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Kim GY, Jalali A, Gard G, Yeung JM, Chau H, Gately L, Houli N, Jones IT, Kosmider S, Lee B, Lee M, Nott L, Shapiro JD, Tie J, Thomson B, To YH, Wong V, Wong R, Dunn C, Johns J, Gibbs P. Initial Assessment of Resectability of Colorectal Cancer Liver Metastases Versus Clinical Outcome. Clin Colorectal Cancer 2025; 24:72-81. [PMID: 39523153 DOI: 10.1016/j.clcc.2024.10.001] [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: 08/17/2024] [Revised: 10/02/2024] [Accepted: 10/06/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Surgery improves long-term survival for resectable, liver-only metastatic colorectal cancer (mCRC). With no consensus definition of "resectable" disease, decisions regarding resectability are reliant on the expertise and judgement of the treating clinician working in consultation with a multidisciplinary team (MDT). This study examines the clinical outcome versus initial assessment of resectability in an Australian population with mCRC. PATIENTS AND METHODS Patients with liver-only mCRC diagnosed January 2009 to December 2022 were identified from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry. Patients were classified based on prospectively documented treatment assessment as "resectable," "potentially resectable," or "unresectable." The correlation between initial assessment of resectability and clinical outcome, and any impact of clinicopathologic factors were examined. Kaplan-Meier analysis assessed overall survival based on initial resectability assessment and resection status. RESULTS Of 4437 patients with mCRC identified through TRACC, 1250 (28%) had liver-only disease at presentation, with 497 (43%), 277 (24%), and 374 (33%) classified as "unresectable," "potentially resectable," and "resectable," respectively. In total, 516 (41%) ultimately underwent surgical resection, including 30 (6%) of the "initially unresectable," 148 (53%) of the "potentially resectable," and 338 (90%) of the "resectable" at a median of 9.5, 5.9, and 2.4 months from the diagnosis of liver metastases, respectively. Resection in the "unresectable" patient population was associated with younger age (mean age 63 vs. 69, P = .0006), better performance status (ECOG 0-1 100% vs. 74%, P = .0017), and fewer comorbidities (Charlson index 0-3 in 73% vs. 53%, P = .0296) compared with no resection. Median overall survival was longer for resected versus nonresected patients across all categories: "unresectable" (59.2 vs. 17.6 months, P < .0001), "potentially resectable" (57.2 vs. 22.8 months, P < .0001), and "resectable" (108 vs. 55 months, P < .0001). CONCLUSIONS This real-world study demonstrates the potential for "initially unresectable" patients to become surgical candidates following systemic therapy, more likely in younger and fitter patients, with overall excellent survival outcomes in resected patients. This highlights the value of routine, repeated MDT assessments for patients with liver-only disease who are continuing to respond to systemic therapy, even for those initially considered never to be surgical candidates.
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Affiliation(s)
- Grace Y Kim
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
| | - Azim Jalali
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Department of Medical Oncology, Western Health, Footscray, Victoria, Australia; Department of Medical Oncology, Northern Health, Epping, Victoria, Australia; Department of Medical Oncology, Latrobe Regional Hospital, Traralgon, Victoria, Australia
| | - Grace Gard
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Department of Medical Oncology, Western Health, Footscray, Victoria, Australia
| | - Justin M Yeung
- Department of Surgery, Western Precinct, University of Melbourne, Footscray, Victoria, Australia; Department of Colorectal Surgery, Western Health, Footscray, Victoria, Australia
| | - Hieu Chau
- Department of Medical Oncology, Latrobe Regional Hospital, Traralgon, Victoria, Australia
| | - Lucy Gately
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Department of Medical Oncology, Alfred Health, Melbourne, Victoria, Australia
| | - Nezor Houli
- Department of Surgery, Western Precinct, University of Melbourne, Footscray, Victoria, Australia
| | - Ian T Jones
- Department of Surgery, Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Suzanne Kosmider
- Department of Medical Oncology, Western Health, Footscray, Victoria, Australia
| | - Belinda Lee
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Department of Medical Oncology, Northern Health, Epping, Victoria, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia
| | - Margaret Lee
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Department of Medical Oncology, Western Health, Footscray, Victoria, Australia; Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia
| | - Louise Nott
- Department of Medical Oncology, Royal Hobart Hospital, Hobart, Tasmania, Australia; Department of Medical Oncology, Icon Cancer Centre, Hobart, Tasmania, Australia
| | - Jeremy D Shapiro
- Department of Medical Oncology, Cabrini Hospital, Malvern, Victoria, Australia
| | - Jeanne Tie
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia
| | - Benjamin Thomson
- Department of Surgery, Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Yat Hang To
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Department of Medical Oncology, Northern Health, Epping, Victoria, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia
| | - Vanessa Wong
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Department of Medical Oncology, Western Health, Footscray, Victoria, Australia; Department of Medical Oncology, Grampians Health, Ballarat, Victoria, Australia
| | - Rachel Wong
- Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia; Department of Medical Oncology, Epworth Health, Victoria, Australia
| | - Catherine Dunn
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
| | - Julie Johns
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
| | - Peter Gibbs
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Department of Medical Oncology, Western Health, Footscray, Victoria, Australia
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Weixler B, Lobbes LA, Scheiner L, Lauscher JC, Staubli SM, Zuber M, Raptis DA. The Value of Indocyanine Green Image-Guided Surgery in Patients with Primary Liver Tumors and Liver Metastases. Life (Basel) 2023; 13:1290. [PMID: 37374073 DOI: 10.3390/life13061290] [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: 04/10/2023] [Revised: 05/13/2023] [Accepted: 05/30/2023] [Indexed: 06/29/2023] Open
Abstract
INTRODUCTION Successful R0 resection is crucial for the survival of patients with primary liver cancer (PLC) or liver metastases. Up to date, surgical resection lacks a sensitive, real-time intraoperative imaging modality to determine R0 resection. Real-time intraoperative visualization with near-infrared light fluorescence (NIRF) using indocyanine green (ICG) may have the potential to meet this demand. This study evaluates the value of ICG visualization in PLC and liver metastases surgery regarding R0 resection rates. MATERIALS AND METHODS Patients with PLC or liver metastases were included in this prospective cohort study. ICG 10 mg was administered intravenously 24 h before surgery. Real-time intraoperative NIRF visualization was created with the SpectrumTM fluorescence imaging camera system. First, all liver segments were inspected with the fluorescence imaging system and intraoperative ultrasound for identification of the known tumor, as well as additional lesions, and were compared to preoperative MRI images. PLC, liver metastases, and additional lesions were then resected according to oncological principles. In all resected specimens, the resection margins were analyzed with the fluorescence imaging system for ICG-positive spots immediately after resection. Histology of additional detected lesions, as well as ICG fluorescence compared to histological resection margins, were assessed. RESULTS Of the 66 included patients, median age was 65.5 years (IQR 58.7-73.9), 27 (40.9%) were female, and 18 (27.3%) were operated on laparoscopically. Additional ICG-positive lesions were detected in 23 (35.4%) patients, of which 9 (29%) were malignant. In patients with no fluorescent signal at the resection margin, R0 rate was 93.9%, R1 rate was 6.1%, and R2 rate was 0% compared to an ICG-positive resection margin with an R0 rate of 64.3%, R1 rate of 21.4%, and R2 rate of 14.3% (p = 0.005). One- and two-year overall survival rates were 95.2% and 88.4%, respectively. CONCLUSION The presented study provides significant evidence that ICG NIRF guidance helps to identify R0 resection intraoperatively. This offers true potential to verify radical resection and improve patient outcomes. Furthermore, implementation of NIRF-guided imaging in liver tumor surgery allows us to detect a considerable amount of additional malignant lesions.
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Affiliation(s)
- Benjamin Weixler
- Department of General and Visceral Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Hindenburgdamm 30, 12203 Berlin, Germany
| | - Leonard A Lobbes
- Department of General and Visceral Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Hindenburgdamm 30, 12203 Berlin, Germany
| | - Luis Scheiner
- Department of General and Visceral Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Hindenburgdamm 30, 12203 Berlin, Germany
| | - Johannes C Lauscher
- Department of General and Visceral Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Hindenburgdamm 30, 12203 Berlin, Germany
| | - Sebastian M Staubli
- Department of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, Royal Free Hospital, London NW3 2QG, UK
| | - Markus Zuber
- Clarunis University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital Basel, 4058 Basel, Switzerland
| | - Dimitri A Raptis
- Department of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, Royal Free Hospital, London NW3 2QG, UK
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Mason MC, Krasnodebski M, Hester CA, Kothari AN, Barker C, Nishioka Y, Chiang YJ, Newhook TE, Tzeng CWD, Chun YS, Vauthey JN, Tran Cao HS. Outcomes of Mixed Pathologic Response in Patients with Multiple Colorectal Liver Metastases Treated with Neoadjuvant Chemotherapy and Liver Resection. Ann Surg Oncol 2022; 29:5156-5164. [DOI: 10.1245/s10434-022-11683-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 02/08/2022] [Indexed: 11/18/2022]
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Verheij FS, Soares KC, Beets GL, Kok NF, Yuval JB, Kemeny NE, Kingham TP, Jarnagin WR, D’Angelica MI, Garcia-Aguilar J. Timing of Primary Tumor Resection in Synchronous Metastatic Colon Cancer Patients Undergoing Hepatic Arterial Infusion Pump Placement. Ann Surg Oncol 2022; 29:2044-2051. [PMID: 34751873 PMCID: PMC8896144 DOI: 10.1245/s10434-021-11029-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 10/05/2021] [Indexed: 01/05/2023]
Abstract
INTRODUCTION Hepatic arterial infusion (HAI) chemotherapy is associated with improved survival in stage IV colon cancer with liver metastases. Whether simultaneous colon resection and HAI pump (HAIP) placement is associated with increased morbidity has not been specifically studied. The purpose of this study was to compare perioperative outcomes of simultaneous colon resection and HAIP placement versus HAIP placement alone. METHODS This was a retrospective study of consecutive patients with colon cancer and synchronous liver metastases who underwent HAIP placement between 2007 and 2018. Clinicopathologic characteristics, operative data, complications, and time to first cycle of HAIP chemotherapy were compared between patients who underwent colon resection simultaneously with HAIP placement and those who underwent HAIP placement alone. RESULTS A total of 258 patients underwent simultaneous colectomy and HAIP placement, and 116 patients underwent HAIP placement alone. Grade 1-2 complications were more common in patients who underwent simultaneous colectomy and HAIP placement (36.8% vs. 19.0%, P < 0.001), but grade 3-4 complications were not observed more frequently (14.3% vs. 12.9%, P = 0.872). The median interval between HAIP placement and start of HAIP chemotherapy did not differ between groups (simultaneous colectomy, 27 days [interquartile range (IQR) 17-34]; HAIP placement alone, 30 days [IQR 21-34]; P = 0.924). Infection of the pump causing either delay of initiation of chemotherapy or explantation of the pump occurred in five patients with simultaneous colectomy and in one patient with HAIP placement alone (P = 0.671). CONCLUSIONS Simultaneous HAIP implantation and colectomy is safe in patients with liver metastases of colon carcinoma.
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Affiliation(s)
- Floris S. Verheij
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York;,Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Kevin C. Soares
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Geerard L. Beets
- Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Niels F.M. Kok
- Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Jonathan B. Yuval
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York;,Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Nancy E. Kemeny
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - T. Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - William R. Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | | | - Julio Garcia-Aguilar
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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BOZBIYIK O, ÇOKER A. Factors affecting survival in liver metastasis of colorectal cancer. EGE TIP DERGISI 2021. [DOI: 10.19161/etd.1036904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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Zhang Y, Ge L, Weng J, Tuo WY, Liu B, Ma SX, Yang KH, Cai H. Neoadjuvant chemotherapy for patients with resectable colorectal cancer liver metastases: A systematic review and meta-analysis. World J Clin Cases 2021; 9:6357-6379. [PMID: 34435001 PMCID: PMC8362587 DOI: 10.12998/wjcc.v9.i22.6357] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 04/14/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In recent years, neoadjuvant chemotherapy (NAC) has been increasingly used in patients with resectable colorectal liver metastases. However, the efficacy and safety of NAC in the treatment of resectable colorectal liver metastases (CRLM) are still controversial.
