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Gurusamy K, Leung J, Vale C, Roberts D, Linden A, Wei Tan X, Taribagil P, Patel S, Pizzo E, Davidson B, Mould T, Saunders M, Aziz O, O'Dwyer S. Hyperthermic intraoperative peritoneal chemotherapy and cytoreductive surgery for people with peritoneal metastases: a systematic review and cost-effectiveness analysis. Health Technol Assess 2024; 28:1-139. [PMID: 39254852 PMCID: PMC11417642 DOI: 10.3310/kwdg6338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/11/2024] Open
Abstract
Background We compared the relative benefits, harms and cost-effectiveness of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery ± systemic chemotherapy versus cytoreductive surgery ± systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric or ovarian cancers by a systematic review, meta-analysis and model-based cost-utility analysis. Methods We searched MEDLINE, EMBASE, Cochrane Library and the Science Citation Index, ClinicalTrials.gov and WHO ICTRP trial registers until 14 April 2022. We included only randomised controlled trials addressing the research objectives. We used the Cochrane risk of bias tool version 2 to assess the risk of bias in randomised controlled trials. We used the random-effects model for data synthesis when applicable. For the cost-effectiveness analysis, we performed a model-based cost-utility analysis using methods recommended by The National Institute for Health and Care Excellence. Results The systematic review included a total of eight randomised controlled trials (seven randomised controlled trials, 955 participants included in the quantitative analysis). All comparisons other than those for stage III or greater epithelial ovarian cancer contained only one trial, indicating the paucity of randomised controlled trials that provided data. For colorectal cancer, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably results in little to no difference in all-cause mortality (60.6% vs. 60.6%; hazard ratio 1.00, 95% confidence interval 0.63 to 1.58) and may increase the serious adverse event proportions compared to cytoreductive surgery ± systemic chemotherapy (25.6% vs. 15.2%; risk ratio 1.69, 95% confidence interval 1.03 to 2.77). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone (40.8% vs. 60.8%; hazard ratio 0.55, 95% confidence interval 0.32 to 0.95). For gastric cancer, there is high uncertainty about the effects of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy versus cytoreductive surgery + systemic chemotherapy or systemic chemotherapy alone on all-cause mortality. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to cytoreductive surgery + systemic chemotherapy (46.3% vs. 57.4%; hazard ratio 0.73, 95% confidence interval 0.57 to 0.93). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy may not be cost-effective versus cytoreductive surgery + systemic chemotherapy for colorectal cancer but may be cost-effective for the remaining comparisons. Limitations We were unable to obtain individual participant data as planned. The limited number of randomised controlled trials for each comparison and the paucity of data on health-related quality of life mean that the recommendations may change as new evidence (from trials with a low risk of bias) emerges. Conclusions In people with peritoneal metastases from colorectal cancer with limited peritoneal metastases and who are likely to withstand major surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should not be used in routine clinical practice (strong recommendation). There is considerable uncertainty as to whether hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy or cytoreductive surgery + systemic chemotherapy should be offered to patients with gastric cancer and peritoneal metastases (no recommendation). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should be offered routinely to women with stage III or greater epithelial ovarian cancer and metastases confined to the abdomen requiring and likely to withstand interval cytoreductive surgery after chemotherapy (strong recommendation). Future work More randomised controlled trials are necessary. Study registration This study is registered as PROSPERO CRD42019130504. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/135/02) and is published in full in Health Technology Assessment; Vol. 28, No. 51. See the NIHR Funding and Awards website for further award information.
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Affiliation(s)
- Kurinchi Gurusamy
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Jeffrey Leung
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Claire Vale
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Danielle Roberts
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Audrey Linden
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Xiao Wei Tan
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Priyal Taribagil
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Sonam Patel
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Elena Pizzo
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Brian Davidson
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Tim Mould
- Department of Gynaecological Oncology, University College London NHS Foundation Trust, London, UK
| | - Mark Saunders
- Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK
| | - Omer Aziz
- Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK
- Institute of Cancer Sciences, University of Manchester, Manchester, UK
| | - Sarah O'Dwyer
- Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK
- Institute of Cancer Sciences, University of Manchester, Manchester, UK
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Sugarbaker PH, Chang D. Extent of Disease on Visceral Peritoneal Surfaces of Mucinous Appendiceal Neoplasms Controls Survival. ANNALS OF SURGERY OPEN 2022; 3:e193. [PMID: 37601148 PMCID: PMC10431514 DOI: 10.1097/as9.0000000000000193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 06/28/2022] [Indexed: 11/26/2022] Open
Abstract
Objective To determine causes of treatment failure of low-grade appendiceal mucinous neoplasms (LAMN). Background For 3 decades, LAMN have been treated by cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy. This combined treatment has resulted in a large change in the survival of these patients. Methods A retrospective review of a prospectively maintained database was performed. A restricted cohort of patients with only LAMN histology and complete CRS were included in the statistical analysis. Results Four hundred and fifty patients were available with a median follow-up of 15.3 years (range 10-35 years). The median age was 49.7 and there were 196 males (43.6%). The mean survival was 24.5 years. Extent of parietal peritonectomy, resection of uterus, ovaries and apex of vagina had no impact on survival. Variables that indicated an increased extent of disease on visceral peritoneal surfaces had a significant impact on survival. Early postoperative intraperitoneal chemotherapy with 5-fluorouracil did not augment hyperthermic intraperitoneal chemotherapy (HIPEC). Patients who required reoperation for recurrence or patients with class 4 adverse events had a reduced prognosis. Conclusions The mean survival of LAMN treated by complete CRS and perioperative chemotherapy was 24.5 years. Extent of disease quantitated on visceral peritoneal surfaces by the extent of visceral resections was the variable associated with treatment failure. Peritonectomy plus HIPEC was able to control disease on parietal peritoneal surfaces. Not only a larger extent of disease but also its location on visceral peritoneal surfaces controlled survival.
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Affiliation(s)
- Paul H. Sugarbaker
- From the Washington Cancer Institute, Program in Peritoneal Surface Malignancy Washington, DC
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Ruan S, Shi N, Chen Z, Han H, Wang H, Jin L, Zou Y, Zhang Y, Yu M, Jin H. The role of hyperthermic intraperitoneal chemotherapy in the treatment of spontaneously ruptured hepatocellular carcinoma: a pilot study. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1132. [PMID: 33240981 PMCID: PMC7576033 DOI: 10.21037/atm-20-5829] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 09/08/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND Spontaneous tumor rupture is a distinctive disease pattern in patients with hepatocellular carcinoma (HCC). The application of hyperthermic intraperitoneal chemotherapy (HIPEC) in spontaneously ruptured hepatocellular carcinoma (srHCC) is debatable. Our study aimed to compare the long-term outcomes of srHCC vs. nrHCC and to test the role of postoperative HIPEC in patients with srHCC after hepatectomy. METHODS From 2014 to 2018, PSM was performed to compare 57 patients who performed liver resection for srHCC and met the research criteria with 57 nrHCC patients selected from 446 consecutive patients. Then patients with srHCC were divided into two groups according to whether they underwent HIPEC after hepatectomy. RESULTS After 1:1 PSM, the clinical characteristics of the patients with srHCC and nrHCC were comparable. In terms of long-term outcomes, the nrHCC group had significantly longer OS (P=0.026) and DFS (P<0.001) than the srHCC group. Of the 57 srHCC patients, the HIPEC group showed added complications compared to the non-HIPEC group, including an increased length of hospital stay and higher in-hospital costs. However, there were no significant differences in the metastatic patterns of these recurrent patients, and there was no statistically significant difference in DFS (P=0.28) or OS (P=0.56) between the two groups. CONCLUSIONS The prognosis of ruptured HCC patients were worse than those of non-ruptured HCC patients. HIPEC may not be a robust treatment for srHCC now.
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Affiliation(s)
- Shiye Ruan
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Ning Shi
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Zhihong Chen
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Hongwei Han
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Hanyue Wang
- Department of Pathology, Jinan University, Guangzhou, China
| | - Liang Jin
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Yiping Zou
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Yuanpeng Zhang
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Min Yu
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Haosheng Jin
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
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Preparation and Evaluation of Intraperitoneal Long-Acting Oxaliplatin-Loaded Multi-Vesicular Liposomal Depot for Colorectal Cancer Treatment. Pharmaceutics 2020; 12:pharmaceutics12080736. [PMID: 32764318 PMCID: PMC7466130 DOI: 10.3390/pharmaceutics12080736] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 07/31/2020] [Accepted: 08/03/2020] [Indexed: 12/21/2022] Open
Abstract
Colorectal cancer with peritoneal metastasis has a poor prognosis because of inadequate responses to systemic chemotherapy. Cytoreductive surgery followed by intraperitoneal (IP) chemotherapy using oxaliplatin has attracted attention; however, the short half-life of oxaliplatin and its rapid clearance from the peritoneal cavity limit its clinical application. Here, a multivesicular liposomal (MVL) depot of oxaliplatin was prepared for IP administration, with an expected prolonged effect. After optimization, a combination of phospholipids, cholesterol, and triolein was used based on its ability to produce MVL depots of monomodal size distribution (1–20 µm; span 1.99) with high entrapment efficiency (EE) (92.16% ± 2.17%). An initial burst release followed by a long lag phase of drug release was observed for the MVL depots system in vitro. An in vivo pharmacokinetic study mimicking the early postoperative IP chemotherapy regimen in rats showed significantly improved bioavailability, and the mean residence time of oxaliplatin after IP administration revealed that slow and continuous erosion of the MVL particles yielded a sustained drug release. Thus, oxaliplatin-loaded MVL depots presented in this study have potential for use in the treatment of colorectal cancer.
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Gurusamy K, Vale CL, Pizzo E, Bhanot R, Davidson BR, Mould T, Mughal M, Saunders M, Aziz O, O'Dwyer S. Cytoreductive surgery (CRS) with hyperthermic intraoperative peritoneal chemotherapy (HIPEC) versus standard of care (SoC) in people with peritoneal metastases from colorectal, ovarian or gastric origin: protocol for a systematic review and individual participant data (IPD) meta-analyses of effectiveness and cost-effectiveness. BMJ Open 2020; 10:e039314. [PMID: 32404398 PMCID: PMC7228534 DOI: 10.1136/bmjopen-2020-039314] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 04/17/2020] [Accepted: 04/20/2020] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION There is uncertainty about whether cytoreductive surgery (CRS)+hyperthermic intraoperative peritoneal chemotherapy (HIPEC) improves survival and/or quality of life compared with standard of care (SoC) in people with peritoneal metastases who can withstand major surgery. PRIMARY OBJECTIVES To compare the relative benefits and harms of CRS+HIPEC versus SoC in people with peritoneal metastases from colorectal, ovarian or gastric cancers eligible to undergo CRS+HIPEC by a systematic review and individual participant data (IPD) meta-analysis. SECONDARY OBJECTIVES To compare the cost-effectiveness of CRS+HIPEC versus SoC from a National Health Service (NHS) and personal social services perspective using a model-based cost-utility analysis. METHODS AND ANALYSIS We will perform a systematic review of literature by updating the searches from MEDLINE, Embase, Cochrane library, Science Citation Index as well as trial registers. Two members of our team will independently screen the search results and identify randomised controlled trials comparing CRS+HIPEC versus SoC for inclusion based on full texts for articles shortlisted during screening. We will assess the risk of bias in the trials and obtain data related to baseline prognostic characteristics, details of intervention and control, and outcome data related to overall survival, disease progression, health-related quality of life, treatment related complications and resource utilisation data. Using IPD, we will perform a two-step IPD, that is, calculate the adjusted effect estimate from each included study and then perform a random-effects model meta-analysis. We will perform various subgroup analyses, meta-regression and sensitivity analyses. We will also perform a model-based cost-utility analysis to assess whether CRS+HIPEC is cost-effective in the NHS setting. ETHICS AND DISSEMINATION This project was approved by the UCL Research Ethics Committee (Ethics number: 16023/001). We aim to present the findings at appropriate international meetings and publish the review, irrespective of the findings, in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER CRD42019130504.
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Affiliation(s)
- Kurinchi Gurusamy
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Claire L Vale
- Meta-analysis Group, MRC Clinical Trials Unit at UCL, London, UK
| | - Elena Pizzo
- Department of Applied Health Research, University College London, London, UK
| | - R Bhanot
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Brian R Davidson
- Division of Surgery and Interventional Science, University College London, London, UK
- Department of HPB Surgery, Royal Free London NHS Foundation Trust, London, UK
| | - Tim Mould
- Gynaecological Oncology, University College London Hospitals NHS Trust, London, UK
| | - Muntzer Mughal
- Surgery, University College London Hospital NHS Foundation Trust, London, UK
| | - Mark Saunders
- Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK
| | - Omer Aziz
- Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK
| | - Sarah O'Dwyer
- Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK
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6
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Somer FD, Ceelen W, Delanghe J, Smet DD, Vanackere M, Pattyn P, Mortier E. Severe Hyponatremia, Hyperglycemia, and Hyperlactatemia Are Associated with Intraoperative Hyperthermic Intraperitoneal Chemoperfusion with Oxaliplatin. Perit Dial Int 2020. [DOI: 10.1177/089686080802800111] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background Since the introduction of surgical debulking in combination with intraoperative hyperthermic intra-peritoneal chemoperfusion (HIPEC) with oxaliplatin in our institution, severe hyponatremia (sodium: 126.5 ± 3.8 mmol/L), hyperglycemia (glucose: 22.37 ± 4.89 mmol/L), and hyperlactatemia (lactate: 3.17 ± 1.8 mmol/L) have been observed post HIPEC. This metabolic disorder was not observed in patients in whom cisplatin or mitomycin C was used as a chemotherapeutic drug. Methods In order to understand the pathophysiology of this finding, an analysis of our data was made. In a first analysis, plasma sodium was corrected for hyperglycemia based on the formula of Hillier. In a second analysis, the influence of total exchangeable sodium, total exchangeable potassium, and total body water on plasma sodium concentration was modeled. Results Analysis of our data revealed a double mechanism for the observed metabolic disorder: hyperglycemia caused by dextrose 5%, which is used as a carrier for the oxaliplatin, and major loss of sodium into the dialysate (256.7 ± 68.7 mmol). Conclusion Better control of hyperglycemia and intravenous compensation of sodium loss into the dialysate can attenuate the reported biochemical disturbance.
