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Dossa F, Weiser MR. The Ugly: Metastatic Colon Cancer-Surgical Options. Clin Colon Rectal Surg 2025; 38:219-228. [PMID: 40291995 PMCID: PMC12020648 DOI: 10.1055/s-0044-1787825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/30/2025]
Abstract
Over 50% of patients with colorectal cancer develop metastatic disease. Although systemic therapy remains the backbone of palliative treatment, select patients may be candidates for surgical resection with curative intent. Given increasing evidence of the association between metastasectomy and prolonged survival, surgery has acquired an increasingly central role in the management of liver, lung, and peritoneal metastases. This is compounded by accumulating advances in local and systemic treatments that have allowed for expansion of the resectability pool, bringing the potential for curative surgical treatment to increasing numbers of patients with stage IV disease. However, as the boundaries of resectability are pushed, patient selection and consideration of tumor-related and technical factors are imperative to the identification of patients for whom surgery would be of the greatest benefit.
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Affiliation(s)
- Fahima Dossa
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Martin R. Weiser
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
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Callesen LB, Hansen TF, Andersen RF, Pallisgaard N, Kramer S, Schlander S, Rafaelsen SR, Boysen AK, Jensen LH, Jakobsen A, Spindler KLG. ctDNA-guided adjuvant treatment after radical-intent treatment of metastatic spread from colorectal cancer-the first interim results from the OPTIMISE study. Acta Oncol 2023; 62:1742-1748. [PMID: 37738268 DOI: 10.1080/0284186x.2023.2259083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 09/10/2023] [Indexed: 09/24/2023]
Abstract
BACKGROUND Patients with detectable ctDNA after radical-intent treatment of metastatic spread from colorectal cancer (mCRC) have a very high risk of recurrence, which may be prevented with intensified adjuvant chemotherapy (aCTh). In the OPTIMISE study, we investigate ctDNA-guided aCTh after radical-intent treatment of mCRC. Here we present results from the preplanned interim analysis. MATERIAL AND METHODS The study is an open-label 1:1 randomized clinical trial comparing ctDNA-guided aCTh against standard of care (SOC), with a run-in phase investigating feasibility measures. Key inclusion criteria; radical-intent treatment for mCRC and clinically eligible for triple-agent chemotherapy. Patients underwent a PET-CT scan before randomization. ctDNA analyses of plasma samples were done by ddPCR, detecting CRC-specific mutations and methylation of the NPY gene. In the ctDNA-guided arm, ctDNA positivity led to an escalation strategy with triple-agent chemotherapy, and conversely ctDNA negativity led to a de-escalation strategy by shared-decision making. Patients randomized to the standard arm were treated according to SOC. Feasibility measures for the run-in phase were; the inclusion of 30 patients over 12 months in two Danish hospitals, compliance with randomization >80%, rate of PET-CT-positive findings <20%, and eligibility for triple-agent chemotherapy >80%. RESULTS Thirty-two patients were included. The rate of PET-CT-positive cases was 22% (n = 7/32). Ninety-seven percent of the patients were randomized. Fourteen patients were randomly assigned to SOC and sixteen to ctDNA-guided adjuvant treatment and follow-up. All analyses of baseline plasma samples in the ctDNA-guided arm passed the quality control, and 19% were ctDNA positive. The median time to result was three working days. All ctDNA-positive patients were eligible for triple-agent chemotherapy. CONCLUSION The study was proven to be feasible and continues in the planned large-scale phase II trial. Results from the OPTIMISE study will potentially optimize the adjuvant treatment of patients undergoing radical-intent treatment of mCRC, thereby improving survival and reducing chemotherapy-related toxicity.
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Affiliation(s)
| | - Torben Frøstrup Hansen
- Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark
| | - Rikke Fredslund Andersen
- Department of Biochemistry and Immunology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark
| | - Niels Pallisgaard
- Department of Pathology, Zealand University Hospital, Næstved, Denmark
| | - Stine Kramer
- Department of Nuclear Medicine & PET-Centre, Aarhus University Hospital, Aarhus, Denmark
| | - Sven Schlander
- Department of Radiology, Aarhus University Hospital, Aarhus, Denmark
| | - Søren Rafael Rafaelsen
- Department of Radiology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark
| | | | - Lars Henrik Jensen
- Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark
| | - Anders Jakobsen
- Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark
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Callesen LB, Hansen TF, Andersen RF, Pallisgaard N, Kramer S, Schlander S, Rafaelsen SR, Boysen AK, Jensen LH, Jakobsen A, Spindler KLG. OPTIMISE: Optimisation of treatment selection and follow-up in oligometastatic colorectal cancer - a ctDNA-guided phase II randomised approach. Study protocol. Acta Oncol 2022; 61:1152-1156. [PMID: 36094310 DOI: 10.1080/0284186x.2022.2116728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Affiliation(s)
| | - Torben Frøstrup Hansen
- Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark
| | - Rikke Fredslund Andersen
- Department of Biochemistry and Immunology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark
| | - Niels Pallisgaard
- Department of Pathology, Zealand University Hospital, Roskilde, Denmark
| | - Stine Kramer
- Department of Nuclear Medicine & PET-Centre, Aarhus University Hospital, Aarhus, Denmark
| | - Sven Schlander
- Department of Radiology, Aarhus University Hospital, Aarhus, Denmark
| | - Søren Rafael Rafaelsen
- Department of Radiology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark
| | | | - Lars Henrik Jensen
- Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark
| | - Anders Jakobsen
- Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark
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Hirokawa F, Ueno M, Nakai T, Kaibori M, Nomi T, Iida H, Tanaka S, Komeda K, Hayami S, Kosaka H, Hokuto D, Kubo S, Uchiyama K. Treatment strategy for resectable colorectal cancer liver metastases from the viewpoint of time to surgical failure. Langenbecks Arch Surg 2021; 407:699-706. [PMID: 34741671 DOI: 10.1007/s00423-021-02372-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 10/31/2021] [Indexed: 11/28/2022]
Abstract
PURPOSE The efficacy of pre or postoperative chemotherapy for resectable colorectal cancer liver metastases (CRLM) is disputed. This study aimed to examine the risk factors for time to surgical failure (TSF) and analyze the efficacy of pre or postoperative chemotherapy prior to liver resection for CRLM. METHODS The clinicopathological factors of 567 patients who underwent initial hepatectomy for CRLM at 7 university hospitals between April 2007 and March 2013 were retrospectively analyzed. The prognostic factors were identified and then stratified into two groups according to the number of preoperative prognostic factors: the high-score group (H-group, score 2-4) and the low-score group (L-group, score 0 or 1). RESULTS Patients who experienced unresectable recurrence within 12 months after initial treatment had a significantly shorter prognosis than other patients (p < 0.001). Multivariate analysis identified age ≥ 70 (p = 0.001), pT4 (p = 0.015), pN1 (p < 0.001), carbohydrate antigen 19-9 ≥ 37 U/ml (p = 0.002), Clavien-Dindo grade ≥ IIIa (p = 0.013), and postoperative chemotherapy (p = 0.006) as independent prognostic factors. In the H-group, patients who received chemotherapy had a better prognosis than those who did not (p = 0.001). CONCLUSION Postoperative chemotherapy is beneficial in colorectal cancer patients with more than two of the following factors: age ≥ 70, carbohydrate antigen 19-9-positivity, pT4, and lymph node metastasis.
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Affiliation(s)
- Fumitoshi Hirokawa
- Department of General and Gastroenterological Surgery, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka, 569-8686, Japan.
| | - Masaki Ueno
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Takuya Nakai
- Department of Surgery, Faculty of Medicine, Kinki University, Osaka-Sayama, Japan
| | - Masaki Kaibori
- Department of Surgery, Hirakata Hospital, Kansai Medical University, Hirakata, Osaka, Japan
| | - Takeo Nomi
- Department of Surgery, Nara Medical University, Kashihara, Japan
| | - Hiroya Iida
- Department of Surgery, Shiga University of Medical Science, Otsu, Japan
| | - Shogo Tanaka
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Koji Komeda
- Department of General and Gastroenterological Surgery, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka, 569-8686, Japan
| | - Shinya Hayami
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Hisashi Kosaka
- Department of Surgery, Hirakata Hospital, Kansai Medical University, Hirakata, Osaka, Japan
| | - Daisuke Hokuto
- Department of Surgery, Nara Medical University, Kashihara, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kazuhisa Uchiyama
- Department of General and Gastroenterological Surgery, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka, 569-8686, Japan
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Kokudo T, Saiura A, Takayama T, Miyagawa S, Yamamoto J, Ijichi M, Teruya M, Yoshimi F, Kawasaki S, Koyama H, Oba M, Takahashi M, Mizunuma N, Matsuyama Y, Ishihara S, Makuuchi M, Kokudo N, Hasegawa K. Adjuvant chemotherapy can prolong recurrence-free survival but did not influence the type of recurrence or subsequent treatment in patients with colorectal liver metastases. Surgery 2021; 170:1151-1154. [PMID: 34030885 DOI: 10.1016/j.surg.2021.04.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 04/07/2021] [Accepted: 04/13/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Although liver resection is the only potentially curative treatment for colorectal liver metastases, recurrence is frequent. We previously published the early results of a randomized controlled phase 3 trial showing that adjuvant therapy with uracil-tegafur and leucovorin significantly prolongs recurrence-free survival. This study sought to elucidate the impact of adjuvant chemotherapy on patient survival after an additional follow-up period, building upon the results of our previous study. METHODS After resection for colorectal liver metastases, patients were randomly assigned in a 1:1 ratio to receive adjuvant uracil-tegafur and leucovorin or surgery alone. Patients assigned to the uracil-tegafur and leucovorin group received 5 cycles of uracil-tegafur and leucovorin within 8 weeks after surgery. RESULTS Patients were assigned to an adjuvant uracil-tegafur and leucovorin (n = 90) or a surgery alone (n = 90) group; 3 patients were excluded because of protocol violations. After a median follow-up period of 7.36 years (95% confidence interval, 6.93-7.87), 60 (68.2%) patients in the uracil-tegafur and leucovorin group and 61 (68.5%) patients in the surgery alone group developed recurrences. The median recurrence-free survival was 1.45 years (95% confidence interval, 0.96-2.16) in the uracil-tegafur and leucovorin group and 0.70 years (95% confidence interval, 0.44-1.07) in the surgery alone group. The locations and treatments of the first recurrences did not differ between the groups, nor did the overall survival (hazard ratio, 0.86; 95% confidence interval, 0.54-1.38; P = .54). The overall survival was significantly longer in patients who underwent curative repeated resection than in patients who received non-surgical treatment (hazard ratio, 0.25; 95% confidence interval, 0.15-0.40; P < .0001). CONCLUSION Adjuvant uracil-tegafur and leucovorin significantly prolonged the recurrence-free survival but not the overall survival. The repeated resection was the most important factor influencing overall survival.
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Affiliation(s)
- Takashi Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Akio Saiura
- Department of Gastrointestinal Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Shinichi Miyagawa
- First Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Junji Yamamoto
- Department of Surgery, National Defense Medical College, Tokorozawa, Japan
| | - Masayoshi Ijichi
- Department of Surgery, JCHO Tokyo Yamate Medical Center, Tokyo, Japan
| | | | - Fuyo Yoshimi
- Department of Surgery, Ibaraki Prefectural Central Hospital and Cancer Center, Ibaraki, Japan
| | - Seiji Kawasaki
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Hiroto Koyama
- Department of Surgery, JCHO Tokyo Takanawa Hospital, Tokyo, Japan
| | - Masaru Oba
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Michiro Takahashi
- Department of Gastrointestinal Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Nobuyuki Mizunuma
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yutaka Matsuyama
- Department of Biostatistics, School of Public Health University of Tokyo, Tokyo, Japan
| | - Soichiro Ishihara
- Department of Surgical Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Masatoshi Makuuchi
- Department of Hepato-Biliary-Pancreatic Surgery, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Norihiro Kokudo
- National Center for Global Health and Medicine, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
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Matsumura M, Yamashita S, Ishizawa T, Akamatsu N, Kaneko J, Arita J, Nakajima J, Kokudo N, Hasegawa K. Oncological benefit of complete metastasectomy for simultaneous colorectal liver and lung metastases. Am J Surg 2020; 219:80-87. [PMID: 31217074 DOI: 10.1016/j.amjsurg.2019.06.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Revised: 06/04/2019] [Accepted: 06/10/2019] [Indexed: 10/26/2022]
Abstract
BACKGROUND The oncological benefit of complete metastasectomy for simultaneous colorectal liver and lung metastases (SLLM) have not been fully investigated. METHODS Patients undergoing initial hepatectomy for colorectal liver metastases (CLM) from 2005 to 2016 were divided into three groups: patients with isolated CLM undergoing complete resection (Group1, n = 317), SLLM undergoing complete metastasectomy (Group2, n = 33), and SLLM undergoing complete hepatectomy but incomplete lung resection (Group3, n = 20). A staged strategy (hepatectomy followed by lung resection) without interval chemotherapy was mainly applied for SLLM. RESULTS The 5-year overall survival rate of Group2 was significantly better than that of Group3 (71.7% vs. 10.2%, P < 0.001) and similar to that of Group1 (63.9%, P = 0.779). The 5-year disease-free survival rate was significantly worse in Group2 than Group1 (15.7% vs. 29.0%, P = 0.035). On multivariable analysis, CEA>200 ng/ml was the sole predictor of incomplete resection of lung metastases (odds ratio, 13.7; 95% confidence interval, 1.30-145; P = 0.011). CONCLUSIONS The prognosis in patients with SLLM who achieve complete metastasectomy is acceptable and might be improved by appropriate selection based on operative indications.