AIM To assess the efficacy and application value of NAC in patients with resectable CRLM.
METHODS We searched PubMed, Embase, Web of Science, and the Cochrane Library from inception to December 2020 to collect clinical studies comparing NAC with non-NAC. Data processing and statistical analyses were performed using Stata V.15.0 and Review Manager 5.0 software.
RESULTS In total, 32 studies involving 11236 patients were included in this analysis. We divided the patients into two groups, the NAC group (that received neoadjuvant chemotherapy) and the non-NAC group (that received no neoadjuvant chemotherapy). The meta-analysis outcome showed a statistically significant difference in the 5-year overall survival and 5-year disease-free survival between the two groups. The hazard ratio (HR) and 95% confidence interval (CI) were HR = 0.49, 95%CI: 0.39-0.61, P = 0.000 and HR = 0.48 95%CI: 0.36-0.63, P = 0.000. The duration of surgery in the NAC group was longer than that of the non-NAC group [standardized mean difference (SMD) = 0.41, 95%CI: 0.01-0.82, P = 0.044)]. The meta-analysis showed that the number of liver metastases in the NAC group was significantly higher than that in the non-NAC group (SMD = 0.73, 95%CI: 0.02-1.43, P = 0.043). The lymph node metastasis in the NAC group was significantly higher than that in the non-NAC group (SMD = 1.24, 95%CI: 1.07-1.43, P = 0.004).
CONCLUSION We found that NAC could improve the long-term prognosis of patients with resectable CRLM. At the same time, the NAC group did not increase the risk of any adverse event compared to the non-NAC group.
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Affiliation(s)
- Yue Zhang
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Long Ge
- Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Jun Weng
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Wen-Yu Tuo
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Bin Liu
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Shi-Xun Ma
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Ke-Hu Yang
- Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Hui Cai
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
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Frühling P, Hellberg K, Ejder P, Strömberg C, Urdzik J, Isaksson B. The prognostic value of C-reactive protein and albumin in patients undergoing resection of colorectal liver metastases. A retrospective cohort study. HPB (Oxford) 2021; 23:970-978. [PMID: 33214053 DOI: 10.1016/j.hpb.2020.10.019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Revised: 10/02/2020] [Accepted: 10/28/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND The systemic inflammation-based Glasgow Prognostic Score (GPS) and modified GPS (mGPS), as measured by preoperative C-reactive protein (CRP) and albumin, correlate with poor survival in several cancers. This study evaluates the prognostic value of these scores in patients with colorectal liver metastases (CRLM). METHODS This retrospective study assessed the prognostic role of preoperatively measured GPS and mGPS in patients undergoing liver resection because of CRLM. Clinicopathological data were retrieved from local databases. The prognostic value of GPS and mGPS were compared and a Cox regression model was used to find independent predictors of overall survival. RESULTS In total, 849 consecutive patients between January 2005 and December 2015 were included. Patients with GPS 0 had a median survival of 70 months compared to 49 months in patients with GPS 1, and 27 months in patients with GPS 2. Multivariable analyses showed that GPS 1 (HR = 1.51, 95%CI [1.14-2.01]) and GPS 2 (HR = 2.78, 95%CI [1.79-4.31]), after correction for age >70 years (HR = 1.75 [1.36-2.26]), and extended resection (HR = 2.53, 95%CI[1.79-3.58]), were associated with poor overall survival. CONCLUSION A preoperative GPS is an independent prognostic factor in patients with CRLM, and appears to be a better prognostic tool than mGPS.
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Affiliation(s)
- Petter Frühling
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
| | - Katarina Hellberg
- Division of Surgery, Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Patric Ejder
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Cecilia Strömberg
- Division of Surgery, Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Jozef Urdzik
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Bengt Isaksson
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
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Bhatti T, Moser M, Tan KT, Chalchal H, Souied O, Le D, Shaw J, Zaidi A, Gill D, Ahmed S. Rate of Curative Surgery in Real-world Patients with Unresectable Metastatic Colorectal Cancer Treated with FOLFOXIRI ± Bevacizumab: A Western Canadian Province Experience. J Gastrointest Cancer 2021; 53:427-433. [PMID: 33779898 DOI: 10.1007/s12029-021-00634-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/21/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND Recent evidence from randomized trials suggests that FOLFOXIRI (fluorouracil, oxaliplatin, and irinotecan) ± bevacizumab is associated with higher response rates, with the potential for conversion of unresectable to resectable disease in metastatic colorectal cancer (mCRC). However, limited evidence is available on the efficacy and safety of this regimen in real-world patients with mCRC. The current study aims to evaluate the conversion rate and safety of FOLFOXIRI ± bevacizumab in real-world patients with unresectable mCRC. METHODS In this retrospective multicenter population-based cohort study, patients who were diagnosed with unresectable mCRC between January 2015 and December 2018 in Saskatchewan and received FOLFOXIRI ± bevacizumab were assessed. Kaplan-Meier survival methods and the log-rank test were performed. RESULTS A total of 28 eligible patients with a median age of 51 years (interquartile range 39-60) and a male:female ratio of 11:17 were identified; 39% had rectal cancer, 46% had extrahepatic disease, and 46% had bilobar liver metastases. Overall, 63% of the patients had a positive response to FOLFOXIRI ± bevacizumab and 53% underwent metastasectomy. Of all patients 60% had grade 3/4 toxicity and 32% required hospital admission. No treatment-related mortality was noted. After 4 years, 50% of the patients were alive. Median progression-free survival of patients who underwent surgery was 18 months (95% CI 11.3-24.7) versus 11 months (4-18.1) without surgery (p = 0.28). Median overall survival of patients with surgery was 33 months (17.5-48.5) versus 16 months (8.3-23.7) without surgery (p = 0.03). CONCLUSION The current study suggests that FOLFOXIRI ± bevacizumab therapy in real-world patients with mCRC is associated with a high rate of conversion from unresectable to resectable metastatic disease. Patients with metastasectomy had better survival.
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Affiliation(s)
- Tayyaba Bhatti
- College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - Michael Moser
- Department of Surgery, University of Saskatchewan, Saskatoon, SK, Canada
| | | | | | | | - Duc Le
- Saskatoon Cancer Centre, University of Saskatchewan, Saskatoon, Canada
| | - John Shaw
- Department of Surgery, University of Saskatchewan, Saskatoon, SK, Canada
| | - Adnan Zaidi
- Saskatoon Cancer Centre, University of Saskatchewan, Saskatoon, Canada
| | - Dilip Gill
- Department of Surgery, University of Saskatchewan, Saskatoon, SK, Canada
| | - Shahid Ahmed
- Saskatoon Cancer Centre, University of Saskatchewan, Saskatoon, Canada.
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Huang J, Liu H, Zhao Y, Luo T, Liu J, Liu J, Pan X, Tang W. MicroRNAs Expression Patterns Predict Tumor Mutational Burden in Colorectal Cancer. Front Oncol 2021; 10:550986. [PMID: 33634010 PMCID: PMC7900489 DOI: 10.3389/fonc.2020.550986] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Accepted: 12/04/2020] [Indexed: 01/10/2023] Open
Abstract
Background Tumor mutational burden (TMB) could be a measure of response to immune checkpoint inhibitors therapy for patients with colorectal cancer (CRC). MicroRNAs (miRNAs) participate in anticancer immune responses. In the present study, we determined miRNA expression patterns in patients with CRC and built a signature that predicts TMB. Methods Next generation sequencing (NGS) on formalin-fixed paraffin-embedded samples from CRC patients was performed to measure TMB levels. We used datasets from The Cancer Genome Atlas to compare miRNA expression patterns in samples with high and low TMB from patients with CRC. We created an miRNA-based signature index using the selection operator (LASSO) and least absolute shrinkage method from the training set. We used an independent test set as internal validation. We used real-time polymerase chain reaction (RT-PCR) to validate the miRNA-based signature classifier. Results Twenty-seven samples from CRC patients underwent NGS to determine the TMB level. We identified four miRNA candidates in the training set for predicting TMB (N = 311). We used the test set (N = 204) for internal validation. The four-miRNA-based signature classifier was an accurate predictor of TMB, with accuracy 0.963 in the training set. In the test set, it was 0.902; and it was 0.946 in the total set. The classifier was superior to microsatellite instability (MSI) for predicting TMB in TCGA dataset. In the validation cohort, MSI status more positively correlated with TMB levels than did the classifier. Validation from RT-qPCR showed good target discrimination of the classifier for TMB prediction. Conclusion To our knowledge, this is the first miRNA-based signature classifier validated using high quality clinical data to accurately predict TMB level in patients with CRC.
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Affiliation(s)
- Jiahao Huang
- Department of Gastrointestinal Surgery, Affiliated Tumor Hospital, Guangxi Medical University, Nanning, China.,Department of Colorectal and Anal Surgery, The First Affiliated Hospital, Guangxi Medical University, Nanning, China.,Guangxi Clinical Research Center for Colorectal Cancer, Nanning, China
| | - Haizhou Liu
- Department of Research, Affiliated Tumor Hospital, Guangxi Medical University, Nanning, China
| | - Yang Zhao
- Department of Radiology, Affiliated Tumor Hospital, Guangxi Medical University, Nanning, China
| | - Tao Luo
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital, Guangxi Medical University, Nanning, China
| | - Jungang Liu
- Department of Gastrointestinal Surgery, Affiliated Tumor Hospital, Guangxi Medical University, Nanning, China.,Guangxi Clinical Research Center for Colorectal Cancer, Nanning, China
| | - Junjie Liu
- Department of Ultrasound, Affiliated Tumor Hospital, Guangxi Medical University, Nanning, China
| | - Xiaoyan Pan
- Department of Comprehensive Internal Medicine, Affiliated Tumor Hospital, Guangxi Medical University, Nanning, China
| | - Weizhong Tang
- Department of Gastrointestinal Surgery, Affiliated Tumor Hospital, Guangxi Medical University, Nanning, China.,Guangxi Clinical Research Center for Colorectal Cancer, Nanning, China
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10
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Berardi G, Antonelli G, Colasanti M, Meniconi R, Guglielmo N, Laurenzi A, Ferretti S, Levi Sandri GB, Spagnoli A, Moschetta G, Schininà V, Antonini M, Marignani M, Ettorre GM. Association of Sarcopenia and Body Composition With Short-term Outcomes After Liver Resection for Malignant Tumors. JAMA Surg 2020; 155:e203336. [PMID: 32965483 DOI: 10.1001/jamasurg.2020.3336] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Importance Previous retrospective studies have shown that sarcopenia substantially alters the postoperative and oncological outcomes after liver resection for malignant tumors. However, the evidence is limited to small retrospective studies with heterogeneous results and the lack of standardized measurements of sarcopenia. Objective To investigate the role of sarcopenia as a risk factor associated with 90-day morbidity after liver resection for malignant tumors. Design, Setting, and Participants This cohort study included 234 consecutive patients undergoing liver resection for malignant tumors at San Camillo Forlanini Hospital, Rome, Italy, between June 1, 2018, and December 15, 2019. Muscle mass and strength were assessed using the skeletal muscle index (SMI) on preoperative computed tomographic scans and the handgrip strength test, respectively. Patients were then divided into the following 4 groups: group A (normal muscle mass and strength), group B (reduced muscle strength), group C (reduced muscle mass), and group D (reduced muscle mass and strength). Main Outcomes and Measures The primary outcome of the study was 90-day morbidity. The following secondary outcomes were investigated: 90-day mortality, hospital stay, and readmission rate. Results Sixty-four major and 170 minor hepatectomies were performed in 234 patients (median age, 66.50 [interquartile range, 58.00-74.25] years; 158 men [67.5%]). The median SMI of the entire population was 46.22 (interquartile range, 38.60-58.20) cm/m2. The median handgrip strength was 30.80 (interquartile range, 22.30-36.90) kg. Patients in group D had a statistically significantly higher rate of 90-day morbidity than patients in the other groups (51.5% [35 of 68] vs 38.7% [29 of 75] in group C, 23.1% [3 of 13] in group B, and 6.4% [5 of 78] in group A; P < .001). Compared with patients in the other groups, those in group D had a longer hospital stay (10 days vs 8 days in group C, 9 days in group B, and 6 days in group A; P < .001), and more patients in this group were readmitted to the hospital (8.8% [6 of 68] vs 5.3% [4 of 75] in group C, 7.7% [1 of 13] in group B, and 0% [0 of 78] in group A; P = .02). Sarcopenia, portal hypertension, liver cirrhosis, and biliary reconstruction were independent risk factors associated with 90-day morbidity. Conclusions and Relevance Sarcopenia appears to be associated with adverse outcomes after liver resection for malignant tumors. Both muscle mass measurements on computed tomographic scans and muscle strength assessments with the handgrip strength test should be performed at the first clinical encounter to better classify patients and to minimize the risk of morbidity.
