disease detected intraoperatively, and previous treatment with neoadjuvant chemotherapy were independently associated with worse survival. CONCLUSIONS In patients with CRLM with EHM (liver + one organ), gross curative resection is necessary when surgical treatment is contemplated, and resection of liver metastases should be performed in patients with CRLM with smaller and fewer tumors (e.g., H1).
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11
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Samoon Z, Naher SK, Sjoquist KM, Zalcberg J. Chemotherapy in resectable or potentially resectable colon cancer with liver metastases. Expert Opin Pharmacother 2022; 23:663-672. [PMID: 35196945 DOI: 10.1080/14656566.2022.2043276] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
INTRODUCTION The treatment of colorectal cancer liver metastases has seen significant improvement in recent years and, for certain patients, the long-term survival and even cure are possible. Despite this improvement, many more questions are yet to be answered: the optimal combination, duration, sequence of therapies, role of biologics and the timing of surgical resection are debated in the literature, with conflicting trial results. AREAS COVERED In this review, the authors highlight the current trial evidence for systemic chemotherapy and biologic therapy for colorectal cancer liver metastases in both the pre and post-resection setting. EXPERT OPINION The treatment of colorectal liver metastases requires a multidisciplinary approach. The role of adjuvant chemotherapy with 5 fluorouracil and oxaliplatin in stage 3 colon cancer is well established. However, the options for patients with resectable or borderline liver metastases, either in the neoadjuvant or adjuvant settings, require further study. For patients with borderline resectable metastases, the combination of triplet chemotherapy with 5 fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI) offers the best conversion rate. The role of biologic agents such as bevacizumab and EGFR inhibitors in these settings is less clear based on current evidence.
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Affiliation(s)
- Zarka Samoon
- The Crown Princess Mary Cancer Care Centre, Medical Oncology Clinical Trials Unit, Westmead Hospital, NSW, Australia
| | - Sayeda Kamrun Naher
- National Health and Medical Research Council Clinical Trials Centre (NHMRC CTC), University of Sydney, Campbelltown, NSW, Australia
| | - Katrin M Sjoquist
- National Health and Medical Research Council Clinical Trials Centre (NHMRC CTC), University of Sydney, Campbelltown, NSW, Australia
| | - John Zalcberg
- Cancer Research Program, School of Public Health and Preventive Medicine, Faculty of Medicine, Monash University, Melbourne, Australia
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12
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Verter E, Berger Y, Perl G, Peretz I, Tovar A, Morgenstern S, Brenner B, Benchimol D, Kashtan H, Sadot E. Neutrophil-to-Lymphocyte Ratio Predicts Recurrence Pattern in Patients with Resectable Colorectal Liver Metastases. Ann Surg Oncol 2021; 28:4320-4329. [PMID: 33886020 DOI: 10.1245/s10434-021-10000-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 02/19/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Studies have suggested that neutrophil-to-lymphocyte ratio (NLR) has value as a predictor of long-term outcomes in various cancer types. Its prognostic potential in patients with CRLM has not been thoroughly investigated. This original, retrospective study assessed the relationship between the preoperative NLR, survival outcomes, and recurrence patterns in patients after colorectal liver metastasis resection (CRLM). METHODS The prospectively maintained database of a tertiary medical center was queried for all patients who underwent CRLM resection between 2005 and 2017. Patients were divided into two groups: NLR <3 (normal) or >3 (high). Recurrence risk was analysed using Fine and Gray correction for competing risk method and cause specific analyses. RESULTS The cohort included 231 patients of whom 53 (23%) had a high neutrophil-to-lymphocyte ratio. At presentation, 35% had synchronous disease and 48% had a solitary metastasis; median tumor size was 2 cm. Patients with a high NLR had a significantly higher rate of simultaneous colorectal resection (P = 0.01). A high NLR was independently associated with worse OS (P = 0.02), worse DFS (P = 0.03), and higher risk of recurrence (P = 0.048), specifically recurrence with an extrahepatic pattern (P = 0.03). CONCLUSIONS A high preoperative NLR was independently associated with poorer survival outcomes and extrahepatic recurrence pattern. The NLR appears to have prognostic importance in CRLM and may serve as a surrogate marker of aggressive systemic disease after resection. These findings warrant external validation, preferably in a prospective design.
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Affiliation(s)
- Eden Verter
- Department of Surgery, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yael Berger
- Department of Surgery, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Gali Perl
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel
| | - Idit Peretz
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel
| | - Ana Tovar
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Institute of Pathology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel
| | - Sara Morgenstern
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Institute of Pathology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel
| | - Baruch Brenner
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel
| | - Daniel Benchimol
- Department of Surgery, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Hanoch Kashtan
- Department of Surgery, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Eran Sadot
- Department of Surgery, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel. .,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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13
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Combined Systemic and Hepatic Artery Infusion Pump Chemo-Therapy as a Liver-Directed Therapy for Colorectal Liver Metastasis-Review of Literature and Case Discussion. Cancers (Basel) 2021; 13:cancers13061283. [PMID: 33805846 PMCID: PMC7998495 DOI: 10.3390/cancers13061283] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 02/26/2021] [Accepted: 03/11/2021] [Indexed: 12/22/2022] Open
Abstract
Simple Summary Liver metastasis is a major therapeutic challenge and common cause of death for patients with colorectal cancer. While systemic treatment especially chemotherapy remains the mainstay of treatment, selected patients with liver-only metastasis may further benefit from liver-directed therapies. Direct infusion of chemotherapy into the liver metastases via an implantable hepatic arterial infusion pump (HAIP) is potentially an effective way to improve treatment response and survival in selected patients. Here, we reviewed the literature utilizing HAIP as a liver-directed modality alone and in combination with systemic chemotherapy. We discussed two cases who were successfully treated with this combinatorial approach and achieved remission or prolongation of disease control. We discussed the limitations, toxicities of combined systemic and HAIP modalities. Lastly, we provided insights on the use of HAIP in the modern era of systemic treatment for colorectal cancer patients with liver metastasis. Abstract Colorectal cancer (CRC) is the third most prevalent malignancy and the second most common cause of death in the US. Liver is the most common site of colorectal metastases. About 13% of patients with colorectal cancer have liver metastasis on initial presentation and 50% develop them during the disease course. Although systemic chemotherapy and immunotherapy are the mainstay treatment for patients with metastatic disease, for selected patients with predominant liver metastasis, liver-directed approaches may provide prolonged disease control when combined with systemic treatments. Hepatic artery infusion pump (HAIP) chemotherapy is an approach which allows direct infusion of chemotherapeutic into the liver and is especially useful in the setting of multifocal liver metastases. When combined with systemic chemotherapy, HAIP improves the response rate, provides more durable disease control, and in some patients leads to successful resection. To ensure safety, use of HAIP requires multidisciplinary collaboration between interventional radiologists, medical oncologists, hepatobiliary surgeons and treatment nurses. Here, we review the benefits and potential risks with this approach and provide our single institution experience on two CRC patients successfully treated with HAIP in combination with systemic chemotherapy. We provide our recommendations in adopting this technique in the current era for patient with colorectal liver metastases.
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14
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Padmanabhan C, Nussbaum DP, D'Angelica M. Surgical Management of Colorectal Cancer Liver Metastases. Surg Oncol Clin N Am 2021; 30:1-25. [PMID: 33220799 DOI: 10.1016/j.soc.2020.09.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Approximately 50% of colorectal cancer patients develop liver metastases. Hepatic metastases represent the most common cause of colorectal cancer-related mortality. Metastasectomy, if possible, represents the most effective treatment strategy; 20% of patients will be cured and more than 50% survive at least 5 years. Nuances to treatment planning hinge on whether patients present with resectable disease upfront, whether the future liver remnant is adequate, and whether the primary tumor, if present, is colon versus rectal in origin. This article discusses considerations impacting our approach to patients with colorectal liver metastases and the role for various multimodal treatment options.
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Affiliation(s)
- Chandrasekhar Padmanabhan
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-1272, New York, NY 10065, USA
| | - Daniel P Nussbaum
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-1272, New York, NY 10065, USA
| | - Michael D'Angelica
- Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-898, New York, NY 10065, USA.
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15
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Serrano PE, Gu CS, Moulton CA, Gallinger S. Positron Emission Tomography Combined With Computed Tomography vs. No Positron Emission Tomography Combined With Computed Tomography for the Management of Patients With Resectable Colorectal Cancer Liver Metastases and Synchronous Extrahepatic Disease. Am Surg 2020; 87:1431-1437. [PMID: 33345573 DOI: 10.1177/0003134820954834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
INTRODUCTION Selected patients with colorectal cancer liver metastases (CRLM) and synchronous extrahepatic disease (EHD) are considered for surgery. OBJECTIVES To evaluate the change in surgical management and long-term survival (disease-free survival [DFS] and overall survival [OS]) for patients with CRLM and EHD who undergo positron emission tomography combined with computed tomography (PET-CT) vs no PET-CT. METHODS Patients with CRLM were enrolled in a trial evaluating the effect of PET-CT (vs no PET-CT) on surgical management, DFS, and OS. This is a sub-study of the trial, including only patients with synchronous EHD. Cox proportional hazard models were used to calculate risks for recurrence and death. Survival were described by Kaplan-Meier method and compared with log-rank test. RESULTS Of 25 patients with EHD (PET-CT arm: 14/270 (5%) and no PET-CT arm: 11/134 (8%)), PET-CT changed surgical management in 14%, all of which avoided liver resection due to more extensive disease. Complete metastasectomy was achieved in 36% (5/14) and 72% (8/11), respectively. Respectively, PET-CT vs no PET-CT had statistically similar median DFS, 5.6 months (95% confidence interval (CI) 3.6-18) vs 7.6 months (95% CI 2.9-15) and median OS, 42 months (95% CI 25-48) vs 29 months (95% CI 17-41). EHD was associated with worse DFS (hazard ratio HR = 1.89, 95% CI 1.41-2.52) and OS (HR = 2.47, 95% CI 1.6-3.83). CONCLUSIONS Preoperative PET-CT for the management of resectable CRLM did not improve long-term outcomes among patients who had synchronous EHD; however, it changed surgical management in a relatively significant proportion of patients.