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Affiliation(s)
- Masaru Matsumura
- Departments of Hepato-Biliary-Pancreatic Surgery, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Suguru Yamashita
- Departments of Hepato-Biliary-Pancreatic Surgery, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Takeaki Ishizawa
- Departments of Hepato-Biliary-Pancreatic Surgery, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Nobuhisa Akamatsu
- Departments of Hepato-Biliary-Pancreatic Surgery, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Junichi Kaneko
- Departments of Hepato-Biliary-Pancreatic Surgery, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Junichi Arita
- Departments of Hepato-Biliary-Pancreatic Surgery, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Jun Nakajima
- Departments of Thoracic Surgery, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Norihiro Kokudo
- Departments of Hepato-Biliary-Pancreatic Surgery, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Kiyoshi Hasegawa
- Departments of Hepato-Biliary-Pancreatic Surgery, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
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Wanis KN, Maleyeff L, Van Koughnett JAM, H D Colquhoun P, Ott M, Leslie K, Hernandez-Alejandro R, Kim JJ. Health and Economic Impact of Intensive Surveillance for Distant Recurrence After Curative Treatment of Colon Cancer: A Mathematical Modeling Study. Dis Colon Rectum 2019; 62:872-881. [PMID: 31188189 DOI: 10.1097/dcr.0000000000001364] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND Intensive surveillance strategies are currently recommended for patients after curative treatment of colon cancer, with the aim of secondary prevention of recurrence. Yet, intensive surveillance has not yielded improvements in overall patient survival compared with minimal follow-up, and more intensive surveillance may be costlier. OBJECTIVE The purpose of this study was to estimate the quality-adjusted life-years, economic costs, and cost-effectiveness of various surveillance strategies after curative treatment of colon cancer. DESIGN A Markov model was calibrated to reflect the natural history of colon cancer recurrence and used to estimate surveillance costs and outcomes. SETTINGS This was a decision-analytic model. PATIENTS Individuals entered the model at age 60 years after curative treatment for stage I, II, or III colon cancer. Other initial age groups were assessed in secondary analyses. MAIN OUTCOME MEASURES We estimated the gains in quality-adjusted life-years achieved by early detection and treatment of recurrence, as well as the economic costs of surveillance under various strategies. RESULTS Cost-effective strategies for patients with stage I colon cancer improved quality-adjusted life-expectancy by 0.02 to 0.06 quality-adjusted life-years at an incremental cost of $1702 to $13,019. For stage II, they improved quality-adjusted life expectancy by 0.03 to 0.09 quality-adjusted life-years at a cost of $2300 to $14,363. For stage III, they improved quality-adjusted life expectancy by 0.03 to 0.17 quality-adjusted life-years for a cost of $1416 to $17,631. At a commonly cited willingness-to-pay threshold of $100,000 per quality-adjusted life-year, the most cost-effective strategy for patients with a history of stage I or II colon cancer was liver ultrasound and chest x-ray annually. For those with a history of stage III colon cancer, the optimal strategy was liver ultrasound and chest x-ray every 6 months with CEA measurement every 6 months. LIMITATIONS The study was limited by model structure assumptions and uncertainty around the values of the model's parameters. CONCLUSIONS Given currently available data and within the limitations of a model-based decision-analytic approach, the effectiveness of routine intensive surveillance for patients after treatment of colon cancer appears, on average, to be small. Compared with testing using lower cost imaging, currently recommended strategies are associated with cost-effectiveness ratios that indicate low value according to well-accepted willingness-to-pay thresholds in the United States. See Video Abstract at http://links.lww.com/DCR/A921.
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Affiliation(s)
- Kerollos N Wanis
- Department of Surgery, Western University, London, Ontario, Canada
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts
| | - Lara Maleyeff
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts
| | - Julie Ann M Van Koughnett
- Department of Surgery, Western University, London, Ontario, Canada
- Department of Oncology, Western University, London, Ontario, Canada
| | - Patrick H D Colquhoun
- Department of Surgery, Western University, London, Ontario, Canada
- Department of Oncology, Western University, London, Ontario, Canada
| | - Michael Ott
- Department of Surgery, Western University, London, Ontario, Canada
- Department of Oncology, Western University, London, Ontario, Canada
| | - Ken Leslie
- Department of Surgery, Western University, London, Ontario, Canada
- Department of Oncology, Western University, London, Ontario, Canada
| | | | - Jane J Kim
- Department of Health Policy and Management and Center for Health Decision Science, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts
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8
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Mao R, Zhao JJ, Bi XY, Zhang YF, Han Y, Li ZY, Zhao H, Cai JQ. Resectable recurrent colorectal liver metastasis: can radiofrequency ablation replace repeated metastasectomy? ANZ J Surg 2019; 89:908-913. [PMID: 31090189 DOI: 10.1111/ans.15080] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Revised: 12/27/2018] [Accepted: 12/29/2018] [Indexed: 11/24/2022]
Abstract
BACKGROUND Percutaneous radiofrequency ablation (RFA) is used as a first-line treatment for colorectal liver metastases that recur after first liver resection in our institution. We aim to evaluate its therapeutic efficacy compared to repeated surgical resection. METHODS A retrospective review was performed in 104 patients treated with curative intent for resectable recurrent colorectal liver metastases. RESULTS Sixty-one patients underwent RFA and 43 patients underwent surgery. The overall recurrence rates were 82% in the RFA group and 65.1% in the resection group (P = 0.05). The local recurrence rate on a lesion-basis was markedly higher after RFA than that after resection (16.7% versus 7.3%, P = 0.04). The difference remained significant in patients with a maximum lesion diameter >3 cm (24.5% versus 7.6%, P = 0.01). RFA treatment was independently associated with recurrence on multivariate analyses (P = 0.01). 69.7% of RFA patients and 42.6% of surgery patients with intrahepatic recurrence were amenable to repeated local treatment (P = 0.05), leading to the equivalent actuarial 3-year progression free survival rates (RFA: 29.1% versus Resection: 33.1%, P = 0.48) and 5-year overall survival rates in the two treatment groups (RFA: 33% versus Resection: 28.4%, P = 0.36). CONCLUSIONS Surgery remains the treatment of choice for resectable recurrence. RFA may offer similar benefit in selected patients.
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Affiliation(s)
- Rui Mao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jian-Jun Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xin-Yu Bi
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ye-Fan Zhang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yue Han
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Department of Interventional Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhi-Yu Li
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jian-Qiang Cai
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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9
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Nierop PMH, Galjart B, Höppener DJ, van der Stok EP, Coebergh van den Braak RRJ, Vermeulen PB, Grünhagen DJ, Verhoef C. Salvage treatment for recurrences after first resection of colorectal liver metastases: the impact of histopathological growth patterns. Clin Exp Metastasis 2019; 36:109-118. [PMID: 30843120 PMCID: PMC6445820 DOI: 10.1007/s10585-019-09960-7] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Accepted: 03/04/2019] [Indexed: 12/23/2022]
Abstract
The majority of patients recur after resection of colorectal liver metastases (CRLM). Patients with CRLM displaying a desmoplastic histopathological growth pattern (dHGP) have a better prognosis and lower probability of recurrence than patients with non-dHGP CRLM. The current study evaluates the impact of HGP type on the pattern and treatment of recurrences after first resection of CRLM. A retrospective cohort study was performed, including patients with known HGP type after complete resection of CRLM. All patients were treated between 2000 and 2015. The HGP was determined on the CRLM resected at first partial hepatectomy. The prognostic value of HGPs, in terms of survival outcome, in the current patient cohort were previously published. In total 690 patients were included, of which 492 (71%) developed recurrent disease. CRLM displaying dHGP were observed in 103 patients (21%). Amongst patients with dHGP CRLM diagnosed with recurrent disease, more liver-limited recurrences were seen (43% vs. 31%, p = 0.030), whereas patients with non-dHGP more often recurred at multiple locations (34% vs. 19%, p = 0.005). Patients with dHGP CRLM were more likely to undergo curatively intended local treatment for recurrent disease (adjusted odds ratio: 2.37; 95% confidence interval (CI) [1.46-3.84]; p < 0.001) compared to patients with non-dHGP. The present study demonstrates that liver-limited disease recurrence after complete resection of CRLM is more often seen in patients with dHGP, whereas patients with non-dHGP more frequently experience multi-organ recurrence. Recurrences in patients with dHGP at first CRLM resection are more likely to be salvageable by local treatment modalities, but no prognostic impact of HGPs after salvage therapy for recurrent disease was found.
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Affiliation(s)
- Pieter M H Nierop
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
| | - Boris Galjart
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
| | - Diederik J Höppener
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
| | - Eric P van der Stok
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
| | | | - Peter B Vermeulen
- Translational Cancer Research Unit, (GZA Hospitals and University of Antwerp), Antwerp, Belgium
| | - Dirk J Grünhagen
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
| | - Cornelis Verhoef
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
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10
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Imai K, Yamashita YI, Miyamoto Y, Nakagawa S, Okabe H, Hashimoto D, Chikamoto A, Baba H. The predictors and oncological outcomes of repeat surgery for recurrence after hepatectomy for colorectal liver metastases. Int J Clin Oncol 2018; 23:908-916. [PMID: 29619592 DOI: 10.1007/s10147-018-1273-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Accepted: 04/02/2018] [Indexed: 12/27/2022]
Abstract
PURPOSE Although recurrence after hepatectomy for colorectal liver metastases (CRLM) is common, the optimal treatment strategy remains unclear. The aims of this study were to clarify the impact of repeat surgery and identify the predictive factors for repeat surgery. METHODS Among the 170 patients who underwent potentially curative surgery for CRLM, 113 developed recurrence. The predictive factors for the performance of repeat surgery were identified and a predictive model was constructed. RESULTS The patterns of recurrence were as follows; single site [n = 100 (liver, n = 61; lung, n = 22; other, n = 17)], multiple site (n = 13). Repeat surgery was performed in 54 patients (47.8%) including re-hepatectomy (n = 25), radiofrequency ablation (n = 12), and resection of the extrahepatic recurrent disease (n = 17), and their overall survival (OS) was significantly better than that of those who could not (5-year OS 60.7 vs 19.5%, P < 0.0001). A multivariate analysis revealed that a primary N-negative status [relative risk (RR) 2.93, P = 0.017], indocyanine retention rate at 15 min ≤ 10% before hepatectomy (RR 2.49, P = 0.04), and carcinoembryonic antigen ≤ 5 ng/mL before hepatectomy (RR 2.96, P = 0.017) independently predicted the performance of repeat surgery. For patients who did not present any factors, the probability of repeat surgery was 19.6%. The addition of each subsequent factor increased the probability to 41.9, 67.8, and 84.0% (for 1, 2, and 3 factors, respectively). CONCLUSIONS Repeat surgery for not only intrahepatic but also extrahepatic recurrence is crucial for prolonging the survival of CRLM patients. The proposed model may help to predict the possibility of repeat surgery and provide optimal individualized treatment.
