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1
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Luo J, He MW, Luo T, Lv GQ. Identification of multiple risk factors for colorectal cancer relapse after laparoscopic radical resection. World J Gastrointest Surg 2023; 15:2211-2221. [PMID: 37969700 PMCID: PMC10642461 DOI: 10.4240/wjgs.v15.i10.2211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 08/08/2023] [Accepted: 08/18/2023] [Indexed: 10/27/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is a common life-threatening disease that often requires surgical intervention, such as laparoscopic radical resection. However, despite successful surgeries, some patients experience disease relapse. Identifying the risk factors for CRC relapse can help guide clinical interventions and improve patient outcomes. AIM To determine the risk factors that may lead to CRC relapse after laparoscopic radical resection. METHODS We performed a retrospective analysis using the baseline data of 140 patients with CRC admitted to our hospital between January 2018 and January 2020. All included participants were followed up until death or for 3 years. The baseline data and laboratory indicators were compared between the patients who experienced relapse and those who did not experienced relapse. RESULTS Among the 140 patients with CRC, 30 experienced relapse within 3 years after laparoscopic radical resection and 110 did not experience relapse. The relapse group had a higher frequency of rectal tumors with low differentiation and lymphatic vessel invasion than that of the non-relapse group. The expression of serum markers and the prognostic nutritional index were lower, whereas the neutrophil-to-lymphocyte ratio, expression of cytokeratin 19 fragment antigen 21-1, vascular endothelial growth factor, and Chitinase-3-like protein 1 were significantly higher in the relapse group than those in the non-relapse group. The groups did not differ significantly based on other parameters. Logistic regression analysis revealed that all the above significantly altered factors were independent risk factors for CRC relapse. CONCLUSION We identified multiple risk factors for CRC relapse following surgery, which can be considered for the clinical monitoring of patients to reduce disease recurrence and improve patient survival.
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Affiliation(s)
- Jun Luo
- Department of Gastrointestinal Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
| | - Mei-Wen He
- Department of Gastrointestinal Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
| | - Ting Luo
- Department of Operating Room, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
| | - Guo-Qing Lv
- Department of Gastrointestinal Surgery, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
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2
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Valenzuela CD, Moaven O, Gawdi R, Stauffer JA, Del Piccolo NR, Cheung TT, Corvera CU, Wisneski AD, Cha C, Pourhabibi Zarandi N, Dourado J, Perry KC, Russell G, Shen P. Outcomes after repeat hepatectomy for colorectal liver metastases from the colorectal liver operative metastasis international collaborative (COLOMIC). J Surg Oncol 2022; 126:1242-1252. [PMID: 35969175 PMCID: PMC9613625 DOI: 10.1002/jso.27056] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Accepted: 07/28/2022] [Indexed: 01/05/2023]
Abstract
BACKGROUND Resection of colorectal liver metastasis (CLM) is beneficial when feasible. However, the benefit of second hepatectomy for hepatic recurrence in CLM remains unclear. METHODS The Colorectal Liver Operative Metastasis International Collaborative retrospectively examined 1004 CLM cases from 2000 to 2018 from a total of 953 patients. Hepatic recurrence after initial hepatectomy was identified in 218 patients. Kaplan-Meier analysis was performed for overall survival (OS) and recurrence-free survival (RFS). Propensity score matching (PSM) was performed to offset selection bias. Cox proportional-hazards regression was performed to identify risk factors associated with OS. RESULTS A total of 51 patients underwent second hepatectomy. Unadjusted median OS was 60.1 months in repeat-hepatectomy versus 38.3 months in the single-hepatectomy group (p = 0.015). In the PSM population, median OS remained significantly better in the repeat-hepatectomy group (60.1 vs. 33.1 months; p = 0.0023); median RFS was 12.4 months for the repeat-hepatectomy group, versus 9.8 months in the single-hepatectomy group (p = 0.0050). Repeat hepatectomy was associated with lower risk of death (hazard ratio: 0.283; p = 0.000012). Obesity, tobacco use, and high intraoperative blood loss were associated with significant risk of death (p < 0.05). CONCLUSION In CLM with hepatic recurrence, second hepatectomy was beneficial for OS. With PSM, the OS benefit of performing a second hepatectomy remained significant.
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Affiliation(s)
- Cristian D. Valenzuela
- Division of Surgical Oncology, Comprehensive Cancer CenterAtrium Health Wake Forest Baptist Medical CenterWinston‐SalemNorth CarolinaUSA
| | - Omeed Moaven
- Division of Surgical Oncology, Comprehensive Cancer CenterAtrium Health Wake Forest Baptist Medical CenterWinston‐SalemNorth CarolinaUSA
| | - Rohin Gawdi
- Division of Surgical Oncology, Comprehensive Cancer CenterAtrium Health Wake Forest Baptist Medical CenterWinston‐SalemNorth CarolinaUSA
| | - John A. Stauffer
- Department of Surgical OncologyMayo Clinic in FloridaJacksonvilleFloridaUSA
| | | | - Tan To Cheung
- Department of SurgeryUniversity of Hong KongHong KongChina
| | - Carlos U. Corvera
- Department of Hepatobiliary & Pancreatic SurgeryUniversity of California San FranciscoSan FranciscoCaliforniaUSA
| | - Andrew D. Wisneski
- Department of Hepatobiliary & Pancreatic SurgeryUniversity of California San FranciscoSan FranciscoCaliforniaUSA
| | - Charles Cha
- Department of SurgeryYale School of MedicineNew HavenConnecticutUSA
| | - Nima Pourhabibi Zarandi
- Division of Surgical Oncology, Comprehensive Cancer CenterAtrium Health Wake Forest Baptist Medical CenterWinston‐SalemNorth CarolinaUSA
| | - Justin Dourado
- Division of Surgical Oncology, Comprehensive Cancer CenterAtrium Health Wake Forest Baptist Medical CenterWinston‐SalemNorth CarolinaUSA
| | - Kathleen C. Perry
- Division of Surgical Oncology, Comprehensive Cancer CenterAtrium Health Wake Forest Baptist Medical CenterWinston‐SalemNorth CarolinaUSA
| | - Gregory Russell
- Department of Biostatistical SciencesWake Forest School of MedicineWinston‐SalemNorth CarolinaUSA
| | - Perry Shen
- Division of Surgical Oncology, Comprehensive Cancer CenterAtrium Health Wake Forest Baptist Medical CenterWinston‐SalemNorth CarolinaUSA
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BASILIO L, STEINBRÜCK K, FERNANDES R, D’OLIVEIRA M, CANO R, VASCONCELOS H, BARBOSA D, ENNE M. RE-HEPATECTOMY MEANS MORE MORBIDITY? A MULTICENTRIC ANALYSIS. ABCD. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA (SÃO PAULO) 2022; 35:e1647. [PMID: 35730876 PMCID: PMC9254632 DOI: 10.1590/0102-672020210002e1647] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 12/19/2021] [Indexed: 11/21/2022]
Abstract
Colorectal cancer generally metastasizes to the liver. Surgical resection of
liver metastasis, which is associated with systemic chemotherapy, is potentially
curative, but many patients will present recurrence. In selected patients,
repeated hepatectomy is feasible and improves overall survival.
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Affiliation(s)
| | - Klaus STEINBRÜCK
- Hepatobiliary Multidisciplinary Service, Brazil; Federal Hospital of Bonsucesso, Brazil
| | - Reinaldo FERNANDES
- Hepatobiliary Multidisciplinary Service, Brazil; Federal Hospital of Bonsucesso, Brazil
| | | | - Renato CANO
- Federal Hospital of Ipanema, Brazil; Hepatobiliary Multidisciplinary Service, Brazil
| | - Hanna VASCONCELOS
- Federal Hospital of Ipanema, Brazil; Hepatobiliary Multidisciplinary Service, Brazil
| | | | - Marcelo ENNE
- Federal Hospital of Ipanema, Brazil; Hepatobiliary Multidisciplinary Service, Brazil
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4
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Kolbeinsson HM, Hoppe A, Walker J, Chandana S, Assifi MM, Chung M, Wright GP. Recurrence and survival after curative-intent treatment for colorectal liver metastases: Implications for adjuvant liver-directed regional chemotherapy. J Surg Oncol 2021; 125:664-670. [PMID: 34796521 DOI: 10.1002/jso.26755] [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: 08/29/2021] [Revised: 11/08/2021] [Accepted: 11/11/2021] [Indexed: 11/11/2022]
Abstract
BACKGROUND This study investigates tumor recurrence patterns and their effect on postrecurrence survival following curative-intent treatment of colorectal liver metastases (CRLM) to identify those who stand to benefit the most from adjuvant liver-directed therapy. METHODS This is a retrospective analysis of all patients that underwent liver resection and/or ablation for CRLM between 2007 and 2019. Postrecurrence survival was compared between recurrence locations. Risk factors for liver recurrence were sought. RESULTS The study included 227 patients. Majority were treated with resection (71.0%) while combination resection/ablation (18.9%) and ablation alone (11.0%), were less common. At a median follow-up of 3.0 years, recurrence was observed in 151 (66.5%) patients. Of those, liver, lung, and peritoneal recurrence were most common at 66.9%, 49.6%, and 9.2%, respectively. Median postrecurrence survival after liver, lung, and multisite recurrence was 39.6-, 68.4-, and 33.6 months, respectively. High tumor grade (p < 0.014), perineural invasion (p = 0.002), and N0 node status (p = 0.017) of primary tumor correlated with liver recurrence on multivariate analysis. CONCLUSIONS Tumor grade, perineural invasion, and N0 node status of the primary tumor are associated with increased risk of liver recurrence after CRLM resection and represent a target population that may benefit the most from adjuvant liver-directed regional chemotherapy.
