肿瘤细胞减灭术加腹腔热灌注化疗围手术期静脉血栓栓塞症的危险因素及防治技术
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摘要
目的分析肿瘤细胞减灭术(cytoreductive surgery, CRS)加腹腔热灌注化疗(hyperthermic intraperitonealchemotherapy,HIPEC)围手术期静脉血栓栓塞症(venousthromboembolism, VTE)的独立危险因素,探索VTE综合防治技术。方法分析CRS+HIPEC治疗患者的VTE风险,通过单因素和多因素分析筛选VTE独立危险因素;分析物理治疗加药物干预对防治VTE的疗效。结果820例腹膜癌患者行CRS+HIPEC治疗,围手术期发生VTE者14例(1.7%),其中6例(0.7%)为无临床症状型VTE,8例(1.0%)发生9个临床症状型VTE事件。未发生VTE相关死亡。单因素分析提示高龄(P=0.043)、超重(P=0.023)、VTE既往史(P=0.001)、术前VTE(P=0.008)、脉管瘤栓(P=0. 0 3 6)是V T E事件的高危险因素;多因素分析显示V T E既往史(O R=1 3. 7 4 4,95%CI:2.391～64.455)、脉管瘤栓(OR=5.858, 95%CI:1.028～33.387)是V T E事件的独立危险因素。结论VTE既往史、脉管瘤栓是腹膜癌CRS+HIPEC围手术期VTE的独立危险因素,以物理预防为主的综合防治技术可有效预防VTE。
Objective To analyze the independent risk factors for perioperative venous thromboembolism(VTE) after cytoreductive surgery(CRS) plus hyperthermic intraperitoneal chemotherapy(HIPEC), and to develop an integrated VTE prevention strategy. Methods The comprehensive database of CRS+HIPEC was first systematically investigated to analyze the risk factors for VTE, and univariate and multivariate analyses were conducted to screen independent risk factors for VTE. An integrated VTE prevention strategy combining physiotherapy and pharmaceutical treatment was developed and applied to the patients. Results Among the 820 patients treated with CRS+HIPEC in the database, 14(1.7%) patients developed VTE in the perioperative period, including 6(0.7%) patients with asymptomatic VTE events and 8(1.0%) patients with 9 symptomatic events. No VTE-related death occurred. Univariate analysis revealed 5 high risk factors: old age(P=0.043), overweight(P=0.023), previous VTE-history(P=0.001), preoperative VTE(P=0.008) and vascular tumor thrombus(P=0.036). Multivariate analysis confirmed two independent risk factors: previous VTE history(OR=13.744, 95%CI: 2.391-64.455) and vascular tumor thrombus(OR=5.858, 95%CI: 1.028-33.387). Conclusion Previous VTE history and vascular tumor thrombus are independent risk factors for peritoneal cancer(PC) patients after CRS+HIPEC. Physiotherapy-based integrated prevention and treatment strategy could help prevent VTE.
Objective To analyze the independent risk factors for perioperative venous thromboembolism(VTE) after cytoreductive surgery(CRS) plus hyperthermic intraperitoneal chemotherapy(HIPEC), and to develop an integrated VTE prevention strategy. Methods The comprehensive database of CRS+HIPEC was first systematically investigated to analyze the risk factors for VTE, and univariate and multivariate analyses were conducted to screen independent risk factors for VTE. An integrated VTE prevention strategy combining physiotherapy and pharmaceutical treatment was developed and applied to the patients. Results Among the 820 patients treated with CRS+HIPEC in the database, 14(1.7%) patients developed VTE in the perioperative period, including 6(0.7%) patients with asymptomatic VTE events and 8(1.0%) patients with 9 symptomatic events. No VTE-related death occurred. Univariate analysis revealed 5 high risk factors: old age(P=0.043), overweight(P=0.023), previous VTE-history(P=0.001), preoperative VTE(P=0.008) and vascular tumor thrombus(P=0.036). Multivariate analysis confirmed two independent risk factors: previous VTE history(OR=13.744, 95%CI: 2.391-64.455) and vascular tumor thrombus(OR=5.858, 95%CI: 1.028-33.387). Conclusion Previous VTE history and vascular tumor thrombus are independent risk factors for peritoneal cancer(PC) patients after CRS+HIPEC. Physiotherapy-based integrated prevention and treatment strategy could help prevent VTE.