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Affiliation(s)
- Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
| | - Yo-Ichi Yamashita
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Yuji Miyamoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Shigeki Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Hirohisa Okabe
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Daisuke Hashimoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Akira Chikamoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
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11
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Lopez-Lopez V, Robles R, Brusadin R, López Conesa A, Torres J, Perez Flores D, Navarro JL, Gil PJ, Parrilla P. Role of 18F-FDG PET/CT vs CT-scan in patients with pulmonary metastases previously operated on for colorectal liver metastases. Br J Radiol 2018; 91:20170216. [PMID: 29034693 PMCID: PMC5966201 DOI: 10.1259/bjr.20170216] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2017] [Revised: 08/31/2017] [Accepted: 10/05/2017] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE There is currently no conclusive scientific evidence available regarding the role of the 18F-FDG PET/CT for detecting pulmonary metastases from colorectal cancer (PMCRC) in patients operated on for colorectal liver metastases (CRLM). In the follow up of patients who underwent surgery for CRLM, we compare CT-scan and 18F-FDG PET/CT in patients with PMCRC. METHODS We designed the study prospectively performing an 18F-FDG PET/CT on all patients operated on for CRLM where the CT-scan detected PMCRC during the follow up. We included patients who were operated on for PMCRC because the histological findings were taken as a control rather than biopsies. RESULTS Of the 101 pulmonary nodules removed from 57 patients, the CT-scan identified a greater number (89 nodules) than the 18F-FDG PET/CT (75 nodules) (p < 0.001). Sensitivity was greater with the CT-scan (90 vs 76%, respectively) with a lower specificity (50 vs 75%, respectively) than with the 18F-FDG PET/CT. There were no differences between positive-predictive value and negative-predictive value. The 18F-FDG PET/CT detected more pulmonary nodules in four patients (one PMCRC in each of these patients) and more extrapulmonary disease in six patients (four mediastinal lymph nodes, one retroperitoneal lymph node and one liver metastases) that the CT-scan had not detected. CONCLUSION Although CT-scans have a greater capacity to detect PMCRC, the 18F-FDG PET/CT could be useful in the detection of more pulmonary and extrapulmonary disease not identified by the CT-scan. Advances in knowledge: We tried to clarify the utility of 18F-FDG PET/CT in the management of this subpopulation of patients.
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Affiliation(s)
- Victor Lopez-Lopez
- Virgen de la arrixaca clinic and university hospital, University of Murcia, IMIB, Murcia, Spain
| | - Ricardo Robles
- Virgen de la arrixaca clinic and university hospital, University of Murcia, IMIB, Murcia, Spain
| | - Roberto Brusadin
- Virgen de la arrixaca clinic and university hospital, University of Murcia, IMIB, Murcia, Spain
| | - Asuncion López Conesa
- Virgen de la arrixaca clinic and university hospital, University of Murcia, IMIB, Murcia, Spain
| | - Juan Torres
- Virgen de la arrixaca clinic and university hospital, University of Murcia, IMIB, Murcia, Spain
| | - Domingo Perez Flores
- Virgen de la arrixaca clinic and university hospital, University of Murcia, IMIB, Murcia, Spain
| | - Jose Luis Navarro
- Virgen de la arrixaca clinic and university hospital, University of Murcia, IMIB, Murcia, Spain
| | - Pedro Jose Gil
- Virgen de la arrixaca clinic and university hospital, University of Murcia, IMIB, Murcia, Spain
| | - Pascual Parrilla
- Virgen de la arrixaca clinic and university hospital, University of Murcia, IMIB, Murcia, Spain
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12
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Rahbari NN, D'Angelica MI. Surgical salvage of recurrence after resection of colorectal liver metastases: incidence and outcomes. Hepat Oncol 2017; 4:25-33. [PMID: 28768424 PMCID: PMC6095401 DOI: 10.2217/hep-2017-0002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Accepted: 06/27/2017] [Indexed: 12/12/2022] Open
Abstract
Surgical resection remains the primary curative treatment option for patients with colorectal liver metastases. While the majority of patients will develop tumor relapse within or outside of the liver after hepatic metastasectomy, a subset of these patients may be amenable to salvage surgical resection. However, outcomes for this approach are not well defined. In this article, we summarize the current evidence for the incidence, feasibility and outcomes of salvage resection for recurrence after initial resection of colorectal liver metastases.
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Affiliation(s)
- Nuh N Rahbari
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
| | - Michael I D'Angelica
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
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13
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Kasuya K, Nagakawa Y, Hosokawa Y, Sahara Y, Takishita C, Nakajima T, Hijikata Y, Soya R, Katsumata K, Tsuchida A. Liver metastasis is established by metastasis of micro cell aggregates but not single cells. Exp Ther Med 2017; 14:221-227. [PMID: 28672918 PMCID: PMC5488600 DOI: 10.3892/etm.2017.4470] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Accepted: 01/06/2017] [Indexed: 12/11/2022] Open
Abstract
Cancer cell engraftment in the target organ is necessary to establish metastasis. Clinically, lymph node metastasis of single cells has been confirmed using cytokeratin staining. In the current study, a LacZ-labeled cancer cell line was used to visualize intrahepatic metastasis of single cells or liver micrometastasis. KM12SM-lacZ stably expressing LacZ was prepared with a highly metastatic colon cancer cell line, KM12SM. KM12SM-lacZ was injected into the spleen of nude mice and following 1 week the spleen was excised. The liver was then examined for metastasis following 1, 2 or 3 weeks. Confirmation of liver metastasis was completed by observing the grade of metastasis. Grade-1 metastasis (DNA level), human DNA in liver tissue was detected; Grade-2 metastasis (metastasis of single cells), confirmed by X-gal staining; Grade-3 metastasis (histopathological micrometastasis), diagnosed by light microscopy and Grade-4 metastasis (typical metastasis), easily detected macroscopically or by hematoxylin and eosin staining. The Grade-1 metastasis detection rates 1, 2 and 3 weeks following splenectomy were 50, 100 and 100%, respectively. Grade-2 metastasis was not detected by microscopy. The Grade-3 metastasis detection rates for 1, 2 and 3 weeks were 75, 100 and 100%, respectively. Micrometastasis was observed in the portal vein lumen and wall. The Grade-4 metastasis detection rates were 50, 100 and 100% for 1, 2 and 3 weeks respectively. Cancer cells were present in vessels surrounding the main tumor. In conclusion, a specific number of cancer cell aggregates may be necessary to establish hematogenous metastasis.
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Affiliation(s)
- Kazuhiko Kasuya
- Department of Gastrointestinal Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Yuichi Nagakawa
- Department of Gastrointestinal Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Yuichi Hosokawa
- Department of Gastrointestinal Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Yatsuka Sahara
- Department of Gastrointestinal Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Chie Takishita
- Department of Gastrointestinal Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Tetsushi Nakajima
- Department of Gastrointestinal Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Yosuke Hijikata
- Department of Gastrointestinal Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Ryoko Soya
- Department of Gastrointestinal Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Kenji Katsumata
- Department of Gastrointestinal Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
| | - Akihiko Tsuchida
- Department of Gastrointestinal Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan
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14
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Liu J, Wei Z, Wang Y, Xia Z, Zhao G. Hepatic resection for post-operative solitary liver metastasis from oesophageal squamous cell carcinoma. ANZ J Surg 2016; 88:E252-E256. [PMID: 27764891 DOI: 10.1111/ans.13810] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2016] [Revised: 08/12/2016] [Accepted: 08/19/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Liver metastasis is common in patients with oesophageal cancer. The effect of operative intervention for post-operative solitary liver metastasis from oesophageal squamous cell carcinoma (ESCC) has not previously been examined. This research was to compare the effect of surgery and non-surgical therapy in patients with post-operative solitary liver metastasis from ESCC. METHODS We retrospectively analysed the clinical data of 69 consecutive patients with solitary hepatic metastasis who had undergone oesophagectomy for ESCC and were subsequently referred to the First Affiliated Hospital of Zhengzhou University from January 2005 to December 2013. The survival rates of the surgical and non-surgical groups were compared. RESULTS There were 26 patients in the surgical group and 43 patients in the non-surgical group. There was no operative death in the surgical group. Post-operative complications were observed in six patients, and all of these patients recovered after additional treatments. Patients in the surgical group had 1- and 2-year cumulative survival rates of 50.8 and 21.2%, respectively, which were significantly higher than the 31.0 and 7.1% survival rates of patients in the non-surgical group (P < 0.05). In each group, the patients with a disease-free interval (DFI) lasting >12 months had a better survival rate than those with a DFI lasting ≤12 months (all P < 0.05). CONCLUSIONS Operative intervention is a better treatment choice for patients with post-operative solitary liver metastasis from ESCC, especially for patients with a DFI lasting >12 months. Patients selected for hepatic resection should be considered on an individual basis through a multidisciplinary team of specialists.
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Affiliation(s)
- Jingeng Liu
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhiru Wei
- Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yuebin Wang
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zongjiang Xia
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Gaofeng Zhao
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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15
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Hashimoto M, Kobayashi T, Ishiyama K, Ide K, Ohira M, Tahara H, Kuroda S, Hamaoka M, Iwako H, Okimoto M, Ohdan H. Efficacy of repeat hepatectomy for recurrence following curative hepatectomy for colorectal liver metastases: A Retrospective Cohort Study of 128 patients. Int J Surg 2016; 36:96-103. [PMID: 27741421 DOI: 10.1016/j.ijsu.2016.10.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Revised: 10/06/2016] [Accepted: 10/08/2016] [Indexed: 01/12/2023]
Abstract
BACKGROUND Despite improvements in surgery and chemotherapy, most patients develop recurrence after initial hepatectomy for colorectal liver metastasis (CRLM). Following initial hepatectomy for CRLM, patterns and surgical management of recurrence have not been widely reported. MATERIALS AND METHODS We identified 128 patients who underwent hepatic resection for CRLM between January 2000 and December 2012. Demographics, operative data, site of recurrence, and long-term survival data were collected and analyzed. Patients were stratified into 3 groups based on their site of recurrence as intrahepatic, intra- and extrahepatic, and extrahepatic. In addition, the influence of potential factors on overall survival (OS) in patients with only liver relapse was analyzed through univariate and multivariate analysis. RESULTS After curative initial hepatectomy, 87 (68.0%) patients had a recurrence: 33 in the intrahepatic group, 11 in the intra- and extrahepatic group, and 43 in the extrahepatic group. The OS for the intra- and extrahepatic group was significantly lower than that for the intrahepatic group. In the intrahepatic group, disease-free interval (DFI) < 12 months and non-repeat hepatectomy were independent poor prognostic factors. Carcinoembryonic antigen (CEA) at the time of hepatectomy was significantly higher in DFI < 12 group than in the DFI ≥ 12 group. CONCLUSION Patterns of recurrence following initial hepatectomy for CRLM have important implications for OS. In the intrahepatic recurrence group, short DFI was correlated with high CEA at hepatectomy, and was a poor prognostic factor.
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Affiliation(s)
- Masakazu Hashimoto
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan.
| | - Kohei Ishiyama
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan
| | - Kentaro Ide
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan
| | - Masahiro Ohira
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan
| | - Hiroyuki Tahara
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan
| | - Shintaro Kuroda
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan
| | - Michinori Hamaoka
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan
| | - Hiroshi Iwako
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan
| | - Masashi Okimoto
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 kasumi, Minami-Ku, Hiroshima, 734-8557, Japan
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16
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Lee-Ying R, Bernard B, Gresham G, Chen L, Speers C, Kennecke HF, Lim HJ, Cheung WY, Renouf DJ. A Comparison of Survival by Site of Metastatic Resection in Metastatic Colorectal Cancer. Clin Colorectal Cancer 2016; 16:e23-e28. [PMID: 27637559 DOI: 10.1016/j.clcc.2016.07.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Revised: 07/19/2016] [Accepted: 07/28/2016] [Indexed: 12/24/2022]
Abstract
BACKGROUND Metastatic resection (MR) of liver-limited disease is an effective therapy for selected patients with metastatic colorectal cancer (mCRC). Despite limited data, this approach has been expanded to include MR of other sites, such as the lung, locoregional, and other distant disease (ODD). We performed a population-based study of patients with mCRC who had undergone MR and compared survival between MR of the liver and MR of other sites. METHODS Patients with mCRC who were referred to the British Columbia Cancer Agency between 1995 and 2010 were reviewed. Patients were included if they had an R0 MR with a negative margin and no residual disease. The site of MR was classified according to collaborative staging criteria as liver, lung, locoregional, or ODD. Median overall survival (mOS) was assessed with Kaplan-Meier methods and compared using the log-rank test. A Cox proportional-hazards model was used to compare mOS, while adjusting for known prognostic factors. RESULTS A total of 2082 patients with mCRC were identified, of whom 257 underwent R0 MR. Sites of MR included liver (65%), lung (16%), locoregional (5%), and ODD (14%). The mOS of liver, lung, locoregional, and ODD were 48.0, 42.8, 37.2, and 26.2 months, respectively (P = .087). On multivariate analysis, only MR of ODD had a significantly different survival estimate than MR of the liver (hazard ratio, 1.78; 95% confidence interval, 1.13-2.80; P = .012). CONCLUSIONS Patients with limited lung and locoregional disease seem to have a comparable survival advantage from MR as patients with liver-limited metastases.
