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Georgakis GV, Goldberg I, Sasson AR. Current Trends in the Surgical Management of Colorectal Cancer Liver Metastases. CURRENT COLORECTAL CANCER REPORTS 2019. [DOI: 10.1007/s11888-019-00440-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Boone BA, Perkins S, Bandi R, Santos E, McCluskey K, Bartlett DL, Pingpank JF. Hepatic artery infusion of melphalan in patients with liver metastases from ocular melanoma. J Surg Oncol 2018; 117:940-946. [PMID: 29878390 DOI: 10.1002/jso.24984] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2017] [Accepted: 12/18/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND OBJECTIVES Ocular melanoma has a predilection for liver metastases. Systemic treatment is ineffective and the optimal regional therapy approach is poorly defined. Isolated hepatic perfusion (IHP) with melphalan has emerged as a viable treatment option, however a subset of patients are not candidates for this treatment. We therefore sought to determine if melphalan could be safely administered via the hepatic artery for these patients. METHODS A retrospective review of patients treated with hepatic artery infusion (HAI) of melphalan was undertaken. All patients had contraindications to IHP and were without other therapy options. Melphalan infusion was repeated every four weeks with consideration for dose escalation in the absence of toxicity or significant disease progression. RESULTS Fourteen patients were treated with HAI of melphalan from 2010 to 2015. All patients had hepatic dysfunction or prohibitive tumor volume precluding IHP. There were no procedure-related complications. Three patients (21%) died within 30 days and the median survival was 2.9 months. Elevated baseline bilirubin > 2.5 mg/dL was associated with worse overall survival (0.93 vs 6.3 months, P < 0.05). CONCLUSION HAI of melphalan is safe and feasible for patients with metastatic ocular melanoma. Further study to determine the optimal utilization of this treatment approach is warranted.
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Affiliation(s)
- Brian A Boone
- Division of Surgical Oncology, Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Samantha Perkins
- Division of Surgical Oncology, Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Rupal Bandi
- Division of Surgical Oncology, Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Ernesto Santos
- Department of Radiology, Memorial Sloan Kettering, New York, New York
| | - Kevin McCluskey
- Department of Radiology, West Virginia University, Morgantown, West Virginia
| | - David L Bartlett
- Division of Surgical Oncology, Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - James F Pingpank
- Division of Surgical Oncology, Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
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Chakedis J, Squires MH, Beal EW, Hughes T, Lewis H, Paredes A, Al-Mansour M, Sun S, Cloyd JM, Pawlik TM. Update on current problems in colorectal liver metastasis. Curr Probl Surg 2017; 54:554-602. [PMID: 29198365 DOI: 10.1067/j.cpsurg.2017.10.002] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Jeffrey Chakedis
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Malcolm H Squires
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Eliza W Beal
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Tasha Hughes
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Heather Lewis
- University of Colorado Health System, Fort Collins, CO
| | - Anghela Paredes
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Mazen Al-Mansour
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Steven Sun
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Jordan M Cloyd
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH
| | - Timothy M Pawlik
- The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH.
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Meng T, Li GQ, Dai MH. Isolated hepatic perfusion for unresectable hepatic malignancies: A systematic review and meta-analysis. World J Meta-Anal 2016; 4:105-117. [DOI: 10.13105/wjma.v4.i5.105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Revised: 06/24/2016] [Accepted: 08/16/2016] [Indexed: 02/05/2023] Open
Abstract
AIM To investigate the efficacy and safety of isolated hepatic perfusion (IHP) in the management of unresectable liver malignancies.
METHODS Studies were identified manually and on-line by using PubMed and EMBASE database. We formulate the eligibility criteria according to the PICOS elements, and accessed the quality of studies using the MINORS instrument. Data from all included studies were carefully investigated. We calculated the pooled response rate and incidences of mortality reported from all eligible studies by using the Meta-Analyst software, and we computed a pooled relative risk (RR) and 95%CI by using the Comprehensive Meta-Analysis software. Heterogeneity was quantified evaluated using I2 statistic.
RESULTS Eight studies, including 502 patients, were selected. Of these, six studies performed IHP, while the other two studies performed percutaneous IHP. The results showed that the pooled response rate was 60.8% (95%CI: 53.1%-68%), I2 = 37.1%. The median overall survival was 20 mo (range: 12.1 to 25 mo) following IHP or PIHP. The pooled mortality rate was 5.4% (95%CI: 2.5%-11.2%), I2 = 37.5%. Prognostic factors predict the response to IHP or survival, and were reported in six studies. Meta-analysis demonstrated that Gender was not associated with overall survival (RR = 0.877, 95%CI: 0.564-1.365); however, carcino-embryonic antigen ≤ 30 ng/mL was associated with a significant improvement in survival outcomes with colorectal cancer patients (RR = 2.082, 95%CI: 1.371-3.163), and there was no significant heterogeneity.
CONCLUSION The present systemic review and meta-analysis suggest that IHP and PIHP are potentially efficient and safe techniques for unresectable liver primary and secondary malignancies.