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Affiliation(s)
- Hordur M Kolbeinsson
- Spectrum Health General Surgery Residency, Grand Rapids, Michigan, USA.,Department of Surgery, Michigan State University, Grand Rapids, Michigan, USA
| | - Allison Hoppe
- Department of Surgery, Michigan State University, Grand Rapids, Michigan, USA
| | - Jessica Walker
- Department of Surgery, Michigan State University, Grand Rapids, Michigan, USA
| | - Sreenivasa Chandana
- Cancer and Hematology Centers of Western Michigan, Grand Rapids, Michigan, USA
| | - M Mura Assifi
- Spectrum Health General Surgery Residency, Grand Rapids, Michigan, USA.,Department of Surgery, Michigan State University, Grand Rapids, Michigan, USA.,Division of Surgical Oncology, Spectrum Health Medical Group, Grand Rapids, Michigan, USA
| | - Mathew Chung
- Spectrum Health General Surgery Residency, Grand Rapids, Michigan, USA.,Department of Surgery, Michigan State University, Grand Rapids, Michigan, USA.,Division of Surgical Oncology, Spectrum Health Medical Group, Grand Rapids, Michigan, USA
| | - Gerald Paul Wright
- Spectrum Health General Surgery Residency, Grand Rapids, Michigan, USA.,Department of Surgery, Michigan State University, Grand Rapids, Michigan, USA.,Division of Surgical Oncology, Spectrum Health Medical Group, Grand Rapids, Michigan, USA
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5
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Park J, Lee SD, Han SS, Kim SH, Park SJ, Oh JH, Joo J. Repeat hepatectomy for recurred colorectal liver metastasis: is it justified? Ann Surg Treat Res 2019; 97:7-14. [PMID: 31297347 PMCID: PMC6609413 DOI: 10.4174/astr.2019.97.1.7] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 04/09/2019] [Accepted: 04/26/2019] [Indexed: 02/08/2023] Open
Abstract
Purpose Liver resection is considered the only curative treatment modality for colorectal liver metastasis. The recurrence rate after hepatectomy is >50%. Two or more hepatectomies are applied to treat recurred metastases. We assessed the efficiency and feasibility of repeat hepatectomy and analyzed the prognostic factors after a repeat hepatectomy. Methods In total, 248 patients were diagnosed with recurred liver metastasis between January 2003 and May 2016. Second and third hepatectomies were performed in 70 and 7 patients, respectively. The other 171 patients did not undergo a repeat hepatectomy. Clinical features were collected from the medical records. We analyzed survival rates of the repeat hepatectomy group and the nonrepeat hepatectomy group. We also investigated factors affecting overall and disease-free survival of patients who received a repeat hepatectomy using univariate and multivariate analyses. Results Median overall survival was significantly higher in the repeat hepatectomy group than in the nonrepeat group (83.0 months vs. 25.0 months, P < 0.001). The morbidity and mortality rates of repeat hepatectomy were 9.1% and 0%, respectively. Median overall and disease-free survival of the repeat hepatectomy group were 62.0 and 51.0 months, respectively. The number of recurred tumors was the only significant factor for disease-free survival (P = 0.029). None of the factors affected overall survival. Conclusion Repeat hepatectomy is necessary, effective, and safe for treating recurred colorectal liver metastasis. Repeat hepatectomy can be considered in patients with fewer than three recurred metastatic tumors.
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Affiliation(s)
- Jangho Park
- Center for Liver Cancer, National Cancer Center, Goyang, Korea
| | - Seung-Duk Lee
- Center for Liver Cancer, National Cancer Center, Goyang, Korea
| | - Sung-Sik Han
- Center for Liver Cancer, National Cancer Center, Goyang, Korea
| | - Seoung Hoon Kim
- Center for Liver Cancer, National Cancer Center, Goyang, Korea
| | - Sang-Jae Park
- Center for Liver Cancer, National Cancer Center, Goyang, Korea
| | - Jae Hwan Oh
- Center for Colorectal Cancer, National Cancer Center, Goyang, Korea
| | - Jungnam Joo
- Biometrics Research Branch, Research Institute and Hospital, National Cancer Center, Goyang, Korea
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Molla NW, Hassanain MM, Fadel Z, Boucher LM, Madkhali A, Altahan RM, Alrijraji EA, Simoneau EB, Alamri H, Salman A, Gao Z, Metrakos PP. Effect of non-alcoholic liver disease on recurrence rate and liver regeneration after liver resection for colorectal liver metastases. ACTA ACUST UNITED AC 2017; 24:e233-e243. [PMID: 28680292 DOI: 10.3747/co.24.3133] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Resection of metastases is the only potential cure for patients with liver metastasis from colorectal cancer (crc-lm). But despite an improved overall 5-year survival, the recurrence rate is still as high as 60%. Non-alcoholic fatty liver disease (nafld) can decrease the liver's capacity to regenerate after resection and might also affect cancer recurrence, potentially by elevating transforming growth factor β, levels of specific metalloproteinases, and oxidative stress. The objective of the present work was to determine the effect of the histologic features of nafld on cancer recurrence and liver regeneration. METHODS This retrospective analysis considered 60 patients who underwent an R0 hepatectomy for crc-lm. Volumetric analysis of the liver was calculated using axial view, portovenous phase, 2.5 mm thickness, multiphasic computed tomography images taken before and after surgery. The histologic features of nafld (steatosis, inflammation, and ballooning) were scored using the nafld activity score, and the degree of fibrosis was determined. RESULTS The hepatic recurrence rate was 38.33%. Median overall survival duration was 56 months. Median disease-free survival duration was 14 months, and median hepatic disease-free survival duration was 56 months. Multivariate analysis revealed significant correlations of hepatic disease-free survival with hepatocyte ballooning (p = 0.0009), lesion diameter (p = 0.014), and synchronous disease (p = 0.006). Univariate and multivariate analyses did not reveal any correlation with degree of steatosis or recurrence rate. CONCLUSIONS This study reveals an important potential negative effect of hepatocyte ballooning on hepatic disease-free survival.
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Affiliation(s)
- N W Molla
- Department of Surgery, Section of Hepatopancreatobiliary, and.,Department of Radiology, McGill University Health Centre, Montreal, QC.,Department of Radiology and
| | - M M Hassanain
- Department of Surgery, Section of Hepatopancreatobiliary, and.,Department of Surgery, King Saud University, Riyadh, Saudi Arabia
| | - Z Fadel
- Department of Surgery, Section of Hepatopancreatobiliary, and
| | - L M Boucher
- Department of Radiology, McGill University Health Centre, Montreal, QC
| | - A Madkhali
- Department of Surgery, Section of Hepatopancreatobiliary, and.,Department of Surgery, King Saud University, Riyadh, Saudi Arabia
| | - R M Altahan
- Department of Surgery, Section of Hepatopancreatobiliary, and
| | - E A Alrijraji
- Department of Surgery, Section of Hepatopancreatobiliary, and
| | - E B Simoneau
- Department of Surgery, Section of Hepatopancreatobiliary, and
| | - H Alamri
- Department of Surgery, Section of Hepatopancreatobiliary, and.,Department of Surgery, King Saud University, Riyadh, Saudi Arabia
| | - A Salman
- Department of Surgery, Section of Hepatopancreatobiliary, and
| | - Z Gao
- Department of Pathology, McGill University Health Centre, Montreal, QC
| | - P P Metrakos
- Department of Surgery, Section of Hepatopancreatobiliary, and.,Department of Pathology, McGill University Health Centre, Montreal, QC
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7
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Hashimoto M, Kobayashi T, Ishiyama K, Ide K, Ohira M, Tahara H, Kuroda S, Hamaoka M, Iwako H, Okimoto M, Ohdan H. Efficacy of repeat hepatectomy for recurrence following curative hepatectomy for colorectal liver metastases: A Retrospective Cohort Study of 128 patients. Int J Surg 2016; 36:96-103. [PMID: 27741421 DOI: 10.1016/j.ijsu.2016.10.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Revised: 10/06/2016] [Accepted: 10/08/2016] [Indexed: 01/12/2023]
Abstract
BACKGROUND Despite improvements in surgery and chemotherapy, most patients develop recurrence after initial hepatectomy for colorectal liver metastasis (CRLM). Following initial hepatectomy for CRLM, patterns and surgical management of recurrence have not been widely reported. MATERIALS AND METHODS We identified 128 patients who underwent hepatic resection for CRLM between January 2000 and December 2012. Demographics, operative data, site of recurrence, and long-term survival data were collected and analyzed. Patients were stratified into 3 groups based on their site of recurrence as intrahepatic, intra- and extrahepatic, and extrahepatic. In addition, the influence of potential factors on overall survival (OS) in patients with only liver relapse was analyzed through univariate and multivariate analysis. RESULTS After curative initial hepatectomy, 87 (68.0%) patients had a recurrence: 33 in the intrahepatic group, 11 in the intra- and extrahepatic group, and 43 in the extrahepatic group. The OS for the intra- and extrahepatic group was significantly lower than that for the intrahepatic group. In the intrahepatic group, disease-free interval (DFI) < 12 months and non-repeat hepatectomy were independent poor prognostic factors. Carcinoembryonic antigen (CEA) at the time of hepatectomy was significantly higher in DFI < 12 group than in the DFI ≥ 12 group. CONCLUSION Patterns of recurrence following initial hepatectomy for CRLM have important implications for OS. In the intrahepatic recurrence group, short DFI was correlated with high CEA at hepatectomy, and was a poor prognostic factor.