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Affiliation(s)
- Richard Lee-Ying
- Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada
| | - Brandon Bernard
- Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada
| | - Gillian Gresham
- Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada
| | - Leo Chen
- Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada
| | - Caroline Speers
- Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada
| | - Hagen F Kennecke
- Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada
| | - Howard John Lim
- Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada
| | - Winson Y Cheung
- Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada
| | - Daniel John Renouf
- Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada.
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17
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Oguro S, Imamura H, Yoshimoto J, Ishizaki Y, Kawasaki S. Liver metastases from gastric cancer represent systemic disease in comparison with those from colorectal cancer. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2016; 23:324-32. [PMID: 26946472 DOI: 10.1002/jhbp.343] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Accepted: 03/01/2016] [Indexed: 12/15/2022]
Abstract
BACKGROUND The aim of this retrospective study was to clarify the difference in behavior and outcome after initial hepatectomy between gastric cancer liver metastases (GCLM) and colorectal cancer liver metastases (CCLM). METHODS Data for patients undergoing curative hepatectomy for liver-only metastases from colorectal cancer (n = 193) and gastric cancer (n = 26) performed at single institution with the same criteria regarding the status of liver metastases were reviewed. Post-hepatectomy recurrence pattern, re-resection for recurrence, and three different endpoints were evaluated. RESULTS There was no significant difference between the GCLM and the CCLM in the incidence of recurrence (69% vs. 63%, P = 0.553) and recurrence-free survival (median, 15.2 months vs. 16.5 months, P = 0.230) following initial hepatectomy for liver metastases. However, the GCLM had a higher frequency of systemic unresectable recurrences than the CCLM. Time to surgical failure (median, 15.2 months vs. 39.7 months, P = 0.006) and overall survival (median, 20.1 months vs. 66.2 months, P < 0.001) were significantly shorter in the GCLM than in the CCLM. CONCLUSIONS GCLM shows more systemic and aggressive oncological behavior than CCLM after curative hepatectomy even when metastases are confined only to the liver at the time of initial hepatectomy.
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Affiliation(s)
- Seiji Oguro
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
| | - Hiroshi Imamura
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
| | - Jiro Yoshimoto
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
| | - Yoichi Ishizaki
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
| | - Seiji Kawasaki
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
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18
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Oba M, Hasegawa K, Shindoh J, Yamashita S, Sakamoto Y, Makuuchi M, Kokudo N. Survival benefit of repeat resection of successive recurrences after the initial hepatic resection for colorectal liver metastases. Surgery 2016; 159:632-640. [PMID: 26477476 DOI: 10.1016/j.surg.2015.09.003] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2015] [Revised: 08/18/2015] [Accepted: 09/02/2015] [Indexed: 01/20/2023]
Abstract
BACKGROUND Relapse is common after the resection of colorectal liver metastases (CLM); however, the optimal treatment for such recurrent disease remains uncertain. We investigated whether repeat resections for successive recurrences of CLM provide survival benefit on the postrecurrence survival. METHODS We reviewed patients who underwent upfront, curative resection for CLM at our center during a 15-year period. Of these, 263 patients who had not received any other perioperative treatment for the metastases were eligible for our analysis. The recurrence-free survival (RFS0) after the initial hepatic resection and after the first (n = 108), second (n = 43), and third (n = 15) repeat resections for recurrent disease were assessed (RFS1-3). The overall survival after the initial hepatic resection and the postrecurrence survival (n = 198) also was assessed. RESULTS The median RFS0 was 0.8 years, and RFS1, RFS2, and RFS3 were 1.3, 1.1, and 2.0 years, respectively. The hazard ratio for RFS for the first, second, and third resections versus the initial hepatic resection was 0.9 (95% confidence interval [95% CI] 0.7-1.1; P = .34), 1.00 (95% CI 0.7-1.4; P = .97), and 0.7 (95% CI 0.4-1.3; P = .29). The 5-year and 10-year OS rates were 54.6% and 42.2%, and the 5-year and 10-year postrecurrence survival was 34.3% and 28.6%, respectively. CONCLUSION Repeat resection in patients with recurrent disease after CLM resection is beneficial, offering the potential for cure in a small proportion of patients with recurrent disease.
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Affiliation(s)
- Masaru Oba
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Junichi Shindoh
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Suguru Yamashita
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yoshihiro Sakamoto
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masatoshi Makuuchi
- Department of Hepato-Biliary-Pancreatic Surgery, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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19
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Arredondo J, Baixauli J, Rodríguez J, Beorlegui C, Arbea L, Zozaya G, Torre W, -Cienfuegos JA, Hernández-Lizoáin JL. Patterns and management of distant failure in locally advanced rectal cancer: a cohort study. Clin Transl Oncol 2015; 18:909-14. [PMID: 26666769 DOI: 10.1007/s12094-015-1462-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Accepted: 11/23/2015] [Indexed: 01/03/2023]
Abstract
PURPOSE To determine the long-term outcomes of locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation (CRT) and surgery, and to analyze the management and survival once distant failure has developed. METHODS Data from LARC patients treated from 2000 to 2010 were retrospectively reviewed. CRT protocols were based on fluoropirimidines ± oxaliplatin. Follow-up consisted of physical examination, carcinoembryonic antigen levels, and chest-abdominal-pelvic CT scan. RESULTS The study included 228 patients with a mean age of 59 years. Forty-eight (21.1 %) patients had distant recurrence and 6 patients (2.6 %) had local recurrence. Median follow-up was 49 months. The 5- and 10-year actuarial disease free survival was 75.3 and 65.0 %, respectively. The 5- and 10-year actuarial overall survival (OS) was 89.6 and 71.2 %, respectively. Patients were classified as having liver (14 patients) or lung (27 patients) relapse according to the organ firstly metastasized. The variables significantly associated by univariate Cox analysis to survival were the achievement of an R0 metastases resection and the Köhne risk index, while the metastatic site showed a statistical trend. By multivariate Cox analysis, the only variable associated with survival was a R0 resection (HR = 16.3, p < 0.001). Median OS for patients undergoing a R0 resection was 73 months (95 % CI 67.8-78.2) compared to 25 months (95 % CI 5.47-44.5) in those non-operated patients (p < 0.001). CONCLUSIONS Combined treatment for LARC obtains a 5-year OS rounding 90 %. Follow-up based on thoracic-abdominal CT scan allows an early diagnosis of metastatic lesions. Surgical resection of metastases, regardless of their location, greatly increases the patient's survival rate.
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Affiliation(s)
- J Arredondo
- Department of General Surgery, Complejo Asistencial Universitario de León, c/Altos de Nava s/n, 24008, León, Spain.
| | - J Baixauli
- Department of General Surgery, Clínica Universidad de Navarra, Avenida Pío XII 36, 31008, Pamplona, Spain
| | - J Rodríguez
- Department of Medical Oncology, Clínica Universidad de Navarra, Avenida Pío XII 36, 31008, Pamplona, Spain
| | - C Beorlegui
- Department of Pathology, School of Medicine, Universidad de Navarra, Avenida Pío XII 36, 31008, Pamplona, Spain
| | - L Arbea
- Department of Radiation Oncology, Clínica Universidad de Navarra, Avenida Pío XII 36, 31008, Pamplona, Spain
| | - G Zozaya
- Department of General Surgery, Clínica Universidad de Navarra, Avenida Pío XII 36, 31008, Pamplona, Spain
| | - W Torre
- Department of Thoracic Surgery, Clínica Universidad de Navarra, Avenida Pío XII 36, 31008, Pamplona, Spain
| | - J A -Cienfuegos
- Department of General Surgery, Clínica Universidad de Navarra, Avenida Pío XII 36, 31008, Pamplona, Spain
| | - J L Hernández-Lizoáin
- Department of General Surgery, Clínica Universidad de Navarra, Avenida Pío XII 36, 31008, Pamplona, Spain
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Angelsen JH, Viste A, Løes IM, Eide GE, Hoem D, Sorbye H, Horn A. Predictive factors for time to recurrence, treatment and post-recurrence survival in patients with initially resected colorectal liver metastases. World J Surg Oncol 2015; 13:328. [PMID: 26631156 PMCID: PMC4668655 DOI: 10.1186/s12957-015-0738-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2015] [Accepted: 11/23/2015] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Despite progress in resection for colorectal liver metastases (CLM), the majority of patients experience recurrence. We aimed to evaluate factors influencing time to recurrence (TTR), treatment and post-recurrence survival (PRS) related to site of recurrence. METHODS This is a retrospective population-based cohort study (1998-2012) of consecutive patients without extrahepatic disease treated with resection for CLM in a referral centre. RESULTS A total of 311 patients underwent resection for CLM. After a median follow-up of 4.2 years (range 1.2-15.2), 209 (67.4 %) patients developed recurrence, hepatic 90, extrahepatic 59 and both 60. Median TTR was 14.0 months, and 5-year recurrence-free status was 25.7 %. Five- and 10-year overall survival (OS) was 38.8 and 22.0 %, respectively. Median OS was 45 months. A multivariate analysis displayed synchronous disease (hazard ratio (HR) 1.50), American Society of Anaesthesiologists (ASA) score (HR 1.40), increasing number (HR 1.24) and size of metastases (HR 1.08) to shorten TTR (all p < 0.05). Perioperative chemotherapy (n = 59) increased overall TTR (HR 0.63) and overall survival (OS; HR 0.55). Hepatic TTR was correlated to synchronous disease (HR 2.07), number of lesions (HR 1.20), R1 resection (HR 2.00) and ASA score (HR 1.69), whereas extrahepatic TTR was correlated to N stage of the primary (HR 1.79), number (HR 1.27) and size of metastases (HR 1.16). Single-site recurrence was most common (135 of 209, 64.5 %), while 58 patients had double- and 16 triple-site relapses. Median PRS was 24.3 months. There was a difference in median PRS (months) according to site of relapse: liver 30.5, lung 32.3, abdominal 22.0, liver and lung 14.3, others 14.8 (p = 0.002). Repeated liver resections were performed in n = 57 patients resulting in 40.6 months median OS and 36.8 % 5-year OS. CONCLUSIONS An adverse overall TTR was correlated to number and size of metastases, ASA score and synchronous disease. Perioperative chemotherapy increased TTR and OS after surgery for CLM. Patients with solitary post-resection relapse in the liver or lungs had the potential for longevity due to multimodal treatment.
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Affiliation(s)
- Jon-Helge Angelsen
- Department of Acute and Digestive Surgery, Haukeland University Hospital, N-5021, Bergen, Norway. .,Department of Clinical Medicine, University of Bergen, Bergen, Norway.
| | - Asgaut Viste
- Department of Acute and Digestive Surgery, Haukeland University Hospital, N-5021, Bergen, Norway. .,Department of Clinical Medicine, University of Bergen, Bergen, Norway.
| | - Inger Marie Løes
- Department of Oncology, Haukeland University Hospital, Bergen, Norway. .,Department of Clinical Science, University of Bergen, Bergen, Norway.
| | - Geir Egil Eide
- Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway. .,Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
| | - Dag Hoem
- Department of Acute and Digestive Surgery, Haukeland University Hospital, N-5021, Bergen, Norway.
| | - Halfdan Sorbye
- Department of Oncology, Haukeland University Hospital, Bergen, Norway. .,Department of Clinical Science, University of Bergen, Bergen, Norway.
| | - Arild Horn
- Department of Acute and Digestive Surgery, Haukeland University Hospital, N-5021, Bergen, Norway.