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Affiliation(s)
- Pablo E Serrano
- Department of Surgery, 153004McMaster University, Canada.,Ontario Clinical Oncology Group, McMaster University, Canada
| | - Chu-Shu Gu
- Ontario Clinical Oncology Group, McMaster University, Canada.,Department of Oncology, 152999McMaster University, Canada
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16
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Lang H. Liver resection is beneficial for patients with colorectal liver metastases and extrahepatic disease. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1122. [PMID: 33240971 PMCID: PMC7576061 DOI: 10.21037/atm-20-4416] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Affiliation(s)
- Hauke Lang
- Department of General, Visceral and Transplantation Surgery, University Medical Center, Mainz, Germany
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17
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Nozawa H, Emoto S, Murono K, Shuno Y, Kawai K, Sasaki K, Sonoda H, Ishii H, Iida Y, Yokoyama Y, Anzai H, Ishihara S. Change in skeletal muscle index and its prognostic significance in patients who underwent successful conversion therapy for initially unresectable colorectal cancer: observational study. Therap Adv Gastroenterol 2020; 13:1756284820971197. [PMID: 33240393 PMCID: PMC7672750 DOI: 10.1177/1756284820971197] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 10/12/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Systemic therapy can cause loss of skeletal muscle mass in colorectal cancer (CRC) patients in the neoadjuvant and palliative settings. However, it is unknown how the body composition is changed by chemotherapy rendering unresectable CRC to resectable disease or how it affects the prognosis. This study aimed at elucidating the effects of systemic therapy on skeletal muscles and survival in stage IV CRC patients who underwent conversion therapy. METHODS We reviewed 98 stage IV CRC patients who received systemic therapy in our hospital. According to the treatment setting, patients were divided into the conversion, neoadjuvant chemotherapy (NAC), and palliation groups. The cross-sectional area of skeletal muscles at the third lumbar level and changes in the skeletal muscle index (SMI), defined as the area divided by height squared, during systemic therapy were compared among patient groups. The effects of these parameters on prognosis were analyzed in the conversion group. RESULTS The mean SMI increased by 9.4% during systemic therapy in the conversion group (n = 38), whereas it decreased by 5.9% in the NAC group (n = 18) and 3.7% in the palliation group (n = 42, p < 0.0001). Moreover, patients with increased SMI during systemic therapy had a better overall survival (OS) than those whose SMI decreased in the conversion group (p = 0.025). The increase in SMI was an independent predictor of favorable OS on multivariate analysis (hazard ratio 0.25). CONCLUSIONS Stage IV CRC patients who underwent conversion to resection often had an increased SMI. On the other hand, a decrease in the SMI during systemic therapy was a negative prognostic factor in such patients.
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Affiliation(s)
| | - Shigenobu Emoto
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Koji Murono
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yasutaka Shuno
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazushige Kawai
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazuhito Sasaki
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hirofumi Sonoda
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroaki Ishii
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yuuki Iida
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yuichiro Yokoyama
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroyuki Anzai
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Soichiro Ishihara
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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18
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Martin J, Petrillo A, Smyth EC, Shaida N, Khwaja S, Cheow HK, Duckworth A, Heister P, Praseedom R, Jah A, Balakrishnan A, Harper S, Liau S, Kosmoliaptsis V, Huguet E. Colorectal liver metastases: Current management and future perspectives. World J Clin Oncol 2020; 11:761-808. [PMID: 33200074 PMCID: PMC7643190 DOI: 10.5306/wjco.v11.i10.761] [Citation(s) in RCA: 135] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 05/14/2020] [Accepted: 08/31/2020] [Indexed: 02/06/2023] Open
Abstract
The liver is the commonest site of metastatic disease for patients with colorectal cancer, with at least 25% developing colorectal liver metastases (CRLM) during the course of their illness. The management of CRLM has evolved into a complex field requiring input from experienced members of a multi-disciplinary team involving radiology (cross sectional, nuclear medicine and interventional), Oncology, Liver surgery, Colorectal surgery, and Histopathology. Patient management is based on assessment of sophisticated clinical, radiological and biomarker information. Despite incomplete evidence in this very heterogeneous patient group, maximising resection of CRLM using all available techniques remains a key objective and provides the best chance of long-term survival and cure. To this end, liver resection is maximised by the use of downsizing chemotherapy, optimisation of liver remnant by portal vein embolization, associating liver partition and portal vein ligation for staged hepatectomy, and combining resection with ablation, in the context of improvements in the functional assessment of the future remnant liver. Liver resection may safely be carried out laparoscopically or open, and synchronously with, or before, colorectal surgery in selected patients. For unresectable patients, treatment options including systemic chemotherapy, targeted biological agents, intra-arterial infusion or bead delivered chemotherapy, tumour ablation, stereotactic radiotherapy, and selective internal radiotherapy contribute to improve survival and may convert initially unresectable patients to operability. Currently evolving areas include biomarker characterisation of tumours, the development of novel systemic agents targeting specific oncogenic pathways, and the potential re-emergence of radical surgical options such as liver transplantation.
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Affiliation(s)
- Jack Martin
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Angelica Petrillo
- Department of Precision Medicine, Division of Medical Oncology, University of Campania "L. Vanvitelli", Napoli 80131, Italy, & Medical Oncology Unit, Ospedale del Mare, 80147 Napoli Italy
| | - Elizabeth C Smyth
- Department of Oncology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Nadeem Shaida
- Department of Radiology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB22 0QQ, United Kingdom
| | - Samir Khwaja
- Department of Radiology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB22 0QQ, United Kingdom
| | - HK Cheow
- Department of Nuclear Medicine, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Adam Duckworth
- Department of Pathology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Paula Heister
- Department of Pathology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Raaj Praseedom
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Asif Jah
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Anita Balakrishnan
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Simon Harper
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Siong Liau
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Vasilis Kosmoliaptsis
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Emmanuel Huguet
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
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19
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Adam R, Kitano Y, Abdelrafee A, Allard MA, Baba H. Debulking surgery for colorectal liver metastases: Foolish or chance? Surg Oncol 2020; 33:266-269. [PMID: 32561091 DOI: 10.1016/j.suronc.2020.02.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Accepted: 02/13/2020] [Indexed: 12/21/2022]
Abstract
Even with the recent advances of surgical techniques and systemic therapies, we are often facing patients with multinodular bilateral disease for whom neither R0 nor R1 resection appears possible to perform. For such extensive cases, the tumor debulking approaches might provide a survival benefit, provided that an objective tumor response is obtained with chemotherapy. Here, we review all the arguments which may defend this strategy and propose some recommendations.
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Affiliation(s)
- René Adam
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Saclay, Inserm U 935, Villejuif, France.
| | - Yuki Kitano
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Saclay, Inserm U 935, Villejuif, France; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Ahmed Abdelrafee
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Saclay, Inserm U 935, Villejuif, France; Gastrointestinal Surgery Center, Department of Surgery, Mansoura University, Egypt
| | - Marc-Antoine Allard
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Saclay, Inserm U 935, Villejuif, France
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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20
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Wang J, Li S, Liu Y, Zhang C, Li H, Lai B. Metastatic patterns and survival outcomes in patients with stage IV colon cancer: A population-based analysis. Cancer Med 2020; 9:361-373. [PMID: 31693304 PMCID: PMC6943094 DOI: 10.1002/cam4.2673] [Citation(s) in RCA: 185] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Revised: 09/12/2019] [Accepted: 10/16/2019] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The goal of this study was to delineate the patterns of distant metastasis from colon adenocarcinoma (CAC) and evaluate the survival differences by metastatic patterns. METHODS Using the Surveillance, Epidemiology, and End Results (SEER) database, we extracted patients diagnosed with stage IV CAC between 2010 and 2016. Kaplan-Meier survival curves were plotted with log-rank tests to compare overall survival (OS) of patients with different metastatic patterns. Univariate and multivariate Cox proportional hazards regression models were used to evaluate the effects of different metastatic patterns on survival outcomes in terms of OS and disease-specific survival (DSS). RESULTS A total of 26 170 patients were analyzed. The 3- and 5-year OS were 20.7% and 10.5%, respectively, for patients with stage IV CAC. The most common distant metastatic site was the liver, followed by the lung, bone, and brain, but the frequency differed greatly by histology subtypes. The site of metastasis was a significant prognostic factor for OS and DSS in patients with stage IV CAC, independent of the number of metastatic sites and other clinical and demographic prognostic factors. Using liver-only metastasis as reference, lung-only metastasis was associated with better OS (hazard ratio [HR] = 0.82, 95% confidence interval [CI], 0.71-0.94) and DSS (HR = 0.75, 95% CI, 0.64-0.88). Older age, black race, unmarried status, grade III/IV tumors, advanced tumor-node-metastasis (TNM) stage, proximal colon, elevated preoperative carcinoembryonic antigen (CEA), no surgery of the primary site, and no chemotherapy were independent predictors of poor OS. CONCLUSIONS The site of distant metastasis and number of metastasis site were independent prognostic factors for survival of patients with stage IV CAC. This study highlights the need for diverse treatment strategies for patients with different metastatic patterns.