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Affiliation(s)
- Giammauro Berardi
- Department of General Surgery and Liver Transplantation, San Camillo Forlanini Hospital, Rome, Italy
| | - Giulio Antonelli
- Department of Digestive and Liver Diseases, University Sapienza, Rome, Italy
| | - Marco Colasanti
- Department of General Surgery and Liver Transplantation, San Camillo Forlanini Hospital, Rome, Italy
| | - Roberto Meniconi
- Department of General Surgery and Liver Transplantation, San Camillo Forlanini Hospital, Rome, Italy
| | - Nicola Guglielmo
- Department of General Surgery and Liver Transplantation, San Camillo Forlanini Hospital, Rome, Italy
| | - Andrea Laurenzi
- Department of General Surgery and Liver Transplantation, San Camillo Forlanini Hospital, Rome, Italy
| | - Stefano Ferretti
- Department of General Surgery and Liver Transplantation, San Camillo Forlanini Hospital, Rome, Italy
| | | | - Alessandra Spagnoli
- Statistics Section, Department of Public Health and Infectious Diseases, University Sapienza, Rome, Italy
| | - Giovanni Moschetta
- Department of Radiology, San Camillo Forlanini Hospital, Rome, Italy.,Department of General Surgery, San Camillo Forlanini Hospital, Rome, Italy
| | - Vincenzo Schininà
- Department of Radiology, San Camillo Forlanini Hospital, Rome, Italy
| | - Mario Antonini
- Department of Radiology, San Camillo Forlanini Hospital, Rome, Italy.,Department of Anesthesiology and Intensive Care, San Camillo Forlanini Hospital, Rome, Italy
| | - Massimo Marignani
- Department of Digestive and Liver Diseases, University Sapienza, Rome, Italy
| | - Giuseppe Maria Ettorre
- Department of General Surgery and Liver Transplantation, San Camillo Forlanini Hospital, Rome, Italy
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11
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Raoof M, Jutric Z, Haye S, Ituarte PHG, Zhao B, Singh G, Melstrom L, Warner SG, Clary B, Fong Y. Systematic failure to operate on colorectal cancer liver metastases in California. Cancer Med 2020; 9:6256-6267. [PMID: 32687265 PMCID: PMC7476837 DOI: 10.1002/cam4.3316] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 04/18/2020] [Accepted: 07/03/2020] [Indexed: 12/30/2022] Open
Abstract
Background Despite evidence that liver resection improves survival in patients with colorectal cancer liver metastases (CRCLM) and may be potentially curative, there are no population‐level data examining utilization and predictors of liver resection in the United States. Methods This is a population‐based cross‐sectional study. We abstracted data on patients with synchronous CRCLM using California Cancer Registry from 2000 to 2012 and linked the records to the Office of Statewide Health Planning Inpatient Database. Quantum Geographic Information System (QGIS) was used to map liver resection rates to California counties. Patient‐ and hospital‐level predictors were determined using mixed‐effects logistic regression. Results Of the 24 828 patients diagnosed with stage‐IV colorectal cancer, 16 382 (70%) had synchronous CRCLM. Overall liver resection rate for synchronous CRCLM was 10% (county resection rates ranging from 0% to 33%) with no improvement over time. There was no correlation between county incidence of synchronous CRCLM and rate of resection (R2 = .0005). On multivariable analysis, sociodemographic and treatment‐initiating‐facility characteristics were independently associated with receipt of liver resection after controlling for patient disease‐ and comorbidity‐related factors. For instance, odds of liver resection decreased in patients with black race (OR 0.75 vs white) and Medicaid insurance (OR 0.62 vs private/PPO); but increased with initial treatment at NCI hospital (OR 1.69 vs Non‐NCI hospital), or a high volume (10 + cases/year) (OR 1.40 vs low volume) liver surgery hospital. Conclusion In this population‐based study, only 10% of patients with liver metastases underwent liver resection. Furthermore, the study identifies wide variations and significant population‐level disparities in the utilization of liver resection for CRCLM in California.
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Affiliation(s)
- Mustafa Raoof
- Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA
| | - Zeljka Jutric
- Department of Surgery, University of California Irvine, Irvine, CA, USA
| | - Sidra Haye
- Department of Economics, University of California Irvine, Irvine, CA, USA
| | - Philip H G Ituarte
- Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA
| | - Beiqun Zhao
- Department of Surgery, University of San Diego, San Diego, CA, USA
| | - Gagandeep Singh
- Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA
| | - Laleh Melstrom
- Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA
| | - Susanne G Warner
- Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA
| | - Bryan Clary
- Department of Surgery, University of San Diego, San Diego, CA, USA
| | - Yuman Fong
- Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA
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12
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Liver Resection Improves Survival in Colorectal Cancer Patients: Causal-effects From Population-level Instrumental Variable Analysis. Ann Surg 2020; 270:692-700. [PMID: 31478979 DOI: 10.1097/sla.0000000000003485] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVE The aim of this study was to estimate population-level causal effects of liver resection on survival of patients with colorectal cancer liver metastases (CRC-LM). BACKGROUND A randomized trial to prove that liver resection improves survival in patients with CRC-LM is neither feasible nor ethical. Here, we test this assertion using instrumental variable (IV) analysis that allows for causal-inference by controlling for observed and unobserved confounding effects. METHODS We abstracted data on patients with synchronous CRC-LM using the California Cancer Registry from 2000 to 2012 and linked the records to the Office of Statewide Health Planning and Development Inpatient Database. We used 2 instruments: resection rates in a patient's neighborhood (within 50-mile radius)-NALR rate; and Medical Service Study Area resection rates-MALR rate. IV analysis was performed using the 2SLS method. RESULTS A total of 24,828 patients were diagnosed with stage-IV colorectal cancer of which 16,382 (70%) had synchronous CRC-LM. Liver resection was performed in 1635 (9.8%) patients. NALR rates ranged from 8% (lowest-quintile) to 11% (highest-quintile), whereas MALR rates ranged from 3% (lowest quintile) to 19% (highest quintile). There was a strong association between instruments and probability of liver resection (F-statistic at median cut-off: NALR 24.8; MALR 266.8; P < 0.001). IV analysis using both instruments revealed a 23.6 month gain in survival (robust SE 4.4, P < 0.001) with liver resection for patients whose treatment choices were influenced by the rates of resection in their geographic area (marginal patients), after accounting for measured and unmeasured confounders. CONCLUSION Less than 10% of patients with CRC-LM had liver resection. Significant geographic variation in resection rates is attributable to community biases. Liver resection leads to extensive survival benefit, accounting for measured and unmeasured confounders.
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13
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Impact of Postoperative Complications on Survival and Recurrence After Resection of Colorectal Liver Metastases. Ann Surg 2019; 270:1018-1027. [DOI: 10.1097/sla.0000000000003254] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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14
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Evaluation of Red Cell Distribution Width to Lymphocyte Ratio as Potential Biomarker for Detection of Colorectal Cancer. BIOMED RESEARCH INTERNATIONAL 2019; 2019:9852782. [PMID: 31467924 PMCID: PMC6699340 DOI: 10.1155/2019/9852782] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 05/13/2019] [Indexed: 12/29/2022]
Abstract
Background and Aim Colorectal cancer (CRC) is the third most lethal cancer globally. This study sought to determine the feasibility of using red cell distribution width-to-lymphocyte ratio (RLR) as a tool to facilitate CRC detection. Methods Seventy-eight healthy controls, 162 patients diagnosed with CRC, and 94 patients with colorectal polyps (CP) from June 2017 to October 2018 were retrospectively reviewed. Clinical data were obtained to analyze preoperative RLR level, and receiver operating characteristic (ROC) curve analysis was performed to estimate the potential role of RLR as a CRC biomarker. Results RLR was higher in patients with CRC than in healthy participants (P < 0.05). ROC analysis indicated that combined detection of RLR and CEA appears to be a more effective marker to distinguish among controls, CP, and CRC patients, yielding 56% sensitivity and 90% specificity. RLR levels were significantly greater in those who had more advanced TNM stages (P < 0.05) and patients with distant metastasis stages (P < 0.05). Conclusions RLR might serve as a potential biomarker for CRC diagnosis.
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15
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Austrian consensus guidelines on imaging requirements prior to hepatic surgery and during follow-up in patients with malignant hepatic lesions. Wien Klin Wochenschr 2018; 130:665-672. [PMID: 30167887 PMCID: PMC6244807 DOI: 10.1007/s00508-018-1387-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Accepted: 07/30/2018] [Indexed: 01/04/2023]
Abstract
Rapid advances in imaging technology have improved the detection, characterization and staging of colorectal liver metastases, hepatocellular carcinoma and cholangiocarcinoma. A variety of imaging modalities are available and play a pivotal role in the work-up of patients, particularly as imaging findings determine resectability. Surgery often represents the only measure that can render long-term survival possible. Imaging is also indispensable for the assessment of responses to neoadjuvant treatment and for the detection of recurrence. At a consensus meeting held in June 2017 in Vienna, Austria, Austrian experts in the fields of surgery and radiology discussed imaging requirements prior to and after hepatic surgery for malignant liver lesions. This consensus was refined by online voting on a total of 47 items. Generally, the degree of consensus was high. The recommendations relate to the type of preferred preoperative imaging modalities, technical settings with respect to computed tomography and magnetic resonance imaging, use of contrast agents, reporting, postoperative follow-up, and long-term follow-up. Taking local resources into account, these consensus recommendations can be implemented in daily clinical practice at specialized centers as well as outpatient diagnostic institutes in Austria.
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16
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Radiofrequency and Microwave Ablation Compared to Systemic Chemotherapy and to Partial Hepatectomy in the Treatment of Colorectal Liver Metastases: A Systematic Review and Meta-Analysis. Cardiovasc Intervent Radiol 2018; 41:1189-1204. [PMID: 29666906 PMCID: PMC6021475 DOI: 10.1007/s00270-018-1959-3] [Citation(s) in RCA: 139] [Impact Index Per Article: 19.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Accepted: 04/05/2018] [Indexed: 12/18/2022]
Abstract
Purpose To assess safety and outcome of radiofrequency ablation (RFA) and microwave ablation (MWA) as compared to systemic chemotherapy and partial hepatectomy (PH) in the treatment of colorectal liver metastases (CRLM). Methods MEDLINE, Embase and the Cochrane Library were searched. Randomized trials and comparative observational studies with multivariate analysis and/or matching were included. Guidelines from National Guideline Clearinghouse and Guidelines International Network were assessed using the AGREE II instrument. Results The search revealed 3530 records; 328 were selected for full-text review; 48 were included: 8 systematic reviews, 2 randomized studies, 26 comparative observational studies, 2 guideline-articles and 10 case series; in addition 13 guidelines were evaluated. Literature to assess the effectiveness of ablation was limited. RFA + systemic chemotherapy was superior to chemotherapy alone. PH was superior to RFA alone but not to RFA + PH or to MWA. Compared to PH, RFA showed fewer complications, MWA did not. Outcomes were subject to residual confounding since ablation was only employed for unresectable disease. Conclusion The results from the EORTC-CLOCC trial, the comparable survival for ablation + PH versus PH alone, the potential to induce long-term disease control and the low complication rate argue in favour of ablation over chemotherapy alone. Further randomized comparisons of ablation to current-day chemotherapy alone should therefore be considered unethical. Hence, the highest achievable level of evidence for unresectable CRLM seems reached. The apparent selection bias from previous studies and the superior safety profile mandate the setup of randomized controlled trials comparing ablation to surgery. Electronic supplementary material The online version of this article (10.1007/s00270-018-1959-3) contains supplementary material, which is available to authorized users.
