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Padmanabhan C, Nussbaum DP, D'Angelica M. Surgical Management of Colorectal Cancer Liver Metastases. Hematol Oncol Clin North Am 2025; 39:1-24. [PMID: 39510667 DOI: 10.1016/j.hoc.2024.08.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2024]
Abstract
Approximately 50% of colorectal cancer patients develop liver metastases. Hepatic metastases represent the most common cause of colorectal cancer-related mortality. Metastasectomy, if possible, represents the most effective treatment strategy; 20% of patients will be cured and more than 50% survive at least 5 years. Nuances to treatment planning hinge on whether patients present with resectable disease upfront, whether the future liver remnant is adequate, and whether the primary tumor, if present, is colon versus rectal in origin. This article discusses considerations impacting our approach to patients with colorectal liver metastases and the role for various multimodal treatment options.
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Affiliation(s)
- Chandrasekhar Padmanabhan
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-1272, New York, NY 10065, USA
| | - Daniel P Nussbaum
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-1272, New York, NY 10065, USA
| | - Michael D'Angelica
- Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-898, New York, NY 10065, USA.
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2
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Nishioka Y, Paez-Arango N, Boettcher FO, Kawaguchi Y, Newhook TE, Chun YS, Tzeng CWD, Tran Cao HS, Lee JE, Vreeland TJ, Vauthey JN. Neither Surgical Margin Status nor Somatic Mutation Predicts Local Recurrence After R0-intent Resection for Colorectal Liver Metastases. J Gastrointest Surg 2022; 26:791-801. [PMID: 34725784 PMCID: PMC11875739 DOI: 10.1007/s11605-021-05173-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 09/04/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND We evaluated the associations of surgical margin status and somatic mutations with the incidence of local recurrence (LR) and oncologic outcomes in patients undergoing R0-intent (microscopically negative margin) resection of colorectal liver metastases (CLM). METHODS Patients with CLM who underwent initial R0-intent resection and analysis of tumor tissue using next-generation sequencing during 2001-2018 were analyzed. Recurrences were classified as LR (at the resection margin), other intrahepatic recurrence, or extrahepatic recurrence. Predictors and survival effect of LR were evaluated using univariate and multivariate analysis. RESULTS Of 552 patients analyzed, 415 (75%) had R0 resection (margin width ≥ 1.0 mm), and 38 (7%) had LR. LR incidence was not affected by surgical margin width. RAS/TP53 co-mutation was associated with increased risk of intrahepatic recurrence (67% vs. 49%; p < 0.001) and overall recurrence (p < 0.001). However, incidence of LR did not differ significantly by RAS/TP53, BRAF, SMAD4, or FBXW7 mutation. Extrahepatic disease (hazard ratio [HR], 1.47; p = 0.034), > 8 cycles of preoperative chemotherapy (HR, 1.98; p = 0.033), tumor viability ≥ 50% (HR, 1.55; p = 0.007), RAS/TP53 co-mutation (HR, 1.69; p = 0.001), and SMAD4 mutation (HR, 2.44; p < 0.001) were independently associated with poor overall survival, but surgical margin status was not. CONCLUSIONS Although somatic mutations were associated with overall recurrence, neither surgical margin width nor somatic mutations affected LR risk after R0-intent hepatectomy for CLM. LR and prognosis were likely driven by individual tumor biology rather than surgical margins.
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Affiliation(s)
- Yujiro Nishioka
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, 77030, USA
| | - Natalia Paez-Arango
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, 77030, USA
| | - Federico Oppliger Boettcher
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, 77030, USA
| | - Yoshikuni Kawaguchi
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, 77030, USA
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Timothy E Newhook
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, 77030, USA
| | - Yun Shin Chun
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, 77030, USA
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, 77030, USA
| | - Hop S Tran Cao
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, 77030, USA
| | - Jeffrey E Lee
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, 77030, USA
| | - Timothy J Vreeland
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, 77030, USA
- Department of Surgery, Brooke Army Medical Center, Ft. Sam Houston, San Antonio, TX, USA
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, 77030, USA.
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Padmanabhan C, Nussbaum DP, D'Angelica M. Surgical Management of Colorectal Cancer Liver Metastases. Surg Oncol Clin N Am 2021; 30:1-25. [PMID: 33220799 DOI: 10.1016/j.soc.2020.09.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Approximately 50% of colorectal cancer patients develop liver metastases. Hepatic metastases represent the most common cause of colorectal cancer-related mortality. Metastasectomy, if possible, represents the most effective treatment strategy; 20% of patients will be cured and more than 50% survive at least 5 years. Nuances to treatment planning hinge on whether patients present with resectable disease upfront, whether the future liver remnant is adequate, and whether the primary tumor, if present, is colon versus rectal in origin. This article discusses considerations impacting our approach to patients with colorectal liver metastases and the role for various multimodal treatment options.
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Affiliation(s)
- Chandrasekhar Padmanabhan
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-1272, New York, NY 10065, USA
| | - Daniel P Nussbaum
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-1272, New York, NY 10065, USA
| | - Michael D'Angelica
- Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C-898, New York, NY 10065, USA.
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Barresi V, Fioravanzo A, Pecori S, Tomezzoli A, Reggiani Bonetti L. The histopathologic report of surgically resected colorectal liver metastases: What is clinically relevant? Pathol Res Pract 2019; 215:152547. [PMID: 31371210 DOI: 10.1016/j.prp.2019.152547] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 07/12/2019] [Accepted: 07/17/2019] [Indexed: 02/08/2023]
Abstract
Colorectal carcinoma (CRC) is one of the most common malignancies and a major cause of cancer-related death worldwide. The liver is the most frequent site of metastatic spread, so that about half of the patients with CRC have or develop liver metastases (LM) during the clinical course of the disease. Colorectal LM can potentially be cured by surgery, but most patients still experience disease progression and recurrence after the surgical treatment. Prediction of a patient's post-surgical clinical course is mainly based on clinical parameters or the histopathological features of the primary tumor, while little attention is given to the pathological characteristics of the LM. In this paper, we review the prognostic relevance of the gross and microscopic pathological features observed in surgically resected LM and propose which information should be included in the histopathological report to guide surgeons and oncologists for the subsequent therapeutic management.
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Affiliation(s)
- Valeria Barresi
- Department of Diagnostics and Public Health, Polyclinic G.B. Rossi, P.le L.A. Scuro, 1, 37134, Verona, Italy.
| | - Adele Fioravanzo
- Department of Diagnostics and Public Health, Polyclinic G.B. Rossi, P.le L.A. Scuro, 1, 37134, Verona, Italy
| | - Sara Pecori
- Department of Diagnostics and Public Health, Polyclinic G.B. Rossi, P.le L.A. Scuro, 1, 37134, Verona, Italy
| | - Anna Tomezzoli
- Department of Diagnostics and Public Health, Polyclinic G.B. Rossi, P.le L.A. Scuro, 1, 37134, Verona, Italy
| | - Luca Reggiani Bonetti
- Department of Laboratory Integrated Activities, Anatomic Pathology and Legal Medicine, University of Modena and Reggio Emilia, Modena, Italy
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Impact of Neoadjuvant Chemotherapy on the Postoperative Outcomes of Patients Undergoing Liver Resection for Colorectal Liver Metastases: A Population-Based Propensity-Matched Analysis. J Am Coll Surg 2019; 229:69-77.e2. [PMID: 30905856 DOI: 10.1016/j.jamcollsurg.2019.03.011] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Revised: 02/26/2019] [Accepted: 03/11/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND The role of neoadjuvant chemotherapy in the management of colorectal liver metastases remains controversial. We sought to investigate whether neoadjuvant systemic chemotherapy contributes to clinically significant increases in postoperative morbidity and mortality using a population-based cohort. STUDY DESIGN The American College of Surgeons NSQIP Targeted Hepatectomy Participant Use Files were queried from 2014 to 2016 to identify patients with colorectal liver metastases who underwent liver resection. Patients were stratified by receipt of neoadjuvant chemotherapy using propensity score matching. Univariate and multivariable analyses were used to characterize the effect of neoadjuvant chemotherapy on perioperative morbidity and mortality. RESULTS After propensity score matching, 1,416 (50%) patients received neoadjuvant chemotherapy before hepatectomy and 1,416 (50%) underwent liver resection without neoadjuvant chemotherapy. There were no differences in age (60 vs 61 years), maximum tumor size (≤5 cm: 79% vs 80%, >5 cm: 21% vs 20%), resection type (partial hepatectomy: 69% vs 70%), simultaneous colectomy (9% vs 9%), or use of preoperative portal vein embolization (5% vs 5%) in those undergoing neoadjuvant chemotherapy compared with those who did not (all, p > 0.05). Overall 30-day postoperative morbidity (34% vs 33%), including rates of biliary fistula (6% vs 5%), post-hepatectomy liver failure (5% vs 5%), and mortality rates (0.8% vs 0.7%), were similar among patients who received neoadjuvant chemotherapy vs those who did not (all, p > 0.05). On multivariable analysis, receipt of neoadjuvant chemotherapy was not associated with increased morbidity (odds ratio 1.07; 95% CI 0.90 to 1.27; p = 0.43) or mortality (odds ratio 1.09; 95% CI 0.44 to 2.72; p = 0.85). CONCLUSIONS In this propensity-matched population-based cohort study, the use of neoadjuvant systemic chemotherapy was not associated with higher rates of complications, biliary fistula, post-hepatectomy liver failure, or mortality among patients with colorectal liver metastases undergoing liver resection.