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Affiliation(s)
- Jiwei Wang
- Department of UltrasoundThe Second Affiliated Hospital of Nanchang UniversityNanchangChina
| | - Song Li
- Mudanjiang Medical CollegeMudanjiangChina
| | - Yanna Liu
- Department of UltrasoundThe Second Affiliated Hospital of Nanchang UniversityNanchangChina
| | - Chunquan Zhang
- Department of UltrasoundThe Second Affiliated Hospital of Nanchang UniversityNanchangChina
| | - Honglang Li
- Department of Gastrointestinal SurgeryThe Second Affiliated Hospital of Nanchang UniversityNanchangChina
| | - Bin Lai
- Department of Gastrointestinal SurgeryThe Second Affiliated Hospital of Nanchang UniversityNanchangChina
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21
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Margonis GA, Buettner S, Andreatos N, Wagner D, Sasaki K, Galjart B, Kamphues C, Pawlik TM, Poultsides G, Kaczirek K, Lønning PE, Verhoef C, Kreis ME, Wolfgang CL, Weiss MJ. The prognosis of colorectal cancer liver metastases associated with inflammatory bowel disease: An exploratory analysis. J Surg Oncol 2018; 118:1074-1080. [PMID: 30261094 DOI: 10.1002/jso.25251] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Accepted: 09/01/2018] [Indexed: 11/10/2022]
Abstract
BACKGROUND AND OBJECTIVES In contrast with sporadic colorectal cancer liver metastases (CRLM), inflammatory bowel disease (IBD)-related CRLM have not been studied to date. METHODS Patients who underwent resection for IBD-related and sporadic CRLM from 2000 to 2015 were identified from an international registry and matched for pertinent prognostic variables. Overall survival (OS) and recurrence-free survival (RFS) were subsequently assessed. RESULTS Twenty-eight patients had IBD-related CRLM. Synchronous extrahepatic disease was more common in IBD-related CRLM patients than patients with sporadic CRLM (28.6% vs 8.3%; P < 0.001), most commonly located in the lungs. In multivariable analysis, IBD did not have a significant influence on OS ( P = 0.835), and had a hazard ratio (HR) close to 1 (HR, 0.95; 95% confidence interval [CI], 0.57-1.57). IBD was also not associated with inferior RFS (HR, 1.07; 95%CI, 0.68-1.68; P = 0.780). Among patients with IBD-related CRLM, 9(50%) had isolated intrahepatic recurrence and 8(44.4%) isolated extrahepatic recurrence, while only 1(5.6%) developed combined recurrence. Of those who experienced recurrence after resection of IBD-related CRLM, 10 had their recurrence treated with curative intent. CONCLUSIONS Patients with IBD-related CRLM had similar survival compared with patients with sporadic CRLM, even though they more often present with extrahepatic disease. In addition, patients with IBD-related CRLM may experience patterns of recurrence different from patients with sporadic CRLM.
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Affiliation(s)
- Georgios Antonios Margonis
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of General, Visceral and Vascular Surgery, Charite Campus Benjamin Franklin, Berlin, Germany
| | - Stefan Buettner
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Nikolaos Andreatos
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Doris Wagner
- Department of General Surgery, Medical University of Graz, Graz, Austria
| | - Kazunari Sasaki
- Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - Boris Galjart
- Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Carsten Kamphues
- Department of General, Visceral and Vascular Surgery, Charite Campus Benjamin Franklin, Berlin, Germany
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - George Poultsides
- Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Klaus Kaczirek
- Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Per Eystein Lønning
- Department of Clinical Science, University of Bergen, Bergen, Norway
- Department of Oncology, Haukeland University Hospital, Bergen, Norway
| | - Cornelis Verhoef
- Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Martin E Kreis
- Department of General, Visceral and Vascular Surgery, Charite Campus Benjamin Franklin, Berlin, Germany
| | | | - Matthew J Weiss
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
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22
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Prasanna T, Karapetis CS, Roder D, Tie J, Padbury R, Price T, Wong R, Shapiro J, Nott L, Lee M, Chua YJ, Craft P, Piantadosi C, Sorich M, Gibbs P, Yip D. The survival outcome of patients with metastatic colorectal cancer based on the site of metastases and the impact of molecular markers and site of primary cancer on metastatic pattern. Acta Oncol 2018. [DOI: 10.1080/0284186x.2018.1487581 10.1080/0284186x.2018.1487581] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Affiliation(s)
- Thiru Prasanna
- Department of Medical Oncology, The Canberra Hospital, Garran, Canberra, Australia
| | - Christos S. Karapetis
- Department of Medical Oncology, Flinders Medical Centre, Bedford Park, Australia
- Flinders Clinical and Molecular Medicine, Surgery, Flinders University, Bedford Park, Australia
| | - David Roder
- South Australian Health & Medical Research Institute (SAHMRI), Adelaide, Australia
- School of Health Sciences, University of South Australia, Adelaide, Australia
| | - Jeanne Tie
- Department of Medical Oncology, Western Hospital, Melbourne, Australia
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Robert Padbury
- Flinders Clinical and Molecular Medicine, Surgery, Flinders University, Bedford Park, Australia
- Department of Surgery, Flinders Medical Centre, Adelaide, Australia
| | - Timothy Price
- The Queen Elizabeth Hospital and University of Adelaide, Adelaide, Australia
| | - Rachel Wong
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
- Department of Medical Oncology, Eastern Health, Melbourne, Australia
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia
| | - Jeremy Shapiro
- Cabrini Haematology and Oncology Centre, Melbourne, Australia
| | - Louise Nott
- Department of Medical Oncology, Royal Hobart Hospital, Tasmania, Australia
- Menzies Research Institute, Hobart, Australia
| | - Margaret Lee
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
- Department of Medical Oncology, Eastern Health, Melbourne, Australia
| | - Yu Jo Chua
- Department of Medical Oncology, The Canberra Hospital, Garran, Canberra, Australia
- ANU Medical School, Australian National University, Canberra, Australia
| | - Paul Craft
- Department of Medical Oncology, The Canberra Hospital, Garran, Canberra, Australia
- ANU Medical School, Australian National University, Canberra, Australia
| | | | - Michael Sorich
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Peter Gibbs
- Department of Medical Oncology, Western Hospital, Melbourne, Australia
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
| | - Desmond Yip
- Department of Medical Oncology, The Canberra Hospital, Garran, Canberra, Australia
- ANU Medical School, Australian National University, Canberra, Australia
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23
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Prasanna T, Karapetis CS, Roder D, Tie J, Padbury R, Price T, Wong R, Shapiro J, Nott L, Lee M, Chua YJ, Craft P, Piantadosi C, Sorich M, Gibbs P, Yip D. The survival outcome of patients with metastatic colorectal cancer based on the site of metastases and the impact of molecular markers and site of primary cancer on metastatic pattern. Acta Oncol 2018; 57:1438-1444. [PMID: 30035653 DOI: 10.1080/0284186x.2018.1487581] [Citation(s) in RCA: 70] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2017] [Accepted: 06/06/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND Pattern of spread in patients with metastatic colorectal cancer (mCRC) is variable and may reflect different biology in subsets of patients. This is a retrospective study to explore the outcome of patients with mCRC based on their site of metastasis at diagnosis and to explore the association between tumor characteristics [KRAS/RAS, BRAF, mismatch repair (MMR) status, site of primary] and the site of metastasis. METHODS Patients from two Australian databases were divided into six groups based on site of metastasis at time of diagnosis of metastatic disease; lung-only, liver-only, lymph node-only or any patients with brain, bone or peritoneal metastases. Primary endpoint was overall survival (OS) of each cohort compared with the rest of the population. A Mantel-Haenszel chi-squared test used to explore the association between site of metastasis and selected tumor characteristics. RESULTS Five thousand nine hundred and sixty-seven patients were included. In a univariate analysis, median OS was significantly higher when metastases were limited to lung or liver and shorter for those with brain, bone or peritoneal metastases (p < .001) in both datasets. BRAF mutation was strongly associated with peritoneal metastases (relative risk = 1.8, p < .001) with lower incidence of lung (RR = 0.3, p = .004) and liver (RR = 0.7, p = .005) limited metastases. Lung-only metastases were more frequent with KRAS/RAS mutation (RR = 1.4, p = .007). Left colon tumors were associated with bone (RR = 1.6, p < .001) and lung-only metastases (RR = 2.3, p = .001) while peritoneal spread was less frequent compared with right colon tumors (RR = 0.6, p < .001). Rectal cancer was associated with brain, bone and lung metastases (RR = 1.7; p = .002, 1.7; p < .001, 2.0; p < .001). Liver-only metastases were less frequent in deficient MMR tumors (RR = 0.7, p = .01). CONCLUSION Survival duration with mCRC is related to the site of metastases with lung limited disease showing a more favorable survival outcome compared to other single metastatic site disease. The BRAF mutation and primary rectal cancer were associated with poor prognostic metastatic sites.