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Affiliation(s)
- Filip De Somer
- Departments of Cardiac Surgery, University Hospital Ghent, Ghent, Belgium
| | - Wim Ceelen
- Abdominal Surgery, University Hospital Ghent, Ghent, Belgium
| | - Joris Delanghe
- Central Laboratory, University Hospital Ghent, Ghent, Belgium
| | - Dirk De Smet
- Departments of Cardiac Surgery, University Hospital Ghent, Ghent, Belgium
| | - Martin Vanackere
- Departments of Cardiac Surgery, University Hospital Ghent, Ghent, Belgium
| | - Piet Pattyn
- Abdominal Surgery, University Hospital Ghent, Ghent, Belgium
| | - Eric Mortier
- Anaesthesia, University Hospital Ghent, Ghent, Belgium
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Nguyen MK. Lessons Learned from Hyponatremia Associated with Hyperthermic Intraperitoneal Chemoperfusion with Oxaliplatin. Perit Dial Int 2020. [DOI: 10.1177/089686080802800107] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Affiliation(s)
- Minhtri K. Nguyen
- Department of Medicine University of California at Los Angeles California, USA
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8
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Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy, Part I: Introduction and Indications. AORN J 2019; 110:479-499. [DOI: 10.1002/aorn.12842] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Shi R, Xiang W, Kang X, Zhang L, Wang J, Miao H, He F. Alteration of Adaptive Immunity in a Colorectal Peritoneal Carcinomatosis Model. J Cancer 2019; 10:367-377. [PMID: 30719130 PMCID: PMC6360308 DOI: 10.7150/jca.27947] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Accepted: 10/03/2018] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) usually gives rise to transcoelomic spread and ultimately causes peritoneal carcinomatosis (PC). However, mechanism studies, especially the immunological basis of colorectal PC, are rarely revealed due to lack of a suitable PC model. Here we selected a mouse colorectal cancer cell line MC-38 for intraperitoneal inoculation in the C57BL/6 mice to mimic the development of colorectal PC. We demonstrated that the injected CRC cells preferentially and rapidly migrated and colonized in the visceral fat tissues, but not in other visceral organs. With flow cytometric analysis, we found the proportions of spleen T cells and B cells were not affected by PC progression, while the ratios of blood CD4+ and CD8+ T cells were largely influenced. Especially, the quantity or activity of CD4+ and CD8+ T cells in visceral fats were intimately regulated by PC development. Taken together, we successfully constructed a colorectal PC model in immune-competent mice and revealed the alteration of adaptive immunity in PC development. Our study might potentiate the research and therapy strategies of colorectal PC.
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Affiliation(s)
- Rongchen Shi
- Department of Biochemistry and Molecular Biology, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Wei Xiang
- Department of Biochemistry and Molecular Biology, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Xia Kang
- Department of Biochemistry and Molecular Biology, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Lili Zhang
- Department of Military Psychology, School of Psychology, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Jinping Wang
- Department of Neurology, Chongqing Emergency Medical Center, Chongqing 400014, China
| | - Hongming Miao
- Department of Biochemistry and Molecular Biology, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Fengtian He
- Department of Biochemistry and Molecular Biology, Third Military Medical University (Army Medical University), Chongqing 400038, China
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McGee S, AlGhareeb W, Ahmad C, Armstrong D, Babak S, Berry S, Biagi J, Booth C, Bossé D, Champion P, Colwell B, Finn N, Goel R, Gray S, Green J, Harb M, Hyde A, Jeyakumar A, Jonker D, Kanagaratnam S, Kavan P, MacMillan A, Muinuddin A, Patil N, Porter G, Powell E, Ramjeesingh R, Raza M, Rorke S, Seal M, Servidio-Italiano F, Siddiqui J, Simms J, Smithson L, Snow S, St-Hilaire E, Stuckless T, Tate A, Tehfe M, Thirlwell M, Tsvetkova E, Valdes M, Vickers M, Virik K, Welch S, Marginean C, Asmis T. Eastern Canadian Colorectal Cancer Consensus Conference 2017. Curr Oncol 2018; 25:262-274. [PMID: 30111967 PMCID: PMC6092057 DOI: 10.3747/co.25.4083] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2017 was held in St. John's, Newfoundland and Labrador, 28-30 September. Experts in radiation oncology, medical oncology, surgical oncology, and cancer genetics who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of gastric, rectal, and colon cancer, including ■ identification and management of hereditary gastric and colorectal cancer (crc);■ palliative systemic therapy for metastatic gastric cancer;■ optimum duration of preoperative radiation in rectal cancer-that is, short- compared with long-course radiation;■ management options for peritoneal carcinomatosis in crc;■ implications of tumour location for treatment and prognosis in crc; and■ new molecular markers in crc.
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Affiliation(s)
- S.F. McGee
- Ontario—The Ottawa Hospital Cancer Centre, Ottawa (AlGhareeb, Asmis, Goel, Hyde, Jonker, Marginean, McGee, Vickers); Queen’s University and Cancer Centre of Southeastern Ontario, Kingston (Biagi, Booth, Virik); Princess Margaret Cancer Centre, Toronto (Dawson); St. Michael’s Hospital, Toronto (Babak); Sunnybrook Odette Cancer Centre, University of Toronto, Toronto (Berry); Cancer Centre of Southeastern Ontario, Kingston (Mahmud); Queensway Health Centre, Toronto (Muinuddin); Colorectal Cancer Canada, North York (Servidio-Italiano); Grand River Regional Cancer Centre, Kitchener (Tsvetkova, Valdes); London Health Sciences Centre, London (Welch)
| | - W. AlGhareeb
- Ontario—The Ottawa Hospital Cancer Centre, Ottawa (AlGhareeb, Asmis, Goel, Hyde, Jonker, Marginean, McGee, Vickers); Queen’s University and Cancer Centre of Southeastern Ontario, Kingston (Biagi, Booth, Virik); Princess Margaret Cancer Centre, Toronto (Dawson); St. Michael’s Hospital, Toronto (Babak); Sunnybrook Odette Cancer Centre, University of Toronto, Toronto (Berry); Cancer Centre of Southeastern Ontario, Kingston (Mahmud); Queensway Health Centre, Toronto (Muinuddin); Colorectal Cancer Canada, North York (Servidio-Italiano); Grand River Regional Cancer Centre, Kitchener (Tsvetkova, Valdes); London Health Sciences Centre, London (Welch)
| | - C.H. Ahmad
- Newfoundland and Labrador— Dr. H. Bliss Murphy Cancer Centre, St. John’s (Ahmad, Armstrong, Powell, Rorke, Seal, Siddiqui, Stuckless); Faculty of Medicine, Memorial University of Newfoundland, St. John’s (Green, Seal, Siddiqui, Tate); Faculty of Surgery, Memorial University of Newfoundland, St. John’s (Kanagaratnam); Eastern Health Authority, St. John’s (MacMillan); Labrador–Grenfell Regional Health Authority, Happy Valley–Goose Bay (Simms, Smithson)
| | - D. Armstrong
- Newfoundland and Labrador— Dr. H. Bliss Murphy Cancer Centre, St. John’s (Ahmad, Armstrong, Powell, Rorke, Seal, Siddiqui, Stuckless); Faculty of Medicine, Memorial University of Newfoundland, St. John’s (Green, Seal, Siddiqui, Tate); Faculty of Surgery, Memorial University of Newfoundland, St. John’s (Kanagaratnam); Eastern Health Authority, St. John’s (MacMillan); Labrador–Grenfell Regional Health Authority, Happy Valley–Goose Bay (Simms, Smithson)
| | - S. Babak
- Ontario—The Ottawa Hospital Cancer Centre, Ottawa (AlGhareeb, Asmis, Goel, Hyde, Jonker, Marginean, McGee, Vickers); Queen’s University and Cancer Centre of Southeastern Ontario, Kingston (Biagi, Booth, Virik); Princess Margaret Cancer Centre, Toronto (Dawson); St. Michael’s Hospital, Toronto (Babak); Sunnybrook Odette Cancer Centre, University of Toronto, Toronto (Berry); Cancer Centre of Southeastern Ontario, Kingston (Mahmud); Queensway Health Centre, Toronto (Muinuddin); Colorectal Cancer Canada, North York (Servidio-Italiano); Grand River Regional Cancer Centre, Kitchener (Tsvetkova, Valdes); London Health Sciences Centre, London (Welch)
| | - S. Berry
- Ontario—The Ottawa Hospital Cancer Centre, Ottawa (AlGhareeb, Asmis, Goel, Hyde, Jonker, Marginean, McGee, Vickers); Queen’s University and Cancer Centre of Southeastern Ontario, Kingston (Biagi, Booth, Virik); Princess Margaret Cancer Centre, Toronto (Dawson); St. Michael’s Hospital, Toronto (Babak); Sunnybrook Odette Cancer Centre, University of Toronto, Toronto (Berry); Cancer Centre of Southeastern Ontario, Kingston (Mahmud); Queensway Health Centre, Toronto (Muinuddin); Colorectal Cancer Canada, North York (Servidio-Italiano); Grand River Regional Cancer Centre, Kitchener (Tsvetkova, Valdes); London Health Sciences Centre, London (Welch)
| | - J. Biagi
- Ontario—The Ottawa Hospital Cancer Centre, Ottawa (AlGhareeb, Asmis, Goel, Hyde, Jonker, Marginean, McGee, Vickers); Queen’s University and Cancer Centre of Southeastern Ontario, Kingston (Biagi, Booth, Virik); Princess Margaret Cancer Centre, Toronto (Dawson); St. Michael’s Hospital, Toronto (Babak); Sunnybrook Odette Cancer Centre, University of Toronto, Toronto (Berry); Cancer Centre of Southeastern Ontario, Kingston (Mahmud); Queensway Health Centre, Toronto (Muinuddin); Colorectal Cancer Canada, North York (Servidio-Italiano); Grand River Regional Cancer Centre, Kitchener (Tsvetkova, Valdes); London Health Sciences Centre, London (Welch)
| | - C. Booth
- Ontario—The Ottawa Hospital Cancer Centre, Ottawa (AlGhareeb, Asmis, Goel, Hyde, Jonker, Marginean, McGee, Vickers); Queen’s University and Cancer Centre of Southeastern Ontario, Kingston (Biagi, Booth, Virik); Princess Margaret Cancer Centre, Toronto (Dawson); St. Michael’s Hospital, Toronto (Babak); Sunnybrook Odette Cancer Centre, University of Toronto, Toronto (Berry); Cancer Centre of Southeastern Ontario, Kingston (Mahmud); Queensway Health Centre, Toronto (Muinuddin); Colorectal Cancer Canada, North York (Servidio-Italiano); Grand River Regional Cancer Centre, Kitchener (Tsvetkova, Valdes); London Health Sciences Centre, London (Welch)
| | - D. Bossé
- Dana–Farber Cancer Institute, Boston, MA, U.S.A
| | - P. Champion
- Prince Edward Island—Prince Edward Island Cancer Treatment Centre, Charlottetown
| | - B. Colwell
- Nova Scotia—qeii Health Sciences Centre, Dalhousie University, Halifax
| | - N. Finn
- New Brunswick—Saint John Regional Hospital, Saint John (Gray); Centre hospitalier universitaire Dr-Georges-L.-Dumont, Moncton (Finn, St-Hilaire); Dr. Everett Chalmers Hospital, Fredericton (Raza); Moncton City Hospital (Harb)
| | - R. Goel
- Ontario—The Ottawa Hospital Cancer Centre, Ottawa (AlGhareeb, Asmis, Goel, Hyde, Jonker, Marginean, McGee, Vickers); Queen’s University and Cancer Centre of Southeastern Ontario, Kingston (Biagi, Booth, Virik); Princess Margaret Cancer Centre, Toronto (Dawson); St. Michael’s Hospital, Toronto (Babak); Sunnybrook Odette Cancer Centre, University of Toronto, Toronto (Berry); Cancer Centre of Southeastern Ontario, Kingston (Mahmud); Queensway Health Centre, Toronto (Muinuddin); Colorectal Cancer Canada, North York (Servidio-Italiano); Grand River Regional Cancer Centre, Kitchener (Tsvetkova, Valdes); London Health Sciences Centre, London (Welch)
| | - S. Gray
- New Brunswick—Saint John Regional Hospital, Saint John (Gray); Centre hospitalier universitaire Dr-Georges-L.-Dumont, Moncton (Finn, St-Hilaire); Dr. Everett Chalmers Hospital, Fredericton (Raza); Moncton City Hospital (Harb)
| | - J. Green
- Newfoundland and Labrador— Dr. H. Bliss Murphy Cancer Centre, St. John’s (Ahmad, Armstrong, Powell, Rorke, Seal, Siddiqui, Stuckless); Faculty of Medicine, Memorial University of Newfoundland, St. John’s (Green, Seal, Siddiqui, Tate); Faculty of Surgery, Memorial University of Newfoundland, St. John’s (Kanagaratnam); Eastern Health Authority, St. John’s (MacMillan); Labrador–Grenfell Regional Health Authority, Happy Valley–Goose Bay (Simms, Smithson)
| | - M. Harb
- New Brunswick—Saint John Regional Hospital, Saint John (Gray); Centre hospitalier universitaire Dr-Georges-L.-Dumont, Moncton (Finn, St-Hilaire); Dr. Everett Chalmers Hospital, Fredericton (Raza); Moncton City Hospital (Harb)
| | - A. Hyde