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17
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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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18
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Pak LM, Kemeny NE, Capanu M, Chou JF, Boucher T, Cercek A, Balachandran VP, Kingham TP, Allen PJ, DeMatteo RP, Jarnagin WR, D'Angelica MI. Prospective phase II trial of combination hepatic artery infusion and systemic chemotherapy for unresectable colorectal liver metastases: Long term results and curative potential. J Surg Oncol 2017; 117:634-643. [PMID: 29165816 DOI: 10.1002/jso.24898] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Accepted: 10/09/2017] [Indexed: 12/22/2022]
Abstract
BACKGROUND/OBJECTIVES Combination hepatic artery infusion (HAI) and systemic (SYS) chemotherapy for unresectable CRLM results in high tumor-response rates. This study represents an update of long-term survival and conversion to resectability in patients with unresectable CRLM treated with HAI and SYS chemotherapy in a phase II study. METHOD The primary endpoint was complete resection. Multivariate and landmark analysis assessed the effect of complete resection on progression-free (PFS) and overall survival (OS). RESULTS From 2007 to 2012, 64 patients with median of 13 tumors were enrolled; 67% had prior chemotherapy. 33 patients (52%) were converted to resection. Median follow-up among survivors was 81 months. Median PFS and OS were 13 and 38 months, respectively, with 5-year-OS of 36%. Chemotherapy-naïve patients had 5-year-OS of 51%. Conversion to resection was the only independent factor prognostic of improved PFS and OS. Nine of 64 patients (14%) are NED (five since initial resection, three after resection of recurrent disease, one from chemotherapy alone) at median follow-up of 86 months from treatment initiation, and 72 months from last operative intervention. CONCLUSION Combination HAI and SYS is an effective therapy for high-volume unresectable CRLM, resulting in a high rate of resection, long-term survival, and the potential for cure.
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Affiliation(s)
- Linda M Pak
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Nancy E Kemeny
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Marinela Capanu
- Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Joanne F Chou
- Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Taryn Boucher
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Andrea Cercek
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Vinod P Balachandran
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - T Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Peter J Allen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Ronald P DeMatteo
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - William R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Michael I D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
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Abstract
OBJECTIVE The aim of the study was to evaluate outcomes after resection of colorectal liver metastases (CRLM) and concurrent extrahepatic disease (EHD), and to define prognostic factors. BACKGROUND There is increasing evidence to support resection of liver metastases and concurrent EHD in selected patients. Long-term survival data are lacking, and prognostic factors are not well defined. METHODS Retrospective review of 219 patients was undertaken between January 1992 and December 2012, who underwent hepatectomy for CRLM and resection of synchronous EHD. Survival outcomes were estimated by the Kaplan-Meier method. Univariate and multivariate analyses of prognostic factors were performed. A scoring system for prognostication was developed. RESULTS The median, 3, 5, and 10-year overall survival were 34.4 months, 49%, 28%, and 10%, respectively. Disease recurred in 185 patients (90.2%) at a median of 8 months. There were 8 actual 10-year survivors. The site of EHD affected survival, with portal, retroperitoneal nodes and multiple sites associated with the worst prognoses. The size of the largest CRLM, the number of CRLM, unfavorable site of EHD, and progression of CRLM on neoadjuvant therapy were associated with overall survival on univariate and multivariate analyses. Three variables, assigned 1 point each, were used to create an EHD risk score: largest CRLM greater than 3 cm, greater than 5 CRLM, and unfavorable site of EHD. The resulting score was prognostic of overall and recurrence-free survival. CONCLUSIONS Long-term survival is possible after resection of liver metastases and concurrent EHD, but true cure is rare. A proposed scoring system may identify patients most likely to benefit from surgery.
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20
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Imai K, Allard MA, Castro Benitez C, Vibert E, Sa Cunha A, Cherqui D, Castaing D, Baba H, Adam R. Long-term outcomes of radiofrequency ablation combined with hepatectomy compared with hepatectomy alone for colorectal liver metastases. Br J Surg 2017; 104:570-579. [DOI: 10.1002/bjs.10447] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2016] [Revised: 10/23/2016] [Accepted: 10/31/2016] [Indexed: 12/15/2022]
Abstract
Abstract
Background
Combining radiofrequency ablation (RFA) with hepatectomy may enable treatment with curative intent for patients with colorectal liver metastasis (CRLM). However, the oncological outcomes in comparison with resection alone remain to be clarified.
Methods
Patients who underwent a first hepatectomy between 2001 and 2012 for CRLM were enrolled. Short- and long-term outcomes of patients who underwent hepatectomy plus RFA were compared with those of patients who had hepatectomy alone using propensity score matching.
Results
Of a total of 553 patients, hepatectomy + RFA and hepatectomy alone were performed in 37 and 516 respectively. Before matching, patients in the hepatectomy + RFA group were characterized primarily by a larger tumour burden. After matching of 31 patients who underwent hepatectomy + RFA with 93 who had hepatectomy alone, background characteristics were well balanced. In the matched cohort, overall and disease-free survival in the hepatectomy + RFA group were no different from those among patients who had hepatectomy alone (5-year overall survival rate 57 versus 61 per cent, P = 0·649; 5-year disease-free survival rate 19 versus 17 per cent, P = 0·865). Local recurrence at the ablated site was observed in four of 31 patients (13 per cent). Although overall local recurrence (ablated site and/or cut surface) was more frequent in the hepatectomy + RFA group (9 of 31 (29 per cent) versus 11 of 93 (12 per cent); P = 0·032), there was no difference in intrahepatic disease-free survival between the two groups (P = 0·705).
Conclusion
Hepatectomy + RFA achieved outcomes comparable to hepatectomy alone. Combining RFA with hepatectomy should be considered as an option to achieve cure.
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Affiliation(s)
- K Imai
- Centre Hépato-Biliaire, Assistance Publique – Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France
- Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 935, Villejuif, France
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - M-A Allard
- Centre Hépato-Biliaire, Assistance Publique – Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France
- Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 935, Villejuif, France
- Université Paris-Sud, Villejuif, France
| | - C Castro Benitez
- Centre Hépato-Biliaire, Assistance Publique – Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France
- Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 935, Villejuif, France
- Université Paris-Sud, Villejuif, France
| | - E Vibert
- Centre Hépato-Biliaire, Assistance Publique – Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France
- INSERM Unité 785, Villejuif, France
- Université Paris-Sud, Villejuif, France
| | - A Sa Cunha
- Centre Hépato-Biliaire, Assistance Publique – Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France
- Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 935, Villejuif, France
- Université Paris-Sud, Villejuif, France
| | - D Cherqui
- Centre Hépato-Biliaire, Assistance Publique – Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France
- INSERM Unité 785, Villejuif, France
- Université Paris-Sud, Villejuif, France
| | - D Castaing
- Centre Hépato-Biliaire, Assistance Publique – Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France
- INSERM Unité 785, Villejuif, France
- Université Paris-Sud, Villejuif, France
| | - H Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - R Adam
- Centre Hépato-Biliaire, Assistance Publique – Hôpitaux de Paris, Hôpital Universitaire Paul Brousse, Villejuif, France
- Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 935, Villejuif, France
- Université Paris-Sud, Villejuif, France
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Laurent C, Adam JP, Denost Q, Smith D, Saric J, Chiche L. Significance of R1 Resection for Advanced Colorectal Liver Metastases in the Era of Modern Effective Chemotherapy. World J Surg 2016; 40:1191-9. [PMID: 26757718 DOI: 10.1007/s00268-016-3404-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The prognosis impact of positive margins after resection of colorectal liver metastases (CLM) in patients treated with modern effective chemotherapy has not been elucidated. The objective was to compare oncologic outcomes after R0 and R1 resections in the era of modern effective chemotherapy. METHODS Between 1999 and 2010, all consecutive patients undergoing liver resection for CLM were analyzed retrospectively. Patients with extrahepatic metastases, macroscopic residual tumor, treated with combined radiofrequency, or not treated with chemotherapy were excluded. Survival and recurrence after R0 (tumor-free margin >0 mm) and R1 resections were analyzed. RESULTS Among 466 patients undergoing hepatectomy for CLM, 191 were eligible. Of them, 164 (86 %) received preoperative chemotherapy and 105 (55 %) received postoperative chemotherapy. R1 resection (10 %) was comparable in patients treated or not by preoperative chemotherapy. R1 status was associated with more intrahepatic recurrences. Overall survival (OS) (44 vs. 61 %; p = 0.047) and disease-free survival (DFS) (8 vs. 26 %; p = 0.082) were lower in patients after R1 compared to R0 resection (32 months of median follow-up). Preoperative chemotherapy and major hepatectomy were prognostic factors of survival, whereas postoperative chemotherapy was a protective factor from recurrences. In patients treated with preoperative chemotherapy, OS and DFS were similar between R1 and R0 resections (40 vs. 55 %, p = 0.104 and 9 vs. 22 %, p = 0.174, respectively). CONCLUSION In the era of modern effective chemotherapy, R1 resection leads to more intrahepatic recurrences but did not affect OS in selected patient responders to neoadjuvant chemotherapy. Postoperative chemotherapy protects from recurrences whatever the margin resection status.
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Affiliation(s)
- Christophe Laurent
- University of Bordeaux Segalen, 33076, Bordeaux, France. .,Department of Hepatobiliary Surgery, CHU Bordeaux, Saint André Hospital, 1 rue Jean Burguet, 33075, Bordeaux, France.
| | - Jean-Philippe Adam
- University of Bordeaux Segalen, 33076, Bordeaux, France.,Department of Hepatobiliary Surgery, CHU Bordeaux, Saint André Hospital, 1 rue Jean Burguet, 33075, Bordeaux, France
| | - Quentin Denost
- University of Bordeaux Segalen, 33076, Bordeaux, France.,Department of Hepatobiliary Surgery, CHU Bordeaux, Saint André Hospital, 1 rue Jean Burguet, 33075, Bordeaux, France
| | - Denis Smith
- University of Bordeaux Segalen, 33076, Bordeaux, France.,Department of Digestive Oncology, CHU Bordeaux, Saint André Hospital, 33075, Bordeaux, France
| | - Jean Saric
- University of Bordeaux Segalen, 33076, Bordeaux, France.,Department of Hepatobiliary Surgery, CHU Bordeaux, Saint André Hospital, 1 rue Jean Burguet, 33075, Bordeaux, France
| | - Laurence Chiche
- University of Bordeaux Segalen, 33076, Bordeaux, France.,Department of Hepatobiliary Surgery, CHU Bordeaux, Haut-Lévèque Hospital, 33600, Pessac, France
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22
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Fairhurst K, Leopardi L, Satyadas T, Maddern G. The safety and effectiveness of liver resection for breast cancer liver metastases: A systematic review. Breast 2016; 30:175-184. [PMID: 27764727 DOI: 10.1016/j.breast.2016.09.011] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Revised: 08/11/2016] [Accepted: 09/15/2016] [Indexed: 02/08/2023] Open
Abstract
Breast cancer liver metastases have traditionally been considered incurable and any treatment given therefore palliative. Liver resections for breast cancer metastases are being performed, despite there being no robust evidence for which patients benefit. This review aims to determine the safety and effectiveness of liver resection for breast cancer metastases. A systematic literature review was performed and resulted in 33 papers being assembled for analysis. All papers were case series and data extracted was heterogeneous so a meta-analysis was not possible. Safety outcomes were mortality and morbidity (in hospital and 30-day). Effectiveness outcomes were local recurrence, re-hepatectomy, survival (months), 1-, 2-, 3-, 5- year overall survival rate (%), disease free survival (months) and 1-, 2-, 3-, 5- year disease free survival rate (%). Overall median figures were calculated using unweighted median data given in each paper. Results demonstrated that mortality was low across all studies with a median of 0% and a maximum of 5.9%. The median morbidity rate was 15%. Overall survival was a median of 35.1 months and a median 1-, 2-, 3- and 5-year survival of 84.55%, 71.4%, 52.85% and 33% respectively. Median disease free survival was 21.5 months with a 3- and 5-year median disease free survival of 36% and 18%. Whilst the results demonstrate seemingly satisfactory levels of overall survival and disease free survival, the data are of poor quality with multiple confounding variables and small study populations. Recommendations are for extensive pilot and feasibility work with the ultimate aim of conducting a large pragmatic randomised control trial to accurately determine which patients benefit from liver resection for breast cancer liver metastases.