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Affiliation(s)
- Thiru Prasanna
- a Department of Medical Oncology , The Canberra Hospital , Garran , Canberra , Australia
| | - Christos S Karapetis
- b Department of Medical Oncology , Flinders Medical Centre , Bedford Park , Australia
- c Flinders Clinical and Molecular Medicine, Surgery, Flinders University , Bedford Park , Australia
| | - David Roder
- d South Australian Health & Medical Research Institute (SAHMRI) , Adelaide, Australia
- e School of Health Sciences, University of South Australia , Adelaide , Australia
| | - Jeanne Tie
- f Department of Medical Oncology , Western Hospital , Melbourne , Australia
- g Walter and Eliza Hall Institute of Medical Research , Melbourne , Australia
- h Department of Medical Oncology , Peter MacCallum Cancer Centre , Melbourne , Australia
| | - Robert Padbury
- c Flinders Clinical and Molecular Medicine, Surgery, Flinders University , Bedford Park , Australia
- i Department of Surgery , Flinders Medical Centre , Adelaide, Australia
| | - Timothy Price
- j The Queen Elizabeth Hospital and University of Adelaide , Adelaide , Australia
| | - Rachel Wong
- g Walter and Eliza Hall Institute of Medical Research , Melbourne , Australia
- k Department of Medical Oncology , Eastern Health , Melbourne , Australia
- l Faculty of Medicine, Nursing and Health Sciences , Monash University , Melbourne , Australia
| | - Jeremy Shapiro
- m Cabrini Haematology and Oncology Centre , Melbourne , Australia
| | - Louise Nott
- n Department of Medical Oncology , Royal Hobart Hospital , Tasmania , Australia
- o Menzies Research Institute , Hobart , Australia
| | - Margaret Lee
- g Walter and Eliza Hall Institute of Medical Research , Melbourne , Australia
- k Department of Medical Oncology , Eastern Health , Melbourne , Australia
| | - Yu Jo Chua
- a Department of Medical Oncology , The Canberra Hospital , Garran , Canberra , Australia
- p ANU Medical School, Australian National University , Canberra , Australia
| | - Paul Craft
- a Department of Medical Oncology , The Canberra Hospital , Garran , Canberra , Australia
- p ANU Medical School, Australian National University , Canberra , Australia
| | | | - Michael Sorich
- r College of Medicine and Public Health , Flinders University , Adelaide , Australia
| | - Peter Gibbs
- f Department of Medical Oncology , Western Hospital , Melbourne , Australia
- g Walter and Eliza Hall Institute of Medical Research , Melbourne , Australia
| | - Desmond Yip
- a Department of Medical Oncology , The Canberra Hospital , Garran , Canberra , Australia
- p ANU Medical School, Australian National University , Canberra , Australia
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Peritoneal and extraperitoneal relapse after previous curative treatment of peritoneal metastases from colorectal cancer: What survival can we expect? Eur J Cancer 2018; 100:94-103. [DOI: 10.1016/j.ejca.2018.04.015] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Revised: 04/09/2018] [Accepted: 04/11/2018] [Indexed: 01/08/2023]
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Donadon M, Lleo A, Di Tommaso L, Soldani C, Franceschini B, Roncalli M, Torzilli G. The Shifting Paradigm of Prognostic Factors of Colorectal Liver Metastases: From Tumor-Centered to Host Immune-Centered Factors. Front Oncol 2018; 8:181. [PMID: 29892573 PMCID: PMC5985314 DOI: 10.3389/fonc.2018.00181] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2017] [Accepted: 05/09/2018] [Indexed: 12/20/2022] Open
Abstract
The determinants of prognosis in patients with colorectal liver metastases (CLM) have been traditionally searched among the tumoral factors, either of the primary colorectal tumor or of the CLM. While many different scoring systems have been developed based on those clinic-pathological factors with disparate results, there has been the introduction of genetic biological markers that added a theranostic perspective. More recently, other important elements, such as those factors related to the host immune system, have been proposed as determinants of prognosis of CLM patients. In the present work, we review the current prognostic factors of CLM patients as well as the burgeoning shifting paradigm of prognostication that relies on the host immune system.
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Affiliation(s)
- Matteo Donadon
- Department of Hepatobiliary and General Surgery, Humanitas Clinical and Research Center, Rozzano, Italy
- Department of Biomedical Science, Humanitas University, Rozzano, Italy
| | - Ana Lleo
- Department of Biomedical Science, Humanitas University, Rozzano, Italy
- Department of Internal Medicine, Humanitas Clinical and Research Center, Rozzano, Italy
| | - Luca Di Tommaso
- Department of Biomedical Science, Humanitas University, Rozzano, Italy
- Department of Pathology, Humanitas Clinical and Research Center, Rozzano, Italy
| | - Cristiana Soldani
- Department of Hepatobiliary and General Surgery, Humanitas Clinical and Research Center, Rozzano, Italy
| | - Barbara Franceschini
- Department of Hepatobiliary and General Surgery, Humanitas Clinical and Research Center, Rozzano, Italy
| | - Massimo Roncalli
- Department of Biomedical Science, Humanitas University, Rozzano, Italy
- Department of Pathology, Humanitas Clinical and Research Center, Rozzano, Italy
| | - Guido Torzilli
- Department of Hepatobiliary and General Surgery, Humanitas Clinical and Research Center, Rozzano, Italy
- Department of Biomedical Science, Humanitas University, Rozzano, Italy
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Acciuffi S, Meyer F, Bauschke A, Settmacher U, Lippert H, Croner R, Altendorf-Hofmann A. Analysis of prognostic factors after resection of solitary liver metastasis in colorectal cancer: a 22-year bicentre study. J Cancer Res Clin Oncol 2018; 144:593-599. [PMID: 29340767 DOI: 10.1007/s00432-018-2583-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Accepted: 01/11/2018] [Indexed: 02/08/2023]
Abstract
PURPOSE The investigation of the predictors of outcome after hepatic resection for solitary colorectal liver metastasis. METHODS We recruited 350 patients with solitary colorectal liver metastasis at the University Hospitals of Jena and Magdeburg, who underwent curative liver resection between 1993 and 2014. All patients had follow-up until death or till summer 2016. RESULTS The follow-up data concern 96.6% of observed patients. The 5- and 10-year overall survival rates were 47 and 28%, respectively. The 5- and 10-year disease-free survival rates were 30 and 20%, respectively. The analysis of the prognostic factors revealed that the pT category of primary tumour, size and grade of the metastasis and extension of the liver resection had no statistically significant impact on survival and recurrence rates. In multivariate analysis, age, status of lymph node metastasis at the primary tumour, location of primary tumour, time of appearance of the metastasis, the use of preoperative chemotherapy and the presence of extrahepatic tumour proved to be independent statistically significant predictors for the prognosis. Moreover, patients with rectal cancer had a lower intrahepatic recurrence rate, but a higher extrahepatic recurrence rate. CONCLUSION The long-term follow-up of patients with R0-resected liver metastasis is multifactorially influenced. Age and comorbidity have a role only in the overall survival. More than three lymph node metastasis reduced both the overall and disease-free survival. Extrahepatic tumour had a negative influence on the extrahepatic recurrence and on the overall survival. Neither overall survival nor recurrence rates was improved using neoadjuvant chemotherapy.
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Affiliation(s)
- Sara Acciuffi
- Department of General, Abdominal and Vascular Surgery, University Hospital, Magdeburg, Germany
| | - Frank Meyer
- Department of General, Abdominal and Vascular Surgery, University Hospital, Magdeburg, Germany
| | - Astrid Bauschke
- Department of General, Abdominal and Vascular Surgery, University Hospital, Am Klinikum 1, 07747, Jena, Germany
| | - Utz Settmacher
- Department of General, Abdominal and Vascular Surgery, University Hospital, Am Klinikum 1, 07747, Jena, Germany
| | - Hans Lippert
- Department of General, Abdominal and Vascular Surgery, University Hospital, Magdeburg, Germany
| | - Roland Croner
- Department of General, Abdominal and Vascular Surgery, University Hospital, Magdeburg, Germany
| | - Annelore Altendorf-Hofmann
- Department of General, Abdominal and Vascular Surgery, University Hospital, Am Klinikum 1, 07747, Jena, Germany.
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27
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Actual 10-year survival after hepatic resection of colorectal liver metastases: what factors preclude cure? Surgery 2018; 163:1238-1244. [PMID: 29455841 DOI: 10.1016/j.surg.2018.01.004] [Citation(s) in RCA: 154] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 12/07/2017] [Accepted: 01/02/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatic resection of colorectal liver metastases is associated with long-term survival. This study analyzes actual 10-year survivors after resection of colorectal liver metastases, reports the observed rate of cure, and identifies factors that preclude cure. METHODS A single-institution, prospectively maintained database was queried for all initial resections for colorectal liver metastases for the years 1992-2004. Observed cure was defined as actual 10-year survival with either no recurrence or resected recurrence with at least 3 years of disease-free follow-up. Clinical risk score was dichotomized into low (0-2) and high (3-5). Semiparametric proportional hazards mixture cure model was utilized to estimate probability of cure. RESULTS We included 1,211 patients with a median follow-up for survivors of 11 years. Median disease-specific survival was 4.9 years (95% CI: 4.4-5.3). 295 patients (24.4%) were actual 10-year survivors. The observed cure rate was 20.6% (n = 250). Among 250 cured patients, 192 (76.8%) had no recurrence and 58 (23.2%) had a resected recurrence with at least 3 years of disease-free follow-up. Extrahepatic disease (n = 88), carcinoembryonic antigen >200 ng/mL (n = 119), positive margin (n = 109), and >10 tumors (n = 31) had observed cure rates less than 10%. In cure model analysis, patients with both extrahepatic disease and high clinical risk score (n = 31) had an estimated probability of cure of 3.5%. CONCLUSION Actual 10-year survival after resection of colorectal liver metastases is 24% with an observed 20% cure rate. Patients with both high clinical risk score and extrahepatic disease have an estimated probability of cure less than 5%. When such factors are identified, strong consideration may be given to preoperative strategies, such as neoadjuvant chemotherapy, to help select patients for surgical therapy.