- Ontario—The Ottawa Hospital Cancer Centre, Ottawa (AlGhareeb, Asmis, Goel, Hyde, Jonker, Marginean, McGee, Vickers); Queen’s University and Cancer Centre of Southeastern Ontario, Kingston (Biagi, Booth, Virik); Princess Margaret Cancer Centre, Toronto (Dawson); St. Michael’s Hospital, Toronto (Babak); Sunnybrook Odette Cancer Centre, University of Toronto, Toronto (Berry); Cancer Centre of Southeastern Ontario, Kingston (Mahmud); Queensway Health Centre, Toronto (Muinuddin); Colorectal Cancer Canada, North York (Servidio-Italiano); Grand River Regional Cancer Centre, Kitchener (Tsvetkova, Valdes); London Health Sciences Centre, London (Welch)
| | - A. Jeyakumar
- Nova Scotia—qeii Health Sciences Centre, Dalhousie University, Halifax
| | - D. Jonker
- Ontario—The Ottawa Hospital Cancer Centre, Ottawa (AlGhareeb, Asmis, Goel, Hyde, Jonker, Marginean, McGee, Vickers); Queen’s University and Cancer Centre of Southeastern Ontario, Kingston (Biagi, Booth, Virik); Princess Margaret Cancer Centre, Toronto (Dawson); St. Michael’s Hospital, Toronto (Babak); Sunnybrook Odette Cancer Centre, University of Toronto, Toronto (Berry); Cancer Centre of Southeastern Ontario, Kingston (Mahmud); Queensway Health Centre, Toronto (Muinuddin); Colorectal Cancer Canada, North York (Servidio-Italiano); Grand River Regional Cancer Centre, Kitchener (Tsvetkova, Valdes); London Health Sciences Centre, London (Welch)
| | - S. Kanagaratnam
- Newfoundland and Labrador— Dr. H. Bliss Murphy Cancer Centre, St. John’s (Ahmad, Armstrong, Powell, Rorke, Seal, Siddiqui, Stuckless); Faculty of Medicine, Memorial University of Newfoundland, St. John’s (Green, Seal, Siddiqui, Tate); Faculty of Surgery, Memorial University of Newfoundland, St. John’s (Kanagaratnam); Eastern Health Authority, St. John’s (MacMillan); Labrador–Grenfell Regional Health Authority, Happy Valley–Goose Bay (Simms, Smithson)
| | - P. Kavan
- Quebec—McGill University Health Centre, Montreal (Kavan, Thirlwell); Centre hospitalier de l’Université de Montréal, Montreal (Tehfé)
| | - A. MacMillan
- Newfoundland and Labrador— Dr. H. Bliss Murphy Cancer Centre, St. John’s (Ahmad, Armstrong, Powell, Rorke, Seal, Siddiqui, Stuckless); Faculty of Medicine, Memorial University of Newfoundland, St. John’s (Green, Seal, Siddiqui, Tate); Faculty of Surgery, Memorial University of Newfoundland, St. John’s (Kanagaratnam); Eastern Health Authority, St. John’s (MacMillan); Labrador–Grenfell Regional Health Authority, Happy Valley–Goose Bay (Simms, Smithson)
| | - A. Muinuddin
- Ontario—The Ottawa Hospital Cancer Centre, Ottawa (AlGhareeb, Asmis, Goel, Hyde, Jonker, Marginean, McGee, Vickers); Queen’s University and Cancer Centre of Southeastern Ontario, Kingston (Biagi, Booth, Virik); Princess Margaret Cancer Centre, Toronto (Dawson); St. Michael’s Hospital, Toronto (Babak); Sunnybrook Odette Cancer Centre, University of Toronto, Toronto (Berry); Cancer Centre of Southeastern Ontario, Kingston (Mahmud); Queensway Health Centre, Toronto (Muinuddin); Colorectal Cancer Canada, North York (Servidio-Italiano); Grand River Regional Cancer Centre, Kitchener (Tsvetkova, Valdes); London Health Sciences Centre, London (Welch)
| | - N. Patil
- Nova Scotia—qeii Health Sciences Centre, Dalhousie University, Halifax
| | - G. Porter
- Nova Scotia—qeii Health Sciences Centre, Dalhousie University, Halifax
| | - E. Powell
- Newfoundland and Labrador— Dr. H. Bliss Murphy Cancer Centre, St. John’s (Ahmad, Armstrong, Powell, Rorke, Seal, Siddiqui, Stuckless); Faculty of Medicine, Memorial University of Newfoundland, St. John’s (Green, Seal, Siddiqui, Tate); Faculty of Surgery, Memorial University of Newfoundland, St. John’s (Kanagaratnam); Eastern Health Authority, St. John’s (MacMillan); Labrador–Grenfell Regional Health Authority, Happy Valley–Goose Bay (Simms, Smithson)
| | - R. Ramjeesingh
- Nova Scotia—qeii Health Sciences Centre, Dalhousie University, Halifax
| | - M. Raza
- New Brunswick—Saint John Regional Hospital, Saint John (Gray); Centre hospitalier universitaire Dr-Georges-L.-Dumont, Moncton (Finn, St-Hilaire); Dr. Everett Chalmers Hospital, Fredericton (Raza); Moncton City Hospital (Harb)
| | - S. Rorke
- Newfoundland and Labrador— Dr. H. Bliss Murphy Cancer Centre, St. John’s (Ahmad, Armstrong, Powell, Rorke, Seal, Siddiqui, Stuckless); Faculty of Medicine, Memorial University of Newfoundland, St. John’s (Green, Seal, Siddiqui, Tate); Faculty of Surgery, Memorial University of Newfoundland, St. John’s (Kanagaratnam); Eastern Health Authority, St. John’s (MacMillan); Labrador–Grenfell Regional Health Authority, Happy Valley–Goose Bay (Simms, Smithson)
| | - M. Seal
- Newfoundland and Labrador— Dr. H. Bliss Murphy Cancer Centre, St. John’s (Ahmad, Armstrong, Powell, Rorke, Seal, Siddiqui, Stuckless); Faculty of Medicine, Memorial University of Newfoundland, St. John’s (Green, Seal, Siddiqui, Tate); Faculty of Surgery, Memorial University of Newfoundland, St. John’s (Kanagaratnam); Eastern Health Authority, St. John’s (MacMillan); Labrador–Grenfell Regional Health Authority, Happy Valley–Goose Bay (Simms, Smithson)
| | - F. Servidio-Italiano
- Ontario—The Ottawa Hospital Cancer Centre, Ottawa (AlGhareeb, Asmis, Goel, Hyde, Jonker, Marginean, McGee, Vickers); Queen’s University and Cancer Centre of Southeastern Ontario, Kingston (Biagi, Booth, Virik); Princess Margaret Cancer Centre, Toronto (Dawson); St. Michael’s Hospital, Toronto (Babak); Sunnybrook Odette Cancer Centre, University of Toronto, Toronto (Berry); Cancer Centre of Southeastern Ontario, Kingston (Mahmud); Queensway Health Centre, Toronto (Muinuddin); Colorectal Cancer Canada, North York (Servidio-Italiano); Grand River Regional Cancer Centre, Kitchener (Tsvetkova, Valdes); London Health Sciences Centre, London (Welch)
| | - J. Siddiqui
- Newfoundland and Labrador— Dr. H. Bliss Murphy Cancer Centre, St. John’s (Ahmad, Armstrong, Powell, Rorke, Seal, Siddiqui, Stuckless); Faculty of Medicine, Memorial University of Newfoundland, St. John’s (Green, Seal, Siddiqui, Tate); Faculty of Surgery, Memorial University of Newfoundland, St. John’s (Kanagaratnam); Eastern Health Authority, St. John’s (MacMillan); Labrador–Grenfell Regional Health Authority, Happy Valley–Goose Bay (Simms, Smithson)
| | - J. Simms
- Newfoundland and Labrador— Dr. H. Bliss Murphy Cancer Centre, St. John’s (Ahmad, Armstrong, Powell, Rorke, Seal, Siddiqui, Stuckless); Faculty of Medicine, Memorial University of Newfoundland, St. John’s (Green, Seal, Siddiqui, Tate); Faculty of Surgery, Memorial University of Newfoundland, St. John’s (Kanagaratnam); Eastern Health Authority, St. John’s (MacMillan); Labrador–Grenfell Regional Health Authority, Happy Valley–Goose Bay (Simms, Smithson)
| | - L. Smithson
- Newfoundland and Labrador— Dr. H. Bliss Murphy Cancer Centre, St. John’s (Ahmad, Armstrong, Powell, Rorke, Seal, Siddiqui, Stuckless); Faculty of Medicine, Memorial University of Newfoundland, St. John’s (Green, Seal, Siddiqui, Tate); Faculty of Surgery, Memorial University of Newfoundland, St. John’s (Kanagaratnam); Eastern Health Authority, St. John’s (MacMillan); Labrador–Grenfell Regional Health Authority, Happy Valley–Goose Bay (Simms, Smithson)
| | - S. Snow
- Nova Scotia—qeii Health Sciences Centre, Dalhousie University, Halifax
| | - E. St-Hilaire
- New Brunswick—Saint John Regional Hospital, Saint John (Gray); Centre hospitalier universitaire Dr-Georges-L.-Dumont, Moncton (Finn, St-Hilaire); Dr. Everett Chalmers Hospital, Fredericton (Raza); Moncton City Hospital (Harb)
| | - T. Stuckless
- Newfoundland and Labrador— Dr. H. Bliss Murphy Cancer Centre, St. John’s (Ahmad, Armstrong, Powell, Rorke, Seal, Siddiqui, Stuckless); Faculty of Medicine, Memorial University of Newfoundland, St. John’s (Green, Seal, Siddiqui, Tate); Faculty of Surgery, Memorial University of Newfoundland, St. John’s (Kanagaratnam); Eastern Health Authority, St. John’s (MacMillan); Labrador–Grenfell Regional Health Authority, Happy Valley–Goose Bay (Simms, Smithson)
| | - A. Tate
- Newfoundland and Labrador— Dr. H. Bliss Murphy Cancer Centre, St. John’s (Ahmad, Armstrong, Powell, Rorke, Seal, Siddiqui, Stuckless); Faculty of Medicine, Memorial University of Newfoundland, St. John’s (Green, Seal, Siddiqui, Tate); Faculty of Surgery, Memorial University of Newfoundland, St. John’s (Kanagaratnam); Eastern Health Authority, St. John’s (MacMillan); Labrador–Grenfell Regional Health Authority, Happy Valley–Goose Bay (Simms, Smithson)
| | - M. Tehfe
- Quebec—McGill University Health Centre, Montreal (Kavan, Thirlwell); Centre hospitalier de l’Université de Montréal, Montreal (Tehfé)
| | - M. Thirlwell
- Quebec—McGill University Health Centre, Montreal (Kavan, Thirlwell); Centre hospitalier de l’Université de Montréal, Montreal (Tehfé)
| | - E. Tsvetkova
- Ontario—The Ottawa Hospital Cancer Centre, Ottawa (AlGhareeb, Asmis, Goel, Hyde, Jonker, Marginean, McGee, Vickers); Queen’s University and Cancer Centre of Southeastern Ontario, Kingston (Biagi, Booth, Virik); Princess Margaret Cancer Centre, Toronto (Dawson); St. Michael’s Hospital, Toronto (Babak); Sunnybrook Odette Cancer Centre, University of Toronto, Toronto (Berry); Cancer Centre of Southeastern Ontario, Kingston (Mahmud); Queensway Health Centre, Toronto (Muinuddin); Colorectal Cancer Canada, North York (Servidio-Italiano); Grand River Regional Cancer Centre, Kitchener (Tsvetkova, Valdes); London Health Sciences Centre, London (Welch)
| | - M. Valdes
- Ontario—The Ottawa Hospital Cancer Centre, Ottawa (AlGhareeb, Asmis, Goel, Hyde, Jonker, Marginean, McGee, Vickers); Queen’s University and Cancer Centre of Southeastern Ontario, Kingston (Biagi, Booth, Virik); Princess Margaret Cancer Centre, Toronto (Dawson); St. Michael’s Hospital, Toronto (Babak); Sunnybrook Odette Cancer Centre, University of Toronto, Toronto (Berry); Cancer Centre of Southeastern Ontario, Kingston (Mahmud); Queensway Health Centre, Toronto (Muinuddin); Colorectal Cancer Canada, North York (Servidio-Italiano); Grand River Regional Cancer Centre, Kitchener (Tsvetkova, Valdes); London Health Sciences Centre, London (Welch)
| | - M. Vickers
- Ontario—The Ottawa Hospital Cancer Centre, Ottawa (AlGhareeb, Asmis, Goel, Hyde, Jonker, Marginean, McGee, Vickers); Queen’s University and Cancer Centre of Southeastern Ontario, Kingston (Biagi, Booth, Virik); Princess Margaret Cancer Centre, Toronto (Dawson); St. Michael’s Hospital, Toronto (Babak); Sunnybrook Odette Cancer Centre, University of Toronto, Toronto (Berry); Cancer Centre of Southeastern Ontario, Kingston (Mahmud); Queensway Health Centre, Toronto (Muinuddin); Colorectal Cancer Canada, North York (Servidio-Italiano); Grand River Regional Cancer Centre, Kitchener (Tsvetkova, Valdes); London Health Sciences Centre, London (Welch)
| | - K. Virik
- Ontario—The Ottawa Hospital Cancer Centre, Ottawa (AlGhareeb, Asmis, Goel, Hyde, Jonker, Marginean, McGee, Vickers); Queen’s University and Cancer Centre of Southeastern Ontario, Kingston (Biagi, Booth, Virik); Princess Margaret Cancer Centre, Toronto (Dawson); St. Michael’s Hospital, Toronto (Babak); Sunnybrook Odette Cancer Centre, University of Toronto, Toronto (Berry); Cancer Centre of Southeastern Ontario, Kingston (Mahmud); Queensway Health Centre, Toronto (Muinuddin); Colorectal Cancer Canada, North York (Servidio-Italiano); Grand River Regional Cancer Centre, Kitchener (Tsvetkova, Valdes); London Health Sciences Centre, London (Welch)
| | - S. Welch
- Ontario—The Ottawa Hospital Cancer Centre, Ottawa (AlGhareeb, Asmis, Goel, Hyde, Jonker, Marginean, McGee, Vickers); Queen’s University and Cancer Centre of Southeastern Ontario, Kingston (Biagi, Booth, Virik); Princess Margaret Cancer Centre, Toronto (Dawson); St. Michael’s Hospital, Toronto (Babak); Sunnybrook Odette Cancer Centre, University of Toronto, Toronto (Berry); Cancer Centre of Southeastern Ontario, Kingston (Mahmud); Queensway Health Centre, Toronto (Muinuddin); Colorectal Cancer Canada, North York (Servidio-Italiano); Grand River Regional Cancer Centre, Kitchener (Tsvetkova, Valdes); London Health Sciences Centre, London (Welch)
| | - C. Marginean
- Ontario—The Ottawa Hospital Cancer Centre, Ottawa (AlGhareeb, Asmis, Goel, Hyde, Jonker, Marginean, McGee, Vickers); Queen’s University and Cancer Centre of Southeastern Ontario, Kingston (Biagi, Booth, Virik); Princess Margaret Cancer Centre, Toronto (Dawson); St. Michael’s Hospital, Toronto (Babak); Sunnybrook Odette Cancer Centre, University of Toronto, Toronto (Berry); Cancer Centre of Southeastern Ontario, Kingston (Mahmud); Queensway Health Centre, Toronto (Muinuddin); Colorectal Cancer Canada, North York (Servidio-Italiano); Grand River Regional Cancer Centre, Kitchener (Tsvetkova, Valdes); London Health Sciences Centre, London (Welch)