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Affiliation(s)
- Masakazu Hashimoto
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan.
| | - Kohei Ishiyama
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan
| | - Kentaro Ide
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan
| | - Masahiro Ohira
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan
| | - Hiroyuki Tahara
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan
| | - Shintaro Kuroda
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan
| | - Michinori Hamaoka
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan
| | - Hiroshi Iwako
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan
| | - Masashi Okimoto
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan
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8
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Hallet J, Sa Cunha A, Adam R, Goéré D, Bachellier P, Azoulay D, Ayav A, Grégoire E, Navarro F, Pessaux P. Factors influencing recurrence following initial hepatectomy for colorectal liver metastases. Br J Surg 2016; 103:1366-1376. [PMID: 27306949 DOI: 10.1002/bjs.10191] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2015] [Revised: 01/11/2016] [Accepted: 03/09/2016] [Indexed: 12/22/2022]
Abstract
BACKGROUND Data on recurrence patterns following hepatectomy for colorectal liver metastases (CRLMs) and their impact on long-term outcomes are limited in the setting of modern multimodal management. This study sought to characterize the patterns of, factors associated with, and survival impact of recurrence following initial hepatectomy for CRLMs. METHODS A retrospective cohort study of patients undergoing initial hepatectomy for CRLMs at 39 institutions (2006-2013) was conducted. Kaplan-Meier methods were used for survival analyses. Overall survival landmark analysis at 12 months after hepatectomy was performed to compare groups based on recurrence. Multivariable Cox and regression models were used to determine factors associated with recurrence. RESULTS Among 2320 patients, tumours recurred in 47·4 per cent at median of 10·1 (range 0-88) months; 89·1 per cent of recurrences developed within 3 years. Recurrence was intrahepatic in 46·2 per cent, extrahepatic in 31·8 per cent and combined intra/extrahepatic in 22·0 per cent. The 5-year overall survival rate decreased from 74·3 (95 per cent c.i. 72·2 to 76·4) per cent without recurrence to 57·5 (55·0 to 60·0) per cent with recurrence (adjusted hazard ratio (HR) 3·08, 95 per cent c.i. 2·31 to 4·09). After adjusting for clinicopathological variables, prehepatectomy factors associated with increased risk of recurrence were node-positive primary tumour (HR 1·27, 1·09 to 1·49), more than three liver metastases (HR 1·27, 1·06 to 1·52) and largest metastasis greater than 4 cm (HR 1·19; 1·01 to 1·43). CONCLUSION Recurrence after CRLM resection remains common. Although overall survival is inferior with recurrence, excellent survival rates can still be achieved.
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Affiliation(s)
- J Hallet
- Institut Hospitalo-Universitaire, Institute for Minimally Hybrid Invasive Image-Guided Surgery, Université de Strasbourg, Strasbourg, France
- Institut de Recherche sur les Cancers de l'Appareil Digestif (IRCAD), Strasbourg, France
- Division of General Surgery, Sunnybrook Health Sciences Center - Odette Cancer Center, Toronto, Ontario, Canada
| | - A Sa Cunha
- Department of Surgery, Hôpital Paul Brousse, Villejuif, France
| | - R Adam
- Department of Surgery, Hôpital Paul Brousse, Villejuif, France
| | - D Goéré
- Department of Surgery, Institut Gustave Roussy, Villejuif, France
| | - P Bachellier
- Department of Surgery, Hôpital Hautepierre, Strasbourg, France
| | - D Azoulay
- Department of Surgery, Hôpital Henri Mondor, Créteil, France
| | - A Ayav
- Department of Surgery, Hôpital de Brabois, Centre Régional Hospitalier Universitaire de Nancy, Nancy, France
| | - E Grégoire
- Department of Surgery, Hôpital de la Timone, Marseilles, France
| | - F Navarro
- Department of Surgery, Université de Montpellier, Hôpital Saint-Eloi, Montpellier, France
| | - P Pessaux
- Institut Hospitalo-Universitaire, Institute for Minimally Hybrid Invasive Image-Guided Surgery, Université de Strasbourg, Strasbourg, France
- Institut de Recherche sur les Cancers de l'Appareil Digestif (IRCAD), Strasbourg, France
- General Digestive and Endocrine Surgery, Nouvel Hôpital Civil, Strasbourg, France
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9
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Cho CS. Prognostication systems as applied to primary and metastatic hepatic malignancies. Surg Oncol Clin N Am 2014; 24:41-56. [PMID: 25444468 DOI: 10.1016/j.soc.2014.09.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Staging systems are an attempt to incorporate the biology and therapy for cancer in a way that enables categorization and prediction of oncologic outcomes. Because of unusual disease biology and complexities related to treatment intervention, efforts to develop reliable staging systems for hepatic malignancies have been challenging. This article discusses the ways in which improved understanding of these diseases has informed the evolution of prognostication systems as applied to hepatocellular carcinoma, cholangiocarcinoma, and hepatic colorectal adenocarcinoma.
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Affiliation(s)
- Clifford S Cho
- Section of Surgical Oncology, Department of Surgery, University of Wisconsin School of Medicine and Public Health, J4/703 Clinical Sciences Center, 600 Highland Avenue, Madison, WI 53792, USA.
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10
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Luo LX, Yu ZY, Huang JW, Wu H. Selecting patients for a second hepatectomy for colorectal metastases: an systemic review and meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2014; 40:1036-48. [PMID: 24915859 DOI: 10.1016/j.ejso.2014.03.012] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Revised: 03/02/2014] [Accepted: 03/07/2014] [Indexed: 02/05/2023]
Abstract
BACKGROUND Opinions on the suitability of repeat hepatectomy for patients with recurrent colorectal liver metastases (CRLMs) vary among studies. We conducted a meta-analysis to establish the criteria for selecting the best candidates for a second hepatectomy. METHODS Database and manual searches were performed to identify comparative or prognostic studies published up to October 2013. Outcomes of interest included disease characteristics, perioperative outcomes, and long-term survival after initial and second hepatectomies for patients with CRLM. Study quality was appraised using the Newcastle-Ottawa scale and a modified Hayden's score. RESULTS A total of 7226 patients from 27 studies were included. Recurrent CRLMs after initial hepatectomy were more likely to be solitary (RR = 0.86, P = 0.045), unilobar (RR = 0.60, P < 0.001), and smaller (WMD = -0.66, P < 0.001). Postoperative morbidity and mortality were comparable between initial and second hepatectomies (RR = 1.10, P = 0.191; RR = 0.78, P = 0.678, respectively). In high-quality studies, patients showed better survival after a second hepatectomy than those after a single hepatectomy (HR = 0.68, P = 0.022). Patients meeting the following six predictors survived longer after second hepatectomy: disease-free survival after initial hepatectomy >1 y (P = 0.034); solitary CRLM at second hepatectomy (P < 0.001); unilobar CRLM at second hepatectomy (P = 0.009); maximal size of CRLM at second hepatectomy ≤ 5 cm (P = 0.035); lack of extrahepatic metastases at second hepatectomy (P < 0.001); and R0 resection at second hepatectomy (P < 0.001). CONCLUSIONS Second hepatectomy is a safe and feasible procedure for patients with recurrent CRLM. In fact, in well-selected patients it improves overall survival. The established criteria can help clinicians to select the best candidates for second hepatectomy and to achieve better long-term outcomes after resection.
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Affiliation(s)
- L X Luo
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, China.
| | - Z Y Yu
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, China
| | - J W Huang
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, China
| | - H Wu
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, China
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Jones R, Malik H, Fenwick S, Poston G. Perioperative chemotherapy for resectable colorectal liver metastases: Where now? Eur J Surg Oncol 2013; 39:807-11. [DOI: 10.1016/j.ejso.2013.04.002] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2012] [Revised: 11/27/2012] [Accepted: 04/25/2013] [Indexed: 12/28/2022] Open
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12
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Jones RP, Dunne D, Sutton P, Malik HZ, Fenwick SW, Terlizzo M, O'Grady E, Koelblinger C, Stättner S, Stremitzer S, Gruenberger T, Poston GJ. Segmental and lobar administration of drug-eluting beads delivering irinotecan leads to tumour destruction: a case-control series. HPB (Oxford) 2013; 15:71-7. [PMID: 23216781 PMCID: PMC3533714 DOI: 10.1111/j.1477-2574.2012.00587.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2012] [Accepted: 09/05/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND Irinotecan-loaded drug-eluting beads represent a novel drug delivery method that allows for the locoregional delivery of irinotecan to colorectal liver metastases (CRLM). The method has shown impressive response rates. However, the pathological response to this treatment has not previously been demonstrated. METHODS Patients with easily resectable CRLM were treated with drug-eluting beads delivering irinotecan (DEBIRI) 4 weeks prior to resection. Pathological tumour response was graded using a validated system. The intraoperative detection of previously unidentified disease allowed for the assessment of pathological responses directly attributable to bead treatment. RESULTS In Patient 1, segmental embolization of the target lesion in segment VIII resulted in 100% necrosis (0% viability). An untreated lesion in segment IV was found to be 30% viable. In Patient 2, subsegmental embolization of the target lesion in segment VI resulted in 60% necrosis and 40% fibrosis (0% viability). An untreated lesion in segment VI remained 60% viable. In Patient 3, lobar embolization of the target lesion in segment II resulted in 0% viability. Two further lesions within the treated hemiliver, both with 0% viability, and one lesion in the untreated hemiliver with 45% viability were discovered at laparotomy. CONCLUSIONS This series demonstrates the effectiveness of DEBIRI in the treatment of CRLM. High rates of tumour destruction are possible, even with the proximal lobar administration of DEBIRI. Lobar administration appears to be an appropriate method of delivery for integration into future therapeutic regimens.