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28
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Swaid F, Tsung A. Current Management of Liver Metastasis From Colorectal Cancer. CURRENT COLORECTAL CANCER REPORTS 2018. [DOI: 10.1007/s11888-018-0397-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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29
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Pathological diaphragmatic invasion by colorectal liver metastases is associated with RAS mutation, peritoneal recurrence and worse survival. HPB (Oxford) 2018; 20:57-63. [PMID: 28943395 PMCID: PMC5748267 DOI: 10.1016/j.hpb.2017.08.020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Revised: 08/10/2017] [Accepted: 08/15/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Risk factors for pathological diaphragmatic invasion from colorectal liver metastases (CRLM) and differences in recurrence patterns and survival between patients with true pathological diaphragmatic invasion versus inflammatory adhesions only remain poorly understood. This study aimed at identifying risk factors for and survival impact of pathological diaphragmatic invasion in patients with CRLM. METHODS Patients with CRLM who underwent hepatectomy with or without diaphragmatic resection from 1998 to 2015 were retrospectively analyzed. Recurrence-free survival (RFS), overall survival (OS), and recurrence patterns were examined according to the presence or absence of pathological invasion. RESULTS Of 1860 patients, 70 underwent hepatectomy with diaphragmatic resection and 1799 had hepatectomy only. Among the patients with gross diaphragmatic involvement, 15 (21%) had pathological invasion, and 55 (79%) had inflammatory adhesion only. Multiple tumors (p = 0.019) and RAS mutation (p = 0.047) were significantly associated with pathological invasion. Pathological invasion was associated with a higher incidence of peritoneal recurrence (33% vs. 11%, p = 0.041), worse median RFS (6 months vs. 11 months, p = 0.21) and OS (26 months vs. 51 months, p = 0.046) compared to inflammatory adhesion. CONCLUSION Multiple tumors and RAS mutant were predictors for pathological diaphragmatic invasion, which was associated with a higher incidence of peritoneal recurrence and worse OS.
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Abstract
Surgical treatment of metastatic colorectal cancer offers a chance for cure or prolonged survival, particularly for those with more favorable prognostic factors and limited tumor burden. The treatment plan requires multidisciplinary evaluation because multiple therapy options exist. Advanced surgical techniques, adjuncts to resection, and modern chemotherapy all contribute to best outcomes for patients with hepatic metastases. Although cure is less common for patients with metastasis to lung or peritoneum, surgical resection for the former and cytoreduction and intraperitoneal chemotherapy for the latter may help to achieve cancer control in selected patients.
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Affiliation(s)
- Jeffery Chakedis
- Division of Surgical Oncology, Department of Surgery, Complex General Surgical Oncology, The Ohio State University Wexner Medical Center, Arthur G. James Cancer Hospital and Solove Research Institute, 395 West 12th Avenue, Suite 670, Columbus, OH 43210-1267, USA
| | - Carl R Schmidt
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Arthur G. James Cancer Hospital and Solove Research Institute, 395 West 12th Avenue, Suite 670, Columbus, OH 43210-1267, USA.
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31
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Creasy JM, Sadot E, Koerkamp BG, Chou JF, Gonen M, Kemeny NE, Saltz LB, Balachandran VP, Peter Kingham T, DeMatteo RP, Allen PJ, Jarnagin WR, D'Angelica MI. The Impact of Primary Tumor Location on Long-Term Survival in Patients Undergoing Hepatic Resection for Metastatic Colon Cancer. Ann Surg Oncol 2017; 25:431-438. [PMID: 29181680 DOI: 10.1245/s10434-017-6264-x] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND The impact of primary tumor location on overall survival (OS), recurrence-free survival (RFS), and long-term outcomes has not been well established in patients undergoing potentially curative resection of colorectal liver metastases (CRLM). METHODS A single-institution database was queried for initial resections for CRLM 1992-2004. Primary tumor location determined by chart review (right = cecum to transverse; left = splenic flexure to sigmoid). Rectal cancer (distal 16 cm), multiple primaries, and unknown location were excluded. Kaplan-Meier and Cox regression methods were used. Cure was defined as actual 10-year survival with either no recurrence or resected recurrence with at least 3 years of disease-free follow-up. RESULTS A total of 907 patients were included with a median follow-up of 11 years; 578 patients (64%) had left-sided and 329 (36%) right-sided primaries. Median OS for patients with a left-sided primary was 5.2 years (95% confidence interval [CI] 4.6-6.0) versus 3.6 years (95% CI 3.2-4.2) for right-sided (p = 0.004). On multivariable analysis, the hazard ratio for right-sided tumors was 1.22 (95% CI 1.02-1.45, p = 0.028) after adjusting for common clinicopathologic factors. Median RFS was marginally different stratified by primary location (1.3 vs. 1.7 years; p = 0.065). On multivariable analysis, location of primary was not significantly associated with RFS (p = 0.105). Observed cure rates were 22% for left-sided and 20% for right-sided tumors. CONCLUSIONS Among patients undergoing resection of CRLM, left-sided primary tumors were associated with improved median OS. However, long-term survival and recurrence-free survival were not significantly different stratified by primary location. Patients with left-sided primary tumors displayed a prolonged clinical course suggestive of more indolent biology.
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Affiliation(s)
- John M Creasy
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Eran Sadot
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Bas Groot Koerkamp
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Joanne F Chou
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Mithat Gonen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Nancy E Kemeny
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Leonard B Saltz
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Vinod P Balachandran
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - T Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Ronald P DeMatteo
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Peter J Allen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - William R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Michael I D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. .,Cornell University, Weill Medical College, New York, NY, 10065, USA.
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Haraldsdottir S, Goldberg RM. Conversion Therapy for Initially Borderline/Unresectable Metastases in Colon Cancer: What Is the Best Neoadjuvant Chemotherapy? CURRENT COLORECTAL CANCER REPORTS 2017. [DOI: 10.1007/s11888-017-0393-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Imai K, Castro Benitez C, Allard MA, Vibert E, Sa Cunha A, Cherqui D, Castaing D, Bismuth H, Baba H, Adam R. Potential of a cure in patients with colorectal liver metastases and concomitant extrahepatic disease. J Surg Oncol 2017; 115:488-496. [DOI: 10.1002/jso.24539] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Accepted: 12/08/2016] [Indexed: 12/15/2022]
Affiliation(s)
- Katsunori Imai
- Centre Hépato-Biliaire, AP-HP; Hôpital Universitaire Paul Brousse; Villejuif France
- Inserm, Unité 935; Villejuif France
- Department of Gastroenterological Surgery, Graduate School of Life Sciences; Kumamoto University; Kumamoto Japan
| | - Carlos Castro Benitez
- Centre Hépato-Biliaire, AP-HP; Hôpital Universitaire Paul Brousse; Villejuif France
- Inserm, Unité 935; Villejuif France
- Université Paris-Sud; Villejuif France
| | - Marc-Antoine Allard
- Centre Hépato-Biliaire, AP-HP; Hôpital Universitaire Paul Brousse; Villejuif France
- Inserm, Unité 935; Villejuif France
- Université Paris-Sud; Villejuif France
| | - Eric Vibert
- Centre Hépato-Biliaire, AP-HP; Hôpital Universitaire Paul Brousse; Villejuif France
- Université Paris-Sud; Villejuif France
- Inserm Unité 785; Villejuif France
| | - Antonio Sa Cunha
- Centre Hépato-Biliaire, AP-HP; Hôpital Universitaire Paul Brousse; Villejuif France
- Inserm, Unité 935; Villejuif France
- Université Paris-Sud; Villejuif France
| | - Daniel Cherqui
- Centre Hépato-Biliaire, AP-HP; Hôpital Universitaire Paul Brousse; Villejuif France
- Université Paris-Sud; Villejuif France
- Inserm Unité 785; Villejuif France
| | - Denis Castaing
- Centre Hépato-Biliaire, AP-HP; Hôpital Universitaire Paul Brousse; Villejuif France
- Université Paris-Sud; Villejuif France
- Inserm Unité 785; Villejuif France
| | - Henri Bismuth
- Centre Hépato-Biliaire, AP-HP; Hôpital Universitaire Paul Brousse; Villejuif France
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences; Kumamoto University; Kumamoto Japan
| | - René Adam
- Centre Hépato-Biliaire, AP-HP; Hôpital Universitaire Paul Brousse; Villejuif France
- Inserm, Unité 935; Villejuif France
- Université Paris-Sud; Villejuif France
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Torres OJM, Marques MC, Santos FN, Farias ICD, Coutinho AK, Oliveira CVCD, Kalil AN, Mello CALD, Kruger JAP, Fernandes GDS, Quireze C, Murad AM, Silva MJDBE, Zurstrassen CE, Freitas HC, Cruz MR, Weschenfelder R, Linhares MM, Castro LDS, Vollmer C, Dixon E, Ribeiro HSDC, Coimbra FJF. BRAZILIAN CONSENSUS FOR MULTIMODAL TREATMENT OF COLORECTAL LIVER METASTASES. MODULE 3: CONTROVERSIES AND UNRESECTABLE METASTASES. ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA 2017; 29:173-179. [PMID: 27759781 PMCID: PMC5074669 DOI: 10.1590/0102-6720201600030011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Accepted: 04/26/2016] [Indexed: 12/14/2022]
Abstract
In the last module of this consensus, controversial topics were discussed. Management of the disease after progression during first line chemotherapy was the first discussion. Next, the benefits of liver resection in the presence of extra-hepatic disease were debated, as soon as, the best sequence of treatment. Conversion chemotherapy in the presence of unresectable liver disease was also discussed in this module. Lastly, the approach to the unresectable disease was also discussed, focusing in the best chemotherapy regimens and hole of chemo-embolization.