| | - T. Asmis
- Ontario—The Ottawa Hospital Cancer Centre, Ottawa (AlGhareeb, Asmis, Goel, Hyde, Jonker, Marginean, McGee, Vickers); Queen’s University and Cancer Centre of Southeastern Ontario, Kingston (Biagi, Booth, Virik); Princess Margaret Cancer Centre, Toronto (Dawson); St. Michael’s Hospital, Toronto (Babak); Sunnybrook Odette Cancer Centre, University of Toronto, Toronto (Berry); Cancer Centre of Southeastern Ontario, Kingston (Mahmud); Queensway Health Centre, Toronto (Muinuddin); Colorectal Cancer Canada, North York (Servidio-Italiano); Grand River Regional Cancer Centre, Kitchener (Tsvetkova, Valdes); London Health Sciences Centre, London (Welch)
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11
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Kong P, Chen L, Shi X, Pan H, Yu M, Ge H, Zhu J, Ma G, Li L, Ding Q, Zhou W, Wang S. Microwave ablation combined with doxorubicin enhances cell death via promoting reactive oxygen species generation in breast cancer cells. Diagn Interv Imaging 2018; 99:783-791. [PMID: 30037745 DOI: 10.1016/j.diii.2018.06.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2018] [Revised: 04/19/2018] [Accepted: 06/25/2018] [Indexed: 12/15/2022]
Abstract
PURPOSE To evaluate the mechanism for enhancing cell death induced by microwave ablation (MWA) combined with doxorubicin treatment in breast cancer cells. MATERIALS AND METHODS Different temperatures of heat treatment were used to mimic the tumor affected by sublethal heat during MWA in vitro. Breast cancer cells were treated at 43°C and 45°C, with or without doxorubicin. Cell viability, apoptosis, and intracellular reactive oxygen species (ROS) were evaluated in MDA-MB-231 and SUM-1315 cells. Nude mice breast cancer models were randomly divided into control, MWA, doxorubicin, and combined treatment groups. Tumor apoptosis and DNA damage were evaluated in these groups. RESULTS The combined group had lower cell viability than the heat or doxorubicin group (all P<0.05), and enhanced apoptosis rate was observed in the combined group compared to others (all P<0.01) in MDA-MB-231 and SUM-1315. Increased capase3 (all P<0.01) and decreased Bcl-Xl (all P<0.01) were detected after combined therapy compared to single treated group in vitro. The raisedCaspase3 and DNA damage marker histone H2A.X induced by combined treatment were also approved in the nude mice models. Combined treatment promoted ROS generation compared to doxorubicin or MWA treatment (all P < 0.01). NF-κB expression in the combined group was higher than that of the single treatment group (all P<0.05). N-acetylcysteine (NAC), a ROS scavenger, partly restrained the combined treatment induced cell proliferation inhibition, Caspase3 and NF-κB compared to doxorubicin treatment (all P<0.05). CONCLUSION MWA combined with doxorubicin promote cell death via ROS induced cell apoptosis and DNA damage. Increasing ROS has potential for improving the efficiency of combined treatment.
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Affiliation(s)
- P Kong
- Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, 210029 Nanjing, China
| | - L Chen
- Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, 210029 Nanjing, China
| | - X Shi
- Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, 210029 Nanjing, China
| | - H Pan
- Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, 210029 Nanjing, China
| | - M Yu
- Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, 210029 Nanjing, China
| | - H Ge
- Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, 210029 Nanjing, China
| | - J Zhu
- Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, 210029 Nanjing, China
| | - G Ma
- Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, 210029 Nanjing, China
| | - L Li
- Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, 210029 Nanjing, China
| | - Q Ding
- Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, 210029 Nanjing, China
| | - W Zhou
- Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, 210029 Nanjing, China.
| | - S Wang
- Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, 210029 Nanjing, China.
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12
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Teixeira Farinha H, Grass F, Labgaa I, Pache B, Demartines N, Hübner M. Inflammatory Response and Toxicity After Pressurized IntraPeritoneal Aerosol Chemotherapy. J Cancer 2018; 9:13-20. [PMID: 29290765 PMCID: PMC5743707 DOI: 10.7150/jca.21460] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2017] [Accepted: 10/08/2017] [Indexed: 01/27/2023] Open
Abstract
Background: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a novel mode of intraperitoneal (IP) drug delivery claiming high IP tissue concentrations with low systemic uptake. The aim was to study inflammatory response and systemic toxicity after PIPAC. Methods: Retrospective monocentric analysis of a consecutive cohort of PIPAC patients between January 2015 and April 2016. Detailed hematological and biochemical analysis was performed the day before surgery and once daily until discharge. Comparative statistics were performed using Mann-Whitney U test and Wilcoxon signed ranked test. Results: Fourty-two consecutive patients underwent a total of 91 PIPAC procedures. Twenty patients received oxaliplatin and 22 cisplatin+doxorubicin (37 vs. 54 procedures). Creatinine, AST and ALT were not significantly altered after PIPAC (p=0.095, p= p=0.153 and p=0.351) and not different between oxaliplatin and cisplatin+doxorubicin regimens (p=0.371, p=0.251 and p=0.288). C-reactive protein (CRP) and procalcitonin (PCT) increased on post-operative day (POD) 2: ∆max 29±5 mg/L (p<0.001) and ∆max 0.05±0.01 μg/L (p=0.005), respectively. Leucocytes increased at POD 1: ∆max 2.2±0.3 G/L (p<0.001). Albumin decreased at POD 2: ∆max -6.0±0.5 g/L (p<0.001). CRP increase correlated positively with Peritoneal Cancer Index (tumor load) (ρ =0.521, p<0.001). Conclusion: PIPAC was followed by a modest and transitory inflammatory response that was commensurate to the disease extent. No hematological, renal or hepatic toxicity was observed even after repetitive administration.
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Affiliation(s)
| | - Fabian Grass
- Department of Visceral Surgery, University Hospital of Lausanne (CHUV), Switzerland
| | - Ismaïl Labgaa
- Department of Visceral Surgery, University Hospital of Lausanne (CHUV), Switzerland
| | - Basile Pache
- Department of Visceral Surgery, University Hospital of Lausanne (CHUV), Switzerland
| | - Nicolas Demartines
- Department of Visceral Surgery, University Hospital of Lausanne (CHUV), Switzerland
| | - Martin Hübner
- Department of Visceral Surgery, University Hospital of Lausanne (CHUV), Switzerland
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13
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MicroCT image based simulation to design heating protocols in magnetic nanoparticle hyperthermia for cancer treatment. J Therm Biol 2016; 62:129-137. [DOI: 10.1016/j.jtherbio.2016.06.025] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Accepted: 06/29/2016] [Indexed: 11/23/2022]
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14
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Detroz B, Laurent S, Honoré P, Blaffart F, Limet R, Meurisse M. Rationale for Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the Treatment or Prevention of Peritoneal Carcinomatosis. Acta Chir Belg 2016. [DOI: 10.1080/00015458.2004.11679577] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Affiliation(s)
- B. Detroz
- Department of Abdominal Surgery, Department of Cardio-vascular Surgery (*) CHU of Liège, Belgium
| | - S. Laurent
- Department of Abdominal Surgery, Department of Cardio-vascular Surgery (*) CHU of Liège, Belgium
| | - P. Honoré
- Department of Abdominal Surgery, Department of Cardio-vascular Surgery (*) CHU of Liège, Belgium
| | - F. Blaffart
- Department of Abdominal Surgery, Department of Cardio-vascular Surgery (*) CHU of Liège, Belgium
| | - R. Limet
- Department of Abdominal Surgery, Department of Cardio-vascular Surgery (*) CHU of Liège, Belgium
| | - M. Meurisse
- Department of Abdominal Surgery, Department of Cardio-vascular Surgery (*) CHU of Liège, Belgium
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15
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Feist M, Smith J, Enkelmann S, Hommel K, Brandl A, Rau B. Intraoperative Chemotherapie. DER ONKOLOGE 2016; 22:651-658. [DOI: 10.1007/s00761-016-0061-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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16
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Maluta S, Kolff MW. Role of Hyperthermia in Breast Cancer Locoregional Recurrence: A Review. Breast Care (Basel) 2015; 10:408-12. [PMID: 26989361 DOI: 10.1159/000440792] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
In patients with locoregional recurrences of breast cancer not suitable for resection, subsequent local control is difficult to maintain in previously irradiated areas when reirradiation alone or reirradiation with chemotherapy is used. Due to the limited number of treatment options there is a high risk of subsequent failure and uncontrollable local disease. In this group of patients, local hyperthermia combined with radiotherapy increases the clinical response and local control, adding limited acute and late toxicity, as has been shown in randomized trials. Hyperthermia is an artificial elevation of tissue temperature (range 40-44°C for 30-60 min). If hyperthermia is applied shortly before or after radiation, the effect of radiation is enhanced by influencing intratumoral hypoxia and by inhibiting sublethal damage repair in the tumor. Moreover, hyperthermia combined with radiation reduces the total dose of radiation needed compared to radiation alone, of which a higher dose is needed to obtain the same effect. Few data are available on the combination of radiotherapy and hyperthermia with chemotherapy, although the results of trimodality treatment consisting of reirradiation and hyperthermia together with liposomal doxorubicin are promising. Therefore, this literature review was performed to provide more comprehensive data on the mechanism and use of hyperthermia in locoregional recurrence of breast cancer.
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Affiliation(s)
- Sergio Maluta
- Department of Hyperthermia, Serena Medical Center, Padova, Italy
| | - Merel Willemijn Kolff
- Department of Radiotherapy and Hyperthermia, Academic Medical Center, Amsterdam, The Netherlands
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17
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Yang S, Feng R, Pan ZC, Jiang T, Xu Q, Chen Q. A Comparison of Intravenous plus Intraperitoneal Chemotherapy with Intravenous Chemotherapy Alone for the Treatment of Gastric Cancer: A Meta-Analysis. Sci Rep 2015. [PMID: 26220081 PMCID: PMC4518228 DOI: 10.1038/srep12538] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
We aimed to evaluate the effectiveness and safety of intravenous (IV) plus intraperitoneal (IP) chemotherapy compared to intravenous (IV) chemotherapy alone for patients with gastric cancer. Electronic databases were searched up to June 2013. Two authors independently selected studies, extracted data and assessed the quality of included studies. The GRADE System was adopted to rate the level of evidence. Of 392 citations, five RCTs involving 1072 patients were included. Overall, a significant improvement in in one- and three- and five-year survival rate was observed in the IV plus IP chemotherapy group (3 RCTs, n = 360, RR = 1.10, 95% CI 1.04 to 1.17), (5 RCTs, n = 953, RR = 1.22, 95% CI 1.11 to 1.35) and (3 RCTs, n = 347, RR = 1.42, 95% CI 1.12 to 1.80), respectively. Results supported a significant decrease in the rate of metastases (1 RCT, n = 85, RR = 0.41 95% CI 0.19 to 0.89) and peritoneal recurrence (2 RCTs, n = 297, RR = 0.41, 95% CI 0.26 to 0.62) in the IV plus IP chemotherapy group, however, the incidence of adverse events was increased. For patients with gastric cancer, IV plus IP chemotherapy can improve the overall survival rate and prevent the distant or peritoneal metastases. An increased risk of neutropenia, peripheral edema and neuropathy was observed.