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Affiliation(s)
- Katherine Fairhurst
- University of Adelaide Discipline of Surgery, The Queen Elizabeth Hospital, Woodville, Adelaide, South Australia, 5011, Australia.
| | - Lisa Leopardi
- University of Adelaide Discipline of Surgery, The Queen Elizabeth Hospital, Woodville, Adelaide, South Australia, 5011, Australia.
| | - Thomas Satyadas
- University of Adelaide Discipline of Surgery, The Queen Elizabeth Hospital, Woodville, Adelaide, South Australia, 5011, Australia.
| | - Guy Maddern
- University of Adelaide Discipline of Surgery, The Queen Elizabeth Hospital, Woodville, Adelaide, South Australia, 5011, Australia.
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Kumar R, Dennison AR, Robertson V, Jones MJ, Neal CP, Garcea G. Clinical risk scores in the current era of neoadjuvant chemotherapy for colorectal liver metastases. ANZ J Surg 2016; 88:E16-E20. [PMID: 27621179 DOI: 10.1111/ans.13688] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2016] [Accepted: 05/29/2016] [Indexed: 12/18/2022]
Abstract
BACKGROUND Clinical risk scores (CRS) within the context of neoadjuvant chemotherapy for colorectal liver metastases (CRLM) has not been validated. The predictive value of clinical risk scoring in patients administered neoadjuvant chemotherapy prior to liver surgery for CRLM is evaluated. METHODS A prospective database over a 15-year period (April 1999 to March 2014) was analysed. We identified two groups: A, neoadjuvant chemotherapy prior to CRLM surgery; and B, no neoadjuvant chemotherapy. RESULTS Overall median survival in groups A and B were 36 (2-137) months and 33 (2-137) months. In group A, nodal status, size, number of metastases and carcinoembryonic antigen levels were not found to be independent predictors of overall survival (OS). However, patients with a shorter disease-free interval of less than 12 months had an increased OS (P = 0.0001). Multivariate analysis of high- and low-risk scores compared against survival in group B (P < 0.05) confirms the applicability of the scoring system in traditional settings. CONCLUSION Traditional CRS are not a prognostic predictive tool when applied to patients receiving neoadjuvant chemotherapy for CRLM. Disease-free interval may be one independent variable for use in future risk score systems specifically developed for the neoadjuvant chemotherapy era.
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Affiliation(s)
- Rohan Kumar
- Department of Hepato-Pancreato-Biliary Surgery, University Hospitals of Leicester, Leicester, UK
| | - Ashley R Dennison
- Department of Hepato-Pancreato-Biliary Surgery, University Hospitals of Leicester, Leicester, UK
| | - Vaux Robertson
- Department of Hepato-Pancreato-Biliary Surgery, University Hospitals of Leicester, Leicester, UK
| | - Michael J Jones
- Department of Hepato-Pancreato-Biliary Surgery, University Hospitals of Leicester, Leicester, UK
| | - Christopher P Neal
- Department of Hepato-Pancreato-Biliary Surgery, University Hospitals of Leicester, Leicester, UK
| | - Giuseppe Garcea
- Department of Hepato-Pancreato-Biliary Surgery, University Hospitals of Leicester, Leicester, UK
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Adherence to early mobilisation: Key for successful enhanced recovery after liver resection. Eur J Surg Oncol 2016; 42:1561-7. [PMID: 27528466 DOI: 10.1016/j.ejso.2016.07.015] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2016] [Revised: 07/18/2016] [Accepted: 07/25/2016] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Enhanced Recovery After Surgery (ERAS) has been proven effective in liver surgery. Adherence to the ERAS pathway is variable. This study seeks to evaluate adherence to key components of an ERAS protocol in liver resection, and identify the components associated with successful clinical outcomes. METHOD All patients undergoing liver resections for two consecutive years were included in our ERAS pathway. Six key components of ERAS included preoperative assessment, nutrition and gastrointestinal function, postoperative analgesia, mobilisation and discharges. Successful accomplishment of ERAS was defined as hospital discharge by postop day (POD) 6. Adherences of these elements were compared between the successful and un-successful groups. RESULTS During the studied period, 223 patients underwent liver resections, among which 103 had major hepatectomies. N = 147 patients (66%) were discharged within our ERAS protocol target (6 days). On multivariable analysis, sitting out of bed by POD 1 (p < 0.03), walking by POD 3 (p = 0.03), removal of urinary catheter by POD 3 (p < 0.01), and avoiding major complications (p < 0.01) were factors associated with successful completion to our ERAS protocol; whereas advanced age (p = 0.34) and discontinuation of PCA/epidural by POD 3 (p = 0.50) were not significant parameters. There was a significant difference in the length of stay (p < 0.01) following major and minor liver resection, of which the indications for surgery also varied significantly. There was no difference in hospital re-admission rate, and morbidity and mortality between major and minor liver resection. CONCLUSIONS Facilitating early mobilisation and reducing postoperative complications are keys to successful outcomes of ERAS in liver resection.
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Hill TK, Mohs AM. Image-guided tumor surgery: will there be a role for fluorescent nanoparticles? WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2016; 8:498-511. [PMID: 26585556 PMCID: PMC4903082 DOI: 10.1002/wnan.1381] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/13/2015] [Revised: 10/07/2015] [Accepted: 10/12/2015] [Indexed: 01/05/2023]
Abstract
Image-guided surgery (IGS) using fluorescent nanoparticles (NPs) has the potential to substantially impact patient treatment. The use of fluorescence imaging provides surgeons with real-time feedback on the location of diseased tissue using safe, low-cost imaging agents and instrumentation. Fluorescent NPs are likely to play a role as they are capable of taking advantage of the enhanced permeability and retention (EPR) effect and can be modified to avoid clearance, increase circulation time, and specifically target tumors. Clinical trials of IGS using the FDA-approved fluorophores indocyanine green and methylene blue have already shown preliminary successes, and incorporation of fluorescent NPs will likely improve detection by providing higher signal to background ratio and reducing false-positive rates through active targeting. Preclinical development of fluorescent NP formulations is advancing rapidly, with strategies ranging from passive targeting to active targeting of cell surface receptors, creating pH-responsive NPs, and increasing cell uptake through cleavable proteins. This collective effort could lead to clinical trials using fluorescent NPs in the near future. WIREs Nanomed Nanobiotechnol 2016, 8:498-511. doi: 10.1002/wnan.1381 For further resources related to this article, please visit the WIREs website.
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Affiliation(s)
- Tanner K. Hill
- Department of Pharmaceutical Sciences and the Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
| | - Aaron M. Mohs
- Department of Pharmaceutical Sciences and the Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
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Rentsch M, Schiergens T, Khandoga A, Werner J. Surgery for Colorectal Cancer - Trends, Developments, and Future Perspectives. Visc Med 2016; 32:184-91. [PMID: 27493946 DOI: 10.1159/000446490] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Although colorectal surgery is long established as the mainstay treatment for colon cancer, certain topics regarding technical fine-tuning to increase postsurgical recurrence-free survival have remained a matter of debate throughout the past years. These include complete mesocolic excision (CME), treatment strategies for metastatic disease, significance of hyperthermic intraperitoneal chemotherapy (HIPEC), and surgical techniques for the treatment of colorectal cancer recurrence. In addition, new surgical techniques have been introduced in oncologic colorectal surgery, and their potential to provide sufficiently radical resection has yet to be proven. METHODS A structured review of the literature was performed to identify the current state of the art with regard to the mentioned key issues in colorectal surgery. RESULTS This article provides a comprehensive review of the current literature addressing the above-mentioned current challenges in colorectal surgery. The focus lies on the impact of CME and, in relation to this, on lymph node dissection, as well as on treatment of metastatic disease including peritoneal spread, and finally on the treatment of recurrent disease. CONCLUSION Uniformly, the current literature reveals that surgery aiming at complete malignancy elimination within multimodal treatment approaches represents the fundamental quantum leap for the achievement of long-term tumor-free survival.
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Affiliation(s)
- Markus Rentsch
- Department of General, Visceral, Transplantation Surgery, University of Munich, Campus Großhadern, Munich, Germany
| | - Tobias Schiergens
- Department of General, Visceral, Transplantation Surgery, University of Munich, Campus Großhadern, Munich, Germany
| | - Andrej Khandoga
- Department of General, Visceral, Transplantation Surgery, University of Munich, Campus Großhadern, Munich, Germany
| | - Jens Werner
- Department of General, Visceral, Transplantation Surgery, University of Munich, Campus Großhadern, Munich, Germany
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Giglio MC, Giakoustidis A, Draz A, Jawad ZAR, Pai M, Habib NA, Tait P, Frampton AE, Jiao LR. Oncological Outcomes of Major Liver Resection Following Portal Vein Embolization: A Systematic Review and Meta-analysis. Ann Surg Oncol 2016; 23:3709-3717. [PMID: 27272106 DOI: 10.1245/s10434-016-5264-6] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Indexed: 12/14/2022]
Abstract
BACKGROUND Preoperative portal vein occlusion with either percutaneous portal vein embolization (PVE) or portal vein ligation is routinely used to induce liver hypertrophy prior to major liver resection in patients with hepatic malignancy. While this increases the future liver remnant, and hence the number of patients suitable for resection, recent evidence suggests that induction of liver hypertrophy preoperatively may promote tumor growth and increase recurrence rates. The aims of this current study were to evaluate the impact of PVE on hepatic recurrence rate and survival in patients with colorectal liver metastases (CRLM). METHODS The MEDLINE, EMBASE and Web of Science databases were searched to identify studies assessing the oncological outcomes of patients undergoing major liver resection for CRLM following PVE. Studies comparing patients undergoing one-stage liver resection with or without preoperative PVE were included. The primary outcome was postoperative hepatic recurrence (PHR), while secondary outcomes were 3- and 5-year overall survival (OS). RESULTS Of the 2131 studies identified, six non-randomized studies (n = 668) met the eligibility criteria, comparing outcomes of patients undergoing major liver resection with or without PVE (n = 182 and n = 486, respectively). No significant difference was observed in PHR (odds ratio [OR] 0.78; 95 % confidence interval [CI] 0.42-1.44), 3-year OS (OR 0.80; 95 % CI 0.56-1.14) or 5-year OS (OR 1.12; 95 % CI 0.40-3.11). CONCLUSIONS PVE does not have any adverse effect on PHR or OS in patients undergoing major liver resection for CRLM. Further studies based on individual patient data are needed to provide definitive answers.
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Affiliation(s)
- Mariano Cesare Giglio
- Hepatopancreatobiliary Surgical Unit, Department of Surgery and Cancer, Hammersmith Hospital, Imperial College London, London, UK
| | - Alexandros Giakoustidis
- Hepatopancreatobiliary Surgical Unit, Department of Surgery and Cancer, Hammersmith Hospital, Imperial College London, London, UK
| | - Ahmed Draz
- Hepatopancreatobiliary Surgical Unit, Department of Surgery and Cancer, Hammersmith Hospital, Imperial College London, London, UK
| | - Zaynab A R Jawad
- Hepatopancreatobiliary Surgical Unit, Department of Surgery and Cancer, Hammersmith Hospital, Imperial College London, London, UK
| | - Madhava Pai
- Hepatopancreatobiliary Surgical Unit, Department of Surgery and Cancer, Hammersmith Hospital, Imperial College London, London, UK
| | - Nagy A Habib
- Hepatopancreatobiliary Surgical Unit, Department of Surgery and Cancer, Hammersmith Hospital, Imperial College London, London, UK
| | - Paul Tait
- Hepatopancreatobiliary Surgical Unit, Department of Surgery and Cancer, Hammersmith Hospital, Imperial College London, London, UK
| | - Adam E Frampton
- Hepatopancreatobiliary Surgical Unit, Department of Surgery and Cancer, Hammersmith Hospital, Imperial College London, London, UK
| | - Long R Jiao
- Hepatopancreatobiliary Surgical Unit, Department of Surgery and Cancer, Hammersmith Hospital, Imperial College London, London, UK.