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Takahashi M, Hasegawa K, Oba M, Aoki T, Sakamoto Y, Sugawara Y, Kokudo N. Repeat resection leads to long-term survival: analysis of 10-year follow-up of patients with colorectal liver metastases. Am J Surg 2015; 210:904-10. [PMID: 26021389 DOI: 10.1016/j.amjsurg.2015.01.026] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2014] [Revised: 01/05/2015] [Accepted: 01/11/2015] [Indexed: 01/01/2023]
Abstract
BACKGROUND Some reports have shown that a significant number of patients experience recurrence, even after 5 or more years after surgery for colorectal liver metastases (CLMs). This study aimed to determine the actual cure rate and identify clinical characteristics among long-term survivors. METHODS A prospectively maintained database was used to retrospectively review patients who underwent liver resection for CLM between 1994 and 2001. RESULTS A total of 130 patients underwent liver resection for CLM with a complete 10-year follow-up. The 10-year disease-specific survival rate was 31.1%, and the survival curve reached a plateau after 10 years from the time of hepatic resection. There were 35 actual 10-year survivors. Multivariate analysis revealed that female patients and those with negative surgical margins were independent prognostic factors for disease-specific survival. CONCLUSION A 10-year survival following initial hepatectomy should be defined as cure.
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Affiliation(s)
- Michiro Takahashi
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Masaru Oba
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Taku Aoki
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Yoshihiro Sakamoto
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Yasuhiko Sugawara
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
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Use of mouse liver mesothelial cells to prevent postoperative adhesion and promote liver regeneration after hepatectomy. J Hepatol 2015; 62:1141-7. [PMID: 25514558 DOI: 10.1016/j.jhep.2014.12.010] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2014] [Revised: 11/12/2014] [Accepted: 12/06/2014] [Indexed: 12/22/2022]
Abstract
BACKGROUND & AIMS Repeated hepatectomy is widely accepted as one of the most effective curative treatment for recurrent hepatocellular carcinoma or liver metastasis from colorectal cancer. It has, however, two critical issues; postoperative adhesion and decrease of liver regenerative capacity. Postoperative adhesion makes surgical operations technically more demanding, leading to increased mortality and morbidity rates. Although the liver has a remarkable regenerative ability, volume and functional restoration after multiple repeated hepatectomy is not generally complete. So a new procedure that overcomes these two issues is required. We examined if a fetal liver mesothelial cells (FL-MCs) sheet could solve these two clinical issues simultaneously. METHODS We established a novel mouse hepatectomy model that reproduces postoperative adhesion on the resected liver surface. We isolated FL-MCs from mouse fetal liver and prepared a cell sheet. The FL-MCs sheet was then transplanted to the resected liver surface. RESULTS The FL-MCs sheet effectively prevented postoperative adhesion by expressing PCLP1, one of the transmembrane sialomucin family proteins and by activating the fibrinolytic system. Furthermore, the FL-MCs sheet facilitated liver regeneration by providing growth factors for hepatocytes, allowing quick recovery of liver weight and function. Additionally, we showed that an allogeneic FL-MCs sheet was as effective as a syngeneic cell sheet. CONCLUSIONS We demonstrate that the FL-MCs sheet is able to not only prevent postoperative adhesion but also promote liver regeneration in both syngeneic and allogeneic transplantation, and hence FL-MCs may serve as a potentially useful cell source for regenerative medicine after hepatectomy.
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23
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Butte JM, Gönen M, Allen PJ, Peter Kingham T, Sofocleous CT, DeMatteo RP, Fong Y, Kemeny NE, Jarnagin WR, D'Angelica MI. Recurrence After Partial Hepatectomy for Metastatic Colorectal Cancer: Potentially Curative Role of Salvage Repeat Resection. Ann Surg Oncol 2015; 22:2761-71. [PMID: 25572686 DOI: 10.1245/s10434-015-4370-1] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2014] [Indexed: 12/29/2022]
Abstract
PURPOSE Patients with recurrence after complete resection of colorectal liver metastases (CLM) are considered for repeat resection as a potential salvage therapy (PST). However, outcomes for this approach are not well defined. We sought to analyze the natural history of recurrence and PST in a large cohort of patients with long-term follow-up. METHODS Recurrence patterns, treatments, and outcomes in consecutive patients undergoing resection for colorectal liver metastases were analyzed retrospectively. PST was defined as repeat resection of all recurrent disease and effective salvage therapy (EST) as free of disease for 36 months after last PST. Factors associated with PST, EST, and outcomes were analyzed. RESULTS Of 952 patients who underwent resection, 594 (62 %) experienced recurrence (median interval = 13 months). Initial recurrences involved liver (n = 157,26 %), lung (n = 167,28 %), multiple sites (n = 171,29 %), and other single sites (n = 99,17 %). PST was performed in 160 (27 %) of 594, most commonly with a single site of recurrence (n = 149). Young age (p = 0.01), negative initial resection margin (p = 0.003), initial tumor size <5 cm (p = 0.006), and recurrence pattern (p < 0.001) were independently associated with PST. Thirty-six patients experienced EST (25 % of PSTs). Overall median survival was 61 and 43 months in those with recurrence. Median survival of patients undergoing PST was 87 months compared to 34 months for those who did not. CONCLUSIONS Recurrence is common after CLM resection, but 27 % of patients were able to undergo PST. Approximately one-quarter of these experienced EST and may be cured. PST is associated with long-term survival and possible cure, and therefore active surveillance after CLM resection is justified.
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Affiliation(s)
- Jean M Butte
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Saiura A, Yamamoto J, Koga R, Takahashi Y, Takahashi M, Inoue Y, Ono Y, Kokudo N. Favorable Outcome After Repeat Resection for Colorectal Liver Metastases. Ann Surg Oncol 2014; 21:4293-4299. [DOI: 10.1245/s10434-014-3863-7] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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25
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Recurrence patterns after resection of liver metastases from colorectal cancer. Recent Results Cancer Res 2014; 203:243-52. [PMID: 25103010 DOI: 10.1007/978-3-319-08060-4_17] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Recurrence of metastatic disease after resection of liver metastases from colorectal cancer remains a major problem as 70-80 % of patients will have a recurrence, most commonly in the liver or lung. To predict patterns of recurrence and outcome may guide follow-up and further treatment, as patients with recurrence might be candidates for repeated surgery or ablation therapy. A summary of studies shows that after hepatectomy 20-43 % will have a recurrence only in the remaining liver without extrahepatic disease, whereas 15-37 % will have a recurrence only to the lung. Early recurrence is associated with poorer outcome compared to late recurrence. Site of first recurrence after resection of liver metastases is predicted by several baseline variables; synchronous disease, primary tumor site, hepatic tumor size, CEA level, number of hepatic lesions, and RAS mutation status. Pattern of recurrence is a predictor for survival after hepatectomy, with liver-only and lung-only recurrences having the best survival. In the majority of patients with isolated hepatic or lung recurrence, repeated metastasectomy is possible resulting in a 40 % 5-year survival rate. Perioperative chemotherapy reduces the risk of liver recurrence after hepatectomy of colorectal cancer liver metastases.
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26
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Kulaylat AN, Bhayani NH, Stokes AL, Schubart JR, Wong J, Kimchi ET, Staveley-O'Carroll KF, Kaifi JT, Gusani NJ. Determinants of repeat curative intent surgery in colorectal liver metastasis. J Gastrointest Surg 2014; 18:1894-901. [PMID: 24950776 DOI: 10.1007/s11605-014-2580-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Accepted: 06/11/2014] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Following curative intent surgery (CIS) for colorectal liver metastasis (CRLM), repeat CIS for recurrence improves survival. The factors associated with repeat CIS are not widely reported. METHODS An institutional database (January 2002-December 2012) was reviewed to evaluate factors influencing repeat CIS. RESULTS One hundred sixty-three patients with colorectal liver metastasis (CRLM) underwent successful CIS. Median follow-up and disease-free interval (DFI) was 33 and 16 months, respectively. After initial CIS, 102 patients (63%) recurred. Fifty-three patients (52%) underwent a repeat CIS. After repeat CIS, 33 patients (62%) developed a second recurrence, and in 13 patients (39%), a third CIS was possible. DFI decreased following initial CIS (first CIS vs. second CIS vs. third CIS [20 vs. 15 vs. 8.5 months], p < 0.001). Overall 5-year survival in all patients was 55%; patients who recurred had a 5-year survival of 67% if they underwent repeat CIS vs. 7.8% if they were managed palliatively. Second CIS was less likely with a postoperative complication, other/multifocal recurrence, or DFI <12 months. CONCLUSION Despite high recurrence and decreasing DFI, repeat CIS provides a survival benefit. Postoperative complications, DFI, number, and pattern of recurrence influence the decision to pursue repeat CIS.
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Affiliation(s)
- Afif N Kulaylat
- Program for Liver, Pancreas, and Foregut Tumors, Department of Surgery, College of Medicine, The Pennsylvania State University, Hershey, PA, 17033-0850, USA
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Khan K, Wale A, Brown G, Chau I. Colorectal cancer with liver metastases: Neoadjuvant chemotherapy, surgical resection first or palliation alone? World J Gastroenterol 2014; 20:12391-12406. [PMID: 25253940 PMCID: PMC4168073 DOI: 10.3748/wjg.v20.i35.12391] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2013] [Revised: 01/30/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is one of the commonest cancers with 1.2 million new cases diagnosed each year in the world. It remains the fourth most common cause of cancer-related mortality in the world and accounts for > 600000 cancer-related deaths each year. There have been significant advances in treatment of metastatic CRC in last decade or so, due to availability of new active targeted agents and more aggressive approach towards the management of CRC, particularly with liver-only-metastases; however, these drugs work best when combined with conventional chemotherapy agents. Despite these advances, there is a lack of biomarkers to inform us about the accurate management of the patients with metastatic CRC. It is therefore imperative to carefully select the patients with comprehensive multi-disciplinary team input in order to optimise the management of these patients. In this review we will discuss various treatment options available in management of colorectal liver metastases with potential guidance on how and when to choose these options along with consideration on future directions in management of this disease.
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28
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Luo LX, Yu ZY, Huang JW, Wu H. Selecting patients for a second hepatectomy for colorectal metastases: an systemic review and meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2014; 40:1036-48. [PMID: 24915859 DOI: 10.1016/j.ejso.2014.03.012] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Revised: 03/02/2014] [Accepted: 03/07/2014] [Indexed: 02/05/2023]
Abstract
BACKGROUND Opinions on the suitability of repeat hepatectomy for patients with recurrent colorectal liver metastases (CRLMs) vary among studies. We conducted a meta-analysis to establish the criteria for selecting the best candidates for a second hepatectomy. METHODS Database and manual searches were performed to identify comparative or prognostic studies published up to October 2013. Outcomes of interest included disease characteristics, perioperative outcomes, and long-term survival after initial and second hepatectomies for patients with CRLM. Study quality was appraised using the Newcastle-Ottawa scale and a modified Hayden's score. RESULTS A total of 7226 patients from 27 studies were included. Recurrent CRLMs after initial hepatectomy were more likely to be solitary (RR = 0.86, P = 0.045), unilobar (RR = 0.60, P < 0.001), and smaller (WMD = -0.66, P < 0.001). Postoperative morbidity and mortality were comparable between initial and second hepatectomies (RR = 1.10, P = 0.191; RR = 0.78, P = 0.678, respectively). In high-quality studies, patients showed better survival after a second hepatectomy than those after a single hepatectomy (HR = 0.68, P = 0.022). Patients meeting the following six predictors survived longer after second hepatectomy: disease-free survival after initial hepatectomy >1 y (P = 0.034); solitary CRLM at second hepatectomy (P < 0.001); unilobar CRLM at second hepatectomy (P = 0.009); maximal size of CRLM at second hepatectomy ≤ 5 cm (P = 0.035); lack of extrahepatic metastases at second hepatectomy (P < 0.001); and R0 resection at second hepatectomy (P < 0.001). CONCLUSIONS Second hepatectomy is a safe and feasible procedure for patients with recurrent CRLM. In fact, in well-selected patients it improves overall survival. The established criteria can help clinicians to select the best candidates for second hepatectomy and to achieve better long-term outcomes after resection.