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Lee AJ, Loyer EM, Kang HC, Aloia TA, Tzeng CWD, Vauthey JN, Chun YS. Intrahepatic Recurrence Patterns Predict Survival After Resection of Colorectal Liver Metastases. Ann Surg Oncol 2018; 26:275-281. [DOI: 10.1245/s10434-018-6945-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Indexed: 12/15/2022]
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Madkhali A, Alalem F, Aljuhani G, Alsharaabi A, Alsaif F, Hassanain M. Preoperative Selection and Optimization for Liver Resection in Colorectal Cancer Liver Metastases. CURRENT COLORECTAL CANCER REPORTS 2018. [DOI: 10.1007/s11888-018-0405-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Yamashita S, Chun YS, Kopetz SE, Vauthey JN. Biomarkers in colorectal liver metastases. Br J Surg 2018; 105:618-627. [PMID: 29579319 DOI: 10.1002/bjs.10834] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Revised: 01/05/2018] [Accepted: 01/11/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND Despite a 5-year overall survival rate of 58 per cent after liver resection for colorectal liver metastases (CLMs), more than half of patients develop recurrence, highlighting the need for accurate risk stratification and prognostication. Traditional prognostic factors have been superseded by newer outcome predictors, including those defined by the molecular origin of the primary tumour. METHODS This review synthesized findings in the literature using the PubMed database of articles in the English language published between 1998 and 2017 on prognostic and predictive biomarkers in patients undergoing resection of CLMs. RESULTS Responses to preoperative chemotherapy define prognosis in patients undergoing CLM resection. There are differences by embryological origin too. Somatic mutations in the proto-oncogenes KRAS and NRAS are associated with positive surgical margins and tumour regrowth after ablation. Other mutations (such as BRAF) and co-occurring mutations in RAS/TP53 and APC/PIK3CA have emerged as important biomarkers that determine an individual patient's tumour biology and may be used to predict outcome after CLM resection. CONCLUSION Knowledge of somatic mutations can guide the use of preoperative therapy, extent of surgical margin and selection for ablation alone.
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Affiliation(s)
- S Yamashita
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Y S Chun
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - S E Kopetz
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - J-N Vauthey
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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SMAD4 gene mutation predicts poor prognosis in patients undergoing resection for colorectal liver metastases. Eur J Surg Oncol 2018; 44:684-692. [PMID: 29551247 DOI: 10.1016/j.ejso.2018.02.247] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Revised: 02/22/2018] [Accepted: 02/27/2018] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Dorsophilia protein, mothers against decapentaplegic homolog 4 (SMAD4) is a key mediator in the transforming growth factor (TGF)-β signaling pathway and SMAD4 gene mutations are thought to play a critical role in colorectal cancer (CRC) progression. However, little is known about its influence on survival in patients undergoing resection for colorectal liver metastases (CLM). METHODS Between 2005 and 2015, all patients with known SMAD4 mutation status who underwent resection of CLM were identified. Patients with SMAD4 mutation were compared to those with SMAD4 wild type. Next, the prognostic value of SMAD4 mutation was validated in a separate cohort of patients with synchronous stage IV CRC who underwent systemic therapy alone. RESULTS Of 278 patients, 37 (13%) were SMAD4 mutant while 241 (87%) were wild type. Overall survival (OS) after hepatic resection was worse in SMAD4-mutant patients compared to SMAD4 wild type (OS rate at 3 years, 62% vs. 82%; P < 0.0001). Independent predictors for worse OS were poor differentiation (hazard ratio [HR] 2.586; P = 0.007), multiple tumors (HR 1.970; P = 0.01), diameter greater than 3 cm (HR 1.752; P = 0.017), R1 margin status (HR 2.452; P = 0.014), RAS mutation (HR 2.044; P = 0.002), and SMAD4 mutation (HR 2.773; P < 0.0001). Among 237 patients in the validation cohort, SMAD4-mutations were significantly associated with worse 3-year OS rate (22% vs. 38%; P = 0.012) and was an independent predictor for worse OS (HR, 1.647; P = 0.032). CONCLUSION SMAD4 mutation is independently associated with worse outcomes among patients undergoing resection of CLM.
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10
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Mizuno T, Cloyd JM, Omichi K, Chun YS, Conrad C, Tzeng CWD, Wei SH, Aloia TA, Vauthey JN. Two-Stage Hepatectomy vs One-Stage Major Hepatectomy with Contralateral Resection or Ablation for Advanced Bilobar Colorectal Liver Metastases. J Am Coll Surg 2018; 226:825-834. [PMID: 29454099 DOI: 10.1016/j.jamcollsurg.2018.01.054] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Revised: 01/30/2018] [Accepted: 01/30/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Both 2-stage hepatectomy (TSH) and 1-stage hepatectomy (OSH) represent feasible strategies for resection of advanced bilobar colorectal liver metastases (CLM). However, the influence of the surgical approach on postoperative outcomes and overall survival (OS) is unknown. To define the optimal surgical approach for advanced bilobar CLM requiring right hemihepatectomy, we compared short-term and long-term outcomes after TSH and OSH with contralateral resection or radiofrequency ablation (RFA). STUDY DESIGN We retrospectively reviewed 227 patients with bilobar CLM, who underwent right or extended right hepatectomy with treatment of synchronous CLM in segments I, II, and/or III, between 1998 and 2015. Postoperative outcomes and OS were compared between patients who underwent TSH and those who underwent OSH. RESULTS Of the 227 patients, 126 (56%) underwent at least the first stage of TSH, and 101 (44%) underwent OSH, 29 (13%) without RFA and 72 (32%) with RFA. Two-stage hepatectomy was associated with a lower incidence of postoperative major complications (14% vs 26%, p = 0.03) and postoperative hepatic insufficiency (6% vs 20%, p = 0.001) than OSH. The 5-year OS rate was higher for patients assigned to TSH than for those who underwent OSH (35% vs 24%, p = 0.016). Patients who completed both stages of TSH had a higher 5-year OS rate than patients who underwent OSH without RFA (50% vs 20%, p = 0.023) or OSH with RFA (50% vs 24%, p < 0.0001). CONCLUSIONS In patients with advanced bilobar CLM, TSH is associated with fewer complications than OSH. Both TSH in intention-to-treat analysis and completed TSH in as-treated analysis were associated with better OS than OSH.
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Affiliation(s)
- Takashi Mizuno
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jordan M Cloyd
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Kiyohiko Omichi
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Yun Shin Chun
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Claudius Conrad
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Steven H Wei
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Thomas A Aloia
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
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Fonseca GM, Herman P, Faraj SF, Kruger JAP, Coelho FF, Jeismann VB, Cecconello I, Alves VAF, Pawlik TM, de Mello ES. Pathological factors and prognosis of resected liver metastases of colorectal carcinoma: implications and proposal for a pathological reporting protocol. Histopathology 2017; 72:377-390. [PMID: 28858385 DOI: 10.1111/his.13378] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Colorectal cancer is a leading cause of death worldwide. The liver is the most common site of distant metastases, and surgery is the only potentially curative treatment, although the recurrence rate following surgery is high. In order to define prognosis after surgery, many histopathological features have been identified in the primary tumour. In turn, pathologists routinely report specific findings to guide oncologists on the decision to recommend adjuvant therapy. In general, the pathological report of resected colorectal liver metastases is limited to confirmation of the malignancy and details regarding the margin status. Most pathological reports of a liver resection for colorectal liver metastasis lack information on other important features that have been reported to be independent prognostic factors. We herein review the evidence to support a more detailed pathological report of the resected liver specimen, with attention to: the number and size of liver metastases; margin size; the presence of lymphatic, vascular, perineural and biliary invasion; mucinous pattern; tumour growth pattern; the presence of a tumour pseudocapsule; and the pathological response to neoadjuvant chemotherapy. In addition, we propose a new protocol for the evaluation of colorectal liver metastasis resection specimens.
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Affiliation(s)
- Gilton M Fonseca
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo Medical School, São Paulo, Brazil
| | - Paulo Herman
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo Medical School, São Paulo, Brazil
| | - Sheila F Faraj
- Department of Pathology, São Paulo State Cancer Institute, University of São Paulo Medical School, São Paulo, Brazil
| | - Jaime A P Kruger
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo Medical School, São Paulo, Brazil
| | - Fabricio F Coelho
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo Medical School, São Paulo, Brazil
| | - Vagner B Jeismann
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo Medical School, São Paulo, Brazil
| | - Ivan Cecconello
- Digestive Surgery Division, Department of Gastroenterology, University of São Paulo Medical School, São Paulo, Brazil
| | - Venancio A F Alves
- Department of Pathology, São Paulo State Cancer Institute, University of São Paulo Medical School, São Paulo, Brazil
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Evandro S de Mello
- Department of Pathology, São Paulo State Cancer Institute, University of São Paulo Medical School, São Paulo, Brazil
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12
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Effect of KRAS and BRAF Mutations on Survival of Metastatic Colorectal Cancer After Liver Resection: A Systematic Review and Meta-Analysis. Clin Colorectal Cancer 2017; 16:e153-e163. [DOI: 10.1016/j.clcc.2017.01.004] [Citation(s) in RCA: 99] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2016] [Revised: 11/28/2016] [Accepted: 01/13/2017] [Indexed: 02/07/2023]
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13
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Duwe G, Knitter S, Pesthy S, Beierle AS, Bahra M, Schmelzle M, Schmuck RB, Lohneis P, Raschzok N, Öllinger R, Sinn M, Struecker B, Sauer IM, Pratschke J, Andreou A. Hepatotoxicity following systemic therapy for colorectal liver metastases and the impact of chemotherapy-associated liver injury on outcomes after curative liver resection. Eur J Surg Oncol 2017; 43:1668-1681. [PMID: 28599872 DOI: 10.1016/j.ejso.2017.05.008] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2017] [Revised: 05/05/2017] [Accepted: 05/08/2017] [Indexed: 02/08/2023] Open
Abstract
Patients with colorectal liver metastases (CLM) have remarkably benefited from the advances in medical multimodal treatment and surgical techniques over the last two decades leading to significant improvements in long-term survival. More patients are currently undergoing liver resection following neoadjuvant chemotherapy, which has been increasingly established within the framework of curative-indented treatment strategies. However, the use of several cytotoxic agents has been linked to specific liver injuries that not only impair the ability of liver tissue to regenerate but also decrease long-term survival. One of the most common agents included in modern chemotherapy regimens is oxaliplatin, which is considered to induce a parenchymal damage of the liver primarily involving the sinusoids defined as sinusoidal obstruction syndrome (SOS). Administration of bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF), has been reported to improve response of CLM to chemotherapy in clinical studies, concomitantly protecting the liver from the development of SOS. In this review, we aim to summarize current data on multimodal treatment concepts for CLM, give an in-depth overview of liver damage caused by cytostatic agents focusing on oxaliplatin-induced SOS, and evaluate the role of bevacizumab to improve clinical outcomes of patients with CLM and to protect the liver from the development of SOS.
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Affiliation(s)
- G Duwe
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - S Knitter
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - S Pesthy
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - A S Beierle
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - M Bahra
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - M Schmelzle
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - R B Schmuck
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - P Lohneis
- Institute of Pathology, Charité - Universitätsmedizin Berlin, Germany
| | - N Raschzok
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - R Öllinger
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - M Sinn
- Department of Hematology, Oncology and Tumor Immunology, Charité - Universitätsmedizin Berlin, Germany
| | - B Struecker
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - I M Sauer
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - J Pratschke
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany
| | - A Andreou
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Germany; Berlin School of Integrative Oncology, Charité - Universitätsmedizin Berlin, Germany.