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Affiliation(s)
- Robert P Jones
- School of Cancer Studies, Institute of Translational Medicine, University of LiverpoolLiverpool, UK,Northwestern Hepatobiliary Unit, Aintree University HospitalLiverpool, UK
| | - Declan Dunne
- School of Cancer Studies, Institute of Translational Medicine, University of LiverpoolLiverpool, UK,Northwestern Hepatobiliary Unit, Aintree University HospitalLiverpool, UK
| | - Paul Sutton
- School of Cancer Studies, Institute of Translational Medicine, University of LiverpoolLiverpool, UK,Northwestern Hepatobiliary Unit, Aintree University HospitalLiverpool, UK
| | - Hassan Z Malik
- Northwestern Hepatobiliary Unit, Aintree University HospitalLiverpool, UK
| | - Stephen W Fenwick
- Northwestern Hepatobiliary Unit, Aintree University HospitalLiverpool, UK
| | - Monica Terlizzo
- Department of Histopathology, Aintree University HospitalLiverpool, UK
| | | | - Claus Koelblinger
- Department of Radiology, Medical University of ViennaVienna, Austria
| | - Stefan Stättner
- Northwestern Hepatobiliary Unit, Aintree University HospitalLiverpool, UK
| | | | | | - Graeme J Poston
- Northwestern Hepatobiliary Unit, Aintree University HospitalLiverpool, UK
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13
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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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Jones RP, Vauthey JN, Adam R, Rees M, Berry D, Jackson R, Grimes N, Fenwick SW, Poston GJ, Malik HZ. Effect of specialist decision-making on treatment strategies for colorectal liver metastases. Br J Surg 2012; 99:1263-9. [DOI: 10.1002/bjs.8835] [Citation(s) in RCA: 103] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Abstract
Background
One hundred and ten patients were treated with palliative chemotherapy, of whom 53 had liver-only disease and had not been reviewed by a specialist liver surgeon. One scan was excluded as all reviewers felt it to be of insufficient quality to assess. Improved surgical technique and better chemotherapeutic manipulation of metastatic disease has increased the number of patients eligible for potentially curative resection of colorectal liver metastases. The rapid evolution in this field suggests that non-specialist decision-making may lead to inappropriate management. This study aimed to assess the management of colorectal liver metastases by non-liver surgeons.
Methods
All patients who underwent chemotherapy with palliative intent for metastatic colorectal cancer at a regional oncology centre between 1 January and 31 December 2009 were identified from a prospectively maintained local database. Six resectional liver surgeons blinded to patient management and outcome reviewed pretreatment imaging and assigned each scan a score based on their own management choice. A consensus decision was reached on the appropriateness of palliative chemotherapy.
Results
Tumours in 33 patients (63 per cent) were considered potentially resectable, with a high level of interobserver agreement (κ = 0·577). When individual approach to management was considered, interobserver agreement was less marked (κ = 0·378).
Conclusion
Management of patients with colorectal liver metastases without the involvement of a specialist liver multidisciplinary team can lead to patients being denied potentially curative treatments. Management of these patients must involve a specialist liver surgeon to ensure appropriate management.
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Affiliation(s)
- R P Jones
- School of Cancer Studies, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
- Northwestern Hepatobiliary Unit, Aintree University Hospital, Liverpool, UK
| | - J-N Vauthey
- Division of Surgery, MD Anderson Cancer Center, Houston, Texas, USA
| | - R Adam
- Assistance Publique–Hôpitaux de Paris Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris-Sud, Unité Mixte de Recherche en Santé 776, Villejuif, France
| | - M Rees
- Department of Hepatobiliary Surgery, Basingstoke and North Hampshire NHS Foundation Trust, Basingstoke, UK
| | - D Berry
- Department of Hepatobiliary Surgery, University Hospital Wales, Heath Park, Cardiff, UK
| | - R Jackson
- Liverpool Cancer Trials Unit, University of Liverpool, Liverpool, UK
| | - N Grimes
- Northwestern Hepatobiliary Unit, Aintree University Hospital, Liverpool, UK
| | - S W Fenwick
- Northwestern Hepatobiliary Unit, Aintree University Hospital, Liverpool, UK
| | - G J Poston
- Northwestern Hepatobiliary Unit, Aintree University Hospital, Liverpool, UK
| | - H Z Malik
- Northwestern Hepatobiliary Unit, Aintree University Hospital, Liverpool, UK
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15
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Butte JM, Gonen M, Ding P, Goodman KA, Allen PJ, Nash GM, Guillem J, Paty PB, Saltz LB, Kemeny NE, Dematteo RP, Fong Y, Jarnagin WR, Weiser MR, D'Angelica MI. Patterns of failure in patients with early onset (synchronous) resectable liver metastases from rectal cancer. Cancer 2012; 118:5414-23. [PMID: 22517058 DOI: 10.1002/cncr.27567] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2011] [Revised: 02/14/2012] [Accepted: 02/16/2012] [Indexed: 12/19/2022]
Abstract
BACKGROUND The optimal combination of available therapies for patients with resectable synchronous liver metastases from rectal cancer (SLMRC) is unknown, and the pattern of recurrence after resection has been poorly investigated. In this study, the authors examined recurrence patterns and survival after resection of SLMRC. METHODS Consecutive patients with SLMRC (disease-free interval, ≤12 months) who underwent complete resection of the rectal primary and liver metastases between 1990 and 2008 were identified from a prospective database. Demographics, tumor-related variables, and treatment-related variables were correlated with recurrence patterns. Competing risk analysis was used to determine the risk of pelvic and extrapelvic recurrence. RESULTS In total, 185 patients underwent complete resection of rectal primary and liver metastases. One hundred eighty patients (97%) received chemotherapy during their treatment course, and 91 patients (49%) received pelvic radiation therapy either before (N = 65; 71.4%), or after (N = 26; 28.6%) rectal resection. The 5-year disease-specific survival rate was 51% for the entire cohort with a median follow-up of 44 months for survivors. One hundred thirty patients (70%) developed a recurrence: Eighteen patients (10%) had recurrences in the pelvis in combination with other sites, and 7 of these (4%) had an isolated pelvic recurrence. Recurrence pattern did not correlate with survival. Competing risk analysis demonstrated that the likelihood of a pelvic recurrence was significantly lower than that of an extrapelvic recurrence (P < .001). CONCLUSIONS Of the patients with SLMRC who developed recurrent disease, systemic sites were overwhelmingly more common than pelvic recurrences. The current results indicated that the selective exclusion of radiotherapy may be considered in patients who are diagnosed with simultaneous disease.
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Affiliation(s)
- Jean M Butte
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
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Jones RP, Jackson R, Dunne DFJ, Malik HZ, Fenwick SW, Poston GJ, Ghaneh P. Systematic review and meta-analysis of follow-up after hepatectomy for colorectal liver metastases2. Br J Surg 2012; 99:477-86. [DOI: 10.1002/bjs.8667] [Citation(s) in RCA: 129] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/30/2011] [Indexed: 12/22/2022]
Abstract
Abstract
Background
The evidence surrounding optimal follow-up after liver resection for colorectal metastases remains unclear. A significant proportion of recurrences occur in the early postoperative period, and some groups advocate more intensive review at this time.
Methods
A systematic review of literature published between January 2003 and May 2010 was performed. Studies that described potentially curative primary resection of colorectal liver metastases that involved a defined follow-up protocol and long-term survival data were included. For meta-analysis, studies were grouped into intensive (more frequent review in the first 5 years after resection) and uniform (same throughout) follow-up.
Results
Thirty-five studies were identified that met the inclusion criteria, involving 7330 patients. Only five specifically addressed follow-up. Patients undergoing intensive early follow-up had a median survival of 39·8 (95 per cent confidence interval 34·3 to 45·3) months with a 5-year overall survival rate of 41·9 (34·4 to 49·4) per cent. Patients undergoing routine follow-up had a median survival of 40·2 (33·4 to 47·0) months, with a 5-year overall survival rate of 38·4 (32·6 to 44·3) months.
Conclusion
Evidence regarding follow-up after liver resection is poor. Meta-analysis failed to identify a survival advantage for intensive early follow-up.