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Affiliation(s)
- L X Luo
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, China.
| | - Z Y Yu
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, China
| | - J W Huang
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, China
| | - H Wu
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, China
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Kulaylat AN, Schubart JR, Stokes AL, Bhayani NH, Wong J, Kimchi ET, O'Carroll KFS, Kaifi JT, Gusani NJ. Overall survival by pattern of recurrence following curative intent surgery for colorectal liver metastasis. J Surg Oncol 2014; 110:1011-5. [PMID: 25146500 DOI: 10.1002/jso.23756] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2014] [Accepted: 07/27/2014] [Indexed: 01/06/2023]
Abstract
BACKGROUND Following curative intent surgery (CIS) for colorectal liver metastasis (CRLM), patterns of recurrence and subsequent survival outcomes are not widely reported. METHODS An institutional database (January 2002-December 2012) was reviewed to evaluate patterns of recurrence following CIS for CRLM. RESULTS 163 patients with CRLM underwent successful CIS. Median follow-up and disease-free interval were 33 and 16 months, respectively. 5-year overall survival (OS) was 55%. After initial CIS, 102 (63%) patients recurred: liver-44% (5-year OS 55%), lung-15% (5-year OS 45%), and other/multifocal-41% (5-year OS 24%). OS for isolated liver and lung recurrences were not significantly different. Liver only recurrence was associated with 1-5 mm liver resection margins (P = 0.048). Lung only recurrence was associated with extrahepatic metastasis (at the time of initial CRLM) (P = 0.025). Other/multifocal recurrence was associated with bilobar CRLM (P = 0.026), and extrahepatic metastasis (P = 0.028). CONCLUSIONS Patterns of recurrence following CIS for CRLM have important implications for OS. 5-year OS was similar between isolated lung and liver recurrences. During CIS, decreased liver resection margin may be associated with increased risk of liver only recurrence. Patients with aggressive primary or metastatic liver disease are at higher risk for pulmonary or other/multifocal recurrence.
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Affiliation(s)
- Afif N Kulaylat
- Department of Surgery, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania
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Williams BHM, Alzahrani NA, Chan DL, Chua TC, Morris DL. Repeat cytoreductive surgery (CRS) for recurrent colorectal peritoneal metastases: yes or no? EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2014; 40:943-949. [PMID: 24378009 DOI: 10.1016/j.ejso.2013.10.022] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2013] [Revised: 10/18/2013] [Accepted: 10/27/2013] [Indexed: 12/27/2022]
Abstract
PURPOSE To clarify the role of repeat CRS for recurrent colorectal carcinoma (CRC) through: (i) Systematic review of the literature (ii) Analysis of survival outcomes in a prospective cohort. METHODS (i) Pubmed and MEDLINE from 1980 to July 2013 searched using terms: colorectal carcinoma, peritonectomy, cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), redo, repeat, and iterative. (ii) Kaplan-Meier Survival analysis of consecutive patients undergoing repeat CRS at St George Hospital between Jan 2000 and July 2013. RESULTS (i) The search strategy yielded 309 articles, 5 meeting inclusion criteria, reporting on 91 patients. Median overall survival from first CRS ranged from 39 to 57.6 months with 3-yr survival of 50%, and 5-year survival of 30%. Median survival from second CRS was 20-months with 1-yr survivals of 72% and 66% and 2-year survivals of 50% and 44%. (ii) Repeat CRS performed on 18 patients found median survival from first CRS was 59 months, with 1, 3, and 5-year survival of 100%, 52% and 26% respectively. Median survival from repeat CRS was 22.6 months with 1, 2, and 3-year survival of 94%, 48% and 12% respectively. CONCLUSION The current data on repeat CRS in CRC is relatively immature and more data is required before drawing clear conclusions. Patient selection should be on a case by case basis conducted through a MDT process with emphasis on surrogate markers for favourable outcomes.
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Affiliation(s)
- B H M Williams
- Hepatobiliary and Surgical Oncology Unit, UNSW Department of Surgery, St George Hospital, Australia; St George Clinical School, University of New South Wales, Australia
| | - N A Alzahrani
- Hepatobiliary and Surgical Oncology Unit, UNSW Department of Surgery, St George Hospital, Australia
| | - D L Chan
- Hepatobiliary and Surgical Oncology Unit, UNSW Department of Surgery, St George Hospital, Australia; St George Clinical School, University of New South Wales, Australia
| | - T C Chua
- Hepatobiliary and Surgical Oncology Unit, UNSW Department of Surgery, St George Hospital, Australia; St George Clinical School, University of New South Wales, Australia
| | - D L Morris
- Hepatobiliary and Surgical Oncology Unit, UNSW Department of Surgery, St George Hospital, Australia; St George Clinical School, University of New South Wales, Australia.
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Hobson's choice two-stage hepatectomy for multiple and bilobar colorectal liver metastases with portal vein embolization: report of two cases. Surg Today 2014; 45:511-6. [PMID: 24943807 DOI: 10.1007/s00595-014-0953-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2013] [Accepted: 12/16/2013] [Indexed: 12/18/2022]
Abstract
Liver resection is recognized as the preferred treatment for patients with colorectal liver metastases (CLM) because it offers long-term survival; it is the only hope for a cure. However, in the majority of cases, liver surgery is contraindicated due to the small volume of the future remnant liver. To extend the surgical indications for CLM, a planned two-stage hepatectomy procedure with portal vein embolization (PVE) was developed specifically for patients with multiple and bilobar CLM. The rationale for performing the procedure was a concern about the possible overgrowth of intrafuture remnant liver lesions following PVE, and it was therefore recommended for all multiple bilobar CLM cases, even when one-stage hepatectomy was technically feasible. We recently performed Hobson's choice two-stage hepatectomy in two cases for reasons different from those of the original planned two-stage hepatectomy. In the present report, we describe our Hobson's choice two-stage hepatectomy strategy, which provided favorable short-term outcomes.
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Oba M, Hasegawa K, Matsuyama Y, Shindoh J, Mise Y, Aoki T, Sakamoto Y, Sugawara Y, Makuuchi M, Kokudo N. Discrepancy between recurrence-free survival and overall survival in patients with resectable colorectal liver metastases: a potential surrogate endpoint for time to surgical failure. Ann Surg Oncol 2014; 21:1817-1824. [PMID: 24499828 DOI: 10.1245/s10434-014-3504-1] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2013] [Indexed: 02/19/2025]
Abstract
BACKGROUND Recurrence-free survival (RFS) may not be a surrogate for overall survival (OS) in patients with resectable colorectal liver metastases (CLM). We investigated whether a new composite tool-time to surgical failure (TSF)-is a suitable endpoint. METHODS The medical records of consecutive patients who underwent curative resection for CLM at our center over a 17-year period were reviewed. Patients with liver-limited tumors (n = 371) who had not received previous treatment for metastasis were eligible for analysis. TSF was defined as the time until unresectable relapse or death. The correlations between TSF and OS, and between RFS and OS, were assessed for all the eligible patients. RESULTS The median OS, TSF, and RFS were 5.7, 2.7, and 0.7 years, respectively, and the 5-year OS, TSF, and RFS rates were 52.6, 39.8, and 23.7 %, respectively, for all patients. The rates of first, second, and third relapse were 75.5, 77.6, and 70.8 %, respectively, and repeat resections were performed in 54.3 % (first relapses), 40.7 % (second relapses), and 47.1 % (third relapses) of patients. The concordance proportions of TSF and RFS for OS events were 0.83 and 0.65, respectively. The correlation between TSF and OS was stronger than that between RFS and OS in terms of the predicted probabilities. CONCLUSIONS The correlation between TSF and OS was stronger than that between RFS and OS after curative hepatic resection. TSF could be a suitable endpoint for CLM overall management.
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Affiliation(s)
- Masaru Oba
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Ziff O, Rajput I, Adair R, Toogood GJ, Prasad KR, Lodge JPA. Repeat liver resection after a hepatic or extended hepatic trisectionectomy for colorectal liver metastasis. HPB (Oxford) 2014; 16:212-9. [PMID: 23870012 PMCID: PMC3945846 DOI: 10.1111/hpb.12123] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2012] [Accepted: 02/21/2013] [Indexed: 12/12/2022]
Abstract
OBJECTIVE A right and left hepatic trisectionectomy and an extended trisectionectomy are the largest liver resections performed for malignancy. This report analyses a series of 23 patients who had at least one repeat resection after a hepatic trisectionectomy for colorectal liver metastasis (CRLM). METHODS A retrospective analysis of a single-centre prospective liver resection database from May 1996 to April 2009 was used for patient identification. Full notes, radiology and patient reviews were analysed for a variety of factors with respect to survival. RESULTS Twenty-three patients underwent up to 3 repeat hepatic resections after 20 right and 3 left hepatic trisectionectomies. In 18 patients the initial surgery was an extended trisectionectomy. Overall 1-, 3- and 5-year survival rates after a repeat resection were 100%, 46% and 32%, respectively. No factors predictive for survival were identified. CONCLUSION A repeat resection after a hepatic trisectionectomy for CRLM can offer extended survival and should be considered where appropriate.
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Affiliation(s)
- Oliver Ziff
- HPB and Transplant Unit, St. James's University HospitalLeeds, UK
| | - Ibrahim Rajput
- HPB and Transplant Unit, St. James's University HospitalLeeds, UK
| | - Robert Adair
- HPB and Transplant Unit, St. James's University HospitalLeeds, UK
| | - Giles J Toogood
- HPB and Transplant Unit, St. James's University HospitalLeeds, UK
| | | | - J Peter A Lodge
- HPB and Transplant Unit, St. James's University HospitalLeeds, UK
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Battula N, Tsapralis D, Mayer D, Isaac J, Muiesan P, Sutcliffe RP, Bramhall S, Mirza D, Marudanayagam R. Repeat liver resection for recurrent colorectal metastases: a single-centre, 13-year experience. HPB (Oxford) 2014; 16:157-63. [PMID: 23530978 PMCID: PMC3921011 DOI: 10.1111/hpb.12096] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2012] [Accepted: 02/07/2013] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Isolated intrahepatic recurrence is noted in up to 40% of patients following curative liver resection for colorectal liver metastases (CLM). The aims of this study were to analyse the outcomes of repeat hepatectomy for recurrent CLM and to identify factors predicting survival. METHODS Data for all liver resections for CLM carried out at one centre between 1998 and 2011 were analysed. RESULTS A total of 1027 liver resections were performed for CLM. Of these, 58 were repeat liver resections performed in 53 patients. Median time intervals were 10.5 months between the primary resection and first hepatectomy, and 15.4 months between the first and repeat hepatectomies. The median tumour size was 3.0 cm and the median number of tumours was one. Six patients had a positive margin (R1) resection following first hepatectomy. There were no perioperative deaths. Significant complications included transient liver dysfunction in one and bile leak in two patients. Rates of 1-, 3- and 5-year overall survival following repeat liver resection were 85%, 61% and 52%, respectively, at a median follow-up of 23 months. R1 resection at first hepatectomy (P = 0.002), a shorter time interval between the first and second hepatectomies (P = 0.02) and the presence of extrahepatic disease (P = 0.02) were associated with significantly worse overall survival. CONCLUSIONS Repeat resection of CLM is safe and can achieve longterm survival in carefully selected patients. A preoperative knowledge of poor prognostic factors helps to facilitate better patient selection.