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Torzilli G, Nagino M, Tzeng CWD, Kingham TP, Alatise OI, Ayandipo OO, Yamashita S, Arrington AK, Kim J, Chun YS, Vauthey JN. SSAT State-of-the-Art Conference: New Frontiers in Liver Surgery. J Gastrointest Surg 2017; 21:175-185. [PMID: 27480411 DOI: 10.1007/s11605-016-3193-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Accepted: 06/14/2016] [Indexed: 01/31/2023]
Affiliation(s)
- Guido Torzilli
- Department of Hepatobiliary and General Surgery, Humanitas Research Hospital, IRCCS, Humanitas University, Milan, Italy
| | - Masato Nagino
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Ching-Wei D Tzeng
- Department of Surgery, University of Kentucky College of Medicine, Lexington, KY, USA
| | - T Peter Kingham
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
| | | | | | - Suguru Yamashita
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1484, Houston, TX, 77030, USA
| | | | - Joseph Kim
- Division of Surgical Oncology, Department of Surgery, Stony Brook School of Medicine, Stony Brook, NY, USA
| | - Yun Shin Chun
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1484, Houston, TX, 77030, USA.
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1484, Houston, TX, 77030, USA
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Passot G, Denbo JW, Yamashita S, Kopetz SE, Chun YS, Maru D, Overman MJ, Brudvik KW, Conrad C, Aloia TA, Vauthey JN. Is hepatectomy justified for patients with RAS mutant colorectal liver metastases? An analysis of 524 patients undergoing curative liver resection. Surgery 2016; 161:332-340. [PMID: 27592215 DOI: 10.1016/j.surg.2016.07.032] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Revised: 06/24/2016] [Accepted: 07/18/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND RAS mutations are associated with limited overall survival after resection of colorectal liver metastases. Our aim was to determine criteria for considering hepatectomy for patients with RAS mutant colorectal liver metastases. METHODS Of 1,163 patients who underwent liver resection for colorectal liver metastases during 2005-2014, all patients operated on with curative intent who had known RAS mutation status were included. Factors associated with overall survival were determined using multivariate analysis. RESULTS A total of 524 patients met the inclusion criteria; 212 (40%) had mutated RAS. Mutations were located on codon 12 in 128 patients (60%) and codon 13 in 29 (14%). At median follow-up of 38 months, median overall survival was 72.6 months for wild-type RAS and 50.9 months for mutated RAS (P < .001). Median overall survival for patients with codon 12 and 13 mutations was 51.9 and 50.9 months, respectively (P = .839), significantly worse than for patients with wild-type RAS (P = .005, and P = .038 for codon 12 and 13, respectively). For patients with RAS mutation, factors associated independently with worse overall survival were node-positive primary tumor, tumor >3 cm, and >7 cycles of preoperative chemotherapy. Major and 2-stage hepatectomy were not associated independently with overall survival. Median overall survival was 57, 41, and 21.5 months for patients with 1, 2, and 3 risk factors, respectively. There were no 4-year survivors in the highest-risk group. CONCLUSION Patients with multiple risk factors had poor overall survival after curative resection of RAS mutant colorectal liver metastases. For such patients, hepatectomy may be ill advised, and alternative therapies or further systemic therapy should be considered.
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Affiliation(s)
- Guillaume Passot
- Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Jason W Denbo
- Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Suguru Yamashita
- Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Scott E Kopetz
- Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Yun S Chun
- Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Dipen Maru
- Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Michael J Overman
- Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | | | - Claudius Conrad
- Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Thomas A Aloia
- Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
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17
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Pinter M, Trauner M, Peck-Radosavljevic M, Sieghart W. Cancer and liver cirrhosis: implications on prognosis and management. ESMO Open 2016; 1:e000042. [PMID: 27843598 PMCID: PMC5070280 DOI: 10.1136/esmoopen-2016-000042] [Citation(s) in RCA: 196] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2016] [Accepted: 02/06/2016] [Indexed: 12/11/2022] Open
Abstract
Liver cirrhosis, the end-stage of every chronic liver disease, is not only the major risk factor for the development of hepatocellular carcinoma but also a limiting factor for anticancer therapy of liver and non-hepatic malignancies. Liver cirrhosis may limit surgical and interventional approaches to cancer treatment, influence pharmacokinetics of anticancer drugs, increase side effects of chemotherapy, render patients susceptible for hepatotoxicity, and ultimately result in a competitive risk for morbidity and mortality. In this review, we provide a concise overview about the impact of liver cirrhosis on the management and prognosis of patients with primary liver cancer or non-hepatic malignancies.
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Affiliation(s)
- Matthias Pinter
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Harvard Medical School & Massachusetts General Hospital, Boston, USA
| | - Michael Trauner
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III , Medical University of Vienna , Vienna , Austria
| | - Markus Peck-Radosavljevic
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Department of Gastroenterology & Hepatology, Endocrinology and Nephrology, Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria
| | - Wolfgang Sieghart
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Austrian Society of Gastroenterology & Hepatology, Working Group GI-Oncology
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18
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Passot G, Chun YS, Kopetz SE, Overman MJ, Conrad C, Aloia TA, Vauthey JN. Prognostic factors after resection of colorectal liver metastases following preoperative second-line chemotherapy: Impact of RAS mutations. Eur J Surg Oncol 2016; 42:1378-84. [PMID: 27358198 DOI: 10.1016/j.ejso.2016.02.249] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Accepted: 02/20/2016] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND After resection of colorectal liver metastases (CLM), RAS mutations are associated with modest survival benefit and second-line chemotherapy confers limited hope for cure. OBJECTIVE To evaluate the impact of RAS mutation after second-line chemotherapy for patients undergoing potentially curative liver resection for CLM. METHODS Among 1357 patients operated for CLM between January 2005 and November 2014, patients with known RAS mutational status were identified. Outcomes after second-line chemotherapy were analyzed by RAS status. RESULTS Among 635 patients undergoing resection of CLM, 46 received second-line chemotherapy before resection, including 14 patients (30%) with RAS mutations. Patients who received second-line chemotherapy had significantly larger and greater number of liver metastases and were more likely to undergo major hepatectomy. Median overall (OS) and recurrence free survival (RFS) were significantly worse among patients requiring second-line chemotherapy (OS: 44.4 vs. 61.1 months, p = 0.021; RFS: 7.3 vs. 12.0 months, p = 0.001). Among patients undergoing liver resection after second-line chemotherapy, RAS mutations were associated with worse median OS and RFS (OS: 35.2 vs. 60.7 months, p = 0.038; RFS: 3.6 vs. 8.3 months, p = 0.015). RAS mutation was the only independent factor associated with OS and RFS. All patients with RAS mutations recurred within 18 months. Among patients with RAS wild-type tumors, the receipt of second-line chemotherapy did not affect OS (p = 0.493). CONCLUSION Among patients undergoing resection of CLM after second-line chemotherapy, RAS mutational status is an independent predictor of survival and outweighs other factors to select patients for liver resection.
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Affiliation(s)
- G Passot
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, USA
| | - Y S Chun
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, USA
| | - S E Kopetz
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, USA
| | - M J Overman
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, USA
| | - C Conrad
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, USA
| | - T A Aloia
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, USA
| | - J-N Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, USA.
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Passot G, Chun YS, Kopetz SE, Zorzi D, Brudvik KW, Kim BJ, Conrad C, Aloia TA, Vauthey JN. Predictors of Safety and Efficacy of 2-Stage Hepatectomy for Bilateral Colorectal Liver Metastases. J Am Coll Surg 2016; 223:99-108. [PMID: 26968325 DOI: 10.1016/j.jamcollsurg.2015.12.057] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Revised: 12/14/2015] [Accepted: 12/14/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND In patients with bilateral colorectal liver metastases (CLM) not resectable in 1 operation, 2-stage hepatectomy is the standard surgical approach. The objective of this study was to determine factors associated with safety and efficacy of 2-stage hepatectomy. STUDY DESIGN The study included all 109 patients for whom 2-stage hepatectomy for CLM was planned during 2003 to 2014. The RAS mutation status and other clinicopathologic factors were evaluated for association with major complications and survival using multivariate analysis. RESULTS Two-stage hepatectomy was completed in 89 of 109 patients (82%). Reasons for dropout after the first stage were disease progression (n = 12), insufficient liver growth (n = 5), and complications after first stage or portal vein embolization (n = 3). More than 6 cycles of preoperative chemotherapy were associated with failure to proceed to the second stage (p = 0.009). Rates of major complications (26% vs 6%; p < 0.001) and 90-day mortality (7% vs 0%; p = 0.006) were higher after the second stage. The cumulative rate of major complications was 15% (n = 29). Factors independently associated with major complications were rectal primary tumor, metachronous CLM, and more than 1 lesion resected at first stage. At median follow-up of 29.5 months, 3-year (68% vs 6%; p < 0.001) and 5-year overall survival rates (49% vs 0%; p < 0.001) were better after 2-stage hepatectomy completion than noncompletion. Factors independently associated with poor overall survival were rectal primary tumor (p = 0.044), more than 5 CLMs (p = 0.043), need for chemotherapy after first stage (p = 0.046), and RAS mutation (p < 0.001). CONCLUSIONS The RAS mutation independently predicts the oncologic efficacy of 2-stage hepatectomy and may help guide patient selection for this aggressive surgical strategy.