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Affiliation(s)
- R P Jones
- Division of Surgery and Oncology, School of Cancer Studies, University of Liverpool, Liverpool, UK
- Department of Hepatobiliary Surgery, Aintree University Hospital NHS Foundation Trust, Liverpool, UK
| | - R Jackson
- Liverpool Cancer Trials Unit, University of Liverpool, Liverpool, UK
| | - D F J Dunne
- Department of Hepatobiliary Surgery, Aintree University Hospital NHS Foundation Trust, Liverpool, UK
| | - H Z Malik
- Department of Hepatobiliary Surgery, Aintree University Hospital NHS Foundation Trust, Liverpool, UK
| | - S W Fenwick
- Department of Hepatobiliary Surgery, Aintree University Hospital NHS Foundation Trust, Liverpool, UK
| | - G J Poston
- Department of Hepatobiliary Surgery, Aintree University Hospital NHS Foundation Trust, Liverpool, UK
| | - P Ghaneh
- Division of Surgery and Oncology, School of Cancer Studies, University of Liverpool, Liverpool, UK
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Pathak S, Jones R, Tang JMF, Parmar C, Fenwick S, Malik H, Poston G. Ablative therapies for colorectal liver metastases: a systematic review. Colorectal Dis 2011; 13:e252-65. [PMID: 21689362 DOI: 10.1111/j.1463-1318.2011.02695.x] [Citation(s) in RCA: 122] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
AIM The standard treatment for colorectal liver metastases (CRLM) is surgical resection. Only 20-30% of patients are deemed suitable for surgery. Recently, much attention has focused on ablative therapies either to treat unresectable CRLM or to extend the margins of resectability. This review aims to assess the long-term outcome and complication rates of various ablative therapies used in the management of CRLM. METHOD A literature search was performed of electronic databases including Medline, Cochrane Collaboration Library and the National Library of Medicine's ClinicalTrials.gov. Inclusion criteria were ablation for CRLM with minimum 1 year follow-up and >10 patients, published between January 1994 and January 2010. RESULTS In all, 226 potentially relevant studies were identified, of which 75 met the inclusion criteria. Cryotherapy (26 studies) had local recurrence rates of 12-39%, with mean 1-, 3- and 5-year survival rates of 84%, 37% and 17%. The major complication rate ranged from 7% to 66%. Microwave ablation (13 studies) had a local recurrence rate of 5-13%, with a mean 1-, 3- and 5-year survival of 73%, 30% and 16%, and a major complication rate ranging from 3% to 16%. Radiofrequency ablation (36 studies) had a local recurrence rate of 10-31%, with a mean 1-, 3- and 5-year survival of 85%, 36% and 24%, with major complication rate ranging from 0% to 33%. CONCLUSION Ablative therapies offer significantly improved survival compared with palliative chemotherapy alone with 5-year survival rates of 17-24%. Complication rates amongst commonly used techniques are low.
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Affiliation(s)
- S Pathak
- Department of Hepatobiliary Surgery, Aintree University NHS Foundation Trust, Liverpool, UK.
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18
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Hill CRS, Chagpar RB, Callender GG, Brown RE, Gilbert JE, Martin RCG, McMasters KM, Scoggins CR. recurrence following hepatectomy for metastatic colorectal cancer: development of a model that predicts patterns of recurrence and survival. Ann Surg Oncol 2011; 19:139-44. [PMID: 21751045 DOI: 10.1245/s10434-011-1921-y] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2011] [Indexed: 12/22/2022]
Abstract
BACKGROUND While several prognostic models have been developed to predict survival of patients who undergo hepatectomy for metastatic colorectal cancer (mCRC), few data exist to predict survival after recurrence. We sought to develop a model that predicts survival for patients who have developed recurrence following hepatectomy for mCRC. METHODS A retrospective analysis was performed on data from consecutive patients that underwent hepatectomy for mCRC. Clinicopathologic data, recurrence patterns, and outcomes were analyzed. Kaplan-Meier survival analysis and univariate and multivariate analyses were performed. An integer-based model was created to predict the patterns of recurrence and survival after recurrence. RESULTS This analysis included 280 patients with a median follow-up of 50.1 months. Of these, 53% underwent major hepatectomy and 87% had negative margins. Recurrent disease developed in 63% of patients. After hepatectomy, factors associated with short disease-free interval (DFI) and overall survival (OS) included CEA > 200 ng/ml (P < 0.0005), >1 metastasis (P < 0.0005), and a high Fong score (P < 0.0005). After recurrence, the pattern of recurrence was a strong predictor of OS (P < 0.0005). Independent predictors of the pattern of recurrence on multivariate analysis include CEA > 200 ng/ml, tumor size >5 cm, and >1 liver metastasis. A simple predictive scoring system was developed from the beta coefficients of this analysis that correlated with recurrence pattern (P < 0.0005). CONCLUSIONS After hepatectomy, survival of patients with recurrent mCRC is strongly predicted by the patterns of recurrence, and the recurrence pattern can be predicted with a simple model. This can also be extended to create a scoring system that estimates expected survival.
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Affiliation(s)
- Charles R St Hill
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, KY, USA
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19
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D'Angelica M, Kornprat P, Gonen M, DeMatteo RP, Fong Y, Blumgart LH, Jarnagin WR. Effect on outcome of recurrence patterns after hepatectomy for colorectal metastases. Ann Surg Oncol 2010; 18:1096-103. [PMID: 21042942 DOI: 10.1245/s10434-010-1409-1] [Citation(s) in RCA: 142] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2009] [Indexed: 12/21/2022]
Abstract
BACKGROUND Despite improvements in surgery and chemotherapy, most patients develop recurrence after hepatectomy for metastatic colorectal cancer. Data are lacking on the effect of these patterns on outcome. METHODS A retrospective review of a prospectively maintained hepatobiliary database was performed. Pattern and timing of recurrence and outcome after recurrence were analyzed. Univariate and multivariate analyses of factors associated with outcome after recurrence were carried out. RESULTS From January 1997 through May 2003, a total of 733 patients underwent hepatectomy for colorectal metastases. Of these, 637 patients (87%) were included in the analysis, and in 393 patients (62%), recurrence was documented at the time of last follow-up. Initial recurrence patterns included the following: liver only in 120 patients (31%), lung only in 107 (27%), other single sites in 49 (12%), and multiple sites in 117 (30%). Recurrence occurred within 2 years of hepatectomy in 75% of patients and after 3 years in 11%. Margins at hepatectomy, recurrence pattern, resected recurrence, and disease-free interval from time of colectomy to hepatic metastasis and from time of hepatectomy to recurrence were independently associated with survival as measured from the time of recurrence. Recurrence in the lung, resected recurrence, and time to recurrence after hepatectomy were associated with prolonged survival as measured from the time of hepatectomy and the time of recurrence. CONCLUSIONS The timing and pattern of recurrence after hepatic resection for metastatic colorectal cancer are important predictors of long-term survival.
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Affiliation(s)
- Michael D'Angelica
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
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20
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Gomez D, Sangha VK, Morris-Stiff G, Malik HZ, Guthrie AJ, Toogood GJ, Lodge JPA, Prasad KR. Outcomes of intensive surveillance after resection of hepatic colorectal metastases. Br J Surg 2010; 97:1552-60. [PMID: 20632325 DOI: 10.1002/bjs.7136] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND The impact of computed tomography (CT)-based follow-up for the detection of resectable disease recurrence following surgery for colorectal liver metastases (CRLM) was evaluated. METHODS Some 705 patients undergoing resection of CRLM between January 1993 and March 2007 were included. Surveillance comprised 3-monthly CT (thorax, abdomen and pelvis) in the first 2 years after surgery, 6 monthly for 3 years and annually from years 6 to 10. Survival differences following recurrence between patients managed surgically and palliatively were determined, and the cost was calculated. RESULTS Five-year disease-free and overall survival rates were 28.3 and 32.3 per cent respectively. Of 402 patients who developed recurrence within 2 years, 88 were treated with liver resection alone and 36 with lung and/or liver resection. Their 5-year overall survival rates were 31 and 30 per cent respectively, compared with 3.9 per cent in 278 patients managed palliatively (P < 0.001). For each 3-month interval during the first year of follow-up, patients with recurrence treated surgically had better overall survival than those treated palliatively. The cost of surveillance that identified 124 patients amenable to further resection was 12,338 pounds per operated recurrence. Assuming that patients with recurrence gained 5 years' survival, the mean survival gain was 4.28 years per resection and the cost per life-year gained was 2883 pounds. CONCLUSION Intensive 3-monthly CT surveillance after liver resection for CRLM detects recurrence that is amenable to further resection in a considerable number of patients. These patients have significantly better survival with a reasonable cost per life-year gained.
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Affiliation(s)
- D Gomez
- Hepatobiliary and Transplantation Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK
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Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: an international multi-institutional analysis of 1669 patients. Ann Surg 2009; 250:440-8. [PMID: 19730175 DOI: 10.1097/sla.0b013e3181b4539b] [Citation(s) in RCA: 578] [Impact Index Per Article: 36.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE(S) To investigate rates and patterns of recurrence in patients following curative intent surgery for colorectal liver metastasis. BACKGROUND Outcomes following surgical management of colorectal liver metastasis have largely focused on overall survival. Contemporary data on rates and patterns of recurrence following surgery for colorectal liver metastasis are limited. METHODS One thousand six hundred sixty-nine patients treated with surgery (resection +/- radiofrequency ablation [RFA]) for colorectal liver metastasis between 1982 and 2008 were identified from an international multi-institutional database. Clinicopathologic data, recurrence patterns, and recurrence-free survival (RFS) were analyzed. RESULTS At the time of the initial liver-directed surgery, surgical treatment was resection only (90.2%), resection plus RFA (8.0%), or RFA alone (1.8%). While 5-year overall survival was 47.3%, 947 (56.7%) patients recurred with a median RFS time of 16.3 months. First recurrence site was intrahepatic only (43.2%), extrahepatic only (35.8%), intra- and extrahepatic (21.0%). There was no difference in RFS based on site of recurrence (intrahepatic: 16.9 months; extrahepatic: 16.6 months; intra- and extrahepatic: 16.2 month; P > 0.05). Receipt of adjuvant chemotherapy was associated with overall recurrence risk (hazard ratio [HR] = 0.56), while history of RFA (HR = 2.39, P = 0.001) and R1 margin status (HR = 1.36) were predictive of intrahepatic recurrence. Pattern of recurrence and RFS remained similar following repeat surgery for recurrent disease. CONCLUSIONS While 5-year survival following surgery for colorectal liver metastasis approaches 50%, over one-half of patients develop recurrence within 2 years. The pattern of failure is distributed relatively equally among intrahepatic, extrahepatic, and intra- plus extrahepatic sites. Patients undergoing repeat surgery for recurrent metastasis have similar patterns of recurrence and RFS time.