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Affiliation(s)
- Narendra Battula
- Narendra Battula, Liver Unit, Queen Elizabeth Hospital, Birmingham B15 2TH, UK. Tel: + 44 7743 846045. Fax: + 44 121 4 141833. E-mail:
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Prognostic factors and treatment effects in patients with curatively resected brain metastasis from colorectal cancer. Dis Colon Rectum 2014; 57:56-63. [PMID: 24316946 DOI: 10.1097/01.dcr.0000436998.30504.98] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Colorectal cancer infrequently causes brain metastasis, and the prognosis is poor. OBJECTIVE The aim of this study was to identify the prognostic factors associated with survival and outcome of treatment for patients with brain metastasis from colorectal cancer. DESIGN This is a retrospective study from a prospectively collected database. SETTINGS The investigation took place in a high-volume multidisciplinary tertiary cancer center in Japan. PATIENTS From 1979 to 2010, 113 consecutive patients who were treated for brain metastasis from colorectal cancer were identified. MAIN OUTCOME MEASURES The primary outcome measure was overall survival. RESULTS Sixty-three patients had neurosurgical resection (including curative resection for 46 patients) followed by whole brain radiotherapy, 9 had stereotactic radiosurgery, 30 had whole brain radiotherapy, and 11 had steroid and palliative care. As a whole, the overall median survival time from diagnosis of brain metastasis was 5.4 months (95% CI, 4.3-7.6 months), and the 1-year survival rate was 29% (95% CI, 22%-38%). In the group of patients who underwent curative neurosurgical resection, the overall median survival time was 15.2 months (95% CI, 9.2-17.8 months), and the 1-year survival rate was 57% (95% CI, 43%-71%). On multivariate analysis, 1 or 2 brain metastatic lesions, no extracranial metastatic lesions, and neurosurgical resection were independent favorable prognostic factors overall (p = 0.0057, 0.0197, and <0.0001), and 1 or 2 brain metastatic lesions, no extracranial metastatic lesion, and no emergence of secondary brain metastatic lesions were independent favorable prognostic factors in the group of patients who underwent curative neurosurgical resection (p = 0.0137, 0.0081, and 0.0010). LIMITATIONS This study was limited by its single-institute, retrospective, nonrandomized design and selection bias. CONCLUSIONS Neurosurgical resection in select patients is a reasonable option for brain metastasis from colorectal cancer, although it is not associated with long-term (5-year) survival. (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A121 ).
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Hasegawa K, Takahashi M, Ohba M, Kaneko J, Aoki T, Sakamoto Y, Sugawara Y, Kokudo N. Perioperative chemotherapy and liver resection for hepatic metastases of colorectal cancer. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2013; 19:503-8. [PMID: 22426591 DOI: 10.1007/s00534-012-0509-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Surgical resection has played a major role in the treatment for colorectal liver metastases. The safety and efficacy of surgery for liver metastasis are obvious, although there are some differences between the western countries and Japan concerning the surgical indication, procedures, timing of chemotherapies in a perioperative period, and treatment of a primary disease. In future, long-term outcomes after surgical resection for colorectal liver metastases would be expected to be prolonged by combination of surgery and chemotherapies.
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Affiliation(s)
- Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
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Zimmitti G, Roses RE, Andreou A, Shindoh J, Curley SA, Aloia TA, Vauthey JN. Greater complexity of liver surgery is not associated with an increased incidence of liver-related complications except for bile leak: an experience with 2,628 consecutive resections. J Gastrointest Surg 2013; 17:57-p.65. [PMID: 22956403 PMCID: PMC3855461 DOI: 10.1007/s11605-012-2000-9] [Citation(s) in RCA: 89] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2012] [Accepted: 08/06/2012] [Indexed: 01/31/2023]
Abstract
BACKGROUND Advances in technique, technology, and perioperative care have allowed for the more frequent performance of complex and extended hepatic resections. The purpose of this study was to determine if this increasing complexity has been accompanied by a rise in liver-related complications. METHODS A large prospective single-institution database of patients who underwent hepatic resection was used to identify the incidence of liver-related complications. Liver resections were divided into an early era and a late era with equal number of patients (surgery performed before or after 18 May 2006). Patient characteristics and perioperative factors were compared between the two groups. RESULTS Between 1997 and 2011, 2,628 hepatic resections were performed, with a 90-day morbidity and mortality rate of 37 and 2 %, respectively. We identified higher rates of repeat hepatectomy (12.2 vs 6.1 %; p < 0.001), two-stage resection (4.0 vs 1 %; p < 0.001), extended right hepatectomy (17.6 vs 14.6 %; p = 0.04), and preoperative portal vein embolization (9.1 vs 5.9 %; p < 0.001) in the late era. The incidence of perihepatic abscess (3.7 vs 2.1 %; p = 0.02) and hemorrhage (0.9 vs 0.3 %; p = 0.045) decreased in the late era and the incidence of hepatic insufficiency (3.1 vs 2.6 %; p = 0.41) remained stable. In contrast, the rate of bile leak increased (5.9 vs 3.7 %; p = 0.011). Independent predictors of bile leak included bile duct resection, extended hepatectomy, repeat hepatectomy, en bloc diaphragmatic resection, and intraoperative transfusion. CONCLUSIONS The complexity of liver surgery has increased over time, with a concomitant increase in bile leak rate. Given the strong association between bile leak and other poor outcomes, the development of novel technical strategies to reduce bile leaks is indicated.
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Affiliation(s)
- Giuseppe Zimmitti
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX 77030, USA
| | - Robert E. Roses
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX 77030, USA
| | - Andreas Andreou
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX 77030, USA
| | - Junichi Shindoh
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX 77030, USA
| | - Steven A. Curley
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX 77030, USA
| | - Thomas A. Aloia
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX 77030, 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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Metastatic recurrence after complete resection of colorectal liver metastases: impact of surgery and chemotherapy on survival. Int J Colorectal Dis 2013; 28:1009-17. [PMID: 23371333 PMCID: PMC3712136 DOI: 10.1007/s00384-013-1648-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/21/2013] [Indexed: 02/04/2023]
Abstract
PURPOSE Surgery is the standard of care for resectable colorectal liver metastases (CRC-LM). Unfortunately, 60% of patients develop secondary metastatic recurrence (SMR) after R0-resection of CRC-LM. We investigated the impact of surgical re-intervention and chemotherapy (Ctx) on survival in a consecutive series of patients with SMR. METHODS From 01/2001 to 11/2011, 104 out of 178 consecutive patients with R0-resection of CRC-LM developed SMR and were evaluated. The impact of surgical and Ctx re-interventions on recurrence free (RFS) and cancer-specific survival (CSS) was analyzed. Median follow-up was 28.0 (95%CI: 19.4-37.4) months. RESULTS SMR occurred in 81 patients at a single site (49× liver, 18× lung, 14× other) and in 23 patients at multiple sites. Forty-two patients were scheduled for primary surgery. Fifty-three patients were classified as non-resectable and treated with median 5.0 [IQR, 3.0-10.0] cycles of Ctx, combined with an EGFR/VEGF-antibody in 27 patients. Nine patients received best supportive care only. R0/R1 resection could be achieved in 35 patients primarily and even in 8 patients secondarily after Ctx. Surgical morbidity and mortality were 16 and 0%, respectively. The 5-year RFS rates for patients with R0 versus R1-resection were 22 and 24% (p = 0.948). The 5-year CSS rate for R0/R1-resected patients was 38% versus 10% for those patients treated by Ctx alone (p < 0.001). CONCLUSION In SMR, surgical re-intervention is feasible and safe in a remarkable number of patients and offers significantly longer CSS compared to patients without resection.
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One-Stage Hepatectomy Following Portal Vein Embolization for Colorectal Liver Metastasis. World J Surg 2012; 37:622-8. [DOI: 10.1007/s00268-012-1861-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Pattern of Postoperative Recurrence and Hepatic and/or Pulmonary Resection for Liver and/or Lung Metastases From Esophageal Carcinoma. World J Surg 2012; 37:398-407. [DOI: 10.1007/s00268-012-1830-7] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Brandi G, Corbelli J, de Rosa F, Di Girolamo S, Longobardi C, Agostini V, Garajová I, La Rovere S, Ercolani G, Grazi GL, Pinna AD, Biasco G. Second surgery or chemotherapy for relapse after radical resection of colorectal cancer metastases. Langenbecks Arch Surg 2012; 397:1069-77. [PMID: 22711237 DOI: 10.1007/s00423-012-0974-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2012] [Accepted: 06/08/2012] [Indexed: 02/08/2023]
Abstract
PURPOSE Limited data suggest that second resections for colorectal cancer metastases may improve survival, but no study has compared surgery with chemotherapy in this setting. Therefore, we retrospectively compared the clinical outcome of potentially resectable patients who received a second metastasectomy with those who did not in our single-centre experience. METHODS We retrospectively reviewed the clinical records of all patients treated for metastatic colorectal cancer in our centre over a period of 12 years. We selected patients who relapsed after radical resection of metastases from colorectal cancer and were deemed resectable again by our multidisciplinary team. We then compared the clinical outcome of those who received a second operation with those who refused surgery and also evaluated the role of prognostic factors. RESULTS We identified 60 patients fulfilling the inclusion criteria. Twenty-nine underwent a second resection and 31 refused surgery. Median overall survival rates were 58.7 and 24.0 months, median times to progression were 14.4 and 6.6 months. Patients who received surgery plus perioperatory chemotherapy (18/29) had a significantly better outcome; 4/29 achieved long-term disease-free survival. CONCLUSIONS Our study suggests that in highly selected metastatic colorectal cancer patients, a multimodal treatment plan, including a second resection, can achieve longer survival with respect to medical therapy.
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Affiliation(s)
- Giovanni Brandi
- Department of Haematology and Oncological Sciences "L. e A. Seràgnoli", University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
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Safety of intermittent Pringle maneuver cumulative time exceeding 120 minutes in liver resection: a further step in favor of the "radical but conservative" policy. Ann Surg 2012; 255:270-80. [PMID: 21975322 DOI: 10.1097/sla.0b013e318232b375] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
OBJECTIVE We retrospectively compared the short-term outcome of a consecutive cohort of patients who underwent hepatectomy with intermittent clamping ranging between 60 and 120 minutes with those having a clamping time exceeding 120 minutes. BACKGROUND Intermittent Pringle maneuver is widely used to minimize blood loss during hepatectomy, without an established time limit. However, many authors claim it is dangerous for patient outcome. MATERIAL AND METHODS Among 426 consecutive patients who underwent hepatectomy, we retrospectively selected 189 whose intermittent clamping time exceeded 60 minutes: 117 of these had intermittent Pringle maneuver lasting less than 120 minutes (group 1) and 72 clamping time exceeded 120 minutes (group 2). Groups were homogeneous for demographics, preoperative laboratory tests, background liver, and type of tumors. RESULTS Operation length, and number of lesions removed, was significantly higher in group 2. Conversely, the two groups experienced similar amount of blood loss, rate of blood transfusions, overall and major morbidity, and 30- and 90-day postoperative mortality. In particular, in group 2 there was no mortality at all. Mean serum total bilirubin and alanine aminotransferase level on seventh pod resulted significantly higher in group 2, conversely mean aspartate aminotransferase, cholinesterases, and prothrombin time not differed in 2 groups. CONCLUSIONS This study shows that hepatectomies done with intermittent clamping exceeding 120 minutes are as safe as those performed with shorter one despite more complex tumor presentations. This seems encouraging the diffusion of procedures done in 1 stage for extensive liver diseases despite the prolonged clamping time.
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Abstract
Approximately 20-25% of patients with colorectal cancer present with liver metastases at the time of diagnosis. Traditionally, resection of the primary tumor has been advocated in order to prevent complications of the primary tumor colorectal cancer in patients with synchronous liver metastases. The published data concerning long-term prognosis in this group of patients are discordant. Although some of the reports show survival benefits from resection of the primary tumor, these studies are retrospective with small number of patients and using single drug chemotherapy. For patients with resectable liver metastases, new studies indicate that progression-free survival is best in patients receiving perioperative chemotherapy. In patients with synchronous nonresectable liver metastases and colorectal cancer, there is no published prospective randomized study comparing initial surgery of the primary tumor with neoadjuvant chemotherapy. However, recent publications show that in patients receiving chemotherapy based on oxaliplatin or irinotecan combined with targeted treatments, the complications associated with the primary tumor are less than 10%. The conclusion should be that today prophylactic surgery of asymptomatic primary colorectal cancer in patients with liver metastases cannot be recommended.
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Affiliation(s)
- Bengt Gustavsson
- Department of Surgery, University of Gothenburg, Sahlgrenska University Hospital/Östra Institute of Clinical Sciences, Göteborg, Sweden.