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Affiliation(s)
- Guillaume Passot
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Yun Shin Chun
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Scott E Kopetz
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Daria Zorzi
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | | | - Bradford J Kim
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Claudius Conrad
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Thomas A Aloia
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
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20
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Wei SH, Samp LA. Surgical Management of Colorectal Liver Metastases: Prognostic Indicators and the Impact of RAS Mutation Status. J Adv Pract Oncol 2015; 6:460-6. [PMID: 27069738 PMCID: PMC4803463 DOI: 10.6004/jadpro.2015.6.5.6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
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Semrad TJ, Fahrni AR, Gong IY, Khatri VP. Integrating Chemotherapy into the Management of Oligometastatic Colorectal Cancer: Evidence-Based Approach Using Clinical Trial Findings. Ann Surg Oncol 2015; 22 Suppl 3:S855-62. [PMID: 26100816 DOI: 10.1245/s10434-015-4610-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2015] [Indexed: 01/04/2023]
Abstract
BACKGROUND This study used case reports to review the role of systemic chemotherapy in oligometastatic colorectal cancer (CRC) and to suggest ways to integrate clinical research findings into the interdisciplinary management of this potentially curable subset of patients. METHODS This educational review discusses the role of chemotherapy in the management of oligometastatic metastatic CRC. RESULTS In initially resectable oligometastatic CRC, the goal of chemotherapy is to eradicate micrometastatic disease. Perioperative 5-fluorouracil and oxaliplatin together with surgical resection can result in 5-year survival rates as high as 57 %. With the development of increasingly successful chemotherapy regimens, attention is being paid to chemotherapy used to convert patients with initially unresectable metastasis to patients with a chance of surgical cure. The choice of chemotherapy regimen requires consideration of the goals for therapy and assessment of both tumor- and patient-specific factors. CONCLUSION This report discusses the choice and timing of chemotherapy in patients with initially resectable and borderline resectable metastatic CRC. Coordinated multidisciplinary care of such patients can optimize survival outcomes and result in cure for patients with this otherwise lethal disease.
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Affiliation(s)
- Thomas J Semrad
- Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA
| | | | - I-Yeh Gong
- Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA
| | - Vijay P Khatri
- Division of Surgical Oncology, Department of Surgery, University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA.
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Zimmitti G, Shindoh J, Mise Y, Kopetz S, Loyer EM, Andreou A, Cooper AB, Kaur H, Aloia TA, Maru DM, Vauthey JN. RAS mutations predict radiologic and pathologic response in patients treated with chemotherapy before resection of colorectal liver metastases. Ann Surg Oncol 2015; 22:834-842. [PMID: 25227306 PMCID: PMC4318708 DOI: 10.1245/s10434-014-4042-6] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND RAS mutations have been reported to be a potential prognostic factor in patients with colorectal liver metastases (CLM). However, the impact of RAS mutations on response to chemotherapy remains unclear. The purpose of this study was to investigate the correlation between RAS mutations and response to preoperative chemotherapy and their impact on survival in patients undergoing curative resection of CLM. METHODS RAS mutational status was assessed and its relation to morphologic response and pathologic response was investigated in 184 patients meeting inclusion criteria. Predictors of survival were assessed. The prognostic impact of RAS mutational status was then analyzed using two different multivariate models, including either radiologic morphologic response (model 1) or pathologic response (model 2). RESULTS Optimal morphologic response and major pathologic response were more common in patients with wild-type RAS (32.9 and 58.9%, respectively) than in patients with RAS mutations (10.5 and 36.8%; P = 0.006 and 0.015, respectively). Multivariate analysis confirmed that wild-type RAS was a strong predictor of optimal morphologic response [odds ratio (OR), 4.38; 95% CI 1.45-13.15] and major pathologic response (OR, 2.61; 95% CI 1.17-5.80). RAS mutations were independently correlated with both overall survival and recurrence free-survival (hazard ratios, 3.57 and 2.30, respectively, in model 1, and 3.19 and 2.09, respectively, in model 2). Subanalysis revealed that RAS mutational status clearly stratified survival in patients with inadequate response to preoperative chemotherapy. CONCLUSIONS RAS mutational status can be used to complement the current prognostic indicators for patients undergoing curative resection of CLM after preoperative modern chemotherapy.
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Affiliation(s)
- Giuseppe Zimmitti
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030
| | - Junichi Shindoh
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030
| | - Yoshihiro Mise
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030
| | - Scott Kopetz
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030
| | - Evelyne M. Loyer
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030
| | - Andreas Andreou
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030
| | - Amanda B. Cooper
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030
| | - Harmeet Kaur
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030
| | - Thomas A. Aloia
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030
| | - Dipen M. Maru
- Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030
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Shindoh J, Zimmitti G, Vauthey JN. Management of Liver Metastases from Colorectal Cancer. Surg Oncol 2015. [DOI: 10.1007/978-1-4939-1423-4_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Zendel A, Lahat E, Dreznik Y, Zakai BB, Eshkenazy R, Ariche A. "Vanishing liver metastases"-A real challenge for liver surgeons. Hepatobiliary Surg Nutr 2014; 3:295-302. [PMID: 25392841 DOI: 10.3978/j.issn.2304-3881.2014.09.13] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2014] [Accepted: 09/16/2014] [Indexed: 12/21/2022]
Abstract
Expanded surgical intervention in colorectal liver metastasis (LM) and improved chemotherapy led to increasing problem of disappearing liver metastases (DLM). Treatment of those continues to evolve and poses a real challenge for HPB surgeons. This review discusses a clinical approach to DLM, emphasizing crucial steps in clinical algorithm. Particular issues such as imaging, intraoperative detection and surgical techniques are addressed. A step-by-step algorithm is suggested.
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Affiliation(s)
- Alex Zendel
- 1 Department of Surgery C, 2 Department of Surgery B, 3 Department of HPB Surgery, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Eylon Lahat
- 1 Department of Surgery C, 2 Department of Surgery B, 3 Department of HPB Surgery, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Yael Dreznik
- 1 Department of Surgery C, 2 Department of Surgery B, 3 Department of HPB Surgery, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Barak Bar Zakai
- 1 Department of Surgery C, 2 Department of Surgery B, 3 Department of HPB Surgery, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Rony Eshkenazy
- 1 Department of Surgery C, 2 Department of Surgery B, 3 Department of HPB Surgery, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Arie Ariche
- 1 Department of Surgery C, 2 Department of Surgery B, 3 Department of HPB Surgery, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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Aloia TA, Zimmitti G, Conrad C, Gottumukalla V, Kopetz S, Vauthey JN. Return to intended oncologic treatment (RIOT): a novel metric for evaluating the quality of oncosurgical therapy for malignancy. J Surg Oncol 2014; 110:107-114. [PMID: 24846705 PMCID: PMC5527828 DOI: 10.1002/jso.23626] [Citation(s) in RCA: 138] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2014] [Accepted: 03/17/2014] [Indexed: 12/25/2022]
Abstract
BACKGROUND After cancer surgery, complications, and disability prevent some patients from receiving subsequent treatments. Given that an inability to complete all intended cancer therapies might negate the oncologic benefits of surgical therapy, strategies to improve return to intended oncologic treatment (RIOT), including minimally invasive surgery (MIS), are being investigated. METHODS This project was designed to evaluate liver tumor patients to determine the RIOT rate, risk factors for inability to RIOT, and its impact on survivals. Outcomes for a homogenous cohort of 223 patients who underwent open-approach surgery for metachronous colorectal liver metastases and a group of 27 liver tumor patients treated with MIS hepatectomy were examined. RESULTS Of the 223 open-approach patients, 167 were offered postoperative therapy, yielding a RIOT rate of 75%. The remaining 56 (25%) patients were unable to receive further treatment due to surgical complications (n = 29 pts) or poor performance status (n = 27 pts). Risk factors associated with inability to RIOT were hypertension (OR 2.2, P = 0.025), multiple preoperative chemotherapy regimens (OR 5.9, P = 0.039), and postoperative complications (OR 2.0, P = 0.039). Inability to RIOT correlated with shorter disease-free and overall survivals (P < 0.001, HR = 2.16; and P = 0.005, HR = 2.07, respectively). In contrast to the open surgery group, 100% of MIS patients who were intended to initiate postoperative therapy did so (P = 0.038) within a shorter median time interval (MIS: 15 days vs. open: 42 days; P < 0.001). CONCLUSIONS The relationship between RIOT and long-term oncologic outcomes suggests that RIOT rates for both open- and MIS-approach cancer surgery should routinely be reported as a quality indicator.
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Affiliation(s)
- Thomas A. Aloia
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Herman Pressler, Unit 1484, Houston, Texas 77030
| | - Giuseppe Zimmitti
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Herman Pressler, Unit 1484, Houston, Texas 77030
| | - Claudius Conrad
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Herman Pressler, Unit 1484, Houston, Texas 77030
| | - Vijaya Gottumukalla
- Department of Anesthesia, The University of Texas MD Anderson Cancer Center, 1400 Herman Pressler, Unit 1484, Houston, Texas 77030
| | - Scott Kopetz
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Herman Pressler, Unit 1484, Houston, Texas 77030
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Herman Pressler, Unit 1484, Houston, Texas 77030
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Vauthey JN, Zimmitti G, Kopetz SE, Shindoh J, Chen SS, Andreou A, Curley SA, Aloia TA, Maru DM. RAS mutation status predicts survival and patterns of recurrence in patients undergoing hepatectomy for colorectal liver metastases. Ann Surg 2013; 258:619-627. [PMID: 24018645 PMCID: PMC3856211 DOI: 10.1097/sla.0b013e3182a5025a] [Citation(s) in RCA: 286] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To determine the impact of RAS mutation status on survival and patterns of recurrence in patients undergoing curative resection of colorectal liver metastases (CLM) after preoperative modern chemotherapy. BACKGROUND RAS mutation has been reported to be associated with aggressive tumor biology. However, the effect of RAS mutation on survival and patterns of recurrence after resection of CLM remains unclear. METHODS Somatic mutations were analyzed using mass spectroscopy in 193 patients who underwent single-regimen modern chemotherapy before resection of CLM. The relationship between RAS mutation status and survival outcomes was investigated. RESULTS Detected somatic mutations included RAS (KRAS/NRAS) in 34 (18%), PIK3CA in 13 (7%), and BRAF in 2 (1%) patients. At a median follow-up of 33 months, 3-year overall survival (OS) rates were 81% in patients with wild-type versus 52.2% in patients with mutant RAS (P = 0.002); 3-year recurrence-free survival (RFS) rates were 33.5% with wild-type versus 13.5% with mutant RAS (P = 0.001). Liver and lung recurrences were observed in 89 and 83 patients, respectively. Patients with RAS mutation had a lower 3-year lung RFS rate (34.6% vs 59.3%, P < 0.001) but not a lower 3-year liver RFS rate (43.8% vs 50.2%, P = 0.181). In multivariate analyses, RAS mutation predicted worse OS [hazard ratio (HR) = 2.3, P = 0.002), overall RFS (HR = 1.9, P = 0.005), and lung RFS (HR = 2.0, P = 0.01), but not liver RFS (P = 0.181). CONCLUSIONS RAS mutation predicts early lung recurrence and worse survival after curative resection of CLM. This information may be used to individualize systemic and local tumor-directed therapies and follow-up strategies.