引文
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[15]Blom JW,Doggen CJ,Osanto S,et al.Malignancies,prothrombotic mutations,and the risk of venous thrombosis[J].JAMA,2005,293(6):715-22.
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[19]Lanuke K,Mack LA,Temple WJ.A prospective evaluation of venous thromboembolism in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy[J].Can JSurg,2009,52(1):18-22.
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[21]Sparks DS,Morris B,Xu W,et al.Cytoreductive surgery and heated intraperitoneal chemotherapy for peritoneal carcinomatosis secondary to mucinous adenocarcinoma of the appendix[J].Int Surg,2015,100(1):21-8.
[22]Farge D,Bounameaux H,Brenner B,et al.International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer[J].Lancet Oncol,2016,17(10):e452-66.
[23]Stein PD,Yaekoub AY,Ahsan ST,et al.Ankle exercise and venous blood velocity[J].Thromb Haemost,2009,101(6):1100-3.
[24]Caldwell K,Prior SJ,Kampmann M,et al.Upper body exercise increases lower extremity venous blood flow in deep venous thrombosis[J].J Vasc Surg Venous Lymphat Disord,2013,1(2):126-33.
[25]Jahangard T,Torkaman G,Ghoosheh B,et al.The effect of shortterm aerobic training on coagulation and fibrinolytic factors in sedentary healthy postmenopausal women[J].Maturitas,2009,64(4):223-7.
[26]Gainsbury ML,Erdrich J,Taubman D,et al.Prevalence and Predictors of Preoperative Venous Thromboembolism in Asymptomatic Patients Undergoing Major Oncologic Surgery[J].Ann Surg Oncol,2018,25(6):1640-5.
[27]Arai H,Hironaka S,Minashi K,et al.Cumulative incidence,risk factors and prognostic impact of venous thromboembolism in Japanese patients with advanced gastric cancer[J].Jpn J Clin Oncol,2017,47(10):942-8.
[28]Osaki T,Saito H,Fukumoto Y,et al.Risk and incidence of perioperative deep vein thrombosis in patients undergoing gastric cancer surgery[J].Surg Today,2018,48(5):525-33.
[2]Verwaal VJ,Van Ruth S,de Bree E,et al.Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer[J].J Clin Oncol,2003,21(20):3737-43.
[3]Yang XJ,Huang CQ,Suo T,et al.Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer:final results of a phaseⅢrandomized clinical trial[J].Ann Surg Oncol,2011,18(6):1575-81.
[4]Spiliotis J,Halkia E,Lianos E,et al.Cytoreductive surgery and HIPEC in recurrent epithelial ovarian cancer:a prospective randomized phaseⅢstudy[J].Ann Surg Oncol,2015,22(5):1570-5.
[5]Van Driel WJ,Koole SN,Sikorska K,et al.Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer[J].N Engl JMed,2018,378(3):230-40.
[6]Li Y,Yu Y,Liu Y.Report on the 9(th)International Congress on Peritoneal Surface Malignancies[J].Cancer Biol Med,2014,11(4):281-4.
[7]Yang XJ,Li Y,Yonemura Y.Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy to treat gastric cancer with ascites and/or peritoneal carcinomatosis:Results from a Chinese center[J].J Surg Oncol,2010,101(6):457-64.
[8]Jacquet P,Sugarbaker PH.Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis[J].Cancer Treat Res,1996,82:359-74.
[9]Sugarbaker PH.Peritonectomy procedures[J].Ann Surg,1995,221(1):29-42.
[10]Sugarbaker PH.Cytoreductive surgery and peri-operative intraperitoneal chemotherapy as a curative approach to pseudomyxoma peritonei syndrome[J].Eur J Surg Oncol,2001,27(3):239-43.
[11]Caprini JA.Risk assessment as a guide to thrombosis prophylaxis[J].Curr Opin Pulm Med,2010,16(5):448-52.