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Affiliation(s)
- Sheng Yang
- Department of Medical Oncology, Fujian Medical University Union Hospital, Fujian, China.,Teaching and Research Department of Oncology, Union Clinical medical College of Fujian Medical University, Fujian, China.,Fujian Key Laboratory of Translational Cancer Medicine, Fujian, China.,Fujian Medical University Stem Cell Research Institute, Fujian, China
| | - Rui Feng
- Teaching and Research Department of Oncology, Union Clinical medical College of Fujian Medical University, Fujian, China
| | - Zhang-Chi Pan
- Teaching and Research Department of Oncology, Union Clinical medical College of Fujian Medical University, Fujian, China
| | - Tao Jiang
- Teaching and Research Department of Oncology, Union Clinical medical College of Fujian Medical University, Fujian, China
| | - Qian Xu
- Teaching and Research Department of Oncology, Union Clinical medical College of Fujian Medical University, Fujian, China
| | - Qiang Chen
- Department of Medical Oncology, Fujian Medical University Union Hospital, Fujian, China.,Teaching and Research Department of Oncology, Union Clinical medical College of Fujian Medical University, Fujian, China.,Fujian Key Laboratory of Translational Cancer Medicine, Fujian, China.,Fujian Medical University Stem Cell Research Institute, Fujian, China
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Chiu B, Coburn J, Pilichowska M, Holcroft C, Seib FP, Charest A, Kaplan DL. Surgery combined with controlled-release doxorubicin silk films as a treatment strategy in an orthotopic neuroblastoma mouse model. Br J Cancer 2014; 111:708-15. [PMID: 24921912 PMCID: PMC4134491 DOI: 10.1038/bjc.2014.324] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2014] [Revised: 05/07/2014] [Accepted: 05/13/2014] [Indexed: 12/05/2022] Open
Abstract
BACKGROUND Neuroblastoma tumour resection goal is maximal tumour removal. We hypothesise that combining surgery with sustained, local doxorubicin application can control tumour growth. METHODS We injected human neuroblastoma cells into immunocompromised mouse adrenal gland. When KELLY cell-induced tumour volume was >300 mm(3), 80-90% of tumour was resected and treated as follows: instantaneous-release silk film with 100 μg doxorubicin (100IR), controlled-release film with 200 μg (200CR) over residual tumour bed; and 100 and 200 μg intravenous doxorubicin (100IV and 200IV). Tumour volume was measured and histology analysed. RESULTS Orthotopic tumours formed with KELLY, SK-N-AS, IMR-32, SH-SY5Y cells. Tumours reached 1800±180 mm(3) after 28 days, 2200±290 mm(3) after 35 days, 1280±260 mm(3) after 63 days, and 1700±360 mm(3) after 84 days, respectively. At 3 days post KELLY tumour resection, tumour volumes were similar across all groups (P=0.6210). Tumour growth rate was similar in untreated vs control film, 100IV vs 100IR, and 100IV vs 200IV. There was significant difference in 100IR vs 200CR (P=0.0004) and 200IV vs 200CR (P=0.0003). Tumour growth with all doxorubicin groups was slower than that of control (P: <0.0001-0.0069). At the interface of the 200CR film and tumour, there was cellular necrosis, surrounded by apoptotic cells before reaching viable tumour cells. CONCLUSIONS Combining surgical resection and sustained local doxorubicin treatment is effective in tumour control. Administering doxorubicin in a local, controlled manner is superior to giving an equivalent intravenous dose in tumour control.
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Affiliation(s)
- B Chiu
- Department of Surgery, University of Illinois at Chicago, 840 S. Wood Street, Suite 416, Chicago, IL 60612, USA
| | - J Coburn
- Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA
| | - M Pilichowska
- Department of Pathology, Tufts Medical Center, 800 Washington Street, Box 115, Boston, MA 02111, USA
| | - C Holcroft
- Tufts Clinical and Translational Science Institute, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA
| | - F P Seib
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK
| | - A Charest
- Department of Neurosurgery, Tufts Medical Center, 800 Washington Street, Tufts Medical Center, Box 5609, Boston, MA 02111, USA
| | - D L Kaplan
- Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA
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Carmignani CP, Sugarbaker PH. Comprehensive approach to advanced primary and recurrent ovarian cancer: a personal experience. Expert Rev Anticancer Ther 2014; 4:477-87. [PMID: 15161446 DOI: 10.1586/14737140.4.3.477] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Despite improvements in chemotherapy agents and schedules and new drug combinations, epithelial ovarian cancer remains a leading cause of gynecologic cancer death in Western countries. It is usually diagnosed at late stages of the disease, which makes complete surgical resection technically more difficult. The targeted comprehensive approach described in this review includes cytoreductive surgery and perioperative intraperitoneal chemotherapy. The goal of this aggressive therapy is to remove all the macroscopic disease with the use of peritonectomy procedures and visceral resections, and also to eradicate microscopic disease using heated intraoperative intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy. Patients that received a complete cytoreduction followed by perioperative intraperitoneal chemotherapy had an improved survival, with reasonable morbidity and mortality, as compared with those who received incomplete cytoreduction.
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Affiliation(s)
- C Pablo Carmignani
- Washington Cancer Institute, 110 Irving Street NW, Washington, DC 20010, USA
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20
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Munasinghe A, Kazi W, Taniere P, Hallissey MT, Alderson D, Tucker O. The incremental benefit of two quadrant lavage for peritoneal cytology at staging laparoscopy for oesophagogastric adenocarcinoma. Surg Endosc 2013; 27:4049-53. [PMID: 23836122 DOI: 10.1007/s00464-013-3058-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2013] [Accepted: 06/09/2013] [Indexed: 01/18/2023]
Abstract
BACKGROUND Patients with positive peritoneal cytology from oesophagogastric cancer have a poor prognosis. The purpose of this study was to compare lavage cytology from the pelvis alone with the pelvis and subphrenic areas at staging laparoscopy in patients with potentially resectable oesophagogastric adenocarcinoma. METHODS Between November 2006 and November 2010, all patients with operable oesophagogastric adenocarcinoma on spiral CT considered fit for surgical resection underwent staging laparoscopy. Subphrenic and pelvic peritoneal lavage for cytology was performed followed by laparoscopic biopsy of any visible peritoneal disease. Patients were divided into groups: macroscopic peritoneal metastases (P+), no macroscopic peritoneal disease with negative cytology (P-C-), no macroscopic peritoneal disease with positive pelvic cytology (P-PC+), no macroscopic peritoneal disease with positive subphrenic cytology (P-SC+), or both (P-PSC+). RESULTS A total of 316 staging laparoscopy procedures were performed; 245 patients (78 %) were P-C-, 28 (9 %) were P+, and 43 (14 %) were P-C+, of whom 29 (9 %) were P-PSC+, 10 (3 %) were P-SC+, and 4 (1 %) were P-PC+. Pelvic cytology alone had 76.7 % sensitivity for peritoneal disease, and subphrenic cytology alone had 90.7 % sensitivity. CONCLUSIONS Peritoneal lavage for cytology at staging laparoscopy has an incremental benefit for staging oesophagogastric adenocarcinoma in the absence of macroscopic metastatic disease. Subphrenic washings have the highest yield of positive results. Performing isolated pelvic washings for cytology will understage 23.3 % of patients with microscopic peritoneal disease. The routine use of subphrenic in combination with pelvic lavage for cytology at staging laparoscopy in patients with oesophagogastric adenocarcinoma has an incremental benefit in detecting cytology-positive disease over either pelvic or subphrenic cytology alone.
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Affiliation(s)
- Aruna Munasinghe
- Academic Department of Surgery, University Hospital Birmingham, Edgbaston, Birmingham, B15 2TH, UK,
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21
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Yu L, Jing Y, Ma S, Li F, Zhang YF. Cytoreductive surgery combined with hyperthermic intrapleural chemotherapy to treat thymoma or thymic carcinoma with pleural dissemination. Onco Targets Ther 2013; 6:517-21. [PMID: 23690692 PMCID: PMC3656918 DOI: 10.2147/ott.s41347] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND The treatment of thymoma or thymic carcinoma with pleural dissemination remains controversial due to the unpredictable natural history of this tumor. Our study discusses the combination of cytoreductive surgery with hyperthermic intrapleural chemotherapy to treat thymoma or thymic carcinoma with pleural dissemination. METHODS From February 2008 to January 2010, there were four patients with pleural thymoma metastases undergoing cytoreductive surgery and intrathoracic hyperthermic perfusion with chemotherapy at our department. After video-assisted thoracoscopic surgery, the hyperthermic perfusion system was set up for hyperthermic intrapleural chemotherapy. The thoracic cavity was perfused at a speed of approximately 1.8-2.3 L/min with 0.9% normal saline. The intrathoracic temperature remained between 42°C and 43°C. The perfusion process lasted for 2 hours. RESULTS There were no perioperative deaths. During the hyperthermic perfusion, the patient's core temperature varied from 36.3°C and 39.3°C and pulse varied from 59 beats/min and 126 beats/min. Intraoperative sinus tachycardia occurred in two elderly patients. No hematologic toxicity and nephrotoxicity was observed within 1 week after surgery. Postoperative pneumonia occurred in one elderly patient. Patients were followed up for 1-4 years. One elderly patient died of heart failure 1 year after surgery. There were no patients with local recurrence or metastases to distant sites. CONCLUSIONS Cytoreductive surgery and intrathoracic hyperthermic perfusion with chemotherapy may be effective in treating thymoma or thymic carcinoma with pleural dissemination and has an encouraging impact on the patients' long-term survival.
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Affiliation(s)
- Lei Yu
- Department of Thoracic Surgery, Beijing Tongren Hospital, Capital Medical University, People's Republic of China
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Guo Y, Zhang H, Sun L. Effects of intraoperative magnetic resonance imaging on the neuromuscular blockade of vecuronium bromide in neurosurgery. Neurol Med Chir (Tokyo) 2013; 53:201-6. [PMID: 23615407 DOI: 10.2176/nmc.53.201] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
The effects of intraoperative magnetic resonance (iMR) imaging on the neuromuscular blockade of vecuronium bromide were investigated in neurosurgery. Fifty patients with American Society of Anesthesiologists grades I-II scheduled for craniotomy operation were divided into two groups (n = 25 each) with no difference in demographic data: the iMR imaging group and control group. Train-of-four (TOF) stimulation through an accelerometer was used to monitor onset, maintenance, and recovery of muscle relaxation caused by vecuronium. Vecuronium bromide was intravenously injected after anesthesia induction. The dosage of vecuronium bromide in the iMR imaging group was larger than in the control group, but not significantly. Duration of vecuronium bromide administration and operation time were significantly longer in the iMR imaging group than in the control group. Time from drug discontinuation to operation termination, and to return to neurosurgery intensive care unit were not different. Time taken by first twitch (T1) in response to TOF stimulation to recover by 25%, and muscle relaxant recovery index were significantly greater in the control group than in the iMR imaging group. The body temperature of the patients increased gradually in the iMR imaging group but decreased in the control group. iMR imaging can prolong the operation time, increase the body temperature of the patient, and remarkably shorten the clinical action time and muscle relaxation recovery index of vecuronium.
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Affiliation(s)
- Ying Guo
- Anesthesia and Operation Center of People's Liberation Army General Hospital, 100853 Beijing, China
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Gao Y, Liu Z, Chen X, Luo W, Zhang L, Wang J. Intraoperative radiotherapy electron boost in advanced and recurrent epithelial ovarian carcinoma: a retrospective study. BMC Cancer 2011; 11:439. [PMID: 21989202 PMCID: PMC3198723 DOI: 10.1186/1471-2407-11-439] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2011] [Accepted: 10/11/2011] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND Relapses of epithelial ovarian carcinoma (EOC) have a poor prognosis and are almost always fatal. The aim of this study was to evaluate the clinical outcome and toxicity of intraoperative electron beam radiation therapy (IOERT) in advanced and recurrent EOC. METHODS Forty-five women with EOC were treated with IOERT. Twenty-five patients had primary disease (PD) without distant metastasis at IOERT, and 20 patients had an isolated local recurrence (ILR) after surgery. All 45 patients in this series underwent optimal cytoreductive (≤ 1 cm) surgery. The whole pelvic (WP) radiotherapy was intraoperatively delivered using 12 Mev electron beam; 43 patients received 18-20 Gy and two patients received 10 Gy. Thirty-three patients received postoperateive intraperitoneal (IP) chemotherapy, while seven patients received intravenous (IV) chemotherapy. Five patients refused concurrent chemotherapy. Overall survival (OS) rates were analyzed using the Kaplan-Meier method. RESULTS Tumor recurrence and metastasis were observed in 16 patients (35.6%). Of those, 14 patients (31.1%) relapsed and two patients (4.4%) had distant metastasis alone. Eight of 25 (32%) local failures were observed in the PD group, as compared to 6/20 (30%) in the ILR group (P = 0.885). Actuarial local control at five year follow-up was 31/45 (68.9%). Seventeen of the total 45 (37.8%) patients died. Nine of 25 (36%) in the PD group died, as compared to 8 of 20 (40%) in the ILR group. The 5-year OS and disease-free survival (DFS) rates were 28/45 (62.2%) and 25/45 (55.6%), respectively. In the PD group, the 5-year OS and DFS rates were 16/25 (64%) and 14/25 (56%) (P > 0.05, vs. the ILR group at 12/20 and 11/20, respectively). The OS and DFS in the IOERT plus IP group were 25/33 (75.8%) and 23/33 (69.7%), respectively, which were superior to the rates achieved with IOERT plus IV chemotherapy (P < 0.05, 2/7 and 1/7, respectively). The major complication of IOERT was neuropathy. Five (11.1%) patients developed peripheral neurotoxicity. CONCLUSIONS IOERT may be feasible and effective as a boosting technique for advanced and recurrent ovarian cancer. IOERT plus IP chemotherapy may achieve high locoregional disease control and survival benefit with a low risk of toxicity. Peripheral nerves in the IOERT field are dose-limiting structures requiring nerve protection policies or a dose compromise to ensure against severe neurological damage.