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Affiliation(s)
- Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515, Holcombe Boulevard, Houston, Texas 77030
| | - Giuseppe Zimmitti
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515, Holcombe Boulevard, Houston, Texas 77030
| | - Scott E. Kopetz
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515, Holcombe Boulevard, Houston, Texas 77030
| | - Junichi Shindoh
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515, Holcombe Boulevard, Houston, Texas 77030
| | - Su S. Chen
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515, Holcombe Boulevard, Houston, Texas 77030
| | - Andreas Andreou
- Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515, Holcombe Boulevard, Houston, Texas 77030
| | - Steven A. Curley
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515, Holcombe Boulevard, Houston, Texas 77030
| | - Thomas A. Aloia
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515, Holcombe Boulevard, Houston, Texas 77030
| | - Dipen M. Maru
- Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515, Holcombe Boulevard, Houston, Texas 77030
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Maor Y, Malnick S. Liver injury induced by anticancer chemotherapy and radiation therapy. Int J Hepatol 2013; 2013:815105. [PMID: 23970972 PMCID: PMC3732607 DOI: 10.1155/2013/815105] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2012] [Accepted: 05/03/2013] [Indexed: 12/12/2022] Open
Abstract
Cytotoxic chemotherapy prolongs survival of patients with advanced and metastatic tumors. This is, however, a double-edged sword with many adverse effects. Since the liver has a rich blood supply and plays an active role in the metabolism of medications, it is not surprising that there can be hepatic injury related to chemotherapy. In addition, radioembolization may affect the parenchyma of normal and cirrhotic livers. We review chemotherapy-associated liver injury in patients with colorectal liver metastases, including downsizing chemotherapy and neoadjuvant chemotherapy. We discuss the mechanism of the hepatic injury, secondary to reactive oxygen species, and the spectrum of hepatic injury including, steatosis, steatohepatitis, hepatic sinusoidal injury and highlight the pharmacogenomics of such liver insults. Methods for reducing and treating the hepatotoxicity are discussed for specific agents including tamxifen and the newly introduced targeted antibodies.
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Affiliation(s)
- Y. Maor
- Department of Gastroenterology and Hepatology, Sheba Medical Center, 52621 Tel-Hashomer, Israel
| | - S. Malnick
- Department of Internal Medicine C, Kaplan Medical Center, The Hebrew University of Jerusalem, 76100 Rehovot, Israel
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Lu QY, Zhao AL, Deng W, Li ZW, Shen L. Hepatic histopathology and postoperative outcome after preoperative chemotherapy for Chinese patients with colorectal liver metastases. World J Gastrointest Surg 2013; 5:30-6. [PMID: 23556058 PMCID: PMC3615301 DOI: 10.4240/wjgs.v5.i3.30] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2012] [Revised: 10/03/2012] [Accepted: 12/20/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the effects of preoperative treatment on the hepatic histology of non-tumoral liver and the postoperative outcome.
METHODS: One hundred and six patients underwent hepatic resection for colorectal metastases between 1999 and 2009. The surgical specimens were reviewed with established criteria for diagnosis and grading of pathological hepatic injury. The impact of preoperative therapy on liver injury and postoperative outcome was analyzed.
RESULTS: Fifty-three patients (50%) received surgery alone, whereas 42 patients (39.6%) received neoadjuvant chemotherapy and 11 (10.4%) patients received preoperative hepatic artery infusion (HAI). Chemotherapy included oxaliplatin-based regimens (31.1%) and irinotecan-based regimens (8.5%). On histopathological analysis, 16 patients (15.1%) had steatosis, 31 (29.2%) had sinusoidal dilation and 20 patients (18.9%) had steatohepatitis. Preoperative oxaliplatin was associated with sinusoidal dilation compared with surgery alone (42.4% vs 20.8%, P = 0.03); however, the perioperative complication rate was not significantly different between the oxaliplatin group and surgery group (27.3% vs 13.2%, P = 0.1). HAI was associated with more steatosis, sinusoidal dilation and steatohepatitis than the surgery group, with higher perioperative morbidity (36.4% vs 13.2%, P = 0.06) and mortality (9.1% vs 0% P = 0.02).
CONCLUSION: Preoperative oxaliplatin was associated with sinusoidal dilation compared with surgery alone. However, the preoperative oxaliplatin had no significant impact on perioperative outcomes. HAI can cause pathological changes and tends to increase perioperative morbidity and mortality.
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Affiliation(s)
- Qi-Ying Lu
- Qi-Ying Lu, Wei Deng, Lin Shen, Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital and Institute, Beijing 100142, China
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Shindoh J, Loyer EM, Kopetz S, Boonsirikamchai P, Maru DM, Chun YS, Zimmitti G, Curley SA, Charnsangavej C, Aloia TA, Vauthey JN. Optimal morphologic response to preoperative chemotherapy: an alternate outcome end point before resection of hepatic colorectal metastases. J Clin Oncol 2012; 30:4566-4572. [PMID: 23150701 PMCID: PMC3518730 DOI: 10.1200/jco.2012.45.2854] [Citation(s) in RCA: 162] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2012] [Accepted: 09/17/2012] [Indexed: 12/11/2022] Open
Abstract
PURPOSE The purposes of this study were to confirm the prognostic value of an optimal morphologic response to preoperative chemotherapy in patients undergoing chemotherapy with or without bevacizumab before resection of colorectal liver metastases (CLM) and to identify predictors of the optimal morphologic response. PATIENTS AND METHODS The study included 209 patients who underwent resection of CLM after preoperative chemotherapy with oxaliplatin- or irinotecan-based regimens with or without bevacizumab. Radiologic responses were classified as optimal or suboptimal according to the morphologic response criteria. Overall survival (OS) was determined, and prognostic factors associated with an optimal response were identified in multivariate analysis. RESULTS An optimal morphologic response was observed in 47% of patients treated with bevacizumab and 12% of patients treated without bevacizumab (P < .001). The 3- and 5-year OS rates were higher in the optimal response group (82% and 74%, respectively) compared with the suboptimal response group (60% and 45%, respectively; P < .001). On multivariate analysis, suboptimal morphologic response was an independent predictor of worse OS (hazard ratio, 2.09; P = .007). Receipt of bevacizumab (odds ratio, 6.71; P < .001) and largest metastasis before chemotherapy of ≤ 3 cm (odds ratio, 2.12; P = .025) were significantly associated with optimal morphologic response. The morphologic response showed no specific correlation with conventional size-based RECIST criteria, and it was superior to RECIST in predicting major pathologic response. CONCLUSION Independent of preoperative chemotherapy regimen, optimal morphologic response is sufficiently correlated with OS to be considered a surrogate therapeutic end point for patients with CLM.
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Affiliation(s)
- Junichi Shindoh
- Junichi Shindoh, Evelyne M. Loyer, Scott Kopetz, Piyaporn Boonsirikamchai, Dipen M. Maru, Giuseppe Zimmitti, Steven A. Curley, Chusilp Charnsangavej, Thomas A. Aloia, and Jean-Nicolas Vauthey, The University of Texas MD Anderson Cancer Center, Houston, TX; Yun Shin Chun, Fox Chase Cancer Center, Philadelphia, PA
| | - Evelyne M. Loyer
- Junichi Shindoh, Evelyne M. Loyer, Scott Kopetz, Piyaporn Boonsirikamchai, Dipen M. Maru, Giuseppe Zimmitti, Steven A. Curley, Chusilp Charnsangavej, Thomas A. Aloia, and Jean-Nicolas Vauthey, The University of Texas MD Anderson Cancer Center, Houston, TX; Yun Shin Chun, Fox Chase Cancer Center, Philadelphia, PA
| | - Scott Kopetz
- Junichi Shindoh, Evelyne M. Loyer, Scott Kopetz, Piyaporn Boonsirikamchai, Dipen M. Maru, Giuseppe Zimmitti, Steven A. Curley, Chusilp Charnsangavej, Thomas A. Aloia, and Jean-Nicolas Vauthey, The University of Texas MD Anderson Cancer Center, Houston, TX; Yun Shin Chun, Fox Chase Cancer Center, Philadelphia, PA
| | - Piyaporn Boonsirikamchai
- Junichi Shindoh, Evelyne M. Loyer, Scott Kopetz, Piyaporn Boonsirikamchai, Dipen M. Maru, Giuseppe Zimmitti, Steven A. Curley, Chusilp Charnsangavej, Thomas A. Aloia, and Jean-Nicolas Vauthey, The University of Texas MD Anderson Cancer Center, Houston, TX; Yun Shin Chun, Fox Chase Cancer Center, Philadelphia, PA
| | - Dipen M. Maru
- Junichi Shindoh, Evelyne M. Loyer, Scott Kopetz, Piyaporn Boonsirikamchai, Dipen M. Maru, Giuseppe Zimmitti, Steven A. Curley, Chusilp Charnsangavej, Thomas A. Aloia, and Jean-Nicolas Vauthey, The University of Texas MD Anderson Cancer Center, Houston, TX; Yun Shin Chun, Fox Chase Cancer Center, Philadelphia, PA
| | - Yun Shin Chun
- Junichi Shindoh, Evelyne M. Loyer, Scott Kopetz, Piyaporn Boonsirikamchai, Dipen M. Maru, Giuseppe Zimmitti, Steven A. Curley, Chusilp Charnsangavej, Thomas A. Aloia, and Jean-Nicolas Vauthey, The University of Texas MD Anderson Cancer Center, Houston, TX; Yun Shin Chun, Fox Chase Cancer Center, Philadelphia, PA
| | - Giuseppe Zimmitti
- Junichi Shindoh, Evelyne M. Loyer, Scott Kopetz, Piyaporn Boonsirikamchai, Dipen M. Maru, Giuseppe Zimmitti, Steven A. Curley, Chusilp Charnsangavej, Thomas A. Aloia, and Jean-Nicolas Vauthey, The University of Texas MD Anderson Cancer Center, Houston, TX; Yun Shin Chun, Fox Chase Cancer Center, Philadelphia, PA
| | - Steven A. Curley
- Junichi Shindoh, Evelyne M. Loyer, Scott Kopetz, Piyaporn Boonsirikamchai, Dipen M. Maru, Giuseppe Zimmitti, Steven A. Curley, Chusilp Charnsangavej, Thomas A. Aloia, and Jean-Nicolas Vauthey, The University of Texas MD Anderson Cancer Center, Houston, TX; Yun Shin Chun, Fox Chase Cancer Center, Philadelphia, PA
| | - Chusilp Charnsangavej
- Junichi Shindoh, Evelyne M. Loyer, Scott Kopetz, Piyaporn Boonsirikamchai, Dipen M. Maru, Giuseppe Zimmitti, Steven A. Curley, Chusilp Charnsangavej, Thomas A. Aloia, and Jean-Nicolas Vauthey, The University of Texas MD Anderson Cancer Center, Houston, TX; Yun Shin Chun, Fox Chase Cancer Center, Philadelphia, PA
| | - Thomas A. Aloia
- Junichi Shindoh, Evelyne M. Loyer, Scott Kopetz, Piyaporn Boonsirikamchai, Dipen M. Maru, Giuseppe Zimmitti, Steven A. Curley, Chusilp Charnsangavej, Thomas A. Aloia, and Jean-Nicolas Vauthey, The University of Texas MD Anderson Cancer Center, Houston, TX; Yun Shin Chun, Fox Chase Cancer Center, Philadelphia, PA
| | - Jean-Nicolas Vauthey
- Junichi Shindoh, Evelyne M. Loyer, Scott Kopetz, Piyaporn Boonsirikamchai, Dipen M. Maru, Giuseppe Zimmitti, Steven A. Curley, Chusilp Charnsangavej, Thomas A. Aloia, and Jean-Nicolas Vauthey, The University of Texas MD Anderson Cancer Center, Houston, TX; Yun Shin Chun, Fox Chase Cancer Center, Philadelphia, PA
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Abstract
Surgical resection of liver metastases of colorectal cancer can improve clinical outcome and even cure some patients with metastatic disease. For patients with unresectable liver metastases, the ultimate treatment goal is to let them become eligible for resection. In recent years, considerable attention has been paid to molecular targeted therapies to improve the efficacy of the available chemotherapeutic regimens in order to increase the downsizing rate of liver metastases and increase resectability. This overview will focus on the oncological management and chemotherapeutic options of patients with unresectable liver metastases.