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Abstract
Isolated hepatic perfusion uses the unique vascular supply of hepatic malignancies to deliver cytotoxic chemotherapy. The procedure involves vascular isolation of the liver and delivery of chemotherapy via the hepatic artery and extraction from retrohepatic vena cava. Benefits of hepatic perfusion have been observed in hepatic metastases of ocular melanoma and colorectal cancer and primary hepatocellular carcinoma. Percutaneous and prophylactic perfusions are avenues of ongoing research.
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Affiliation(s)
- Rahul Rajeev
- Division of Surgical Oncology, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA
| | - T Clark Gamblin
- Division of Surgical Oncology, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA
| | - Kiran K Turaga
- Division of Surgical Oncology, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA.
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van Iersel LBJ, de Leede EM, Vahrmeijer AL, Tijl FGJ, den Hartigh J, Kuppen PJK, Hartgrink HH, Gelderblom H, Nortier JWR, Tollenaar RAEM, van de Velde CJH. Isolated hepatic perfusion with oxaliplatin combined with 100 mg melphalan in patients with metastases confined to the liver: A phase I study. Eur J Surg Oncol 2014; 40:1557-63. [PMID: 25125340 DOI: 10.1016/j.ejso.2014.06.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Revised: 06/18/2014] [Accepted: 06/26/2014] [Indexed: 12/31/2022] Open
Abstract
AIM To improve isolated hepatic perfusion (IHP), we performed a phase I dose-escalation study to determine the optimal oxaliplatin dose in combination with a fixed melphalan dose. METHODS Between June 2007 and July 2008, 11 patients, comprising of 8 colorectal cancer and 3 uveal melanoma patients and all with isolated liver metastases, were treated with a one hour IHP with escalating doses of oxaliplatin combined with 100 mg melphalan. Samples of blood and perfusate were taken during IHP treatment for pharmacokinetic analysis of both drugs and patients were monitored for toxicity, response and survival. RESULTS Dose limiting sinusoidal obstruction syndrome (SOS) occurred at 150 mg oxaliplatin. The areas under the concentration-time curves (AUC) of oxaliplatin at the maximal tolerated dose (MTD) of 100 mg oxaliplatin ranged from 11.9 mg/L h to 16.5 mg/L h. All 4 patients treated at the MTD showed progressive disease 3 months after IHP. CONCLUSIONS In view of similar and even higher doses of oxaliplatin applied in both systemic treatment and hepatic artery infusion (HAI), applying this dose in IHP is not expected to improve treatment results in patients with isolated hepatic metastases.
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Affiliation(s)
- L B J van Iersel
- Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - E M de Leede
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - A L Vahrmeijer
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - F G J Tijl
- Department of Extra Corporal Circulation, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - J den Hartigh
- Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - P J K Kuppen
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - H H Hartgrink
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - H Gelderblom
- Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - J W R Nortier
- Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - R A E M Tollenaar
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
| | - C J H van de Velde
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
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Chen Z, Zhu X, Xie T, Xie J, Quo K, Liu X. Drug resistance reversed by silencing LIM domain-containing protein 1 expression in colorectal carcinoma. Oncol Lett 2014; 8:795-798. [PMID: 25013501 PMCID: PMC4081406 DOI: 10.3892/ol.2014.2155] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2013] [Accepted: 03/20/2014] [Indexed: 12/12/2022] Open
Abstract
The role of LIM domain-containing protein 1 (LIMD1) in the multidrug resistance of colorectal carcinoma (CRC) has not yet been established. The aim of the current study was to investigate the chemosensitivity of CRC multidrug-resistant (MDR) cells following the silencing of LIMD1. The MDR phenotypic Colo205 and HCT-8 cell lines were examined, which were established by exposure to increasing doses of 5-fluorouracil (5-FU) over a period of one year. LIMD1 siRNA constructs were transfected into CRC MDR cells and the phenotypic effects were determined comprehensively. The Colo205 and HCT-8 cell lines were more resistant to 5-FU compared with their respective parental cell lines. In addition, the two MDR cell types expressed significantly more LIMD1 compared with their parental lines. The stably transfected cells showed various degrees of reversal of the MDR phenotype, and 5-FU-induced apoptosis was increased in the transfected cells compared with the controls. In conclusion, RNA interference targeting LIMD1 may present a novel therapeutic option for CRC.
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Affiliation(s)
- Zhangxing Chen
- Department of Gastroenterology, The 174th Hospital of the PLA, Xiamen University, Xiamen, Fujian 361003, USA
| | - Xiaosan Zhu
- Department of Gastroenterology, The 174th Hospital of the PLA, Xiamen University, Xiamen, Fujian 361003, USA ; Department of Gastroenterology, Chenggong Hospital, Xiamen University, Xiamen, Fujian 361003, USA
| | - Tao Xie
- Department of Gastroenterology, The 174th Hospital of the PLA, Xiamen University, Xiamen, Fujian 361003, USA
| | - Junpei Xie
- Department of Gastroenterology, The 174th Hospital of the PLA, Xiamen University, Xiamen, Fujian 361003, USA
| | - Kong Quo
- Center for Clinical and Translational Science, Creighton University School of Medicine, Omaha, NE 68178, USA
| | - Xiang Liu
- Department of Gastroenterology, The 174th Hospital of the PLA, Xiamen University, Xiamen, Fujian 361003, USA
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