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Affiliation(s)
- Orlando Jorge Martins Torres
- Brazilian Chapter of the International Hepato-Pancreato Biliary Association (BC-IHPBA).,Brazilian Society of Surgical Oncology (BSSO).,Brazilian Society of Clinical Oncology (BSCO)
| | - Márcio Carmona Marques
- Brazilian Society of Surgical Oncology (BSSO).,Americas Hepato-Pancreato-Biliary Association - AHPBA
| | - Fabio Nasser Santos
- Brazilian Chapter of the International Hepato-Pancreato Biliary Association (BC-IHPBA)
| | - Igor Correia de Farias
- Brazilian Society of Surgical Oncology (BSSO).,Americas Hepato-Pancreato-Biliary Association - AHPBA
| | | | - Cássio Virgílio Cavalcante de Oliveira
- Brazilian Chapter of the International Hepato-Pancreato Biliary Association (BC-IHPBA).,Brazilian College of Digestive Surgery (BCDS).,Brazilian College of Surgeons (BCS)
| | - Antonio Nocchi Kalil
- Brazilian Chapter of the International Hepato-Pancreato Biliary Association (BC-IHPBA).,Brazilian Society of Surgical Oncology (BSSO).,Brazilian College of Digestive Surgery (BCDS).,Americas Hepato-Pancreato-Biliary Association - AHPBA
| | | | - Jaime Arthur Pirola Kruger
- Brazilian Chapter of the International Hepato-Pancreato Biliary Association (BC-IHPBA).,Brazilian College of Digestive Surgery (BCDS).,Brazilian College of Surgeons (BCS).,Americas Hepato-Pancreato-Biliary Association - AHPBA
| | | | - Claudemiro Quireze
- Brazilian Chapter of the International Hepato-Pancreato Biliary Association (BC-IHPBA).,Brazilian College of Digestive Surgery (BCDS).,Brazilian College of Surgeons (BCS).,Americas Hepato-Pancreato-Biliary Association - AHPBA
| | | | | | | | | | | | | | - Marcelo Moura Linhares
- Brazilian Chapter of the International Hepato-Pancreato Biliary Association (BC-IHPBA).,Brazilian College of Digestive Surgery (BCDS).,Brazilian College of Surgeons (BCS).,Americas Hepato-Pancreato-Biliary Association - AHPBA
| | - Leonaldson Dos Santos Castro
- Brazilian Chapter of the International Hepato-Pancreato Biliary Association (BC-IHPBA).,Brazilian Society of Surgical Oncology (BSSO).,Americas Hepato-Pancreato-Biliary Association - AHPBA
| | | | - Elijah Dixon
- Americas Hepato-Pancreato-Biliary Association - AHPBA
| | - Héber Salvador de Castro Ribeiro
- Brazilian Chapter of the International Hepato-Pancreato Biliary Association (BC-IHPBA).,Brazilian Society of Surgical Oncology (BSSO).,Americas Hepato-Pancreato-Biliary Association - AHPBA
| | - Felipe José Fernandez Coimbra
- Brazilian Chapter of the International Hepato-Pancreato Biliary Association (BC-IHPBA).,Brazilian Society of Surgical Oncology (BSSO).,Brazilian College of Surgeons (BCS).,Americas Hepato-Pancreato-Biliary Association - AHPBA
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Araujo RLC, Riechelmann RP, Fong Y. Patient selection for the surgical treatment of resectable colorectal liver metastases. J Surg Oncol 2016; 115:213-220. [PMID: 27778357 DOI: 10.1002/jso.24482] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2016] [Accepted: 09/30/2016] [Indexed: 12/14/2022]
Abstract
Advances in surgery and chemotherapy regimens have increased the long-term survival of patients with colorectal liver metastases (CRLM). Although liver resection remains an essential part of any curative strategy for resectable CRLM, chemotherapy regimens have also improved the long-term outcomes. However, the optimal timing for chemotherapy regimens remains unclear. Thus, this review addressed key points to aid the decision-making process regarding the timing of chemotherapy and surgery for patients with resectable CRLM. J. Surg. Oncol. 2017;115:213-220. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Raphael L C Araujo
- Department of Upper Gastrointestinal and Hepato-Pancreato-Biliary Surgery, Barretos Cancer Hospital, Barretos, São Paulo, Brazil
| | - Rachel P Riechelmann
- Department of Radiology and Oncology, Instituto do Câncer do Estado de São Paulo, University of São Paulo Medical School, São Paulo, Brazil
| | - Yuman Fong
- Department of Surgery, City of Hope National Medical Center, Duarte, California
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Andres A, Majno P, Terraz S, Morel P, Roth A, Rubbia-Brandt L, Schiffer E, Ris F, Toso C. Management of patients with colorectal liver metastasis in eleven questions and answers. Expert Rev Anticancer Ther 2016; 16:1277-1290. [PMID: 27744725 DOI: 10.1080/14737140.2016.1249855] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
INTRODUCTION Colorectal liver metastasis (CRLM) is the most frequent indication for liver resection in many centers. Recent improvements in oncology, surgery, interventional radiology, pathology and anesthesiology allow curative treatment in a larger proportion of patients with CRLM. Areas covered: We illustrate the various aspects of the management of CRLM through 11 questions that summarize the topic, from the current obtained survival to future perspectives such as transplantation. The limits of a curative treatment are also presented from different angles, such as the benefits of pathology, the surgical options for extreme resections, the available chemotherapies and their efficacy, or the non-surgical ablative treatments. Expert commentary: Given the increasing therapeutic possibilities, we strengthen the importance to analyze the situation of each patient with CRLM in a dedicated multidisciplinary team, in order to offer the best individualized treatment combination.
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Affiliation(s)
- Axel Andres
- a Faculty of Medicine, Hepato-Pancreato-Biliary Centre , Geneva University Hospital , Geneva , Switzerland.,b Faculty of Medicine, Division of Abdominal Surgery , Geneva University Hospital , Geneva , Switzerland
| | - Pietro Majno
- a Faculty of Medicine, Hepato-Pancreato-Biliary Centre , Geneva University Hospital , Geneva , Switzerland.,b Faculty of Medicine, Division of Abdominal Surgery , Geneva University Hospital , Geneva , Switzerland
| | - Sylvain Terraz
- a Faculty of Medicine, Hepato-Pancreato-Biliary Centre , Geneva University Hospital , Geneva , Switzerland.,c Faculty of Medicine, Division of Radiology , Geneva University Hospital , Geneva , Switzerland
| | - Philippe Morel
- a Faculty of Medicine, Hepato-Pancreato-Biliary Centre , Geneva University Hospital , Geneva , Switzerland.,b Faculty of Medicine, Division of Abdominal Surgery , Geneva University Hospital , Geneva , Switzerland
| | - Arnaud Roth
- a Faculty of Medicine, Hepato-Pancreato-Biliary Centre , Geneva University Hospital , Geneva , Switzerland.,d Faculty of Medicine, Division of Oncology , Geneva University Hospital , Geneva , Switzerland
| | - Laura Rubbia-Brandt
- a Faculty of Medicine, Hepato-Pancreato-Biliary Centre , Geneva University Hospital , Geneva , Switzerland.,e Faculty of Medicine, Division of Clinical Pathology , Geneva University Hospital , Geneva , Switzerland
| | - Eduardo Schiffer
- a Faculty of Medicine, Hepato-Pancreato-Biliary Centre , Geneva University Hospital , Geneva , Switzerland.,f Faculty of Medicine, Division of Anesthesiology , Geneva University Hospital , Geneva , Switzerland
| | - Frederic Ris
- b Faculty of Medicine, Division of Abdominal Surgery , Geneva University Hospital , Geneva , Switzerland
| | - Christian Toso
- a Faculty of Medicine, Hepato-Pancreato-Biliary Centre , Geneva University Hospital , Geneva , Switzerland.,b Faculty of Medicine, Division of Abdominal Surgery , Geneva University Hospital , Geneva , Switzerland
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Wei AC, Coburn NG, Devitt KS, Serrano PE, Moulton CA, Cleary SP, Law C, Moore MJ, Gallinger S. Survival Following Resection of Intra- and Extra-Hepatic Metastases from Colorectal Cancer: A Phase II Trial. Ann Surg Oncol 2016; 23:2644-51. [PMID: 27027312 DOI: 10.1245/s10434-016-5189-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Indexed: 12/26/2022]
Abstract
PURPOSE Metastasectomy for intrahepatic metastases (IHM) from colorectal cancer (CRC) provides excellent 5-year overall survival (OS). Presence of extrahepatic metastases (EHM) has been a historic contraindication to surgery. Due to improved safety of hepatectomy, there is growing interest in multisite metastasectomy for IHM and EHM. The objective of this study was to evaluate the results of metastasectomy for patients with IHM and EHM from CRC. METHODS A phase II study of metastasectomy for both IHM and EHM from CRC. Eligible patients with any number of IHM and up to three EHM foci, resectable with RO intent, were offered metastasectomy. Clinical, survival, and quality of life (QoL) data were analyzed using standard statistical methods. RESULTS Twenty-six patients were enrolled with a median age of 58 (range 32-84) years; 14/26 (54 %) presented with synchronous disease. The lung was the most common EHM site (13/26, 50 %). Protocol surgery was completed in 20/26 (77 %), including 12/26 (46 %) planned sequential resections. Major morbidity and perioperative mortality were 5/26 (19 %) and 1/26 (4 %), respectively. The QoL decline appeared to be transient. All QoL domains returned to baseline by 1-year posttreatment. The median recurrence-free survival (RFS) was 5 months by intent-to-treat analysis. The median OS from the time of CRC diagnosis and metastasectomy were 50 and 38 months (3-year OS 80 and 53 %), respectively. CONCLUSIONS Complete metastasectomy of multisite CRC is safe, but disease recurs in the majority of patients. Data suggest that aggressive multisite metastasectomy may provide OS benefit for selected patients.