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Affiliation(s)
- Hans Prenen
- Department of Gastroenterology, Digestive Oncology Unit, University Hospitals Leuven, Leuven, Belgium.
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31
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Fowler KJ, Linehan DC, Menias CO. Colorectal liver metastases: state of the art imaging. Ann Surg Oncol 2012; 20:1185-93. [PMID: 23115006 DOI: 10.1245/s10434-012-2730-7] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2012] [Indexed: 12/14/2022]
Abstract
Colorectal cancer is a leading cause of death with mortality determined predominately by metastatic involvement of the liver. Treatment of liver metastases continues to evolve and imaging plays an essential role in initial staging, preoperative planning, and treatment monitoring. This review article discusses the current role of imaging in the management of patients with colorectal liver metastases. Particular challenges such as hepatic steatosis, disappearing metastases, and following treated lesions are addressed.
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32
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Pilgrim CHC, Satgunaseelan L, Pham A, Murray W, Link E, Smith M, Usatoff V, Evans PM, Banting S, Thomson BN, Phillips WA, Michael M. Correlations between histopathological diagnosis of chemotherapy-induced hepatic injury, clinical features, and perioperative morbidity. HPB (Oxford) 2012; 14:333-40. [PMID: 22487071 PMCID: PMC3384853 DOI: 10.1111/j.1477-2574.2012.00454.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Chemotherapy has in some series been linked with increased morbidity after a hepatectomy. Hepatic injuries may result from the treatment with chemotherapy, but can also be secondary to co-morbid diseases. The aim of the present study was to draw correlations between clinical features, treatment with chemotherapy and injury phenotypes and assess the impact of each upon perioperative morbidity. PATIENTS AND METHODS Retrospective samples (n= 232) were scored grading steatosis, steatohepatitis and sinusoidal injury (SI). Clinical data were retrieved from medical records. Correlations were drawn between injury, clinical features and perioperative morbidity. RESULTS Injury rates were 18%, 4% and 19% for steatosis, steatohepatitis and SI, respectively. High-grade steatosis was more common in patients with diabetes [odds ratio (OR) = 3.33, P= 0.01] and patients with a higher weight (OR/kg = 1.04, P= 0.02). Steatohepatitis was increased with metabolic syndrome (OR = 5.88, P= 0.02). Chemotherapy overall demonstrated a trend towards an approximately doubled risk of high-grade steatosis and steatohepatitis although not affecting SI. However, pre-operative chemotherapy was associated with an increased SI (OR = 2.18, P= 0.05). Operative morbidity was not increased with chemotherapy, but was increased with steatosis (OR = 2.38, P= 0.02). CONCLUSIONS Diabetes and higher weight significantly increased the risk of steatosis, whereas metabolic syndrome significantly increased risk of steatohepatitis. The presence of high-grade steatosis increases perioperative morbidity, not administration of chemotherapy per se.
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Affiliation(s)
- Charles HC Pilgrim
- Division of Cancer Surgery, University of Melbourne, St. Vincent's HospitalMelbourne,Department of Surgery, University of Melbourne, St. Vincent's HospitalMelbourne,Hepatopancreaticobiliary Service, Upper Gastrointestinal Surgery, The Alfred HospitalMelbourne, Australia
| | - Laveniya Satgunaseelan
- Hepatopancreaticobiliary Service, Upper Gastrointestinal Surgery, The Alfred HospitalMelbourne, Australia
| | - Alan Pham
- Department of Pathology, The Alfred HospitalMelbourne, Australia
| | - William Murray
- Department of Pathology, University of Melbourne, St. Vincent's HospitalMelbourne
| | - Emma Link
- Centre for Biostatistics and Clinical Trials, University of Melbourne, St. Vincent's HospitalMelbourne
| | - Marty Smith
- Hepatopancreaticobiliary Service, Upper Gastrointestinal Surgery, The Alfred HospitalMelbourne, Australia
| | - Val Usatoff
- Hepatopancreaticobiliary Service, Upper Gastrointestinal Surgery, The Alfred HospitalMelbourne, Australia
| | - Peter M Evans
- Hepatopancreaticobiliary Service, Upper Gastrointestinal Surgery, The Alfred HospitalMelbourne, Australia
| | - Simon Banting
- Division of Cancer Surgery, University of Melbourne, St. Vincent's HospitalMelbourne,Department of Surgery, University of Melbourne, St. Vincent's HospitalMelbourne
| | - Benjamin N Thomson
- Division of Cancer Surgery, University of Melbourne, St. Vincent's HospitalMelbourne
| | - Wayne A Phillips
- Division of Cancer Surgery, University of Melbourne, St. Vincent's HospitalMelbourne,Department of Surgery, University of Melbourne, St. Vincent's HospitalMelbourne
| | - Michael Michael
- Division of Cancer Medicine, Peter MacCallum Cancer Centre, University of Melbourne, St. Vincent's HospitalMelbourne,Department of Medicine, University of Melbourne, St. Vincent's HospitalMelbourne
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33
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Brouquet A, Overman MJ, Kopetz S, Maru DM, Loyer EM, Andreou A, Cooper A, Curley SA, Garrett CR, Abdalla EK, Vauthey JN. Is resection of colorectal liver metastases after a second-line chemotherapy regimen justified? Cancer 2011; 117:4484-92. [PMID: 21446046 PMCID: PMC3128184 DOI: 10.1002/cncr.26036] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2010] [Revised: 11/22/2010] [Accepted: 01/03/2011] [Indexed: 12/29/2022]
Abstract
BACKGROUND Patient outcomes following resection of colorectal liver metastases (CLM) after second-line chemotherapy regimen is unknown. METHODS From August 1998 to June 2009, data from 1099 patients with CLM were collected prospectively. We retrospectively analyzed outcomes of patients who underwent resection of CLM after second-line (2 or more) chemotherapy regimens. RESULTS Sixty patients underwent resection of CLM after 2 or more chemotherapy regimens. Patients had advanced CLM (mean number of CLM ± standard deviation, 4 ± 3.5; mean maximum size of CLM, 5 ± 3.2 cm) and had received 17 ± 8 cycles of preoperative chemotherapy. In 54 (90%) patients, the switch from the first regimen to another regimen was motivated by tumor progression or suboptimal radiographic response. All patients received irinotecan or oxaliplatin, and the majority (42/60 [70%]) received a monoclonal antibody (bevacizumab or cetuximab) as part of the last preoperative regimen. Postoperative morbidity and mortality rates were 33% and 3%, respectively. At a median follow-up of 32 months, 1-year, 3-year, and 5-year overall survival rates were 83%, 41%, and 22%, respectively. Median chemotherapy-free survival after resection or completion of additional chemotherapy administered after resection was 9 months (95% confidence interval, 4-14 months). Synchronous (vs metachronous) CLM and minor (vs major) pathologic response were independently associated with worse survival. CONCLUSIONS Resection of CLM after a second-line chemotherapy regimen was found to be safe and was associated with a modest hope for definitive cure. This approach represents a viable option in patients with advanced CLM.
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Affiliation(s)
- Antoine Brouquet
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
| | - Michael J. Overman
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
| | - Scott Kopetz
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
| | - Dipen M. Maru
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
| | - Evelyne M. Loyer
- Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
| | - Andreas Andreou
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
| | - Amanda Cooper
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
| | - Steven A. Curley
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
| | - Christopher R. Garrett
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
| | - Eddie K. Abdalla
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
| | - Jean Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030
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Tanaka K, Ichikawa Y, Endo I. Liver resection for advanced or aggressive colorectal cancer metastases in the era of effective chemotherapy: a review. Int J Clin Oncol 2011; 16:452-63. [PMID: 21786210 DOI: 10.1007/s10147-011-0291-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2011] [Indexed: 02/06/2023]
Abstract
Liver surgery has been known to cure metastatic colorectal cancer in a small proportion of patients. However, advances in procedural technique and chemotherapy now allow more patients to have safe, potentially curative surgery. Here we review surgery for unresectable colorectal liver metastases using an expert multidisciplinary approach. With multidisciplinary management of patients with effective chemotherapy that can downstage metastases, more patients with previously inoperable disease can benefit from surgery. Portal vein embolization results in hypertrophy of the future liver remnant; on occasions, combining embolization with staged liver resection permits potentially curative surgery for patients previously unable to survive resection. However, increasing use of chemotherapy has raised awareness of potential hepatotoxicity and other deleterious effects of cytotoxic agents. Prolonged prehepatectomy chemotherapy therefore can reduce resectability even using a 2-stage procedure. Suitable timing of surgery for unresectable liver metastases during chemotherapy is critical. Because of advances in chemotherapy, colorectal cancer, like ovarian cancer, can now show survival benefit from maximum surgical debulking. Benefit from such maximum hepatic debulking surgery for metastatic colorectal disease is uncertain, but likely. Surgery in isolation may be approaching technical limits, but is now likely to help more patients because of the success of complementary strategies, particularly newer chemotherapy and targeted therapy. Expert individualized multidisciplinary treatment planning and problem-solving is essential.