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Zhang K, Yu J, Zhou F, Yu X, Li X, Wang J, Han Z, Cheng Z, Liang P. Impact of timing and cycles of systemic chemotherapy on survival outcome of colorectal liver metastases patients treated by percutaneous microwave ablation. Int J Hyperthermia 2016; 32:531-8. [DOI: 10.3109/02656736.2016.1156169] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
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Lim SY, Gordon-Weeks A, Allen D, Kersemans V, Beech J, Smart S, Muschel RJ. Cd11b(+) myeloid cells support hepatic metastasis through down-regulation of angiopoietin-like 7 in cancer cells. Hepatology 2015; 62:521-33. [PMID: 25854806 DOI: 10.1002/hep.27838] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Accepted: 04/07/2015] [Indexed: 01/03/2023]
Abstract
UNLABELLED Myeloid cells are known to mediate metastatic progression. Here, we attempted to elucidate the mechanisms underlying these effects by identifying gene expression alterations in cancer cells forming hepatic metastases after myeloid cell depletion. Hepatic metastases are heavily infiltrated by CD11b(+) myeloid cells. We established hepatic metastases in transgenic CD11b-diphtheria toxin receptor mice by intrasplenic injection of MC38 colon and Lewis lung carcinoma cells before depleting myeloid cells with diphtheria toxin. Myeloid cell depletion inhibited metastatic growth with a marked diminishment of tumor vasculature. Expression of ANGPTL7 (angiopoietin-like 7), a protein not previously linked to metastasis, was highly up-regulated in cancer cells after myeloid cell depletion. This effect was duplicated in tissue culture, where coculture of cancer cells with tumor-conditioned myeloid cells from liver metastases or myeloid cell conditioned media down-regulated ANGPTL7 expression. Analogous to myeloid cell depletion, overexpression of ANGPTL7 in cancer cells significantly reduced hepatic metastasis formation and angiogenesis. We found that ANGPTL7 itself has strong antiangiogenic effects in vitro. Furthermore, analysis of The Cancer Genome Atlas colorectal and breast cancer data sets revealed striking ANGPTL7 underexpression in cancerous compared to normal tissues. Also, ANGPTL7 was down-regulated in metastatic liver colonies of colorectal cancer patients compared to their adjacent liver tissue. CONCLUSION Myeloid cells promote liver metastasis by down-regulating ANGPTL7 expression in cancer cells; our findings implicate ANGPTL7 as a mediator of metastatic progression and a potential target for interference with liver metastases.
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Affiliation(s)
- Su Yin Lim
- CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom
| | - Alex Gordon-Weeks
- CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom
| | - Danny Allen
- CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom
| | - Veerle Kersemans
- CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom
| | - John Beech
- CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom
| | - Sean Smart
- CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom
| | - Ruth J Muschel
- CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom
- Department of Oncology, University of Oxford, Oxford, United Kingdom
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30
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Management of the Primary Colorectal Cancer and Synchronous Liver Metastases. CURRENT COLORECTAL CANCER REPORTS 2015. [DOI: 10.1007/s11888-015-0273-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Cokmert S, Ellidokuz H, Demir L, Fuzun M, Astarcioglu I, Aslan D, Yilmaz U, Oztop I. Survival outcomes of liver metastasectomy in colorectal cancer cases: a single-center analysis in Turkey. Asian Pac J Cancer Prev 2015; 15:5195-200. [PMID: 25040974 DOI: 10.7314/apjcp.2014.15.13.5195] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The purpose of this study was to analyze our series of liver resections for metastatic colorectal carcinoma (mCRC) to determine prognostic factors affecting survival and to evaluate the potential roles of neoadjuvant or adjuvant chemotherapy. MATERIALS AND METHODS Ninety-nine patients who underwent metastasectomy for liver metastases due to colorectal cancer at the Department of Medical Oncology, 9 Eylul University Hospital between 1996 and 2010 were evaluated in this study. The patients were followed through July 2013. Demographic, perioperative, laboratory, radiological and chemotherapy as well as survival data were obtained by retrospective chart review. RESULTS In 47 (47.5%) patients, liver metastases were unresectable at initial evaluation; the remaining 52 (52.5%) patients exhibited resectable liver metastases. Simultaneous hepatic resection was applied to 52 (35.4%) patients with synchronous metastasis, whereas 5 (64.5%) patients underwent hepatic resection after neoadjuvant chemotherapy. Forty-two patients with metachronous metastasis underwent hepatic resection following neoadjuvant chemotherapy. R0 resection was obtained in 79 (79.8%) patients. A second hepatectomy was performed in 22 (23.2%) patients. Adjuvant chemotherapy was given to 85 (85.9%) patients after metastasectomy. The median disease-free and overall survivals after initial metastasectomy were 12 and 37 months, respectively, the 1-year, 3-year and 5-year disease-free survival (DFS) and overall survival (OS) rates being 46.5%, 24.3% and 17.9%and 92.3%, 59.0% and 39.0%, respectively. On multivariate analysis, the primary tumor site, tumor differentiation, resection margin and DFS were independent factors predicting better overall survival. CONCLUSIONS In selected cases, hepatic metastasectomy for mCRC to the liver can result in long-term survival. Neoadjuvant chemotherapy did not exert a positive effect on DFS or OS. Adjuvant chemotherapy also did not appear to impact DFS and OS.
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Affiliation(s)
- Suna Cokmert
- Department of Basic Oncology, Institute of Oncology, Dokuz Eylul University, Izmir, Turkey E-mail :
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Kulaylat AN, Bhayani NH, Stokes AL, Schubart JR, Wong J, Kimchi ET, Staveley-O'Carroll KF, Kaifi JT, Gusani NJ. Determinants of repeat curative intent surgery in colorectal liver metastasis. J Gastrointest Surg 2014; 18:1894-901. [PMID: 24950776 DOI: 10.1007/s11605-014-2580-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Accepted: 06/11/2014] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Following curative intent surgery (CIS) for colorectal liver metastasis (CRLM), repeat CIS for recurrence improves survival. The factors associated with repeat CIS are not widely reported. METHODS An institutional database (January 2002-December 2012) was reviewed to evaluate factors influencing repeat CIS. RESULTS One hundred sixty-three patients with colorectal liver metastasis (CRLM) underwent successful CIS. Median follow-up and disease-free interval (DFI) was 33 and 16 months, respectively. After initial CIS, 102 patients (63%) recurred. Fifty-three patients (52%) underwent a repeat CIS. After repeat CIS, 33 patients (62%) developed a second recurrence, and in 13 patients (39%), a third CIS was possible. DFI decreased following initial CIS (first CIS vs. second CIS vs. third CIS [20 vs. 15 vs. 8.5 months], p < 0.001). Overall 5-year survival in all patients was 55%; patients who recurred had a 5-year survival of 67% if they underwent repeat CIS vs. 7.8% if they were managed palliatively. Second CIS was less likely with a postoperative complication, other/multifocal recurrence, or DFI <12 months. CONCLUSION Despite high recurrence and decreasing DFI, repeat CIS provides a survival benefit. Postoperative complications, DFI, number, and pattern of recurrence influence the decision to pursue repeat CIS.
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Affiliation(s)
- Afif N Kulaylat
- Program for Liver, Pancreas, and Foregut Tumors, Department of Surgery, College of Medicine, The Pennsylvania State University, Hershey, PA, 17033-0850, USA
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Kulaylat AN, Schubart JR, Stokes AL, Bhayani NH, Wong J, Kimchi ET, O'Carroll KFS, Kaifi JT, Gusani NJ. Overall survival by pattern of recurrence following curative intent surgery for colorectal liver metastasis. J Surg Oncol 2014; 110:1011-5. [PMID: 25146500 DOI: 10.1002/jso.23756] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2014] [Accepted: 07/27/2014] [Indexed: 01/06/2023]
Abstract
BACKGROUND Following curative intent surgery (CIS) for colorectal liver metastasis (CRLM), patterns of recurrence and subsequent survival outcomes are not widely reported. METHODS An institutional database (January 2002-December 2012) was reviewed to evaluate patterns of recurrence following CIS for CRLM. RESULTS 163 patients with CRLM underwent successful CIS. Median follow-up and disease-free interval were 33 and 16 months, respectively. 5-year overall survival (OS) was 55%. After initial CIS, 102 (63%) patients recurred: liver-44% (5-year OS 55%), lung-15% (5-year OS 45%), and other/multifocal-41% (5-year OS 24%). OS for isolated liver and lung recurrences were not significantly different. Liver only recurrence was associated with 1-5 mm liver resection margins (P = 0.048). Lung only recurrence was associated with extrahepatic metastasis (at the time of initial CRLM) (P = 0.025). Other/multifocal recurrence was associated with bilobar CRLM (P = 0.026), and extrahepatic metastasis (P = 0.028). CONCLUSIONS Patterns of recurrence following CIS for CRLM have important implications for OS. 5-year OS was similar between isolated lung and liver recurrences. During CIS, decreased liver resection margin may be associated with increased risk of liver only recurrence. Patients with aggressive primary or metastatic liver disease are at higher risk for pulmonary or other/multifocal recurrence.
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Affiliation(s)
- Afif N Kulaylat
- Department of Surgery, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania
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Boame N, Gresham G, Jonker D, Martel G, Balaa F, Asmis T. Use of chemotherapy and radiofrequency ablation to treat colorectal cancer metastases: a retrospective review of The Ottawa Hospital Cancer Centre over 7 years. ACTA ACUST UNITED AC 2014; 21:e557-63. [PMID: 25089107 DOI: 10.3747/co.21.1929] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
BACKGROUND Almost 40% of people diagnosed with colorectal cancer will die from their disease, most with metastatic spread. When feasible, hepatic resection offers the greatest probability of cure for isolated liver metastases, but there are barriers to curative resection. Those barriers include the extent and distribution of lesions within the liver, extrahepatic disease, comorbidities, and age. Chemotherapy is often administered before or after resection with the intention of improving disease-free and overall survival. The timing of chemotherapy (adjuvant vs. neoadjuvant vs. perioperative) for patients undergoing potentially curative hepatic resection of metastasis of colorectal cancer origin is controversial. METHODS Colorectal cancer patients with liver metastases resected at The Ottawa Hospital between January 1, 2003, and December 31, 2009, were identified, and their clinical records were retrospectively reviewed. Patients receiving intraoperative radiofrequency ablation (rfa) as part of their management were included. Factors associated with overall and disease-free survival were evaluated. RESULTS The 168 identified patients (57% men, 43% women) had a median age of 63 years (range: 31-84 years). After hepatectomy, 10% had positive resection margins. Intraoperative rfa was used in 25 patients (15%). Chemotherapy was administered in the neoadjuvant (19%), adjuvant (31%), or "perioperative" (both neoadjuvant and adjuvant, 50%) setting. Use or omission of intraoperative rfa was not associated with a difference in overall survival (hazard ratio: 0.99; 95% confidence interval: 0.53 to 1.84; p = 0.97). CONCLUSIONS Compared with patients who did not receive chemotherapy, those who received chemotherapy, regardless of timing, experienced improved overall survival and disease-free survival. Use of rfa where required as an adjunct to hepatic resection appears to be effective and is not associated with worse overall survival.
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Affiliation(s)
- N Boame
- Department of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, ON
| | | | - D Jonker
- Department of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, ON
| | - G Martel
- Department of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, ON
| | - F Balaa
- Department of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, ON
| | - T Asmis
- Department of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, ON
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King AJ, Breen DJ. Understanding the current status of image-guided ablation for metastatic colorectal disease. ACTA ACUST UNITED AC 2014; 38:1234-44. [PMID: 23764908 DOI: 10.1007/s00261-013-0020-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Colorectal metastases to the liver are increasingly being detected and accurately characterized at an earlier stage and even at the subcentimeter level. The oncological case for surgical resection of this disease is widely accepted. The advent of smaller volume disease has encouraged the development of in situ ablative technologies over the last two decades and the oncological efficacy of these procedures has continued to improve through stepwise developments in ablation devices and image guidance. This article provides an overview of these techniques, currently available and future technologies, and the imaging findings encountered. It also sets out the current position image-guided ablation merits alongside chemotherapy and surgical resection. In selected cases ablation for colorectal metastases can produce oncological outcomes equivalent to surgery and critically with less morbidity in an increasingly older patient population. We examine whether with careful patient selection, optimal technology, meticulous technique, and diligent follow-up, consistently reproducible high quality outcomes will be achieved in the next few years.