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Zdenkowski N, Chen S, van der Westhuizen A, Ackland S. Curative strategies for liver metastases from colorectal cancer: a review. Oncologist 2012; 17:201-11. [PMID: 22234631 DOI: 10.1634/theoncologist.2011-0300] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Colorectal cancer is a very common malignancy and frequently manifests with liver metastases, often without other systemic disease. Margin-negative (R0) resection of limited metastatic disease, in conjunction with systemic antineoplastic agents, is the primary treatment strategy, leading to long survival times for appropriately selected patients. There is debate over whether the primary tumor and secondaries should be removed at the same time or in a staged manner. Chemotherapy is effective in converting some unresectable liver metastases into resectable disease, with a correspondingly better survival outcome. However, the ideal chemotherapy with or without biological agents and when it should be administered in the course of treatment are uncertain. The role of neoadjuvant chemotherapy in initially resectable liver metastases is controversial. Local delivery of chemotherapy, with and without surgery, can lead to longer disease-free survival times, but it is not routinely used with curative intent. This review focuses on methods to maximize the disease-free survival interval using chemotherapy, surgery, and local methods.
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Affiliation(s)
- Nicholas Zdenkowski
- Department of Medical Oncology, Calvary Mater Hospital, Locked Bag No 7, Hunter Regional Mail Centre, Newcastle, NSW, 2310 Australia.
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Grundmann RT. Current state of surgical treatment of liver metastases from colorectal cancer. World J Gastrointest Surg 2011; 3:183-96. [PMID: 22224173 PMCID: PMC3251742 DOI: 10.4240/wjgs.v3.i12.183] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2010] [Revised: 10/23/2011] [Accepted: 11/01/2011] [Indexed: 02/06/2023] Open
Abstract
Hepatic resection is the procedure of choice for curative treatment of colorectal liver metastases (CLM). Objectives of surgical strategy are low intraoperative blood loss, short liver ischemic times and minor postoperative morbidity and mortality. Blood loss is an independent predictor of mortality and compromises, in common with postoperative complications, long-term outcome after hepatectomy for CLM. The type of liver resection has no impact on the outcome of patients with CLM; wedge resections are not inferior to anatomical resections in terms of tumor clearance, pattern of recurrence or survival. Despite the lack of proof of survival benefit, routine lymphadenectomy has been advocated, allowing the detection of microscopic lymph node metastases and with prognostic value. In experienced hands, minimally invasive liver surgery is safe with acceptable morbidity and mortality and oncological results comparable to open hepatic surgery, but with reduced blood loss and earlier recovery. The European Colorectal Metastases Treatment Group recommended treating up front with chemotherapy for patients with both resectable and unresectable CLM. However, neoadjuvant chemotherapy can induce damage to the remnant liver, dependent on the number of chemotherapy cycles. Therefore, in our opinion, preoperative chemotherapy should be reserved for patients whose CLM are marginally resectable or unresectable. A meta analysis of randomized trials dealing with perioperative chemotherapy for the treatment of resectable CLM demonstrated a benefit of systemic chemotherapy but did not answer the question of whether a neoadjuvant or adjuvant approach should be preferred. Analysis of the literature demonstrates that the results of specialized centers cannot be attained in the reality of comprehensive patient care. Reasons behind the commonly poorer results seen in cancer networks as compared with literature-based data are, on the one hand, geographical disparities in access to specialized surgical and medical care. On the other hand, a selection bias in the reports of the literature may be assumed. Studies of surgical resection for CLM derive almost exclusively from case series generally drawn from large academic centers where patient selection or surgical expertise is superior to what is found in many communities. Therefore, we may conclude that the comprehensive propagation of the standards outlined in this paper constitutes a major task in the near future to reduce the variations in survival of patients with CLM.
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Affiliation(s)
- Reinhart T Grundmann
- Reinhart T Grundmann, Kreiskliniken Altötting-Burghausen, In den Grüben 144, D-84489 Burghausen, Germany
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[Surgical treatment of liver metastasis in patients with colorectal cancer]. Presse Med 2011; 41:58-67. [PMID: 22138292 DOI: 10.1016/j.lpm.2011.10.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2011] [Accepted: 10/19/2011] [Indexed: 02/06/2023] Open
Abstract
Half of patients with colorectal cancer have liver metastasis during their illness. Surgical resection of metastases represents the only curative treatment with prolonged survival in more than 50 % of patients. The aim of liver resection is complete excision of the lesions with histological negative margins while preserving sufficient functional liver parenchyma. In patients with diffuse liver disease, the radiofrequency ablation of metastases may be associated with surgical resection. The use of portal vein remobilization and neoadjuvant chemotherapy can also increase the number of patients for curative treatment. Despite this progress, from 50 to 60 % of patients relapse after complete resection of MHCCR. Surgical treatment of recurrent aggressive and effective chemotherapy allows the prolonged survival of these patients. The modern treatment of liver metastasis of colorectal cancers can be envisaged as part of a multidisciplinary approach to increase the number of patients for curative treatment.
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Survival after lung metastasectomy for colorectal cancer: importance of previous liver metastasis as a prognostic factor. Eur J Surg Oncol 2011; 37:786-90. [PMID: 21723689 DOI: 10.1016/j.ejso.2011.05.014] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2010] [Revised: 03/11/2011] [Accepted: 05/23/2011] [Indexed: 01/12/2023] Open
Abstract
AIMS To analyse patient survival after the resection of lung metastases from colorectal carcinoma and specifically to verify whether presence of liver metastasis prior to lung metastasectomy affects survival. METHODS All patients who, between 1998 and 2008, underwent lung metastasectomy due to colorectal cancer were included in the study. Kaplan-Meier survival analysis was performed with the log-rank test and Cox regression multivariate analysis. RESULTS During this period, 101 metastasectomies were performed on 84 patients. The median age of patients was 65.4 years, and 60% of patients were male. The 30-day mortality rate was 2%, and incidence of complications was 7%. The overall survival was 72 months, with 3-and 5-year survival rates of 70% and 54%, respectively. A total of 17 patients (20%) had previously undergone resection of liver metastasis. No significant differences were found in the distribution of what were supposed to be the main variables between patients with and without previous hepatic metastases. Multivariate analysis identified the following statistically significant factors affecting survival: previous liver metastasectomy (p = 0.03), tumour-infiltrated pulmonary lymph nodes (p = 0.04), disease-free interval ≥ 48 months (p = 0.03), and presence of more than one lung metastasis (p < 0.01). In patients with previous liver metastasis, the shorter the time between primary colorectal surgery and the hepatectomy, the lower the survival rate after pulmonary metastasectomy (p = 0.048). CONCLUSIONS A previous history of liver metastasis shortens survival after lung metastasectomy. The time between hepatic resection and lung metastasectomy does not affect survival; however, patients with synchronous liver metastasis and colorectal neoplasia have poorer survival rates than those with metachronous disease.
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Chua TC, Al-Alem I, Zhao J, Glenn D, Liauw W, Morris DL. Radiofrequency ablation of concomitant and recurrent pulmonary metastases after surgery for colorectal liver metastases. Ann Surg Oncol 2011; 19:75-81. [PMID: 21710327 DOI: 10.1245/s10434-011-1859-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2011] [Indexed: 11/18/2022]
Abstract
BACKGROUND To evaluate our experience of radiofrequency ablation (RFA) of pulmonary metastases in patients with resected colorectal liver metastases who had concomitant or recurrent pulmonary metastases. METHODS Clinical and treatment variables of patients undergoing RFA were collected, and their association with survival was examined. Survival analysis was performed by the Kaplan-Meier method. RESULTS RFA was performed as concomitant sequential treatment of extrahepatic pulmonary metastases after hepatectomy in 19 patients (30%) and as salvage treatment for pulmonary recurrences after hepatectomy in 45 patients (70%). Patients undergoing sequential treatment had a median survival of 31 (95% confidence interval [CI] 21.8-40.6) months compared to 59 (95% CI 35.0-82.0) months in the salvage treatment group (P = 0.142). The disease-free survival (DFS) was 9 (95% CI 1.0-18.8) months in the sequential treatment group and 16 (95% CI 8.1-23.1) months in the salvage treatment group (P = 0.023). Liver metastases occurring within 12 months of the primary tumor negatively influenced overall survival (OS) and DFS in the sequential treatment group (P = 0.003 and P = 0.091). Poorly differentiated tumor (P = 0.001) was associated with a poorer OS, and prehepatectomy carcinoembryonic antigen > 200 ng/ml (P = 0.017) and bilateral pulmonary metastases (P = 0.030) were associated with a shorter DFS in the salvage treatment group. CONCLUSIONS The DFS and OS of patients undergoing sequential RFA of extrahepatic pulmonary metastases after hepatectomy appeared shorter when compared to patients who underwent RFA as salvage treatment for pulmonary recurrences after hepatectomy. It nonetheless remains better than the historical results of chemotherapy alone and thus supports the use of RFA as an ablative technology to achieve tumor control.
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Affiliation(s)
- Terence C Chua
- Hepatobiliary and Surgical Oncology Unit, UNSW Department of Surgery, St George Hospital, Sydney, NSW, Australia.
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Hammill CW, Billingsley KG, Cassera MA, Wolf RF, Ujiki MB, Hansen PD. Outcome after laparoscopic radiofrequency ablation of technically resectable colorectal liver metastases. Ann Surg Oncol 2011; 18:1947-54. [PMID: 21399885 DOI: 10.1245/s10434-010-1535-9] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2010] [Indexed: 02/06/2023]
Abstract
BACKGROUND There continues to be controversy surrounding the appropriate use of radiofrequency ablation (RFA) for the treatment of colorectal liver metastases (CRLM). This study analyzes outcomes data of CRLM patients who underwent laparoscopic RFA. Outcomes of patients determined to be technically resectable were compared to patients with unresectable disease. METHODS Data from all patients with CRLM who underwent laparoscopic RFA between 1996 and 2006 were retrospectively reviewed. A blinded independent hepatobiliary-trained surgical oncologist reviewed preoperative diagnostic imaging studies to determine resectability. Outcomes data for patients with disease deemed anatomically resectable and unresectable were analyzed and compared. Survival was calculated by the Kaplan-Meier method. The log rank test was performed to assess significance in survival. RESULTS A total of 113 patients who underwent laparoscopic RFA for CRLM were identified. Twelve patients who underwent concurrent hepatic resection were excluded. Of the remaining patients, 64 were determined to have disease that was be technically resectable and 37 unresectable as a result of tumor number and/or distribution. Median and 5-year survival of the potentially resectable group was 4.3years and 48.7%, compared to 2.2 years and 18.4% in the unresectable group (P = 0.002). Median disease-free survival in the resectable group was 15.0 months, compared to 16.4 months in the unresectable group (P = 0.796). No postoperative mortality was reported in the technically resectable group, and the rate of major complications was 3.1%. CONCLUSIONS Laparoscopic RFA of resectable CRLM can produce comparable long-term survival to hepatic resection in carefully selected patients, with favorable morbidity and mortality.
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Affiliation(s)
- Chet W Hammill
- Liver and Pancreas Surgery Program, Providence Portland Medical Center, Portland, OR, USA
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Pohlen U, Buhr HJ, Berger G, Ritz JP, Holmer C. Hepatic arterial infusion (HAI) with PEGylated liposomes containing 5-FU improves tumor control of liver metastases in a rat model. Invest New Drugs 2011; 30:927-35. [PMID: 21360049 DOI: 10.1007/s10637-011-9646-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2010] [Accepted: 02/17/2011] [Indexed: 01/16/2023]
Abstract
PURPOSE To investigate the cytostatic effect of 5-fluorouracil (5-FU) encapsulated in polyethylene glycol (PEG) liposomes with or without degradable starch microspheres (DSM) in a long-term trial using a rat liver tumor model. MATERIALS AND METHODS The cytostatics were applied once either as a hepatic arterial infusion (HAI) or were systemically infused via the tail vein. Seven groups were compared with respect to tumor growth and survival times: 5-FU HAI (group I), 5-FU + DSM HAI (group II), PEG-5-FU HAI (group III), PEG-5-FU + DSM HAI (group IV), NaCl HAI (group V), 5-FU i.v. (group VI), and PEG-5-FU i.v. (group VII). RESULTS Seven and 14 days after treatment in groups III and IV, only group IV had significantly inhibited tumor growth on day 21 compared to the groups treated intravenously. On day 28, none of the animals from the intravenously treated groups were still alive compared to a significantly longer survival time of 6 and 8 weeks in groups III and IV. CONCLUSION Locoregional therapy with 5-fluorouracil encapsulated in PEGylated liposomes may further improve the treatment success with longer-lasting tumor regression and prolonged survival times.
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Affiliation(s)
- Uwe Pohlen
- Department of General, Vascular and Thoracic Surgery, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin Hindenburgdamm 30, 12200, Berlin, Germany
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