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Affiliation(s)
- Kuniya Tanaka
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
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35
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Brouquet A, Vauthey JN, Contreras CM, Walsh GL, Vaporciyan AA, Swisher SG, Curley SA, Mehran RJ, Abdalla EK. Improved survival after resection of liver and lung colorectal metastases compared with liver-only metastases: a study of 112 patients with limited lung metastatic disease. J Am Coll Surg 2011; 213:62-9; discussion 69-71. [PMID: 21700179 DOI: 10.1016/j.jamcollsurg.2011.05.001] [Citation(s) in RCA: 79] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2011] [Revised: 04/14/2011] [Accepted: 05/04/2011] [Indexed: 02/03/2023]
Abstract
BACKGROUND Lung metastases are considered a poor prognostic factor in patients with resectable colorectal liver metastases. STUDY DESIGN We reviewed records of 1,260 consecutive patients with liver-only or liver-plus-lung (L+L) metastases from colorectal cancer who underwent resection with curative intent (1995 to 2009). Survival and prognostic factors were analyzed. RESULTS There were 112 patients who underwent resection of L+L (mean 2 liver, 2 lung metastases). Mean tumor sizes were 3 cm and 1 cm, respectively. Thirty-four (31%) had bilateral lung metastases. Ten (9%) had synchronous L+L metastases, 60 (54%) had diagnosis of lung metastases within 1 year of liver resection. Most (108 of 112, 96%) had resection of liver before or at the same time as lung. Preoperative chemotherapy was used in 77 (69%) before liver resection and 56 (50%) before lung resection. Among L+L patients, no postoperative deaths occurred; postoperative morbidity rates were 26% after liver resection and 4% after lung resection. After a median of 49 months follow-up, L+L patients (n = 112) had better survival than liver only (n = 1,148) (5-year overall survival, L+L, 50% vs liver only, 40%; p = 0.01). CEA level > 5 ng/dL (hazard ratio [HR] 2.1, 95% CI 1.1 to 4.4, p = 0.04) and rectal primary (HR 2.9, 95% CI 1.4 to 6, p = 0.004) were associated with worse survival in L+L patients. CONCLUSIONS The survival rate for patients who undergo resection of L+L metastases from colorectal cancer is greater than the survival rate of the general population of patients who undergo resection of liver metastases only. The presence of resectable lung metastases is neither a poor prognostic factor nor a contraindication to resection of liver metastases.
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Affiliation(s)
- Antoine Brouquet
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4008, USA
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36
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Pilgrim CHC, Thomson BN, Banting S, Phillips WA, Michael M. The developing clinical problem of chemotherapy-induced hepatic injury. ANZ J Surg 2011; 82:23-9. [DOI: 10.1111/j.1445-2197.2011.05789.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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Marsman HA, van der Pool AE, Verheij J, Padmos J, Ten Kate FJW, Dwarkasing RS, van Gulik TM, Ijzermans JNM, Verhoef C. Hepatic steatosis assessment with CT or MRI in patients with colorectal liver metastases after neoadjuvant chemotherapy. J Surg Oncol 2011; 104:10-6. [PMID: 21381036 DOI: 10.1002/jso.21874] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2010] [Accepted: 01/04/2011] [Indexed: 12/15/2022]
Abstract
PURPOSE Preoperative radiological assessment of hepatic steatosis is recommended in patients undergoing a liver resection, but few studies investigated the diagnostic accuracy after neoadjuvant chemotherapy. The aim of this study was to compare diagnostic accuracy of preoperative CT or MRI measurements of steatosis in patients with colorectal liver metastases after induction chemotherapy. METHODS MRI measurements (relative signal intensity decrease; RSID), N = 36, and CT scan measurements (Hounsfield units; HU), N = 32, were compared with histological steatosis assessment. Diagnostic accuracy was determined for detecting any (>5%) or marked macrovesicular steatosis (>33%). RESULTS MRI showed the highest correlation with histology (r = 0.82, P < 0.001), compared to CT measurements (r = -0.65, P < 0.001). Based on linear regression analysis, radiological cut-off values for 5% and 33% macrovesicular steatosis, corresponded to 0.7% and 19.2% RSID in the MRI-group, and 60.4 and 54.2 HU in the CT-group, respectively. Sensitivity and specificity for the detection of any and marked macrovesicular steatosis using MRI was 87% and 69%, and 78% and 100%, respectively, and for CT, 83% and 64%, and 70% and 87%, respectively. CONCLUSION In patients treated with neoadjuvant chemotherapy MRI measurements of steatosis showed the highest correlation coefficient and the best diagnostic accuracy, as compared to CT measurements.
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Affiliation(s)
- H A Marsman
- Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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38
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Yang AD, Brouquet A, Vauthey JN. Extending limits of resection for metastatic colorectal cancer: risk benefit ratio. J Surg Oncol 2010; 102:996-1001. [PMID: 21166004 DOI: 10.1002/jso.21701] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Improvements in treatment strategies and a better knowledge of tumor biology have contributed to an increase in the number of patients with colorectal liver metastases (CLM) who are candidate for surgery. These progresses are on going and the introduction of effective systemic therapy agents contributes further to the increase in the resectability of patients with advanced CLM.
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Affiliation(s)
- Anthony D Yang
- Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA
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39
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Rubbia-Brandt L. [Hepatic lesions induced by systemic chemotherapy for digestive cancer]. Ann Pathol 2010; 30:421-5. [PMID: 21167427 DOI: 10.1016/j.annpat.2010.09.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2010] [Accepted: 09/27/2010] [Indexed: 01/30/2023]
Abstract
The anticancerous chemotherapies are often responsible for toxic injury of the nontumoral liver. Two types of histological lesions were recently reported during the treatment of digestive cancers: the sinusoidal obstruction syndrome (SOS); or veno-occlusive disease associated with the use of oxaliplatine, and steatohepatitis associated with the use of irinotecan. The SOS is a cause of increased postoperative morbidity, particularly during major hepatectomy or when more than six cycles of chemotherapy are administered. Steatohepatitis increases the postoperative morbidity and mortality. The new targeted molecules do not seem to modify the postoperative course. Hepatic injury and postoperative complications associated with chemotherapies used in the treatment of digestive cancers are summarized in this review.
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40
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Kishi Y, Zorzi D, Contreras CM, Maru DM, Kopetz S, Ribero D, Motta M, Ravarino N, Risio M, Curley SA, Abdalla EK, Capussotti L, Vauthey JN. Extended preoperative chemotherapy does not improve pathologic response and increases postoperative liver insufficiency after hepatic resection for colorectal liver metastases. Ann Surg Oncol 2010; 17:2870-6. [PMID: 20567921 DOI: 10.1245/s10434-010-1166-1] [Citation(s) in RCA: 176] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2009] [Indexed: 02/03/2023]
Abstract
BACKGROUND The optimal duration, safety, and benefit of preoperative chemotherapy in patients with colorectal liver metastases (CLM) are unclear. We evaluated the association between the duration of preoperative chemotherapy with 5-fluorouracil (5-FU), leucovorin, oxaliplatin (FOLFOX) ± bevacizumab, pathologic response, and hepatotoxicity after hepatic resection for CLM. METHODS A total of 219 patients underwent hepatic resection following FOLFOX with or without bevacizumab and were divided into 2 groups according to the chemotherapy duration: 1-8 cycles (short duration [SD]; N = 157) and ≥9 cycles (long duration [LD]; N = 62). The frequency of complete or major pathologic response, sinusoidal injury, and major postoperative morbidity were compared. RESULTS Treatment consisting of ≥9 cycles was not associated with an increase in complete or major pathologic response (SD vs. LD, 57% vs. 55%; P = .74). The incidence of sinusoidal injury was higher in the LD group (26% vs. 42%; P = .017). The incidence of liver insufficiency was higher in the LD group (4% vs. 11%; P = .035). Sinusoidal injury did not predict postoperative liver insufficiency; multivariate analysis revealed ≥9 cycles was the only independent predictor of postoperative liver insufficiency (P = .031; odds ratio = 3.90). Chemotherapy including bevacizumab was associated with a significantly higher frequency of complete or major response in both SD and LD groups. CONCLUSIONS Extended preoperative chemotherapy increases the risk of hepatotoxicity in CLM without improving the pathologic response. The type of chemotherapy (FOLFOX with bevacizumab) has more impact on pathologic response than the duration of chemotherapy.
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Affiliation(s)
- Yoji Kishi
- Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
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41
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Kobayashi A, Miyagawa S. Advances in therapeutics for liver metastasis from colorectal cancer. World J Gastrointest Oncol 2010; 2:380-9. [PMID: 21160889 PMCID: PMC2999674 DOI: 10.4251/wjgo.v2.i10.380] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2010] [Revised: 09/15/2010] [Accepted: 09/22/2010] [Indexed: 02/05/2023] Open
Abstract
The evolution of chemotherapeutic regimens that include targeted molecular agents has resulted in a breakthrough in the management of advanced colorectal liver metastasis (CLM), improving the progression-free survival after liver resection, and rendering initially unresectable liver tumors resectable, with reported resection rates ranging from 13% to 51%. In addition, the criteria used for selecting patients for hepatectomy have been expanding because of advances in surgical techniques and improvements in chemotherapy. However, the increasing use of chemotherapy has raised concern about potential hepatotoxicities such as steatosis, chemotherapy-associated steatohepatitis, and sinusoidal obstruction syndrome, and their deleterious effects on postoperative outcome. The present review focuses on the advantages and disadvantages of chemotherapy, strategies for the prevention and diagnosis of chemotherapy-associated liver injury, and the adoption of more aggressive surgical approaches, which have changed the traditional paradigm for CLM.