[12]中国临床肿瘤学会肿瘤与血栓专家共识委员会.中国肿瘤相关静脉血栓栓塞症预防与治疗专家指南(2015版)[J].中国实用内科杂志,2015,35(11):907-20.[Chinese Society of Clinical Oncilogy Cancer and Thrombosis Expert Consensus Committee.Guidelines in prevention and treatment of tumor-associated venous thromboembolism in China(Version 2015)[J].Zhongguo Shi Yong Nei Ke Za Zhi,2015,35(11):907-20.]
[13]Farge D,Debourdeau P,Beckers M,et al.International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer[J].J Thromb Haemost,2013,11(1):56-70.
[14]彭开文,张倩,刘九洋,等.肿瘤细胞减灭加腹腔热灌注化疗术后静脉血栓栓塞症的预防[J].中国肿瘤临床,2017,44(8):384-9.[Peng KW,Zhang Q,Liu JY,et al.Venous thromboembolism prevention for peritoneal carcinomatosis patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy[J].Zhongguo Zhong Liu Lin Chuang,2017,44(8):384-9.]
[15]Blom JW,Doggen CJ,Osanto S,et al.Malignancies,prothrombotic mutations,and the risk of venous thrombosis[J].JAMA,2005,293(6):715-22.
[16]Trinh VQ,Karakiewicz PI,Sammon J,et al.Venous thromboembolism after major cancer surgery:temporal trends and patterns of care[J].JAMA Surg,2014,149(1):43-9.
[17]Khorana AA,Francis CW,Culakova E,et al.Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy[J].J Thromb Haemost,2007,5(3):632-4.
[18]Rottenstreich A,Kalish Y,Kleinstern G,et al.Factors associated with thromboembolic events following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy[J].J Surg Oncol,2017,116(7):914-20.
[19]Lanuke K,Mack LA,Temple WJ.A prospective evaluation of venous thromboembolism in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy[J].Can JSurg,2009,52(1):18-22.
[20]Vukadinovic V,Chiou JD,Morris DL.Clinical features of pulmonary emboli in patients following cytoreductive surgery(peritonectomy)and hyperthermic intraperitoneal chemotherapy(hipec),a single centre experience[J].Eur J Surg Oncol,2015,41(5):702-6.
[21]Sparks DS,Morris B,Xu W,et al.Cytoreductive surgery and heated intraperitoneal chemotherapy for peritoneal carcinomatosis secondary to mucinous adenocarcinoma of the appendix[J].Int Surg,2015,100(1):21-8.
[22]Farge D,Bounameaux H,Brenner B,et al.International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer[J].Lancet Oncol,2016,17(10):e452-66.
[23]Stein PD,Yaekoub AY,Ahsan ST,et al.Ankle exercise and venous blood velocity[J].Thromb Haemost,2009,101(6):1100-3.
[24]Caldwell K,Prior SJ,Kampmann M,et al.Upper body exercise increases lower extremity venous blood flow in deep venous thrombosis[J].J Vasc Surg Venous Lymphat Disord,2013,1(2):126-33.
[25]Jahangard T,Torkaman G,Ghoosheh B,et al.The effect of shortterm aerobic training on coagulation and fibrinolytic factors in sedentary healthy postmenopausal women[J].Maturitas,2009,64(4):223-7.
[26]Gainsbury ML,Erdrich J,Taubman D,et al.Prevalence and Predictors of Preoperative Venous Thromboembolism in Asymptomatic Patients Undergoing Major Oncologic Surgery[J].Ann Surg Oncol,2018,25(6):1640-5.
[27]Arai H,Hironaka S,Minashi K,et al.Cumulative incidence,risk factors and prognostic impact of venous thromboembolism in Japanese patients with advanced gastric cancer[J].Jpn J Clin Oncol,2017,47(10):942-8.
[28]Osaki T,Saito H,Fukumoto Y,et al.Risk and incidence of perioperative deep vein thrombosis in patients undergoing gastric cancer surgery[J].Surg Today,2018,48(5):525-33.