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Affiliation(s)
- Ying Gao
- The Department of Radiotherapy Oncology in the 1st Affiliated Hospital of Medical College of Xi'an Jiao Tong University, Xi'an, 710061, China
| | - Zi Liu
- The Department of Radiotherapy Oncology in the 1st Affiliated Hospital of Medical College of Xi'an Jiao Tong University, Xi'an, 710061, China
| | - Xi Chen
- The Department of Radiotherapy Oncology in the 1st Affiliated Hospital of Medical College of Xi'an Jiao Tong University, Xi'an, 710061, China
| | - Wei Luo
- The Department of Radiotherapy Oncology in the 1st Affiliated Hospital of Medical College of Xi'an Jiao Tong University, Xi'an, 710061, China
| | - Long Zhang
- The Department of Radiotherapy Oncology in the 1st Affiliated Hospital of Medical College of Xi'an Jiao Tong University, Xi'an, 710061, China
| | - Juan Wang
- The Department of Radiotherapy Oncology in the 1st Affiliated Hospital of Medical College of Xi'an Jiao Tong University, Xi'an, 710061, China
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Results of two bi-institutional prospective studies using intraperitoneal oxaliplatin with or without irinotecan during HIPEC after cytoreductive surgery for colorectal carcinomatosis. Ann Surg 2011; 254:294-301. [PMID: 21772129 DOI: 10.1097/sla.0b013e3182263933] [Citation(s) in RCA: 133] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To assess the perioperative and long-term results of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) using oxaliplatin+irinotecan (ox-irino) versus oxaliplatin alone (ox-alone). BACKGROUND Treatment of peritoneal carcinomatosis (PC) of colorectal origin with CRS+HIPEC using mitomycin-C or oxaliplatin monotherapy has shown encouraging survival results. This bi-centric study evaluates an intensified intraperitoneal combination of ox-irino and compares it with ox-alone. PATIENTS AND METHODS All consecutive patients with PC undergoing CRS+HIPEC using either ox-alone or ox-irino between 1998 and 2007 were evaluated. RESULTS One hundred forty-six patients underwent CRS+HIPEC for PC, 103 received ox-irino and 43 received ox-alone. The median peritoneal carcinomatosis index (PCI) was 11 in both groups. 90.4% had complete cytoreduction. Overall mortality rate was 4.1%. The overall morbidity rate was 47.2% and was significantly lower with ox-alone (34.9% vs. 52.4%, P = 0.05). After a median follow-up of 48.5 months, the median overall survival (OS) was 41 months (95% CI, 32-60) and median relapse-free survival (RFS) was 15.7 months (95% CI, 12-18). The median RFS of ox-alone (16.8 months; 95% CI, 11-25) was not significantly different from ox-irino (15.7 months; 95% CI, 11-18; P = 0.93). There was no significant difference between median OS of ox-alone (40.83 months; 95% CI, 29-61) and ox-irino (47 months; 95% CI, 32-61; P = 0.94). At 5 years, OS and RFS rates were 41.8% and 13.8% in ox-alone and 42.4% and 14.2% in ox-irino, respectively. Prognostic factors confirmed on multivariate analysis were lymph node metastasis and PCI. CONCLUSION Our study showed no advantage of intensification of HIPEC by adding irinotecan, contrary to the results obtained with IV combination. Ox-alone HIPEC should continue as one of the standard HIPEC regimens for PC.
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Fagotti A, Gallotta V, Romano F, Fanfani F, Rossitto C, Naldini A, Vigliotta M, Scambia G. Peritoneal carcinosis of ovarian origin. World J Gastrointest Oncol 2011. [PMID: 21160928 DOI: 10.4251/wjgo.v2.i4.102] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Epithelial ovarian cancer (EOC) is the second most common genital malignancy in women and is the most lethal gynecological malignancy, with an estimated five-year survival rate of 39%. Despite efforts to develop an effective ovarian cancer screening method, 60% of patients still present with advanced disease. Comprehensive management using surgical cytoreduction to decrease the tumor load to a minimum, and intraperitoneal chemotherapy to eliminate microscopic disease on peritoneal surface, has the potential to greatly improve quality of life and to have an impact on survival in ovarian cancer patients. Despite achieving clinical remission after completion of initial treatment, most patients (60%) with advanced EOC will ultimately develop recurrent disease or show drug resistance; the eventual rate of curability is less than 30%. Given the poor outcome of women with advanced EOC, it is imperative to continue to explore novel therapies.
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Affiliation(s)
- Anna Fagotti
- Anna Fagotti, Valerio Gallotta, Federico Romano, Francesco Fanfani, Cristiano Rossitto, Angelica Naldini, Massimo Vigliotta, Giovanni Scambia, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, 100168, Rome, Italy
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Attaluri A, Ma R, Qiu Y, Li W, Zhu L. Nanoparticle distribution and temperature elevations in prostatic tumours in mice during magnetic nanoparticle hyperthermia. Int J Hyperthermia 2011; 27:491-502. [DOI: 10.3109/02656736.2011.584856] [Citation(s) in RCA: 78] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Roviello F, Caruso S, Marrelli D, Pedrazzani C, Neri A, De Stefano A, Pinto E. Treatment of peritoneal carcinomatosis with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: state of the art and future developments. Surg Oncol 2010; 20:e38-54. [PMID: 20888755 DOI: 10.1016/j.suronc.2010.09.002] [Citation(s) in RCA: 63] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2010] [Revised: 08/06/2010] [Accepted: 09/06/2010] [Indexed: 02/06/2023]
Abstract
Peritoneal carcinomatosis (PC) had long been regarded as a terminal disease, characterized by a very poor survival and worth treating with palliative therapy. A new strategy combining maximal surgery (cytoreductive surgery, CRS), with maximal regional chemotherapy (hyperthermic intraperitoneal chemotherapy, HIPEC), has been proposed to treat PC, resulting in long-term survival rates in selected patients. The emerging trend is to view localised peritoneal carcinomatosis, in the absence of other metastases, as a regional metastatic disease that is amenable to locoregional therapy. In spite of the need for more high quality studies, many international experts now agree that the use of this new strategy is a gold standard for treating selected patients with PC with the intent of curing. The best results are achieved in patients with limited disease who have completed macroscopic tumor removal. To offer a comprehensive review, we summarized the present status and possible future progress of this treatment modality, in particular outlining its rationale, current practice and general outcome.
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Affiliation(s)
- Franco Roviello
- Department of Human Pathology and Oncology, University of Siena, Italy.
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Turcotte S, Sideris L, Younan R, Drolet P, Dubé P. Pharmacokinetics of intraperitoneal irinotecan in a pig model. J Surg Oncol 2010; 101:637-42. [PMID: 20461774 DOI: 10.1002/jso.21569] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Complete surgical cytoreduction of peritoneal implants and immediate intraperitoneal (lP) chemotherapy offers the greatest survival in selected patients with peritoneal carcinomatosis. This study was undertaken to describe the metabolism and pharmacokinetics of normothermic intraperitoneal CPT-11, free and glucuronized SN-38, in a pig model. Thirteen pigs were used for experimentation. Animals were grouped for IV and IP CPT-1 1 administration. Eleven pigs underwent laparotomy through a midline incision and instillation of 100, 200, and 400mg IP CPT-11. Systemic venous blood, portal blood and peritoneal fluid samples were taken at 5, 10, 20, 30, and 45 min, then every hour up to 8 hr for the 100 mg. For the three groups, peritoneal CPT-11 exposition was on average 4.9 times greater in the peritoneum than in the systemic venous or portal circulations and the systemic CPT-11 fraction absorbed from the peritoneum linearly increased with time. Free SN-38 was measurable in the earliest peritoneal samples taken. The initial instillation dose of CPT-11 did not impact on the SN-38 converted fraction, which remained stable at approximately 0.04% during the first 4 hour. Mean peritoneal SN-38: CPT-11 AUC ratio was 0.043. OPT-11 peritoneal conversion into SN-38 appeared slightly Inferior to the systemic conversion ratio. This norrnothermic IP OPT-11 pharmacokinetic study performed in a pig model confirms the possibility to achieve at least a 30 times higher peritoneal than systemic exposure. Peritoneal exposure to active SN-38 begins at the moment of CPT-11 peritoneal instillation. A fixed and small traction of less than 0.1% of CPT-11 is converted into SN-38, underlying the importance of a sufficient initial IP dose of CPT-11.
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Affiliation(s)
- Simon Turcotte
- Department of Surgery, Université de Montréal, Montréal, Québec, Canada
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Fagotti A, Gallotta V, Romano F, Fanfani F, Rossitto C, Naldini A, Vigliotta M, Scambia G. Peritoneal carcinosis of ovarian origin. World J Gastrointest Oncol 2010; 2:102-8. [PMID: 21160928 PMCID: PMC2999166 DOI: 10.4251/wjgo.v2.i2.102] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2009] [Revised: 10/02/2009] [Accepted: 10/09/2009] [Indexed: 02/05/2023] Open
Abstract
Epithelial ovarian cancer (EOC) is the second most common genital malignancy in women and is the most lethal gynecological malignancy, with an estimated five-year survival rate of 39%. Despite efforts to develop an effective ovarian cancer screening method, 60% of patients still present with advanced disease. Comprehensive management using surgical cytoreduction to decrease the tumor load to a minimum, and intraperitoneal chemotherapy to eliminate microscopic disease on peritoneal surface, has the potential to greatly improve quality of life and to have an impact on survival in ovarian cancer patients. Despite achieving clinical remission after completion of initial treatment, most patients (60%) with advanced EOC will ultimately develop recurrent disease or show drug resistance; the eventual rate of curability is less than 30%. Given the poor outcome of women with advanced EOC, it is imperative to continue to explore novel therapies.
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Affiliation(s)
- Anna Fagotti
- Anna Fagotti, Valerio Gallotta, Federico Romano, Francesco Fanfani, Cristiano Rossitto, Angelica Naldini, Massimo Vigliotta, Giovanni Scambia, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, 100168, Rome, Italy
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Santoro L, Boutaleb S, Garambois V, Bascoul-Mollevi C, Boudousq V, Kotzki PO, Pèlegrin M, Navarro-Teulon I, Pèlegrin A, Pouget JP. Noninternalizing monoclonal antibodies are suitable candidates for 125I radioimmunotherapy of small-volume peritoneal carcinomatosis. J Nucl Med 2009; 50:2033-41. [PMID: 19910417 DOI: 10.2967/jnumed.109.066993] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
UNLABELLED We have previously shown that, in vitro, monoclonal antibodies (mAbs) labeled with the Auger electron emitter (125)I are more cytotoxic if they remain at the cell surface and do not internalize in the cytoplasm. Here, we assessed the in vivo biologic efficiency of internalizing and noninternalizing (125)I-labeled mAbs for the treatment of small solid tumors. METHODS Swiss nude mice bearing intraperitoneal tumor cell xenografts were injected with 37 MBq (370 MBq/mg) of internalizing (anti-HER1) (125)I-m225 or noninternalizing (anti-CEA) (125)I-35A7 mAbs at days 4 and 7 after tumor cell grafting. Nonspecific toxicity was assessed using the irrelevant (125)I-PX mAb, and untreated controls were injected with NaCl. Tumor growth was followed by bioluminescence imaging. Mice were sacrificed when the bioluminescence signal reached 4.5 x 10(7) photons/s. Biodistribution analysis was performed to determine the activity contained in healthy organs and tumor nodules, and total cumulative decays were calculated. These values were used to calculate the irradiation dose by the MIRD formalism. RESULTS Median survival (MS) was 19 d in the NaCl-treated group. Similar values were obtained in mice treated with unlabeled PX (MS, 24 d) and 35A7 (MS, 24 d) or with (125)I-PX mAbs (MS, 17 d). Conversely, mice treated with unlabeled or labeled internalizing m225 mAb (MS, 76 and 77 d, respectively) and mice injected with (125)I-35A7 mAb (MS, 59 d) showed a significant increase in survival. Irradiation doses were comparable in all healthy organs, independently from the mAb used, whereas in tumors the irradiation dose was 7.4-fold higher with (125)I-labeled noninternalizing than with internalizing mAbs. This discrepancy might be due to iodotyrosine moiety release occurring during the catabolism of internalizing mAbs associated with high turnover rate. CONCLUSION This study indicates that (125)I-labeled noninternalizing mAbs could be suitable for radioimmunotherapy of small solid tumors and that the use of internalizing mAbs should not be considered as a requirement for the success of treatments with (125)I Auger electrons.
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Affiliation(s)
- Lore Santoro
- Institut de Recherche en Cancérologie de Montpellier, INSERM, U896, Montpellier, France
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Hauck ML, Zalutsky MR. Enhanced tumour uptake of radiolabelled antibodies by hyperthermia: Part I: Timing of injection relative to hyperthermia. Int J Hyperthermia 2009; 21:1-11. [PMID: 15764347 DOI: 10.1080/02656730410001695906] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
Abstract
Improving drug and macromolecular delivery of anti-cancer agents to tumours results in greater efficacy without increased toxicity. The current study was undertaken to assess the effects of the timing of injection of tumour specific and non-specific monoclonal antibodies (mAbs) relative to a hyperthermia treatment on tumour and normal tissue uptake. Using a local hyperthermia protocol of 45 min at 43 degrees C, uptake in tumour and normal tissues was measured at 1, 4, 12, 24, 48 and 72 h after injection. An anti-tenascin chimeric mAb, ch81C6, served as the specific mAb in a D-54 MG glioma xenograft mouse model. The chimeric mAb chTPS3.2 served as the control. A five-to-eight-fold increase in uptake of the tumour-targeted mAb was achieved in the heated tumours when compared with the non-heated tumours at 1 h. Differences in absolute tumour uptake of the specific mAb between the mice injected prior to hyperthermia and mice injected post-hyperthermia were seen only at 1 and 12 h. The median uptakes in the tumours of mice injected pre-heat were 25%ID/g at 1 h and 43.5%ID/g at 12 h, while in the animals injected post-hyperthermia the median uptakes were 45.5%ID/g and 80.2%ID/g, respectively. Blood levels of both the specific and non-specific mAbs were consistently higher over the initial 12 h period in the mice injected post-hyperthermia. Normal tissue uptake was also increased at most time points in the mice injected post-hyperthermia. The clinical importance of the differences in specific mAb uptake in tumour detected statistically at 1 and 12 h is questionable, given the highly variable nature of mAb uptake in vivo. Tumour targeting mAbs administered in combination with heat may be injected either prior to or immediately following hyperthermia treatment, with the expectation that levels of uptake in tumour will be relatively equivalent. Absolute normal tissue levels will be higher in patients receiving the mAb post-hyperthermia.
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Affiliation(s)
- M L Hauck
- Department of Clinical Sciences, North Carolina State University, College of Veterinary Medicine, Raleigh, NC 27606, USA.