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Affiliation(s)
- Akira Kobayashi
- Akira Kobayashi, Shinichi Miyagawa, First Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan
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42
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Brown RE, Bower MR, Martin RCG. Hepatic resection for colorectal liver metastases. Surg Clin North Am 2010; 90:839-52. [PMID: 20637951 DOI: 10.1016/j.suc.2010.04.012] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Colorectal adenocarcinoma remains the third most common cause of cancer death in the United States, with an estimated 146,000 new cases and 50,000 deaths annually. Survival is stage dependent, and the presence of liver metastases is a primary determinant in patient survival. Approximately 25% of new cases will present with synchronous colorectal liver metastases (CLM), and up to one-half will develop CLM during the course of their disease. The importance of safe and effective therapies for CLM cannot be overstated. Safe and appropriately aggressive multimodality therapy for CLM can provide most patients with liver-dominant colorectal metastases with extended survival and an improved quality of life.
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Affiliation(s)
- Russell E Brown
- Division of Surgical Oncology, Department of Surgery, James Graham Brown Cancer, University of Louisville School of Medicine, 315 East Broadway, Louisville, KY 40202, USA
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43
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Zalinski S, Bigourdan JM, Vauthey JN. [Does bevacizumab have a protective effect on hepatotoxicity induced by chemotherapy?]. ACTA ACUST UNITED AC 2010; 147 Suppl 1:S18-24. [PMID: 20172201 DOI: 10.1016/s0021-7697(10)70004-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Although the prognosis of patients with colorectal liver metastases (CLM) has improved dramatically with oxaliplatin and irinotecan, the enthusiasm for the preoperative use of these cytotoxic agents is being tempered by concerns about their impact on the nontumoral liver parenchyma. Bevacizumab, an anti-angiogenic agent that specifically targets the vascular endothelial growth factor, exerts an antitumor effect by inhibiting the development of the vascular network that is promoted by the tumor and mandatory for its growth. Yet angiogenesis is also a physiologic event contributing to wound healing and tissue regeneration. To date, it is well documented that the use of bevacizumab in combination with cytotoxic agents greatly improves pathologic response. Also well described is the protective effect of bevacizumab against sinusoidal injuries induced by oxaliplatin-based chemotherapy. Up to now, no side effects related to the perioperative use of bevacizumab have been reported in the setting of liver resection for CLM, and bevacizumab was shown not to impair liver regeneration following portal vein embolization. The clinical consequences of the protective effect of bevacizumab against sinusoidal injuries are hard to evaluate as patient selection and preparation have improved and these improvements contribute greatly to the favorable outcomes following liver resection for CLM. Indeed, patient safety in the setting of hepatic resection for CLM mainly depends on a careful preoperative evaluation of liver volumes and a limited use of cytotoxic agents followed by a delay of at least 5 weeks before the surgery.
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Affiliation(s)
- S Zalinski
- Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
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44
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Contreras CM, Abdalla EK. Metastasectomy of Combined Liver and Lung Colorectal Cancer Metastases. CURRENT COLORECTAL CANCER REPORTS 2010. [DOI: 10.1007/s11888-010-0047-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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45
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Vauthey JN, Nordlinger B, Kopetz S, Poston G. Sequenced chemotherapy and surgery for potentially resectable colorectal liver metastases: a debate over goals of research and an approach while the jury remains out. Ann Surg Oncol 2010; 17:1983-6. [PMID: 20232164 DOI: 10.1245/s10434-010-1007-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2009] [Indexed: 02/06/2023]
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46
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Anderson CD, Chari RS. Chemotherapy liver injury. Surgery 2010; 147:195-6. [PMID: 20109621 DOI: 10.1016/j.surg.2009.09.030] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2009] [Accepted: 09/25/2009] [Indexed: 01/05/2023]
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47
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Slade JH, Alattar ML, Fogelman DR, Overman MJ, Agarwal A, Maru DM, Coulson RL, Charnsangavej C, Vauthey JN, Wolff RA, Kopetz S. Portal hypertension associated with oxaliplatin administration: clinical manifestations of hepatic sinusoidal injury. Clin Colorectal Cancer 2009; 8:225-30. [PMID: 19822514 DOI: 10.3816/ccc.2009.n.038] [Citation(s) in RCA: 83] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Oxaliplatin-based chemotherapy regimens are currently a standard of care for the treatment of colorectal cancer (CRC) in both the adjuvant treatment and metastatic disease settings. Significant improvements in outcomes have been achieved with oxaliplatin-based combinations in these settings when compared with administration of 5-fluorouracil alone. Pathologic evaluation of normal liver from patients undergoing neoadjuvant oxaliplatin treatment has identified histologic evidence of sinusoidal injury, although the effect of this finding on patient outcomes after hepatic resection appears to be minimal. This article describes the use of oxaliplatin-based chemotherapy in 6 patients with stage III or IV CRC who developed evidence of noncirrhotic portal hypertension. These patients developed complications of portal hypertension including esophageal or hemorrhoidal varices with bleeding, splenomegaly with associated thrombocytopenia, and ascites. In each case, oxaliplatin-induced hepatic sinusoidal injury was identified as the most likely factor contributing to the development of noncirrhotic portal hypertension. The literature on hepatic sinusoidal injury after oxaliplatin is reviewed and the proposed pathophysiology is discussed.
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Affiliation(s)
- Julian H Slade
- Department of Pharmacy, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, USA
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48
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Kishi Y, Abdalla EK, Chun YS, Zorzi D, Madoff DC, Wallace MJ, Curley SA, Vauthey JN. Three hundred and one consecutive extended right hepatectomies: evaluation of outcome based on systematic liver volumetry. Ann Surg 2009; 250:540-8. [PMID: 19730239 DOI: 10.1097/sla.0b013e3181b674df] [Citation(s) in RCA: 361] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE(S) This study aimed to determine the effect of preoperative liver volumetry on postoperative outcomes after extended right hepatectomy. Primary end point was to evaluate whether future liver remnant (FLR)/standardized liver volume ratio (sFLR) >20% is sufficient for a safe hepatic resection. Secondary end point was to assess whether preoperative portal vein embolization (PVE) is associated with improved outcome in patients with initial sFLR ≤ 20%. BACKGROUND DATA An sFLR >20% of the total liver volume has been proposed as sufficient for safe hepatic resection, but this concept has not been validated in a large series. In addition, recent reports suggest preoperative PVE is indicated for sFLR <30%. METHODS The impact of sFLR and PVE on short-term outcomes (postoperative complications, liver insufficiency, and 90-day mortality) was analyzed in 301 consecutive patients after extended right hepatectomy. Liver volumetry accounted for partial resection of segment IV. Liver insufficiency was defined as peak postoperative serum bilirubin >7 mg/dL. Predictors of liver insufficiency were identified by multivariate logistic regression. RESULTS Postoperative liver insufficiency occurred in 45 patients (15%) and accounted for 61% of deaths. Among 290 patients who underwent liver volumetry, sFLR was <20% in 38 patients, 20.1% to 30% in 144, and ≥ 30% in 108. Rates of postoperative liver insufficiency and death from liver failure were similar between patients with sFLR 20.1% to 30% and sFLR ≥ 30% but higher in patients with sFLR ≤ 20% (P 0.05). Postoperative outcomes were similar between patients with increase in sFLR from ≤ 20% to >20% after PVE and patients with initial sFLR >20%. Multivariate analysis revealed that body mass index >25 kg/m2, intraoperative blood transfusion, and sFLR ≤ 20% (odds ratio = 3.18; 95% CI, 1.34-7.54) independently predicted postoperative liver insufficiency. CONCLUSIONS Systematic measurement of FLR volume is important to select patients for PVE and extended right hepatectomy. A sFLR >20% is sufficient for safe hepatic resection and sFLR 20.1% to 30% is not an indication for preoperative PVE.
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Affiliation(s)
- Yoji Kishi
- Department of Surgical Oncology, Unit 444, The University of Texas MD Anderson Cancer Center, Houston, TX 77030–4009, USA
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49
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Vauthey JN, Zorzi D, Kopetz S, Abdalla EK, Kishi Y, Blazer DG. Reply to D.J. Gallagher et al. J Clin Oncol 2009. [DOI: 10.1200/jco.2009.22.5698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
- Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX
| | - Daria Zorzi
- Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX
| | - Scott Kopetz
- Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX
| | - Eddie K. Abdalla
- Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX
| | - Yoji Kishi
- Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX
| | - Dan G. Blazer
- Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX
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50
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Reddy SK, Barbas AS, Clary BM. Synchronous colorectal liver metastases: is it time to reconsider traditional paradigms of management? Ann Surg Oncol 2009; 16:2395-410. [PMID: 19506963 DOI: 10.1245/s10434-009-0372-1] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2008] [Accepted: 10/14/2008] [Indexed: 12/18/2022]
Abstract
BACKGROUND Patients with synchronous colorectal liver metastases (CLM) are typically treated with initial colorectal resection followed by arbitrary and prolonged courses of chemotherapy. Partial hepatectomy is considered only for patients without interval disease progression. This review describes the rationale for this treatment approach and the recent developments suggesting that this management paradigm should be reconsidered. RESULTS Because asymptomatic colorectal cancer often does not lead to complications, and given the potential benefit of chemotherapy in downsizing unresectable to resectable liver disease, most patients with asymptomatic primary tumors and unresectable synchronous CLM should be first treated with chemotherapy. In contrast, initial hepatic resection should be considered for resectable synchronous CLM. Survival benefits from prehepatectomy chemotherapy have not been established. Several reports demonstrate morbidity after hepatic resection from extended durations of irinotecan- and/or oxaliplatin-based prehepatectomy chemotherapy. Although shorter treatment periods may not have these deleterious effects on subsequent hepatic resection, prospective studies reveal that most patients with supposedly aggressive disease with short treatment durations will not be identified. Moreover, a complete radiologic response to prehepatectomy chemotherapy is not only rare but also does not equate with a complete pathological response. Finally, several studies suggest that simultaneous colorectal and minor hepatic resections can performed safely with benefits in total morbidity when compared with traditional staged procedures. CONCLUSIONS The traditional treatment paradigm centering on the utility of prehepatectomy chemotherapy for resectable synchronous CLM should be reconsidered. Recent developments underscore the need for prospective randomized controlled trials evaluating the optimal timing of hepatectomy relative to chemotherapy.
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Affiliation(s)
- Srinevas K Reddy
- Department of Surgery, Duke University Medical Center, Durham, NC, USA.
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