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Affiliation(s)
- Alexander J King
- Department of Radiology, University Hospital Southampton, Tremona Road, Southampton, SO16 6YD, UK
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Tumor Ablation for Treatment of Colorectal Liver Metastases. CURRENT COLORECTAL CANCER REPORTS 2014. [DOI: 10.1007/s11888-014-0214-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Bhayani NH, Hamed OH, Gupta A, Ortenzi G, Kaifi JT, Kimchi ET, Staveley-O'Carroll KF, Gusani NJ. Do patients' outcomes suffer when surgical fellows are involved in hepatic resection? Surgery 2013; 154:1024-30. [PMID: 23891478 DOI: 10.1016/j.surg.2013.05.024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2013] [Accepted: 05/16/2013] [Indexed: 11/17/2022]
Abstract
INTRODUCTION Hepatectomy is an advanced technique learned during surgical fellowship. Outcomes have not been described for hepatectomies involving fellows. METHODS We analyzed hepatectomies from the 2005-2011 National Surgical Quality Improvement Program database. We compared cases with a fellow (FELLOW group) and those without a fellow (ATTENDING group). RESULTS FELLOW cases (n = 1,562; 54%) included more major hepatectomies and more metastasectomies (P < .002). Mortality was 3.2% versus 2.7% (P = .5) and morbidity was 30.7% vs 26.2% (P = .008) for FELLOW versus ATTENDING cases. On multivariate analysis, mortality was similar, but morbidity was greater in FELLOW cases (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.02-1.4; P = .03), with increased superficial surgical site infections (OR, 1.72; 95% CI, 1.2-2.4; P = .001). There were no differences in rates of sepsis, cardiac, pulmonary, or thromboembolic complications. Compared with ATTENDING cases, FELLOW cases during the first half of training, carried greater morbidity (OR, 1.43; 95% CI, 1.1-1.8; P = .006); however, this difference disappears by the second half of the academic year. CONCLUSION Hepatectomy involving a fellow may be associated with an increased risk of surgical site infections. FELLOW cases were more complex. Mortality, cardiac, pulmonary, and other serious morbidities were similar. Despite slightly greater rates of surgical site infections, training in hepatic surgery maintains excellent patient outcomes.
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Affiliation(s)
- Neil H Bhayani
- Program for Liver, Pancreas, and Foregut Tumors, Penn State Cancer Institute, Hershey, PA
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Ardito F, Vellone M, Barbaro B, Grande G, Clemente G, Giovannini I, Federico B, Bonomo L, Nuzzo G, Giuliante F. Right and extended-right hepatectomies for unilobar colorectal metastases: impact of portal vein embolization on long-term outcome and liver recurrence. Surgery 2013; 153:801-10. [PMID: 23701876 DOI: 10.1016/j.surg.2013.02.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2012] [Accepted: 02/05/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND Portal vein embolization (PVE) is an effective procedure to increase the future remnant liver (FRL) before major hepatectomy. A controversial issue is that PVE may stimulate tumor growth and can be associated with poor prognosis after liver resection for colorectal liver metastases (CRLM). The aim of this study was to evaluate the impact of PVE on long-term survival following major hepatectomy for CRLM. METHODS Between 1998 and 2010, 100 right and extended-right hepatectomies for unilobar, right-sided CRLM were performed. Of the group, 20 patients underwent preoperative PVE (group A). The control patients (group B; 20 patients) were selected by matching with the group A patients. RESULTS It was found that 25 patients (25/40; 62.5%) had developed tumor recurrence. The rate of global recurrence was not significantly different in groups A and B (65% vs 60%, respectively; P = .744). The specific overall intrahepatic recurrence rate was 42.5% (17 of 40 patients) and was not significantly different in groups A and B (45% vs 40%, respectively; P = .749). The 5-year overall and disease-free survival rates were similar in groups A and B (42.9% and 33.6% vs 42.1% and 27.7%, respectively). The 5-year specific liver-disease-free survival was 45.3% in group A and 53.5% in group B (P = .572). On multivariate analysis of all 100 hepatectomies, R1 resection (P = .013) was found to be the only independent predictor of liver-disease-free survival. CONCLUSION This study showed that PVE did not affect overall survival and specific liver-disease-free survival in patients undergoing right or right-extended hepatectomy for unilobar, right-sided CRLM.
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Affiliation(s)
- Francesco Ardito
- Department of Surgery, Hepatobiliary Surgery Unit, Catholic University of the Sacred Heart, School of Medicine, Rome, Italy.
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SOONAWALLA ZF, ANDERSON EM. Hepatic resection and radiofrequency ablation for metastatic liver tumours: an update. IMAGING 2013. [DOI: 10.1259/imaging/39521156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
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Kanas GP, Taylor A, Primrose JN, Langeberg WJ, Kelsh MA, Mowat FS, Alexander DD, Choti MA, Poston G. Survival after liver resection in metastatic colorectal cancer: review and meta-analysis of prognostic factors. Clin Epidemiol 2012; 4:283-301. [PMID: 23152705 PMCID: PMC3496330 DOI: 10.2147/clep.s34285] [Citation(s) in RCA: 274] [Impact Index Per Article: 21.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Hepatic metastases develop in approximately 50% of colorectal cancer (CRC) cases. We performed a review and meta-analysis to evaluate survival after resection of CRC liver metastases (CLMs) and estimated the summary effect for seven prognostic factors. Methods Studies published between 1999 and 2010, indexed on Medline, that reported survival after resection of CLMs, were reviewed. Meta-relative risks for survival by prognostic factor were calculated, stratified by study size and annual clinic volume. Cumulative meta-analysis results by annual clinic volume were plotted. Results Five- and 10-year survival ranged from 16% to 74% (median 38%) and 9% to 69% (median 26%), respectively, based on 60 studies. The overall summary median survival time was 3.6 (range: 1.7–7.3) years. Meta-relative risks (95% confidence intervals) by prognostic factor were: node positive primary, 1.6 (1.5–1.7); carcinoembryonic antigen level, 1.9 (1.1–3.2); extrahepatic disease, 1.9 (1.5–2.4); poor tumor grade, 1.9 (1.3–2.7); positive margin, 2.0 (1.7–2.5); >1 liver metastases, 1.6 (1.4–1.8); and >3 cm tumor diameter, 1.5 (1.3–1.8). Cumulative meta-analyses by annual clinic volume suggested improved survival with increasing volume. Conclusion The overall median survival following CLM liver resection was 3.6 years. All seven investigated prognostic factors showed a modest but significant predictive relationship with survival, and certain prognostic factors may prove useful in determining optimal therapeutic options. Due to the increasing complexity of surgical interventions for CLM and the inclusion of patients with higher disease burdens, future studies should consider the potential for selection and referral bias on survival.
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Turan N, Benekli M, Koca D, Ustaalioglu BO, Dane F, Ozdemir N, Ulas A, Oztop I, Gumus M, Ozturk MA, Berk V, Kucukoner M, Uner A, Balakan O, Helvaci K, Ozkan S, Yilmaz U, Buyukberber S. Adjuvant systemic chemotherapy with or without bevacizumab in patients with resected liver metastases from colorectal cancer. Oncology 2012; 84:14-21. [PMID: 23076023 DOI: 10.1159/000342429] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2012] [Accepted: 08/02/2012] [Indexed: 12/14/2022]
Abstract
BACKGROUND We aimed to investigate the impact of adjuvant systemic therapy with modern chemotherapy combinations on survival outcomes in patients with resected liver-confined metastases from colorectal carcinomas, and whether addition of bevacizumab (BEV) provides further benefit. METHODS A total of 229 consecutive patients who underwent resection for liver-confined colorectal liver metastases were retrospectively analyzed. RESULTS Of 229 patients, 204 who received chemotherapy with fluoropyrimidine-based (n = 27), irinotecan-based (n = 84) and oxaliplatin-based (n = 93) combinations were analyzed. Among these, 87 patients received BEV while 117 did not (NoBEV). With a median follow-up of 27 months after metastasectomy, the median recurrence-free survival (RFS) and overall survival (OS) were 17 and 53 months, respectively. OS rates at 3 and 5 years were 71% and 40%, respectively. No significant differences were found in the median RFS (p = 0.744) and OS (p = 0.440) among different chemotherapy regimens. The median RFS (p = 0.375) and OS (p = 0.251) were similar in BEV and NoBEV arms. In multivariate analysis, having 4 liver metastases was the only negative independent factor on both RFS and OS, while positive surgical margin was another negative independent factor for RFS. CONCLUSION Chemotherapy type and addition of BEV have no impact on both RFS and OS in the adjuvant setting following complete resection of colorectal liver metastases.
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Affiliation(s)
- Nedim Turan
- Department of Medical Oncology, Gazi University Faculty of Medicine, Ankara, Turkey.
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Mima K, Beppu T, Chikamoto A, Miyamoto Y, Nakagawa S, Kuroki H, Okabe H, Hayashi H, Sakamoto Y, Watanabe M, Kikuchi K, Baba H. Hepatic resection combined with radiofrequency ablation for initially unresectable colorectal liver metastases after effective chemotherapy is a safe procedure with a low incidence of local recurrence. Int J Clin Oncol 2012; 18:847-55. [DOI: 10.1007/s10147-012-0471-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2012] [Accepted: 08/14/2012] [Indexed: 02/06/2023]
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Kwan BYM, Kielar AZ, El-Maraghi RH, Garcia LM. Retrospective review of efficacy of radiofrequency ablation for treatment of colorectal cancer liver metastases from a Canadian perspective. Can Assoc Radiol J 2012; 65:77-85. [PMID: 22867961 DOI: 10.1016/j.carj.2012.02.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2011] [Revised: 01/22/2012] [Accepted: 02/10/2012] [Indexed: 12/19/2022] Open
Abstract
PURPOSE A retrospective single-center review of ultrasound-guided radiofrequency ablation (RFA) treatment of colorectal cancer liver metastases was performed. This study reviews the primary and secondary technical effectiveness, overall survival of patients, recurrence-free survival, tumour-free survival, rates of local recurrence, and postprocedural RFA complications. Technical effectiveness and rates of complication with respect to tumour location and size were evaluated. Our results were compared with similar studies from Europe and North America. METHODS A total of 63 patients (109 tumours) treated with RFA between February 2004 and December 2009 were reviewed. Average and median follow-up time was 19.4 and 16.5 months, respectively (range, 1-54 months). Data from patient charts, pathology, and Picture Archiving and Communication System was integrated into an Excel database. Statistical Analysis Software was used for statistical analysis. RESULTS Primary and secondary technical effectiveness of percutaneous and intraoperative RFA were 90.8% and 92.7%, respectively. Average (SE) tumour-free survival was 14.4 ± 1.4 months (range, 1-43 months), and average (SE) recurrence-free survival was 33.5 ± 2.3 months (range, 2-50 months). Local recurrence was seen in 31.2% of treated tumours (range, 2-50 months) (34/109). Overall survival was 89.4% at 1 year, 70.0% at 2 years, and 38.1% at 3 years, with an average (SE) overall survival of 37.0 ± 2.8 months. There were 14 postprocedural complications. There was no statistically significant difference in technical effectiveness for small tumours (1-2 cm) vs intermediate ones (3-5 cm). There was no difference in technical effectiveness for peripheral vs parenchymal tumours. CONCLUSIONS This study demonstrated good-quality outcomes for RFA treatment of colorectal cancer liver metastases from a Canadian perspective and compared favorably with published studies.
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Affiliation(s)
- Benjamin Y M Kwan
- Department of Radiology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
| | - Ania Z Kielar
- Department of Radiology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Robert H El-Maraghi
- Department of Radiology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Lourdes M Garcia
- Department of Radiology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
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Lim C, Farges O. Portal vein occlusion before major hepatectomy in patients with colorectal liver metastases: rationale, indications, technical aspects, complications and outcome. J Visc Surg 2012; 149:e86-96. [PMID: 22504072 DOI: 10.1016/j.jviscsurg.2012.03.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Surgery is the only curative treatment for colorectal liver metastases (CRLM), but resection should be total with tumor-free margins and the remaining parenchyma, functionally evaluated. The rationale behind portal vein embolization (PVE) to reduce the risk of these hepatic resections is threefold: (i) surgery for CRLM has become more and more aggressive, and hepatocellular insufficiency represents the leading cause of mortality after major hepatectomy for hepatic metastasis (HM), (ii) underlying hepatic disease occurs more frequently than previously thought in these patients having undergone neoadjuvant chemotherapy, and can alter hepatic function and/or hinder postoperative regeneration, and (iii) the operative risk is increased if major hepatectomy is associated with resection of the primary tumor. The goal of this update is to review the reasons behind and the indications for PVE, to analyze the literature pertaining to whether PVE should be routine or selective, and to tackle certain technical aspects, all within the framework of the treatment of CRLM.