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Affiliation(s)
- Alice C Wei
- Hepato-Pancreato-Biliary Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto General Hospital, Toronto, ON, Canada. .,Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada. .,Department of Surgery, University of Toronto, Toronto, Canada.
| | - Natalie G Coburn
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.,Department of Surgery, University of Toronto, Toronto, Canada.,Odette Cancer Centre, Sunnybrook Health Science Centre, Toronto, Canada
| | - Katharine S Devitt
- Hepato-Pancreato-Biliary Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto General Hospital, Toronto, ON, Canada
| | - Pablo E Serrano
- Hepatobiliary & Pancreatic Surgical Oncology, Juravinski Hospital and Cancer Centre, Hamilton, Ontario, Canada.,Department of Surgery, McMaster University, Hamilton, Ontario, Canada
| | - Carol-Anne Moulton
- Hepato-Pancreato-Biliary Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto General Hospital, Toronto, ON, Canada.,Department of Surgery, University of Toronto, Toronto, Canada
| | - Sean P Cleary
- Hepato-Pancreato-Biliary Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto General Hospital, Toronto, ON, Canada.,Department of Surgery, University of Toronto, Toronto, Canada
| | - Calvin Law
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.,Department of Surgery, University of Toronto, Toronto, Canada.,Odette Cancer Centre, Sunnybrook Health Science Centre, Toronto, Canada
| | | | - Steven Gallinger
- Hepato-Pancreato-Biliary Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto General Hospital, Toronto, ON, Canada.,Department of Surgery, University of Toronto, Toronto, Canada
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Abstract
The nuances of determining resectability for liver tumors can be difficult to navigate, owing to the variety of primary and secondary malignancies involving the liver, the range of patient-specific factors to consider, and the hepatic anatomic and functional variability that seems inevitable. The basic principles, however, are simple;if surgery is deemed appropriate from an oncologic standpoint, the patient is in reasonably good health, and the tumor can be safely removed without compromising the integrity of the future remnant, nearly all patients will be candidates for resection.
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Affiliation(s)
- Cecilia G Ethun
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, 1365C Clifton Road NE, Building C, 2nd Floor, Atlanta, GA 30322, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, 1365C Clifton Road NE, Building C, 2nd Floor, Atlanta, GA 30322, USA.
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Hadden WJ, de Reuver PR, Brown K, Mittal A, Samra JS, Hugh TJ. Resection of colorectal liver metastases and extra-hepatic disease: a systematic review and proportional meta-analysis of survival outcomes. HPB (Oxford) 2016; 18:209-20. [PMID: 27017160 PMCID: PMC4814625 DOI: 10.1016/j.hpb.2015.12.004] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2015] [Accepted: 12/16/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Colorectal cancer (CRC) accounts for 9.7% of all cancers with 1.4 million new cases diagnosed each year. 19-31% of CRC patients develop colorectal liver metastases (CRLM), and 23-38% develop extra-hepatic disease (EHD). The aim of this systematic review was to determine overall survival (OS) in patients resected for CRLM and known EHD. METHODS A systematic review was undertaken to identify studies reporting OS after resection for CRLM in the presence of EHD. Proportional meta-analyses and relative risk of death before five years were assessed between patient groups. RESULTS A total of 15,144 patients with CRLM (2308 with EHD) from 52 studies were included. Three and 5-year OS were 58% and 26% for lung, 37% and 17% for peritoneum, and 35% and 15% for lymph nodes, respectively. The combined relative risk of death by five years was 1.49 (95% CI = 1.34-1.66) for lung, 1.59 (95% CI = 1.16-2.17) for peritoneal and 1.70 (95% CI = 1.57-1.84) for lymph node EHD, in favour of resection in the absence of EHD. CONCLUSION This review supports attempts at R0 resection in selected patients and rejects the notion that EHD is an absolute contraindication to resection.
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Affiliation(s)
- William J. Hadden
- Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia
| | - Philip R. de Reuver
- Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, Sydney, New South Wales, Australia
| | - Kai Brown
- Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia,Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, Sydney, New South Wales, Australia
| | - Anubhav Mittal
- Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia,Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, Sydney, New South Wales, Australia
| | - Jaswinder S. Samra
- Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia,Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, Sydney, New South Wales, Australia
| | - Thomas J. Hugh
- Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia,Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, Sydney, New South Wales, Australia,Correspondence Thomas J. Hugh, Northern Upper GI Surgical Unit, Royal North Shore Hospital, St. Leonards NSW 2065, Australia. Tel: +61 2 9463 2899. Fax: +61 2 9463 2080.
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de Cuba EMV, de Hingh IHJT, Sluiter NR, Kwakman R, Coupé VMH, Beliën JAM, Verwaal VJ, Meijerink WJHJ, Delis-van Diemen PM, Bonjer HJ, Meijer GA, Te Velde EA. Angiogenesis-Related Markers and Prognosis After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Metastatic Colorectal Cancer. Ann Surg Oncol 2016; 23:1601-8. [PMID: 26727921 PMCID: PMC4819744 DOI: 10.1245/s10434-015-5023-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2015] [Indexed: 12/17/2022]
Abstract
BACKGROUND Patients presenting with peritoneal metastases (PM) of colorectal cancer (CRC) can be curatively treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Angiogenesis is under control of multiple molecules of which HIF1a, SDF1, CXCR4, and VEGF are key players. We investigated these angiogenesis-related markers and their prognostic value in patients with PM arising from CRC treated with CRS and HIPEC. PATIENTS AND METHODS Clinicopathological data and tissue specimens were collected in 2 tertiary referral centers from 52 patients who underwent treatment for isolated PM of CRC. Whole tissue specimens were subsequently analyzed for protein expression of HIF1a, SDF1, CXCR4, and VEGF by immunohistochemistry. Microvessel density (MVD) was analyzed by CD31 immunohistochemistry. The relationship between overall survival (OS) and protein expression as well as other clinicopathological characteristics was analyzed. RESULTS Univariate analysis showed that high peritoneal cancer index (PCI), resection with residual disease and high expression of VEGF were negatively correlated with OS after treatment with CRS and HIPEC (P < 0.01, P < 0.01, and P = 0.02, respectively). However, no association was found between the other markers and OS (P > 0.05). Multivariate analysis showed an independent association between OS and PCI, resection outcome and VEGF expression (multivariate HR: 6.1, 7.8 and 3.8, respectively, P ≤ 0.05). CONCLUSIONS An independent association was found between high VEGF expression levels and worse OS after CRS and HIPEC. The addition of VEGF expression to the routine clinicopathological workup could help to identify patients at risk for early treatment failure. Furthermore, VEGF may be a potential target for adjuvant treatment in these patients.
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Affiliation(s)
- E M V de Cuba
- Department of Surgical Oncology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.,Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
| | - I H J T de Hingh
- Department of Surgery, Catharina Ziekenhuis Eindhoven, Eindhoven, The Netherlands
| | - N R Sluiter
- Department of Surgical Oncology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands
| | - R Kwakman
- Department of Surgical Oncology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands
| | - V M H Coupé
- Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
| | - J A M Beliën
- Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
| | - V J Verwaal
- Department of Surgery, Catharina Ziekenhuis Eindhoven, Eindhoven, The Netherlands
| | - W J H J Meijerink
- Department of Surgical Oncology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands
| | - P M Delis-van Diemen
- Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
| | - H J Bonjer
- Department of Surgical Oncology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands
| | - G A Meijer
- Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.,Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - E A Te Velde
- Department of Surgical Oncology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands. .,Department of General Surgery, Section of Surgical Oncology and Digestive Surgery, VU University Medical Center, Amsterdam, The Netherlands.
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McAuliffe JC, Qadan M, D'Angelica MI. Hepatic resection, hepatic arterial infusion pump therapy, and genetic biomarkers in the management of hepatic metastases from colorectal cancer. J Gastrointest Oncol 2015; 6:699-708. [PMID: 26697204 DOI: 10.3978/j.issn.2078-6891.2015.081] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
The liver is the most common site of colorectal cancer metastasis. Fortunately, improvements have been made in the care of patients with colorectal liver metastasis (CRLM). Effective management of CRLM requires a multidisciplinary approach that is tailored to individuals in order to achieve long-term survival, and cure. Resection and systemic chemotherapy provides benefit in selected individuals. An adjunct to resection and/or systemic chemotherapy is the use of hepatic arterial infusion pump (HAIP) therapy. Many studies show HAIP provides benefit for select patients with CRLM. Added to the crucible of a multidisciplinary approach to managing CRLM is the ever growing understanding of tumor biology and genetic profiling. In this review, we discuss the outcomes of resection, systemic therapies and HAIP therapy for CRLM. We also discuss the impact of recent advances in genetic profiling and mutational analysis, namely mutation of KRAS and BRAF, for this disease.
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Affiliation(s)
- John C McAuliffe
- Hepatopancreatobiliary Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Motaz Qadan
- Hepatopancreatobiliary Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Michael I D'Angelica
- Hepatopancreatobiliary Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA
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Resection margin and survival in 2368 patients undergoing hepatic resection for metastatic colorectal cancer: surgical technique or biologic surrogate? Ann Surg 2015; 262:476-85; discussion 483-5. [PMID: 26258316 DOI: 10.1097/sla.0000000000001427] [Citation(s) in RCA: 141] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVES The impact of margin width on overall survival (OS) in the context of other prognostic factors after resection for colorectal liver metastases is unclear. We evaluated the relationship between resection margin and OS utilizing high-resolution histologic distance measurements. METHODS A single-institution prospectively maintained database was queried for all patients who underwent an initial complete resection of colorectal liver metastases between 1992 and 2012. R1 resection was defined as tumor cells at the resection margin (0 mm). R0 resection was further divided into 3 groups: 0.1 to 0.9 mm, 1 to 9 mm, and 10 mm or greater. RESULTS A total of 4915 liver resections were performed at Memorial Sloan Kettering Cancer Center between 1992 and 2012, from which 2368 patients were included in the current study. Half of the patients presented with synchronous disease, 43% had solitary metastasis, and the median tumor size was 3.4 cm. With a median follow-up for survivors of 55 months, the median OS of the R1, 0.1 to 0.9 mm, 1 to 9 mm, and 10 mm or more groups was 32, 40, 53, and 56 months, respectively (P < 0.001). Compared with R1 resection, all margin widths, including submillimeter margins correlated with prolonged OS (P < 0.05). The association between the margin width and OS remained significant when adjusted for all other clinicopathologic prognostic factors. CONCLUSIONS Resection margin width is independently associated with OS. Wide margins should be attempted whenever possible. However, resection should not be precluded if narrow margins are anticipated, as submillimeter margin clearance is associated with improved survival. The prolonged OS observed with submillimeter margins is likely a microscopic surrogate for the biologic behavior of a tumor rather than the result of surgical technique.