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Five-year survival in 309 patients with colorectal liver metastases treated with radiofrequency ablation. Eur Radiol 2009; 19:1206-13. [PMID: 19137310 DOI: 10.1007/s00330-008-1258-5] [Citation(s) in RCA: 179] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2008] [Revised: 10/11/2008] [Accepted: 11/06/2008] [Indexed: 12/15/2022]
Abstract
There is little published long-term survival data for patients with colorectal liver metastases treated with radiofrequency ablation (RFA). We present a multivariate analysis of 5-year survival in 309 patients (198 male, aged 64 (24-92)) treated at 617 sessions. Our standard protocol used internally cooled electrodes introduced percutaneously under combined US and CT guidance/monitoring. The number and size of liver metastases, the presence and location of extrahepatic disease, primary resection, clinical, chemotherapy and follow-up data were recorded. Data analysis was performed using SPSS v.10. On multivariate analysis, significant survival factors were the presence of extrahepatic disease (p < 0.001) and liver tumour volume (p = 0.001). For 123 patients with five or less metastases of 5 cm or less maximum diameter and no extrahepatic disease median survival was 46 and 36 months from liver metastasis diagnosis and ablation, respectively; corresponding 3- and 5-year survival rates were 63%, 34% and 49%, 24%. Sixty-nine patients had three or less tumours of below 3.5 cm in diameter and their 5-year survival from ablation was 33%. There were 23/617(3.7%) local complications requiring intervention. Five-year survival of 24-33% post ablation in selected patients is superior to any published chemotherapy data and approaches the results of liver resection.
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Analysis of Prognostic Factors Influencing Long-term Survival After Hepatic Resection for Metastatic Colorectal Cancer. World J Surg 2007; 32:93-103. [DOI: 10.1007/s00268-007-9285-y] [Citation(s) in RCA: 77] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Mann CD, Metcalfe MS, Neal CP, Rees Y, Dennison AR, Berry DP. Role of ultrasonography in the detection of resectable recurrence after hepatectomy for colorectal liver metastases. Br J Surg 2007; 94:1403-7. [PMID: 17631680 DOI: 10.1002/bjs.5855] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Abstract
Background
Recurrence develops in most patients after hepatectomy for colorectal liver metastases. Repeat resection is feasible in some of these patients. The aim of this study was to evaluate an ultrasound-based follow-up protocol in the detection of resectable recurrent disease.
Methods
All patients undergoing hepatectomy for colorectal liver metastases at a single hepatobiliary referral centre in the UK from January 1999 to December 2004 were identified. Variables reviewed included rates of recurrence, mode and timing of detection, rates of repeat hepatectomy and survival.
Results
During the study period 191 patients underwent initial resection of colorectal liver metastases, of whom 109 developed recurrent disease. In total, 21 patients underwent potentially curative intervention, including 16 hepatic resections, four pulmonary resections and one staged pulmonary/hepatic resection. Ten of 72 patients who presented with recurrent disease within 12 months after initial resection were amenable to curative resection, compared with 11 of 37 patients presenting after 12 months. Sonographic surveillance identified all of the potentially resectable recurrent hepatic disease in the series.
Conclusion
Ultrasonography is effective in the detection of potentially resectable hepatic recurrence after hepatectomy for colorectal liver metastases; however, routine chest imaging is needed.
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Affiliation(s)
- C D Mann
- Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, University Hospitals of Leicester, Gwendolen Road, Leicester LE5 4PW, UK.
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Fioole B, de Haas RJ, Wicherts DA, Elias SG, Scheffers JM, van Hillegersberg R, van Leeuwen MS, Borel Rinkes IHM. Additional value of contrast enhanced intraoperative ultrasound for colorectal liver metastases. Eur J Radiol 2007; 67:169-76. [PMID: 17467944 DOI: 10.1016/j.ejrad.2007.03.017] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2007] [Revised: 03/06/2007] [Accepted: 03/20/2007] [Indexed: 01/09/2023]
Abstract
BACKGROUND Substantial recurrence rates following partial liver resection for colorectal liver metastases (CRM) imply that small metastases remain undetected using intraoperative ultrasound (IOUS). The aim of this study was to evaluate the additional value of contrast enhanced IOUS (CE-IOUS) when compared to preoperative contrast enhanced computed tomography (CE-CT) and IOUS in liver surgery for CRM. METHODS After obtaining informed consent, 39 consecutive patients with CRM were included prospectively for evaluation. The study population consisted of 26 male and 13 female patients with a median (range) age of 62 (49-83) years. A lesion-per-lesion analysis was performed with histopathological examination as the reference standard after resection and follow-up for unresected lesions. The added value of CE-IOUS in correctly diagnosing malignant lesions was statistically evaluated, using receiver operating characteristic curves. RESULTS A total of 234 lesions were identified, 137 of which were malignant, according to the reference standard. The addition of CE-IOUS did not improve the diagnostic accuracy when compared to the combination of CE-CT and IOUS (P=0.617). In one of two patients with newly detected lesions on CE-IOUS the extent of resection changed. CONCLUSIONS The addition of CE-IOUS to preoperative CE-CT and IOUS does not improve the ability to characterize already detected lesions. In a small number of patients it appears to facilitate the detection of new metastatic lesions with implications on surgical strategy.
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Affiliation(s)
- Bram Fioole
- Department of Surgery, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
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Connor S, Hart MG, Redhead DN, Ireland H, Madhavan KK, Parks RW, Garden OJ. Follow-up and outcomes for resection of colorectal liver metastases in Edinburgh. Eur J Surg Oncol 2007; 33:55-60. [PMID: 17095181 DOI: 10.1016/j.ejso.2006.09.017] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2006] [Accepted: 09/21/2006] [Indexed: 01/29/2023] Open
Abstract
AIM The aim of this study was to assess the value of a defined follow-up protocol for patients undergoing potentially curative hepatic resection for colorectal hepatic metastases. METHODS A standard protocol for the duration of the study consisted of clinical assessment, serum carcinoembryonic antigen (CEA) and computed tomography. Patterns of recurrence, method and timing of diagnosis and outcome were recorded. RESULTS One hundred and ninety-one patients underwent potentially curative resection from 1989 to 2004 of whom 103 developed recurrence. The median (inter-quartile range) follow-up was 24.4 (6.5-42.3) months. The median (IQR) time to recurrence and overall survival was 25.0 (10 -not yet reached) and 45.2 (21-123) months, respectively. Seventeen patients (8.9%) underwent further surgery with curative intent. Fifty-five patients (57.9%) had recurrence diagnosed at routine follow-up with 71% (44/62) being diagnosed by CEA and CT. The CEA was elevated in 85.7% (72/84 patients) at the time of diagnosis of recurrence. CONCLUSION Although the detection of recurrent disease is common during follow-up after hepatic resection for colorectal metastases, few patients will be suitable for further intervention with curative intent. The exact nature of the follow-up protocol remains to be determined but if it is going to be performed it should be most intensive within the first 3 years.
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Affiliation(s)
- S Connor
- Division of Clinical and Surgical Sciences (Surgery), University of Edinburgh, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, United Kingdom
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Mazzoni G, Tocchi A, Miccini M, Bettelli E, Cassini D, De Santis M, Colace L, Brozzetti S. Surgical treatment of liver metastases from colorectal cancer in elderly patients. Int J Colorectal Dis 2007; 22:77-83. [PMID: 16538491 DOI: 10.1007/s00384-006-0096-7] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/23/2005] [Indexed: 02/07/2023]
Abstract
INTRODUCTION The liver is the most frequent site of liver metastases (LM) from colorectal cancer. Because of short life expectancies and improved nonoperative modalities, the role of liver resection in elderly patients with LM is unclear. METHODS During a 15-year period, 197 patients underwent liver resection for colorectal metastases. This study was designed to compare morbidity, mortality, and long-term outcome after hepatic resection in patients aged 70 years and older and in patients younger than 70. According to the age at the time of operation, patients were divided into two groups. Group A included patients aged 70 years or older and group B included younger patients. RESULTS The clinical and pathologic parameters of the two groups were compared and tested as factors affecting early and long-term outcomes after resection. A modified oncologic clinical risk score (CRS) was tested on this series of patients. Overall morbidity was 16.3% (group A 20.7% vs group B 14.6%; P=0.18). Hospital mortality was 3% (5.7% in group A and 2.1% in group B; P=0.19). Actuarial 5 years survival were 30% in group A and 38% in group B (P=ns). DISCUSSION The presence of more than three Fong's CRS parameters and microscopic involvement of resectional margin directly affected survival. Under meticulous preoperative assessment and postoperative care, liver resection for LM is justified in patients over 70 years of age; age by itself may not be a controindication to surgery.
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Affiliation(s)
- Gianluca Mazzoni
- Department of Surgery Pietro Valdoni, University of Rome La Sapienza, Medical School, Viale del Policlinico, Rome, 00100, Italy.