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Affiliation(s)
- C Lim
- Service de chirurgie hépatobiliaire et pancréatique, AP-HP, université Paris-7, hôpital Beaujon, 100, boulevard du Général-Leclerc, 92118 Paris, France
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van Vledder MG, Levolger S, Ayez N, Verhoef C, Tran TCK, Ijzermans JNM. Body composition and outcome in patients undergoing resection of colorectal liver metastases. Br J Surg 2012; 99:550-7. [PMID: 22246799 DOI: 10.1002/bjs.7823] [Citation(s) in RCA: 367] [Impact Index Per Article: 28.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/25/2011] [Indexed: 12/18/2022]
Abstract
BACKGROUND Recent evidence suggests that depletion of skeletal muscle mass (sarcopenia) and an increased amount of intra-abdominal fat (central obesity) influence cancer statistics. This study investigated the impact of sarcopenia and central obesity on survival in patients undergoing liver resection for colorectal liver metastases (CLM). METHODS Diagnostic imaging from patients who had hepatic resection for CLM in one centre between 2001 and 2009, and who had assessable perioperative computed tomograms, was analysed retrospectively. Total cross-sectional areas of skeletal muscle and intra-abdominal fat, and their influence on outcome, were analysed. RESULTS Of the 196 patients included in the study, 38 (19·4 per cent) were classified as having sarcopenia. Five-year disease-free (15 per cent versus 28·5 per cent in patients without sarcopenia; P = 0·002) and overall (20 per cent versus 49·9 per cent respectively; P < 0·001) survival rates were lower for patients with sarcopenia at a median follow-up of 29 (range 1-97) months. Sarcopenia was an independent predictor of worse recurrence-free (hazard ratio (HR) 1·88, 95 per cent confidence interval 1·25 to 2·82; P = 0·002) and overall (HR 2·53, 1·60 to 4·01; P < 0·001) survival. Central obesity was associated with an increased risk of recurrence in men (P = 0·032), but not in women (P = 0·712). CONCLUSION Sarcopenia has a negative impact on cancer outcomes following resection of CLM.
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Affiliation(s)
- M G van Vledder
- Department of Surgery, Erasmus MC, Rotterdam, 'S Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands
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Simpson AL, Dumpuri P, Jarnagin WR, Miga MI. Model-Assisted Image-Guided Liver Surgery Using Sparse Intraoperative Data. STUDIES IN MECHANOBIOLOGY, TISSUE ENGINEERING AND BIOMATERIALS 2012. [DOI: 10.1007/8415_2012_117] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Homayounfar K, Bleckmann A, Conradi LC, Sprenger T, Beissbarth T, Lorf T, Niessner M, Sahlmann CO, Meller J, Becker H, Liersch T, Ghadimi BM. Bilobar spreading of colorectal liver metastases does not significantly affect survival after R0 resection in the era of interdisciplinary multimodal treatment. Int J Colorectal Dis 2012; 27:1359-67. [PMID: 22430890 PMCID: PMC3449057 DOI: 10.1007/s00384-012-1455-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/02/2012] [Indexed: 02/04/2023]
Abstract
PURPOSE Bilobar colorectal liver metastases (CRLM) are often considered incurable or associated with poor prognosis even after R0 resection. In this single-center study, we evaluate the impact of CRLM spreading on recurrence-free survival (RFS) and cancer-specific overall survival (CSS) after R0 resection of CRLM with respect to multimodal treatment strategies including perioperative chemotherapy and multistep resections. METHODS Between January 2001 and December 2010, R0 resection could be achieved in 70 patients with bilobar and 100 with unilobar CRLM. Extent of disease, perioperative chemotherapy, surgical procedures, adjuvant treatment, histopathological workup, RFS, and CSS were compared between both cohorts. RESULTS Forty-six (66 %) patients with bilobar and 26 (26 %) patients with unilobar CRLM received preoperative chemotherapy (p < 0.001). For bilobar CRLM, more extended and multistep resection including portal vein occlusion were performed (29 % versus 3 %; p < 0.001). Morbidity (39 % versus 28 %, p = 0.183) and mortality (1 % versus 3 %, p = 0.644) rates were comparable in both patients' cohorts. Postoperative therapy was applied in adjuvant intent to 42 (60 %) versus 51 (51 %) patients (p = 0.275). The 5-year RFS and CSS rates were 24 % versus 31 % (p = 0.169) and 42 % versus 55 % (p = 0.131), respectively. CONCLUSIONS To our single-center experience, there is no significant effect of CRLM spreading (bilobar versus unilobar) on RFS and CSS rates. Bilobar CRLM are more likely to require extended multimodal efforts to achieve R0 resection.
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Affiliation(s)
- K. Homayounfar
- Department of General and Visceral Surgery, University Medical Center, Georg August University Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany
| | - A. Bleckmann
- Department of Hematology and Oncology, University Medical Center, Georg August University Göttingen, Göttingen, Germany ,Department of Medical Statistics, University Medical Center, Georg August University Göttingen, Göttingen, Germany
| | - L. C. Conradi
- Department of General and Visceral Surgery, University Medical Center, Georg August University Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany
| | - T. Sprenger
- Department of General and Visceral Surgery, University Medical Center, Georg August University Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany
| | - T. Beissbarth
- Department of Medical Statistics, University Medical Center, Georg August University Göttingen, Göttingen, Germany
| | - T. Lorf
- Department of General and Visceral Surgery, University Medical Center, Georg August University Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany
| | - M. Niessner
- Department of General and Visceral Surgery, University Medical Center, Georg August University Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany
| | - C. O. Sahlmann
- Department of Nuclear Medicine, University Medical Center, Georg August University Göttingen, Göttingen, Germany
| | - J. Meller
- Department of Nuclear Medicine, University Medical Center, Georg August University Göttingen, Göttingen, Germany
| | - H. Becker
- Department of General and Visceral Surgery, University Medical Center, Georg August University Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany
| | - T. Liersch
- Department of General and Visceral Surgery, University Medical Center, Georg August University Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany
| | - B. M. Ghadimi
- Department of General and Visceral Surgery, University Medical Center, Georg August University Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany
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Gadoxetate disodium-enhanced magnetic resonance imaging versus contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography/computed tomography for the detection of colorectal liver metastases. Invest Radiol 2011; 46:548-55. [PMID: 21577131 DOI: 10.1097/rli.0b013e31821a2163] [Citation(s) in RCA: 78] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE : To compare the diagnostic accuracy of gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI) on a 3-T system and integrated contrast-enhanced F-fluorodeoxyglucose positron emission tomography/computed tomography (CE-PET/CT) for the detection of hepatic metastases from colorectal cancers. MATERIALS AND METHODS : The approval from the institutional review board was obtained, and the requirement for informed consent was waived. We retrospectively evaluated 135 metastases in 68 patients (37 men, 31 women; mean age: 68 years; age range: 37-82 years) who underwent both EOB-MRI and CE-PET/CT. A total of 103 metastases were confirmed during surgery and 32 were confirmed by imaging findings during follow-up. The images were independently reviewed by 2 observers. The diagnostic accuracies of EOB-MRI and CE-PET/CT were determined by calculating the areas under each reader-specific receiver operating characteristic curve (Az). Patient-based lesion sensitivity and specificity were compared using the McNemar test. RESULTS : The mean area under the Az on EOB-MRI versus CE-PET/CT was 0.94 versus 0.81 for all lesions (P < 0.001), 0.92 versus 0.60 for lesions ≤1 cm in size (P < 0.001), and 0.88 versus 0.96 for lesions >1 cm (P = 0.098), respectively. The sensitivity, specificity, positive predictive values, and negative predictive value on a patient basis were 100%, 71%, 97%, and 100% for EOB-MRI and 93%, 71%, 97%, and 57% for CE-PET/CT, respectively. CONCLUSIONS : EOB-MRI using a 3-T system is more accurate than CE-PET/CT, especially for the detection of small (≤1.0 cm) lesions. Patient-based analysis revealed that EOB-MRI has a higher sensitivity and negative predictive value than CE-PET/CT.
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Inoue Y, Hiro J, Toiyama Y, Tanaka K, Mohri Y, Kusunoki M. Optimal use of current chemotherapy in multimodality therapy for advanced colorectal cancer. Oncol Lett 2011; 3:363-368. [PMID: 22740912 DOI: 10.3892/ol.2011.508] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2011] [Accepted: 09/27/2011] [Indexed: 01/06/2023] Open
Abstract
Treatment of advanced colorectal cancer (CRC) increasingly requires a multimodality approach, which adds to the complexity of clinical decision-making. This study investigates the optimal use of current chemotherapy in multimodality therapy for advanced CRC. We enrolled 208 patients with unresectable primary and metastatic (recurrent) CRC who underwent chemotherapy in our hospital. Radiofrequency ablation and/or secondary surgery were used depending on tumor response to chemotherapy. Disease sites varied among patients and included unresectable liver, lung and peritoneal metastasis. Chemotherapy produced cytoreduction in 71 of 208 patients (34%). Multimodality cytoreduction increased overall survival to a median of 46.0 months vs. 20.2 months with chemotherapy alone (P<0.0001). The response rate to chemotherapy was independently associated with cytoreduction. Molecular targeted therapy reduced the number of tumor cells sooner than conventional chemotherapy, and correlated with repeated cytoreduction that further prolonged survival. Aggressive chemotherapy as initial treatment for advanced CRC leads to cytoreduction and is associated with extended survival in patients receiving multimodality therapy.
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Affiliation(s)
- Yasuhiro Inoue
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
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Ayez N, Lalmahomed ZS, Eggermont AMM, Ijzermans JNM, de Jonge J, van Montfort K, Verhoef C. Outcome of microscopic incomplete resection (R1) of colorectal liver metastases in the era of neoadjuvant chemotherapy. Ann Surg Oncol 2011; 19:1618-27. [PMID: 22006375 PMCID: PMC3332355 DOI: 10.1245/s10434-011-2114-4] [Citation(s) in RCA: 91] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2011] [Indexed: 12/17/2022]
Abstract
BACKGROUND Data from patients with colorectal liver metastases (CRLM) who received neoadjuvant chemotherapy before resection were reviewed and evaluated to see whether neoadjuvant chemotherapy influences the predictive outcome of R1 resections (margin is 0 mm) in patients with CRLM. METHODS Between January 2000 and December 2008, all consecutive patients undergoing liver resection for CRLM were analyzed. Patients were divided into those who did and did not receive neoadjuvant chemotherapy. The outcome after R0 (tumor-free margin >0 mm) and R1 (tumor-free margin 0 mm) resection was compared. RESULTS A total of 264 were eligible for analysis. Median follow-up was 34 months. Patients without chemotherapy showed a significant difference in median disease-free survival (DFS) after R0 or R1 resection: 17 [95% confidence interval (CI) 10-24] months versus 8 (95% CI 4-12) months (P < 0.001), whereas in patients with neoadjuvant chemotherapy the difference in DFS between R0 and R1 resection was not significant: 18 (95% CI 10-26) months versus 9 (95% CI 0-20) months (P = 0.303). Patients without chemotherapy showed a significant difference in median overall survival (OS) after R0 or R1 resection: 53 (95% CI 40-66) months versus 30 (95% CI 13-47) months (P < 0.001). In patients with neoadjuvant chemotherapy, the median OS showed no significant difference: 65 (95% CI 39-92) months for the R0 group versus the R1 group, in whom the median OS was not reached (P = 0.645). CONCLUSIONS In patients treated with neoadjuvant chemotherapy, R1 resection was of no predictive value for DFS and OS.
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Affiliation(s)
- Ninos Ayez
- Division of Surgical Oncology, Erasmus MC, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
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