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Hauck ML, Zalutsky MR. Enhanced tumour uptake of radiolabelled antibodies by hyperthermia. Part II: Application of the thermal equivalency equation. Int J Hyperthermia 2009; 21:13-27. [PMID: 15764348 DOI: 10.1080/02656730400011032] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
Abstract
Clinical application of local hyperthermia as a means for modulating drug and macro-molecular tumour uptake have been slow to develop, due in part to the difficulty in designing and comparing heating protocols. The thermal isodose formula developed by Sapareto and Dewey is used in cytotoxicity and radiosensitization hyperthermia protocols to compare different time/temperature combinations; however, its relevance to other end-points has not been evaluated. The current study was undertaken to determine whether heating protocols of different time and temperature, but predicted to be thermally equivalent by this formula, had similar effects on the tumour and normal tissue distribution of radiolabelled tumour-specific (anti-tenascin 81C6) and non-specific (anti-dansyl TPS3.2) monoclonal antibodies (mAbs). Two thermally equivalent heating protocols, 4 h at 41.8 degrees C and 45 min at 43 degrees C, were compared in mice with subcutaneous D54 MG human glioma xenografts. A 4-fold increase in xenograft localization of 81C6 mAb was achieved relative to that in non-heated control groups with both heating protocols. Both hyperthermia protocols also resulted in improved tumour:normal tissue ratios. However, differences in absolute tumour and normal tissue uptake were seen, suggesting that the thermal isodose formula has limited usefulness in the design and comparison of hyperthermia protocols for enhancing the tumour uptake of radiolabelled mAbs.
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Affiliation(s)
- M L Hauck
- Department of Clinical Sciences, North Carolina State University, College of Veterinary Medicine, Raleigh, NC 27606, USA.
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In vitro cytotoxicity of paclitaxel/beta-cyclodextrin complexes for HIPEC. Int J Pharm 2008; 367:148-54. [PMID: 18938234 DOI: 10.1016/j.ijpharm.2008.09.035] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2008] [Revised: 09/16/2008] [Accepted: 09/22/2008] [Indexed: 11/20/2022]
Abstract
Hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising strategy in the treatment of peritoneal carcinomatosis. To perform HIPEC, a tensioactive- and solvent-free paclitaxel formulation consisting of water-soluble paclitaxel/randomly methylated-beta-cyclodextrin (Pac/RAMEB) complexes was developed previously. Using MTT and SRB assays the cytotoxic activity of this formulation versus Taxol, was evaluated as well as the cytotoxicity of the different formulation excipients (RAMEB and Cremophor EL. The possible synergistic effect of heat and paclitaxel-based chemotherapy during HIPEC was also evaluated in vitro. The cytotoxicity assays revealed differences in viability between Cremophor EL and RAMEB treated cells of 40 and 50% for the CaCo-2 human and the CC531s rat colon cancer line, respectively, in favour of RAMEB. Despite the higher cytotoxicity of Cremophor EL, Pac/RAMEB complexes and Taxol were equipotent. Using the MTT and SRB assays the average difference in viability between both cell lines was below 10% and IC50 values showed no significant difference. Hyperthermia after drug administration (41 degrees C during 1h) had no effect on cell viability. These results indicated that it was possible to reformulate paclitaxel with a less cytotoxic vehicle while maintaining the cytotoxic activity of the formulation and that there is no synergism between paclitaxel and heat for in vitro cytotoxicity.
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"Natural history" of complete cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. Eur J Surg Oncol 2008; 35:434-8. [PMID: 18374537 DOI: 10.1016/j.ejso.2008.02.009] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2007] [Accepted: 02/18/2008] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Combining complete cytoreductive surgery (CCRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a new approach allowing curatively intended treatment of multiple malignant peritoneal tumour seedings. This aggressive treatment is frequently followed by a complicated or an unusual postoperative course, that has yet to be described. AIM To describe the clinical and biological post-therapeutic course of patients treated with CCRS plus HIPEC, who were considered uncomplicated cases, and were discharged from hospital before the 15th postoperative day. PATIENTS AND METHODS Thirty-two patients were retrospectively selected on these criteria among 232 treated patients, most of whom had received intraperitoneal high-dose oxaliplatin and intravenous 5-fluorouracil. The daily postoperative clinical and biological parameters are presented in graphs using boxplots. RESULTS Hyperthermia at 38 degrees C was the rule during the first postoperative week. The daily flow rate of the abdominal drains decreased progressively from 500 ml to 50 ml from day 1 to day 7. The flow rate of the nasogastric tube was high and close to 1000 ml/24 h until day 6. Resumption of digestive transit occurred between day 4 and day 6; it was always a diarrheic transit until day 12. Severe hypophosphoremia was observed at day 2 and day 3. White blood cells gradually decreased until day 12 to half the normal value, haemoglobin remained stable and the platelet count, which was low after surgery, continued to decrease progressively until day 3. Other data are presented. CONCLUSION These results, in this selected group of patients, allow a description of the "natural history" of CCRS plus HIPEC, which is not similar to classic uncomplicated postoperative courses following surgery. Knowledge of these "natural" changes may help avoid unnecessary explorations, and allow the early detection of postoperative complications.
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van der Zee J, Vujaskovic Z, Kondo M, Sugahara T. The Kadota Fund International Forum 2004--clinical group consensus. Int J Hyperthermia 2008; 24:111-22. [PMID: 18283588 PMCID: PMC2759185 DOI: 10.1080/02656730801895058] [Citation(s) in RCA: 66] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
Abstract
The results from experimental studies indicate that hyperthermia is both an effective complementary treatment to, and a strong sensitiser of, radiotherapy and many cytotoxic drugs. Since the first international hyperthermia conference in 1975, Washington DC, techniques to increase tumour temperature have been developed and tested clinically. Hyperthermia can be applied by several methods: local hyperthermia by external or internal energy sources, perfusion hyperthermia of organs, limbs, or body cavities, and whole body hyperthermia. The clinical value of hyperthermia in combination with other treatment modalities has been shown by randomised trials. Significant improvement in clinical outcome has been demonstrated for tumours of the head and neck, breast, brain, bladder, cervix, rectum, lung, oesophagus, for melanoma and sarcoma. The addition of hyperthermia resulted in remarkably higher (complete) response rates, accompanied by improved local tumour control rates, better palliative effects, and/or better overall survival rates. Toxicity from hyperthermia cannot always be avoided, but is usually of limited clinical relevance. In spite of these good clinical results, hyperthermia has received little attention. Problems with acceptance concern the limited availability of equipment, the lack of awareness concerning clinical results, and the lack of financial resources. In this paper the most relevant literature describing the clinical effects of hyperthermia is reviewed and discussed, and means to overcome the lack of awareness and use of this modality is described.
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Affiliation(s)
- J van der Zee
- Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, the Netherlands.
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Sarnaik AA, Sussman JJ, Ahmad SA, McIntyre BC, Lowy AM. Technology for the delivery of hyperthermic intraoperative intraperitoneal chemotherapy: a survey of techniques. RECENT RESULTS IN CANCER RESEARCH. FORTSCHRITTE DER KREBSFORSCHUNG. PROGRES DANS LES RECHERCHES SUR LE CANCER 2007; 169:75-82. [PMID: 17506250 DOI: 10.1007/978-3-540-30760-0_6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/04/2023]
Abstract
Peritoneal metastases are common sequelae of gastrointestinal malignancy. The treatment of peritoneal metastases through use of aggressive surgical cytoreduction including peritonectomy coupled with HIPEC has now been reported in several large single-institution series. The available literature suggests that in experienced hands and with appropriate patient selection cytoreduction and HIPEC can be an effective therapy, particularly when all macroscopic tumor deposits are removed. Different techniques involving the administration of intraperitoneal chemotherapy have been reported, including the closed intraoperative technique, the open or coliseum technique, and the open technique using a PCE device. All techniques have been associated with mortality and morbidity that is significant, but generally consistent with other major surgical procedures. In theory, the coliseum and PCE techniques may have less associated morbidity because of improved heat distribution; however, this remains to be definitively proven in a controlled clinical trial. Such controlled studies are critical to defining the best techniques for HIPEC administration and the appropriate role for this treatment regimen in patients with peritoneal metastases. The development of a program in cytoreductive surgery and HIPEC requires a comprehensive patient care team led by appropriately trained surgeons. Such teams are best suited to provide the highest-quality care to patients with peritoneal surface malignancy.
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Affiliation(s)
- Amod A Sarnaik
- Department of Surgery, University of Cincinnati College of Medicine, Barrett Cancer Center, OH 45219-0772, USA
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Bouquet W, Ceelen W, Fritzinger B, Pattyn P, Peeters M, Remon JP, Vervaet C. Paclitaxel/β-cyclodextrin complexes for hyperthermic peritoneal perfusion – Formulation and stability. Eur J Pharm Biopharm 2007; 66:391-7. [PMID: 17240125 DOI: 10.1016/j.ejpb.2006.11.025] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2006] [Revised: 11/16/2006] [Accepted: 11/30/2006] [Indexed: 10/23/2022]
Abstract
Due to its low aqueous solubility paclitaxel is currently formulated in a Cremophor EL/ethanol mixture. However, the vehicle of this formulation causes several side-effects. Our objective was to formulate a tensioactive-free and solvent-free paclitaxel solution, which can be used for a hyperthermic intraperitoneal chemoperfusion procedure (HIPEC). The potential of chemically modified beta-cyclodextrins to form complexes with paclitaxel was investigated as a means to increase the aqueous solubility of paclitaxel. Methylated beta-CDs (randomly methylated and 2,6-dimethylated) showed the best ability to solubilise paclitaxel compared to sulfobutyl-ether- and hydroxypropyl-beta-CD. The minimal ratio of paclitaxel versus randomly methylated-beta-cyclodextrin (RAME-beta-CD) yielding 100% inclusion efficiency was 1/20 (mol/mol). Paclitaxel/RAME-beta-CD inclusion complexes prepared via freeze drying were stable for at least 6 months when stored at 4 degrees C. A 5mg/ml paclitaxel solution was formulated using paclitaxel/RAME-beta-CD-complexes. Upon dilution of these solutions, no precipitation was seen. After 24h storage at room temperature or 2h at HIPEC conditions (41.5 degrees C) the 1/40 (mol/mol) ratio showed the highest stability at paclitaxel concentrations of 0.1 and 0.5mg/ml. When hydroxypropyl methylcellulose (HPMC) was added to the reconstitution medium, the stability significantly increased, offering the opportunity to reduce the amount of RAME-beta-CDs in the formulation.
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Affiliation(s)
- Wim Bouquet
- Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium
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Zanon C, Bortolini M, Chiappino I, Simone P, Bruno F, Gaglia P, Airoldi M, Deriu L, Mashiah A. Cytoreductive surgery combined with intraperitoneal chemohyperthermia for the treatment of advanced colon cancer. World J Surg 2007; 30:2025-32. [PMID: 17058031 DOI: 10.1007/s00268-005-0486-y] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND Chemohyperthermic peritoneal perfusion (CHPP) after extensive cytoreductive surgery is a possible choice as a regional treatment for peritoneal carcinomatosis (PC). The multicentric France EVOCAPE 1 study demonstrated that the median overall survival of patients with colon peritoneal carcinomatosis subjected to conventional surgical and/or chemotherapeutic treatment was 5.2 months. Historically, mitomycin C is the drug of choice in the treatment of intraperitoneal carcinomatosis from colon cancer. METHODS Twenty-five patients affected by stage IV colon cancer with only peritoneal involvement and a prior completion of at least a partial first cycle of systemic chemotherapeutic and/or surgical treatment (24 patients) were enrolled. Immediately following extensive cytoreductive surgery, early postoperative closed abdomen CHPP was performed. RESULTS Complete surgical cytoreduction (CC0-CC1) was obtained in 22 patients. Postoperative mortality was 1 out of 25 (4%). Major postoperative morbidity was 6 out of 25 (24%). Median overall survival estimated by Kaplan-Meier curve was 30.3 months. Locoregional progression-free survival was 17.3 months. Of all the patients 64% and 40% were alive after 1 and 2 years respectively. CONCLUSIONS In referral centers CHPP after optimal surgical debulking is a safe procedure for peritoneal carcinomatosis from colonic cancer. Locoregional control was obtained in the majority of the pretreated patients and 1-year survival was statistically improved. A closed abdomen CHPP procedure lasting 1 hour and standard mitomycin C at a dosage of 15 mg/m(2) is probably as efficacious as other hyperthermic procedures, using higher mitomycin C dosages, with a comparable or lower number of cases of side effects. These results, as in other published phase II studies, justify future randomized trials to assess definitively the role of CHPP in the treatment of locally advanced colon neoplasms in western countries.
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Affiliation(s)
- Claudio Zanon
- Department of Oncology, Service of Surgical Oncology, S. Giovanni Battista Antica Sede Hospital, Via Cavour 31, 10125 Turin, Italy.
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Elias D, Goere D, Blot F, Billard V, Pocard M, Kohneh-Shahri N, Raynard B. Optimization of hyperthermic intraperitoneal chemotherapy with oxaliplatin plus irinotecan at 43 degrees C after compete cytoreductive surgery: mortality and morbidity in 106 consecutive patients. Ann Surg Oncol 2007; 14:1818-24. [PMID: 17356950 DOI: 10.1245/s10434-007-9348-1] [Citation(s) in RCA: 120] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2006] [Accepted: 12/19/2006] [Indexed: 02/06/2023]
Abstract
BACKGROUND Peritoneal carcinomatosis (PC), which has hitherto been regarded as a lethal entity, can now be cured with surgery (treating macroscopic tumor seeding) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) (treating residual microscopic disease). The purpose of this study was to analyze the morbidity and mortality of a particular approach associating optimal (R0-R1) cytoreduction, optimal HIPEC combining oxaliplatin and irinotecan, and an optimal homogeneous intraperitoneal temperature of 43 degrees C. METHODS A total of 106 consecutive patients were included in this prospective phase 2 study. After complete resection of the PC, HIPEC was performed by the Coliseum technique with oxaliplatin (360 mg/m2) combined with irinotecan (360 mg/m2) in 2 L/m2 of 5% dextrose, over 30 minutes at a real intraperitoneal temperature of 43 degrees C. During the hour preceding HIPEC, patients received 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) intravenously, resulting in tritherapy. RESULTS Postoperative mortality and morbidity rates were 4% and 66%, respectively. The most frequent complications were digestive fistula (24%), lung infection (16%), and severe hematological toxicity (11%). Statistical correlation was evidenced between morbidity and the carcinomatosis score (P = .0008), the number of resected organs (P = .0001), the duration of surgery (P = .0001), and blood loss (P = .0001). CONCLUSIONS This new approach, optimized in three respects (complete cytoreduction, combination oxaliplatin with irinotecan, and high temperature) has resulted in a relatively high but acceptable incidence of adverse events considering the expected advantage for survival.