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Bhattacharjya S, Aggarwal R, Davidson BR. Intensive follow-up after liver resection for colorectal liver metastases: results of combined serial tumour marker estimations and computed tomography of the chest and abdomen - a prospective study. Br J Cancer 2006; 95:21-6. [PMID: 16804525 PMCID: PMC2360492 DOI: 10.1038/sj.bjc.6603219] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2006] [Revised: 04/20/2006] [Accepted: 05/15/2006] [Indexed: 12/11/2022] Open
Abstract
The aim of the study was to prospectively evaluate an intensive follow-up programme using serial tumour marker estimations and contrast-enhanced computed tomography (CT) of the chest and abdomen in patients undergoing potentially curative resection of colorectal liver metastases. Seventy-six consecutive patients having undergone potentially curative resections of colorectal liver metastases in a single unit were followed up with a protocol of 3 monthly carcinoembryonic antigen and carbohydrate antigen 19-9 estimations and contrast-enhanced spiral CT of the chest, abdomen and pelvis for the first 2 years following surgery and 6 monthly thereafter. The median period of follow-up was 24 months (range 18-60). Recurrent tumour was classed as early if within 6 months of liver resection. Thirty-seven of the 76 patients (49%) developed recurrence on follow-up. Nineteen recurrences were in the liver alone (51%), 16 liver and extrahepatic (43%) and two extrahepatic alone (6%). Of the 19 patients with isolated liver recurrence, eight developed within 6 months of liver resection none of which were resectable. Of the 11 recurrences after 6 months, five (45%) were resectable. Of the 37 recurrences, CT indicated recurrence despite normal tumour markers in 19 patients. Tumour markers suggested recurrence before imaging in 12 and concurrently with imaging in 6. In the 12 patients who presented with elevated tumour markers before imaging, there was a median lag period of 3 months (range 1-21) in recurrence being detected on further serial imaging. Seventeen patients who developed recurrence had normal tumour markers before initial resection of their liver metastases. Of these 17, 10 (58%) had an elevation of tumour markers associated with recurrence. Over a median follow-up of 2 years following liver resection, the use of CT or tumour markers alone would have failed to demonstrate early recurrence in 12 and 18 patients respectively. A combination of tumour markers and CT detected significantly more (P < 0.05) recurrence than either modality alone. Tumour markers and CT should be used in combination in the follow-up of patients with resected colorectal liver metatases, including patients whose markers are normal at the time of initial liver resection.
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Affiliation(s)
- S Bhattacharjya
- Department of Surgery, Royal Free and University College School of Medicine, University College London, The Royal Free Hospital, Pond Street, London NW3 2QG, UK
| | - R Aggarwal
- Department of Surgery, Royal Free and University College School of Medicine, University College London, The Royal Free Hospital, Pond Street, London NW3 2QG, UK
| | - B R Davidson
- Department of Surgery, Royal Free and University College School of Medicine, University College London, The Royal Free Hospital, Pond Street, London NW3 2QG, UK
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Metcalfe M, Mann C, Mullin E, Maddern G. Detecting curable disease following hepatectomy for colorectal metastases. ANZ J Surg 2005; 75:524-7. [PMID: 15972037 DOI: 10.1111/j.1445-2197.2005.03421.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
INTRODUCTION Although resection may be curative for patients with hepatic colorectal metastases, recurrence occurs in the majority. Recurrence is occasionally amenable to repeated resection. The aim of the present study was to evaluate which modalities, at what intervals, detected potentially curable resection. METHODS The records of patients undergoing hepatectomy for colorectal metastases over 10 years in one centre were retrospectively reviewed to determine when and how recurrence was diagnosed. Specific attention was paid to the detection of potentially curable disease. RESULTS Of 41 recurrences, 22 occurred in the first year postoperatively, 21 of which were suitable for palliative treatment only. Ten of 19 recurrences occurring after 1 year underwent potentially curative intervention, 10 were diagnosed by computed tomography (CT). Carcinoembryonic antigen did not diagnose any curable recurrence. CONCLUSIONS A follow-up protocol is proposed, based on annual CT.
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Affiliation(s)
- Matthew Metcalfe
- University of Adelaide Department of Surgery, The Queen Elizabeth Hospital, Woodville, South Australia, Australia
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Koch M, Kienle P, Hinz U, Antolovic D, Schmidt J, Herfarth C, von Knebel Doeberitz M, Weitz J. Detection of hematogenous tumor cell dissemination predicts tumor relapse in patients undergoing surgical resection of colorectal liver metastases. Ann Surg 2005; 241:199-205. [PMID: 15650626 PMCID: PMC1356902 DOI: 10.1097/01.sla.0000151795.15068.27] [Citation(s) in RCA: 104] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
OBJECTIVE To examine the prognostic significance of disseminated tumor cells in blood and bone marrow of patients undergoing surgical resection of colorectal liver metastases. SUMMARY BACKGROUND DATA Despite curative hepatic resection of colorectal liver metastases, a high percentage of patients develop tumor recurrence. These recurrences probably originate from disseminated tumor cells released into the circulation before or during surgery. METHODS Thirty-seven patients with potentially curative (R0) resection of colorectal liver metastases were prospectively enrolled into the study. Preoperative bone marrow samples and preoperative, intraoperative, and postoperative blood samples were examined for disseminated tumor cells by CK20 RT-PCR. RESULTS Tumor cells were detected in preoperative blood samples in 11 of 37 (30%) patients, in intraoperative blood samples in 17 of 37 (46%) patients, and in postoperative blood samples in 8 of 37 (22%) patients. Four of 25 (16%) patients tested positive for disseminated tumor cells in bone marrow samples. Median follow-up time for all patients was 38 months (range, 10-63 months). Multivariate analysis confirmed tumor cell detection in intraoperative blood (P = 0.009) and in bone marrow samples (P = 0.013) to be independent prognostic factors of tumor relapse. CONCLUSIONS This is the first study demonstrating that detection of hematogenous tumor cell dissemination during hepatic resection of colorectal cancer metastases predicts tumor relapse. Detection of disseminated tumor cells may help to individualize adjuvant therapy for patients with colorectal liver metastases and to develop surgical strategies to prevent intraoperative hematogenous tumor cell shedding.
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Affiliation(s)
- Moritz Koch
- Department of Surgery, University of Heidelberg, Heidelberg, Germany
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Tocchi A, Mazzoni G, Brozzetti S, Miccini M, Cassini D, Bettelli E. Hepatic resection in stage IV colorectal cancer: prognostic predictors of outcome. Int J Colorectal Dis 2004; 19:580-585. [PMID: 15103491 DOI: 10.1007/s00384-004-0594-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/05/2004] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Hepatic resection has been proposed as an effective way to treat metastatic colorectal carcinoma. The aim of the study was to determine if contemporary resection of intestinal primary tumor and hepatic metastases is effective in the treatment of patients with metastases that are recognized at the initial clinical presentation of the primary tumor. METHODS In a retrospective study, univariate and multivariate models were used to analyze the effect of patient demographics, tumor characteristics, and treatment factors on early and long-term outcome of patients submitted to synchronous intestinal and hepatic resection for colorectal liver metastases. From 1988 to 1999, 78 patients underwent surgical resection of primary colorectal tumor and hepatic metastases with curative intent. Criteria for study recruitment included primary tumor controllable, no extrahepatic disease detectable, and negative surgical margins of hepatic resection. RESULTS The univariate analysis disclosed as adverse predictors of the long-term outcome the numbers of metastases (3), pre-operative CEA value >100 ng/ml, resection margin <10 mm, and portal nodal status. Multivariate analysis confirmed number of metastases, resection margin and portal nodal status as independent predictors. CONCLUSIONS Our findings confirm hepatic resection as an effective procedure when undertaking combined bowel and hepatic resection. The applicability and the outcome of this surgical strategy is definitively influenced by the chance of a radical resection of the primary tumor, the number of hepatic metastases, resection margin wider than 1 cm, positive portal nodes, and the absence of any extrahepatic metastatic disease.
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Affiliation(s)
- Adriano Tocchi
- First Department of Surgery, University of Rome La Sapienza Medical School, Viale del Policlinico 155, 00161 Rome, Italy.
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Torzilli G, Del Fabbro D, Olivari N, Calliada F, Montorsi M, Makuuchi M. Contrast-enhanced ultrasonography during liver surgery. Br J Surg 2004; 91:1165-7. [PMID: 15449268 DOI: 10.1002/bjs.4628] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Worthy of wider evaluation
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Affiliation(s)
- G Torzilli
- Hepatobiliary Surgery Unit, First Department of Surgery, Azienda Ospedaliera della Provincia di Lodi, Lodi, Italy.
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Yu B, Li SY, An P, Zhang YN, Liang ZJ, Yuan SJ, Cai HY. Comparative study of proteome between primary cancer and hepatic metastatic tumor in colorectal cancer. World J Gastroenterol 2004; 10:2652-6. [PMID: 15309713 PMCID: PMC4572187 DOI: 10.3748/wjg.v10.i18.2652] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To identify the differential proteins associated with colorectal cancer genesis and hepatic metastasis.
METHODS: Hydrophobic protein samples were extracted from normal colorectal mucosa, primary cancer lesion and hepatic metastatic foci of colorectal cancer. With two-dimensional electrophoresis and image analysis, differentially expressed protein spots were detected, and the proteins were identified by matrix assisted laser desorption/ionization-time of flight-mass spectrometry and peptide mass fingerprint analysis.
RESULTS: Significant alterations of the proteins in number and expression levels were discovered in primary cancer and hepatic metastatic foci, the expression of a number of proteins was lost in 25-40 ku, but protein spots was increased in 14-21 ku, compared with normal mucosa. Nine differentially expressed protein spots were identified. Three proteins expressed in normal mucosa, but lost in primary cancer and hepatic metastasis, were recognized as calmodulin, ribonuclease 6 precursor and mannosidase-α. Proapolipoprotein was expressed progressively from normal mucosa to primary cancer and hepatic metastasis. The differentially expressed protein of beta-globin was found in normal mucosa and hepatic metastatic tumor, but lost in primary cancer lesion. Cdc 42, a GTP-binding protein, was identified in hepatic metastasis. The protein spots of C4 from primary cancer, M7 and M9 from hepatic metastasis had less homology with the proteins in database.