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Fisher SG, Kuhlmann K, Poston G. Defining resectability of colorectal liver metastases. COLORECTAL CANCER 2015. [DOI: 10.2217/crc.15.6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Affiliation(s)
- Simon George Fisher
- Liver Surgery Unit, Aintree University Hospital, Lower Lane, Liverpool L9 7AL, UK
| | - Koert Kuhlmann
- Liver Surgery Unit, Aintree University Hospital, Lower Lane, Liverpool L9 7AL, UK
| | - Graeme Poston
- Liver Surgery Unit, Aintree University Hospital, Lower Lane, Liverpool L9 7AL, UK
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Hepatic Resection for Extrahepatic Metastatic Disease: When Is It Reasonable? CURRENT COLORECTAL CANCER REPORTS 2015. [DOI: 10.1007/s11888-015-0263-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Butte JM, Gönen M, Allen PJ, Peter Kingham T, Sofocleous CT, DeMatteo RP, Fong Y, Kemeny NE, Jarnagin WR, D'Angelica MI. Recurrence After Partial Hepatectomy for Metastatic Colorectal Cancer: Potentially Curative Role of Salvage Repeat Resection. Ann Surg Oncol 2015; 22:2761-71. [PMID: 25572686 DOI: 10.1245/s10434-015-4370-1] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2014] [Indexed: 12/29/2022]
Abstract
PURPOSE Patients with recurrence after complete resection of colorectal liver metastases (CLM) are considered for repeat resection as a potential salvage therapy (PST). However, outcomes for this approach are not well defined. We sought to analyze the natural history of recurrence and PST in a large cohort of patients with long-term follow-up. METHODS Recurrence patterns, treatments, and outcomes in consecutive patients undergoing resection for colorectal liver metastases were analyzed retrospectively. PST was defined as repeat resection of all recurrent disease and effective salvage therapy (EST) as free of disease for 36 months after last PST. Factors associated with PST, EST, and outcomes were analyzed. RESULTS Of 952 patients who underwent resection, 594 (62 %) experienced recurrence (median interval = 13 months). Initial recurrences involved liver (n = 157,26 %), lung (n = 167,28 %), multiple sites (n = 171,29 %), and other single sites (n = 99,17 %). PST was performed in 160 (27 %) of 594, most commonly with a single site of recurrence (n = 149). Young age (p = 0.01), negative initial resection margin (p = 0.003), initial tumor size <5 cm (p = 0.006), and recurrence pattern (p < 0.001) were independently associated with PST. Thirty-six patients experienced EST (25 % of PSTs). Overall median survival was 61 and 43 months in those with recurrence. Median survival of patients undergoing PST was 87 months compared to 34 months for those who did not. CONCLUSIONS Recurrence is common after CLM resection, but 27 % of patients were able to undergo PST. Approximately one-quarter of these experienced EST and may be cured. PST is associated with long-term survival and possible cure, and therefore active surveillance after CLM resection is justified.
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Affiliation(s)
- Jean M Butte
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Shindoh J, Zimmitti G, Vauthey JN. Management of Liver Metastases from Colorectal Cancer. Surg Oncol 2015. [DOI: 10.1007/978-1-4939-1423-4_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Prognostic value of treatment-related factors in metastatic colorectal cancer using a stop-and-go strategy. Int J Colorectal Dis 2014; 29:1453-8. [PMID: 25064391 DOI: 10.1007/s00384-014-1979-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/16/2014] [Indexed: 02/04/2023]
Abstract
PURPOSE The purpose of this study is to identify treatment-related factors prognostic of survival in a cohort of patients with metastatic colorectal cancer (mCRC) receiving a palliative, stop-and-go chemotherapy regimen. METHODS Consecutive patients receiving first-line treatment with biweekly FLIRI plus bevacizumab were included. The outcome was overall survival. Cox regression analysis was used to identify predictors of outcome. We analysed reduction in chemotherapy dosage (no vs. ≤25 or >25 % reduction), bevacizumab administrated to <50, or ≥50 % to chemotherapy treatments, best response during the first 24 weeks of treatment, and local treatment of metastases. RESULTS We included 257 patients. Median survival was 23.6 months. Chemotherapy reduction did not influence outcome. Bevacizumab administrations (≥50 %) were associated with improved outcome: hazard ratios (HR) 0.56 (95 % confidence interval (CI) 0.34-0.90, p = 0.018). Partial response (PR) vs. no change (NC) was borderline significant: HR 0.66 (95 % CI 0.43-0.99, p = 0.048), whereas progressive disease (PD) vs. NC increased mortality HR 2.48 (95 % CI 1.19-5.19, p = 0.016). Local treatment of metastases improved outcome: HR 0.30 (95 % CI 0.15-0.61, p = 0.001). CONCLUSIONS In a cohort of mCRC patients, receiving a palliative, stop-and-go regimen, administration of bevacizumab to ≥50 % of chemotherapy treatments and local treatment of metastases were associated with better survival. PR improved outcome compared to NC, whereas PD was prognostic of increased mortality.
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Nichols SD, Albert S, Shirley L, Schmidt C, Abdel-Misih S, El-Dika S, Groce JR, Wu C, Goldberg RM, Bekaii-Saab T, Bloomston M. Outcomes in patients with obstructive jaundice from metastatic colorectal cancer and implications for management. J Gastrointest Surg 2014; 18:2186-91. [PMID: 25300799 PMCID: PMC4809042 DOI: 10.1007/s11605-014-2670-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2014] [Accepted: 09/25/2014] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Patients with metastatic colorectal cancer can develop jaundice from intrahepatic or extrahepatic causes. Currently, there is little data on the underlying causes and overall survival after onset of jaundice. The purpose of this study was to characterize the causes of jaundice and determine outcomes. METHODS Six hundred twenty-nine patients treated for metastatic colorectal cancer between 2004 and 2010 were retrospectively reviewed. Those developing jaundice were grouped as having intrahepatic or extrahepatic obstruction. Demographics, clinicopathologic, and outcome data were analyzed. RESULTS Sixty-two patients with metastatic colorectal cancer developed jaundice. Intrahepatic biliary obstruction was most common, occurring in younger patients. Time from metastatic diagnosis to presentation of jaundice was similar between groups, as was the mean number of prior lines of chemotherapy. Biliary decompression was successful 41.7 % of the time and was attempted more commonly for extrahepatic causes. Median overall survival after onset of jaundice was 1.5 months and it was similar between groups, but improved to 9.6 months in patients who were able to receive further chemotherapy. CONCLUSIONS Jaundice due to metastatic colorectal cancer is an ominous finding, representing aggressive tumor biology or exhaustion of therapies. Biliary decompression is often difficult and should only be pursued when additional treatment options are available.
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Affiliation(s)
- Shawnn D Nichols
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center, 410 West 10th Ave, N924 Doan Hall, Columbus, OH, 43210, USA
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Exérèse chirurgicale des métastases pulmonaires de cancer colorectal : quelle stratégie en 2014 ? ONCOLOGIE 2014. [DOI: 10.1007/s10269-014-2466-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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50
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Luo LX, Yu ZY, Huang JW, Wu H. Selecting patients for a second hepatectomy for colorectal metastases: an systemic review and meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2014; 40:1036-48. [PMID: 24915859 DOI: 10.1016/j.ejso.2014.03.012] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Revised: 03/02/2014] [Accepted: 03/07/2014] [Indexed: 02/05/2023]
Abstract
BACKGROUND Opinions on the suitability of repeat hepatectomy for patients with recurrent colorectal liver metastases (CRLMs) vary among studies. We conducted a meta-analysis to establish the criteria for selecting the best candidates for a second hepatectomy. METHODS Database and manual searches were performed to identify comparative or prognostic studies published up to October 2013. Outcomes of interest included disease characteristics, perioperative outcomes, and long-term survival after initial and second hepatectomies for patients with CRLM. Study quality was appraised using the Newcastle-Ottawa scale and a modified Hayden's score. RESULTS A total of 7226 patients from 27 studies were included. Recurrent CRLMs after initial hepatectomy were more likely to be solitary (RR = 0.86, P = 0.045), unilobar (RR = 0.60, P < 0.001), and smaller (WMD = -0.66, P < 0.001). Postoperative morbidity and mortality were comparable between initial and second hepatectomies (RR = 1.10, P = 0.191; RR = 0.78, P = 0.678, respectively). In high-quality studies, patients showed better survival after a second hepatectomy than those after a single hepatectomy (HR = 0.68, P = 0.022). Patients meeting the following six predictors survived longer after second hepatectomy: disease-free survival after initial hepatectomy >1 y (P = 0.034); solitary CRLM at second hepatectomy (P < 0.001); unilobar CRLM at second hepatectomy (P = 0.009); maximal size of CRLM at second hepatectomy ≤ 5 cm (P = 0.035); lack of extrahepatic metastases at second hepatectomy (P < 0.001); and R0 resection at second hepatectomy (P < 0.001). CONCLUSIONS Second hepatectomy is a safe and feasible procedure for patients with recurrent CRLM. In fact, in well-selected patients it improves overall survival. The established criteria can help clinicians to select the best candidates for second hepatectomy and to achieve better long-term outcomes after resection.
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Affiliation(s)
- L X Luo
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, China.
| | - Z Y Yu
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, China
| | - J W Huang
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, China
| | - H Wu
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, China
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