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Affiliation(s)
- Dominique Elias
- Department of Surgical Oncology, Institut Gustave Roussy, 39 Rue Camille Desmoulins, 94805 Villejuif, Cedex, France.
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Abstract
PURPOSE Complete resection of macroscopic colorectal peritoneal carcinomatosis (PC), followed by intraoperative intraperitoneal chemohyperthermia (IPCH) to treat residual microscopic disease achieves cure in some patients. We report long-term results concerning survival of a phase II study using oxaliplatin (LOHP). PATIENTS AND METHODS From June 1998 to December 2003, thirty patients with macroscopic colorectal PC underwent complete resection of PC followed by IPCH with LOHP performed in an open abdominal cavity. The dose of LOHP was 460 mg/m2 in 2 L/m2 of iso-osmotic 5% dextrose, over 30 min at an intraperitoneally homogenous temperature of 43 degrees C and at a flow rate of 2 L/min in the continuous closed circuit. During the hour preceding IPCH, patients received 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) intravenously. All patients received neoadjuvant and adjuvant systemic chemotherapy. RESULTS Mean peritoneal tumor extension (Sugarbaker's Score) was 14.3 +/- 3.8, median operative duration, 450 min, and median blood loss, 940 mL. Eleven (37%) patients had associated extra-peritoneal lesions which were resected during the same procedure. There were no postoperative deaths and grade 2-3 morbidity (requiring specific treatment) was 40%. Median follow-up was 55 months (range: 31-84). Twenty-two patients (73%) relapsed after a median interval of 14 months, but 7 of them (32%) were amenable to curative repeat surgery. At 3 and 5 years, overall survival rates (95% confidence interval) were 53% (9-72), and 48.5% (31-66) respectively. At 3 and 5 years, disease-free survival rates were 41.5% (27-59), and 34% (19-52) respectively. Median survival was 60.1 months. CONCLUSION When feasible, this treatment modality yields a 5-year survival rate of 48.5%, with median survival attaining 60.1 months.
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Yang X, Du J, Liu Y. Advances in hyperthermia technology. CONFERENCE PROCEEDINGS : ... ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL CONFERENCE 2007; 2005:6766-9. [PMID: 17281827 DOI: 10.1109/iembs.2005.1616058] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Hyperthermia is a type of cancer treatment in which body tissue is exposed to high temperatures. Research has shown that high temperatures can damage and kill cancer cells, usually with minimal injury to normal tissues. In the clinical application of hyperthermia, three methods can be distinguished: local, regional and whole-body hyperthermia. Hyperthermia is under study in clinical trials and is not widely available. So further technological improvements will need to contribute to an easier and better controlled adequate application of hyperthermia.
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Affiliation(s)
- Xiaoyong Yang
- Biomedical Engineering Center, Beijing, University of Technology, Beijing, China
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Ramírez Plaza CP, Cobo Dols MA, Gómez Portilla A, de la Fuente Perucho A. Cytoreductive surgery and intraoperative intraperitoneal hyperthermic chemotherapy in patients with peritoneal carcinomatosis of colorectal origin. Clin Transl Oncol 2006; 7:421-31. [PMID: 16373050 DOI: 10.1007/bf02716592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
The median survival in patients with peritoneal carcinomatosis from colorectal adenocarcinoma is,with conventional approaches, only about six months. Combined treatment consisting of maxi-mum cytoreductive surgery plus intraoperative intraperitoneal hyperthermic chemotherapy has been shown, albeit in small non-comparative series, to increase disease-free survival and overall survival, compared with previous series. Further, a randomized trial has demonstrated better results (a median survival of 22.4 months) with cytoreduction plus intraperitoneal chemotherapy compared with conventional chemotherapy. Technical considerations, infrastructure requirements and possible complications imply specialized centres and staff. Surgery consists of peritonectomy of affected areas and fulguration of all macroscopic lesions. Intraperitoneal chemotherapy must reach all parts of the peritoneal cavity and the temperature of the hyperthermic procedure must be maintained between 42-44 degrees C. Three prognostic factors associated with this procedure are: pathologic tumour grade, peritoneal carcinomatosis index, and cytoreductive surgery grade.
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Affiliation(s)
- César P Ramírez Plaza
- Servicio de Cirugía General y Aparato Digestivo, Hospital Regional Universitario de Málaga Carlos Haya, Málaga, Spain.
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Gilly FN. Phase II studies: International registry of colorectal carcinomatosis. Eur J Surg Oncol 2006; 32:648-54. [PMID: 16678380 DOI: 10.1016/j.ejso.2006.03.030] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2005] [Accepted: 03/08/2006] [Indexed: 01/09/2023] Open
Abstract
Peritoneal carcinomatosis (PC) is a common manifestation of colorectal cancer and has traditionally been regarded as a terminal disease with a short median survival. Over the last decade, a new local-regional therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy has evolved and promising survival results were reported in large phase II studies. A retrospective multicentric study of 506 patients from 28 institutions was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy) within the 7 days following surgery. The morbidity and mortality rates were 22.9% and 4%, respectively. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months compared to 8.4 months for patients in whom complete cytoreductive surgery was not possible (p < 0.001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis and poor histological differentiation were negative independent prognostic indicators. The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in carefully selected group of patients with PC from colorectal origin and offer a chance for cure or palliation in this condition. Further collaboration between peritoneal surface malignancy treatment centres are needed in order to standardize indications, intraperitoneal chemotherapy and peritonectomy techniques.
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Affiliation(s)
- F N Gilly
- Surgical Department, Centre Hospitalo Universitaire Lyon Sud, 69495 Pierre Bénite Cedex, France.
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Li JK, Zheng M, Miao CW, Zhang JH, Ding GH, Wu WS. Peritoneal lavage cytology and carcinoembryonic antigen determination in predicting peritoneal metastasis and prognosis of gastric cancer. World J Gastroenterol 2006; 11:7374-7. [PMID: 16437646 PMCID: PMC4725135 DOI: 10.3748/wjg.v11.i46.7374] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the role of peritoneal lavage cytology (PLC) and carcinoembryonic antigen (CEA) determination of peritoneal washes (pCEA) in predicting the peritoneal metastasis and prognosis after curative resection of gastric cancer. METHODS PLC and radioimmunoassay of CEA were performed in peritoneal washes from 64 patients with gastric cancer and 8 patients with benign diseases. RESULTS The positive rate of pCEA (40.6%) was significantly higher than that of PLC (23.4%) (P<0.05). The positive rates of PLC and pCEA correlated with the depth of tumor invasion and lymph node metastasis (P<0.05). pCEA was found to have a higher sensitivity and a lower false-positive rate in predicting peritoneal metastasis after curative resection of gastric cancer as compared to PLC. The 1-, 3-, and 5-year survival rates of patients with positive cytologic findings or positive pCEA results were significantly lower than those of patients with negative cytologic findings or negative pCEA results (P<0.05). Multivariate analysis indicated that pCEA was an independent prognostic factor for the survival of patients with gastric cancer. CONCLUSION Intraoperative pCEA is a more sensitive and reliable predictor of peritoneal metastasis as well as prognosis in patients with gastric cancer as compared to PLC method.
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Affiliation(s)
- Ji-Kun Li
- Department of General Surgery, First Affiliated People's Hospital of Shanghai Jiaotong University, Shanghai 200080, China.
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Koppe MJ, Boerman OC, Oyen WJG, Bleichrodt RP. Peritoneal carcinomatosis of colorectal origin: incidence and current treatment strategies. Ann Surg 2006; 243:212-22. [PMID: 16432354 PMCID: PMC1448921 DOI: 10.1097/01.sla.0000197702.46394.16] [Citation(s) in RCA: 400] [Impact Index Per Article: 21.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To review the literature with regard to the incidence and prognostic significance of peritoneal seeding during surgery for primary colorectal cancer (CRC), the incidence of intraperitoneal recurrence of CRC, and the current treatment strategies of established PC of colorectal origin, with special focus on cytoreductive surgery and intraperitoneal chemotherapy (IPEC). SUMMARY BACKGROUND DATA Although hematogenous dissemination forms the greatest threat to patients with CRC, peritoneal carcinomatosis (PC), presumably arising from intraperitoneal seeding of cancer cells, is a relatively frequent event in patients with recurrent CRC. METHODS The PubMed and Medline literature databases were searched for pertinent publications regarding the incidence and prognostic significance of exfoliated tumor cells in the peritoneal cavity during curative surgery for primary CRC, the incidence of intraperitoneal recurrence of CRC, and the therapeutic results of systemic chemotherapy or cytoreductive surgery followed by IPEC. RESULTS The incidence of peritoneal seeding during potentially curative surgery for primary CRC, as reported in 12 patient series, varied widely, from 3% to 28%, which may be explained by differences in methods to detect tumor cells. PC is encountered in approximately 7% of patients at primary surgery, in approximately 4% to 19% of patients during follow-up after curative surgery, in up to 44% of patients with recurrent CRC who require relaparotomy, and in 40% to 80% of patients who succumb to CRC. The reported median survival after systemic 5-fluorouracil-based chemotherapy for PC varies from 5.2 to 12.6 months. Median survival after aggressive cytoreductive surgery followed by (hyperthermic) IPEC in selected patients, as reported in 16 patient series, tends to be better and varies from 12 to 32 months at the cost of morbidity and mortality rates of 14% to 55% and 0% to 19%, respectively. One randomized controlled trial has been published confirming the superiority of aggressive surgical cytoreduction and intraperitoneal chemotherapy over strictly palliative treatment. CONCLUSIONS Peritoneal seeding of cancer cells possibly leading to PC is a rather common phenomenon in patients with CRC. Cytoreductive surgery and adjuvant (hyperthermic) IPEC have been shown to be efficacious in selected patients and should therefore be considered in patients with resectable PC of colorectal origin.
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Affiliation(s)
- Manuel J Koppe
- Department of Surgery, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
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Cerretani D, Nencini C, Urso R, Giorgi G, Marrelli D, De Stefano A, Pinto E, Cioppa T, Nastri G, Roviello F. Pharmacokinetics of mitomycin C after resection of peritoneal carcinomatosis and intraperitoneal chemohyperthermic perfusion. J Chemother 2006; 17:668-73. [PMID: 16433199 DOI: 10.1179/joc.2005.17.6.668] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
Over the last few years surgery on patients with abdominal malignancies has become more aggressive but the majority of patients present locoregional recurrence as peritoneal dissemination. Cytoreductive surgery followed by intraperitoneal chemohyperthermic perfusion (ICHP) has been described for treatment and prevention of locoregional cancer spread from various origins. This paper reports our study of the pharmacokinetics of mitomycin C (MMC) administered by intraperitoneal chemohyperthermic perfusion (ICHP) in patients with peritoneal carcinomatosis. 28 patients received MMC 20 mg/m2 intraperitoneally as a perfusion over 60 min. MMC was determined in perfusate, plasma and urine samples with a UV-HPLC method. A compartmental model was used to fit the drug concentrations in plasma and perfusate. Our results showed a mean maximum plasma concentration (Cmax) of 0.14 +/- 0.086 microg/ml with a peak time (Tmax) of 48..7 +/- 5.61 min. The mean area under the curve (AUC) and terminal half-life (t1/2) were 15.8 +/- 9.8 mg x min/L and 83.7 +/- 31.74 min respectively. Clearance (CL) was estimated by fitting the data by a compartmental model and the mean value was 72 +/- 66 L/h. The percent of the dose absorbed was very variable and ranged between 14 and 57% (mean 37 +/- 14%). The mean percentage of dose recovered unchanged in the urine during 24 hours was 7.21 +/- 3.73%. We conclude that ICHP in patients with peritoneal surface malignancies seems to have clinical value since it gives high peritoneal and tumor MMC concentrations with limited systemic exposure and toxicity.
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Affiliation(s)
- D Cerretani
- Department of Pharmacology G. Segre, University of Siena, Siena, Italy
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Reichman TW, Cracchiolo B, Sama J, Bryan M, Harrison J, Pliner L, Harrison LE. Cytoreductive surgery and intraoperative hyperthermic chemoperfusion for advanced ovarian carcinoma. J Surg Oncol 2005; 90:51-6; discussion 56-8. [PMID: 15844187 DOI: 10.1002/jso.20243] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Optimal cytoreductive surgery combined with intraoperative hyperthermic chemoperfusion (IHCP) is a therapy that potentially could improve survival in a select group of patients with advanced ovarian cancer. The purpose of this study was to review the results of cytoreductive surgery and IHCP for advanced ovarian cancer and to identify factors that may predict which patients maximally benefit from this aggressive treatment. METHODS Patients treated with cytoreduction followed by IHCP for ovarian cancer were identified from an IHCP database from 1/2001 through 3/2004. Several factors including resection status, peritoneal cancer index (PCI), and prior surgery were evaluated for their ability to predict survival in our cohort of patients. RESULTS Thirteen patients with ovarian cancer treated with cytoreductive surgery followed by IHCP were identified. The 3-year overall survival rate for all thirteen patients was 55%. The median disease-free survival was 15.4 months (3-year disease-free survival, 11%). Several factors including PCI score (<6), ability to resect all gross disease, and previous surgical exploration appeared to impart an overall survival advantage. CONCLUSIONS The use of IHCP coupled with optimal cytoreduction is a safe and effective treatment for advanced ovarian carcinoma. However, the proper selection of patients who will benefit most from the therapy is essential for the success of the treatment.
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Affiliation(s)
- Trevor W Reichman
- Division of Surgical Oncology, UMDNJ-New Jersey Medical School, New Jersey 07903, USA
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