CONCLUSION: Variations of hydrophobic protein expression in colorectal cancer initiation and hepatic metastasis are significant and can be observed with two-dimensional electrophoresis. The expression of calmodulin, ribonuclease 6 precursor and mannosidase-α is lost but the expression of proapolipoprotein is enhanced which is associated with colorectal cancer genesis and hepatic metastasis. Cdc 42 and beta-globin are expressed abnormally in hepatic metastasis. Protein C4, M7 and M9 may be associated with colorectal cancer genesis and hepatic metastasis.
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Affiliation(s)
- Bo Yu
- Department of General Surgery, General Hospital of Beijing Military Command, Beijing 100700, China.
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Tanaka K, Shimada H, Fujii Y, Endo I, Sekido H, Togo S, Ike H. Pre-hepatectomy prognostic staging to determine treatment strategy for colorectal cancer metastases to the liver. Langenbecks Arch Surg 2004; 389:371-9. [PMID: 15605168 DOI: 10.1007/s00423-004-0490-y] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2003] [Accepted: 04/18/2004] [Indexed: 02/07/2023]
Abstract
BACKGROUND Attempts at identifying prognostic factors after hepatectomy in patients with colorectal liver metastases have not achieved consensus. We investigated prognostic factors ascertainable before hepatectomy for colorectal metastasis. METHOD Clinicopathological data for 149 consecutive patients with colorectal cancer who underwent curative resection of primary lesions and metastatic liver disease at one institution were subjected to multivariate analysis concerning metastatic status and the primary lesion. RESULTS Poorly differentiated adenocarcinoma or mucinous carcinoma as the primary tumor (Poor/muc; P=0.026), marked vascular invasion by the primary tumor (V; P=0.002), bi-lobar liver metastases ( P=0.048), and short doubling time (DT) of the liver tumor ( P=0.028) were characteristics assessable before hepatectomy that independently indicated poorer survival. A four-stage classification based on these factors was related to overall ( P<0.01) and disease-free ( P<0.01) survival rates. No pattern of recurrence site was evident in stage I (patients with no risk factor). Recurrence was usually extrahepatic in stage IV (patients with Poor/muc) but favored the remnant liver in stage II (patients with bi-lobar metastases or short DT) or III (patients with V; P=0.037). Stage III showed more multiple and early hepatic recurrences than stage II, and repeat hepatectomy was less frequent ( P<0.05). CONCLUSION Pre-hepatectomy prognostic staging should help to guide treatment of liver metastases.
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Affiliation(s)
- Kuniya Tanaka
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, 236-0004 Yokohama, Japan.
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Torzilli G. Contrast-enhanced intraoperative ultrasonography in surgery for liver tumors. Eur J Radiol 2004; 51 Suppl:S25-9. [PMID: 15234022 DOI: 10.1016/j.ejrad.2004.03.025] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2004] [Revised: 03/08/2004] [Accepted: 03/15/2004] [Indexed: 12/11/2022]
Abstract
IOUS is the most accurate diagnostic technique for assessing focal liver lesions, but still has some drawbacks. Contrast-enhanced ultrasound examination done intraoperatively (CE-IOUS), using second generation contrast agents (SonoVue, Bracco-Imaging, Milan, Italy), seems able to overcome those aforementioned lacking aspects of IOUS. In cirrhotic patients with hepatocellular carcinoma (HCC), CE-IOUS provides information about tumor vascularity which are useful for nodules differentiation: this should improve the surgical radicality. Furthermore, two different pattern of enhancement are also recognizable at CE-IOUS in those HCC nodules depicted preoperatively: one of them has no similarity with that observed at computed tomography (CT). In patients who undergo surgery for colorectal liver metastases, CE-IOUS seems to improve the sensitivity of IOUS to small, hypoechoic lesions, reducing the risk to down-stage the disease and enhancing the rate of treatment with curative intent. In conclusion, IOUS accuracy is improved by CE-IOUS with an impact on surgical strategy either for primary than for metastatic tumors. Furthermore, a wider experience with vascular enhancement patterns at CE-IOUS could provide new classification for liver lesions.
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Affiliation(s)
- Guido Torzilli
- Hepatobiliary Surgery Unit, First Department of General Surgery, Azienda Ospedaliera della Provincia di Lodi, Largo Donatori del Sangue, 2 I-26900, Lodi, Italy.
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Tanaka K, Shimada H, Miura M, Fujii Y, Yamaguchi S, Endo I, Sekido H, Togo S, Ike H. Metastatic tumor doubling time: most important prehepatectomy predictor of survival and nonrecurrence of hepatic colorectal cancer metastasis. World J Surg 2004; 28:263-70. [PMID: 14961200 DOI: 10.1007/s00268-003-7088-3] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
We determined the relative value of the metastatic colorectal cancer doubling time as a predictor of recurrence and survival after hepatectomy in comparison with other established predictors. Consecutive patients who underwent hepatic resection ( n = 144) for colorectal cancer liver metastases were studied retrospectively to identify factors that influence overall survival and recurrence in the remnant liver. Overall 5-year survival and nonrecurrence rates were 49.8% and 50.8%, respectively. By multivariate analysis, large liver tumors ( p = 0.038), p53 expression by the liver tumor (p = 0.011), and a short liver metastasis doubling time (< or = 45 days, p = 0.013) negatively affected survival; doubling times > 45 days (adjusted relative risk 0.06; p < 0.001) positively influenced disease-free survival. In patients with remnant liver recurrence, a short doubling time was associated with short disease-free intervals (7.3 +/- 6.2 months), multiple metastases (63.6%), and fewer attempts at repeat hepatectomy (22.7%). The doubling time determines tumor size and reflects the patient's immune and nutritional status. A short doubling time is the most reliable risk factor for multiple metastases, early recurrence, and poor prognosis. Further studies with a larger number of patients are needed to confirm this conclusion.
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Affiliation(s)
- Kuniya Tanaka
- Department of Surgery II, Yokohama City University School of Medicine, 4-57 Urafune-cho, Minami-ku, 232-0024 Yokohama, Japan
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Waas ET, Wobbes T, Lomme RMLM, DeGroot J, Ruers T, Hendriks T. Matrix metalloproteinase 2 and 9 activity in patients with colorectal cancer liver metastasis. Br J Surg 2004; 90:1556-64. [PMID: 14648736 DOI: 10.1002/bjs.4346] [Citation(s) in RCA: 59] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Matrix metalloproteinases (MMPs) have been reported to play an important role in tumour cell invasion and metastasis. The bioactivity of MMPs in liver metastasis from colorectal cancer was investigated and correlated with clinicopathological variables. METHOD Thirty-two patients underwent resection of colorectal cancer liver metastases. Latent and active forms of MMP were measured in tissue extracts, by means of quantitative gelatin zymography and a fluorometric activity assay. RESULTS Broad-spectrum MMP activity, and levels of both active and latent forms of MMP-2 and MMP-9, were higher in tissues containing metastatic tumour than in normal liver tissue. Median metastatic to normal tissue ratios were 15.0 and 17.6 for active and proMMP-2 respectively, and those for active and proMMP-9 were 6.2 and 2.9. The ratios of active to latent enzyme were higher in metastatic tissue than in normal tissue. Lowered MMP-2 activity was associated with large metastatic lesions and increased proMMP-9 levels with preoperative chemotherapy. Both MMP-2 and MMP-9 activity were linked unfavourably to early recurrent disease. CONCLUSION These data suggest a role for MMPs in colorectal cancer liver metastasis, but indicate different roles for individual MMPs.
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Affiliation(s)
- E T Waas
- Department of Surgery, University Medical Centre St Radboud, Nijmegen, The Netherlands
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Topal B, Kaufman L, Aerts R, Penninckx F. Patterns of failure following curative resection of colorectal liver metastases. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2003; 29:248-53. [PMID: 12657235 DOI: 10.1053/ejso.2002.1421] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
AIMS Several studies have focused on factors determining recurrence and survival rate after curative resection of colorectal liver metastases (LM). Data are lacking with regard to patterns of failure indicating where and when recurrences arise. METHODS One-hundred-and-five consecutive patients [F/M: 31/74; mean age 61 years (range 36-80 y)] with primary colorectal liver metastases underwent surgical R0 curative resection between 1990-1999. Patient follow-up was closed in January 2002. The common closing date method was used for survival analysis. Multivariate analysis was performed with the Cox proportional hazard technique. RESULTS The overall (OS) vs disease free survival (DFS) rates at 1, 2, and 5 years were 88.5 vs 63.3, 73.4 vs 40.2, and 36.8 vs 18.1%, respectively. Elevated serum CEA level was the only factor independently related to recurrent disease. Elevated serum CEA level, maximum diameter of liver metastases (LM), and satellitosis were factors significantly related to poor OS. Recurrent liver metastases developed in 43% and extra-hepatic metastases in 60% of the patients. In about half of the patients cancer recurrence was observed within 18 months, almost equally distributed between hepatic and extra-hepatic sites. CONCLUSION Despite optimal patient selection and curative resection of colorectal liver metastases, more than a half of the patients developed cancer recurrence within 2 years.
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Affiliation(s)
- B Topal
- Department of Abdominal Surgery, University Hospital Gasthuisberg, Catholic University Leuven, Belgium.
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