外科手术治疗转移性肾细胞癌合并静脉癌栓患者的临床经验

Clinical experience of surgical treatment in metastatic renal cell carcinoma with venous tumor thrombus

目的探讨转移性肾细胞癌伴肾静脉或下腔静脉癌栓患者行减瘤性肾切除术及静脉癌栓取出术的安全性和有效性。方法回顾性分析2015年2月至2019年5月北京大学第三医院收治的56例转移性肾细胞癌伴静脉癌栓且行手术治疗患者的病例资料。男44例(78.6%),女12例(21.4%)。平均年龄(59.2±10.7)(22~82)岁。临床表现仅有局部症状26例(46.4%),仅有全身症状8例(14.3%),同时合并局部症状和全身症状12例(21.4%),无症状者10例(17.9%)。肾肿瘤位于右侧35例(62.5%),左侧21例(37.5%)。肿瘤直径平均(10.1±3.8)(1.5~21.1)cm。美国麻醉医师协会评分2分45例(80.4%),3分11例(19.6%)。术前血红蛋白(118.2±23.1)(72~178)g/L,白蛋白(37.9±5.6)(23~50)g/L,总蛋白(67.7±6.7)(43~81)g/L,血肌酐(111.3±119.6)(32~958)μmol/L。静脉癌栓Mayo分级0级16例(28.6%),Ⅰ级14例(25.0%),Ⅱ级17例(30.4%),Ⅲ级4例(7.1%),Ⅳ级5例(8.9%)。临床淋巴结分期cN0期14例(25.0%),cN1期42例(75.0%)。单纯骨转移5例(8.9%),单纯肺转移16例(28.6%),单纯肾上腺转移2例(3.6%),单纯肝转移6例(10.7%),≥2个部位的多系统转移27例(48.2%)。56例共发现91处转移灶,发生肺转移37处(40.7%),肝转移18处(19.8%),骨转移21处(23.1%),肾上腺转移15处(16.5%)。56例均为国际转移性肾细胞癌联合数据库(IMDC)预后评分中危组。采用腹腔镜手术22例(39.3%),开放手术30例(53.6%),4例(7.1%)腹腔镜手术中转开放手术。Mayo 0级癌栓的手术处理方法同根治性肾切除术。MayoⅠ级癌栓主要采用satinsky心耳钳部分阻断下腔静脉后取栓。MayoⅡ级癌栓需要依次阻断癌栓远心端腔静脉、对侧肾静脉及近心端腔静脉后切开下腔静脉取栓。MayoⅢ级癌栓需要游离肝脏并采用Pringer法阻断第一肝门后取栓。MayoⅣ级癌栓可采用切开膈肌中心腱或直接切开膈肌取栓,或采用体外循环取栓。6例(10.7%)因肿瘤侵犯血管壁切除下腔静脉壁。32例(57.1%)因术前影像学提示肿瘤侵犯肾上腺或发生肾上腺转移行同侧肾上腺切除术。23例(41.1%)行同侧淋巴结清扫术。本组中孤立性转移灶者11例,其中行手术切除孤立性转移灶者8例,未手术者3例。姑息性肾切除术后辅助治疗采用舒尼替尼43例,培唑帕尼9例,阿西替尼3例,索拉非尼者1例。结果本组56例手术均顺利完成,无术中死亡病例。手术时间(326.8±114.9)(108~589)min。术中出血量(1435.2±1513.4)(20~6000)ml,30例术中输注红细胞,平均(1456.7±832.8)(400~3600)ml;15例术中输注血浆,平均(700.0±473.6)(200~1800)ml。术后住院时间(10.6±4.6)(5~26)d。术后1周血肌酐(109.5±98.7)(47~772)μmol/L。病理诊断为肾透明细胞癌46例(82.1%),乳头状肾细胞癌7例(12.5%),未分类肾细胞癌3例(5.4%)。WHO/ISUP 2016核分级1级1例(1.8%),2级20例(36.4%),3级18例(32.7%),4级16例(29.1%)。22例(39.3%)发生术后早期并发症。其中,Clavien分级Ⅰ级1例,为伤口感染;Clavien分级Ⅱ级16例,包括因贫血输血5例,乳糜瘘3例,术后肺部感染4例,术后下肢静脉血栓2例,房颤1例,附睾炎1例;Clavien分级Ⅲa级1例,为气胸行胸腔闭式引流;Clavien分级Ⅳ级2例,包括术后急性脑梗塞1例,术后肾功能不全1例;Clavien分级Ⅴ级2例,为围术期死亡。56例中5例失访,2例发生围术期死亡,余49例中位随访14(1~39)个月,平均生存时间(25.6±2.5)个月,中位生存时间25个月。结论对转移性肾细胞癌伴静脉癌栓患者行减瘤性肾切除术及静脉癌栓取出术相对安全有效。对于有临床症状、IMDC预后评分中危组、手术意愿强烈的患者,可选择减瘤性肾切除术及静脉癌栓取出术联合术后辅助靶向治疗的综合治疗模式。

Objective To investigate the safety and effectiveness of cytoreductive nephrectomy and tumor thrombectomy in patients with metastatic renal cancer with renal vein or inferior vena cava tumor thrombus.Methods From February 2015 to May 2019,56 cases of metastatic renal cell carcinoma with venous tumor thrombus were analyzed retrospectively,including 44 male(78.6%)and 12 female(21.4%)cases,and the average age was(59.2±10.7)(22-82).The clinical presentations covered local symptoms in 26 cases(46.4%),systemic symptoms in 8 cases(14.3%),both local symptoms and systemic symptoms in 12 cases(21.4%),and asymptomatic in 10 cases(17.9%).Among them,renal tumors were located in 35 cases(62.5%)on the right and 21 cases(37.5%)on the left.The average tumor diameter was(10.1±3.8)(1.5-21.1)cm.Forty-five cases(80.4%)scored 2 points and 11 cases(19.6%)scored 3 points by the American Society of anesthesiologists(ASA).Preoperative hemoglobin was(118.2±23.1)(72-178)g/L,and albumin was(37.9±5.6)(23-50)g/L,total protein was(67.7±6.7)(43-81)g/L,serum creatinine was(111.3±119.6)(32-958)μmol/L.There were 16 cases of Mayo 0(28.6%),14 cases of MayoⅠ(25.0%),17 cases of MayoⅡ(30.4%),4 cases of MayoⅢ(7.1%),and 5 cases of MayoⅣ(8.9%).Fourteen cases(25.0%)were in the stage of cN0 and 42 cases(75.0%)in the stage of cN1.Five cases(8.9%)had simple bone metastasis,16 cases(28.6%)had simple lung metastasis,2 cases(3.6%)had simple adrenal metastasis,6 cases(10.7%)had simple liver metastasis,and 27 cases(48.2%)had 2 or more multiple system metastasis.According to the location of the organ system,91 metastatic lesions were found in 56 patients.Among them,37 cases(40.7%)had lung metastasis,18 cases(19.8%)had liver metastasis,21 cases(23.1%)had bone metastasis and 15 cases(16.5%)had adrenal metastasis.All 56 patients belonged to IMDC prognosis score model medium risk group.The surgical treatment of Mayo grade 0 tumor thrombus was the same as that of routine radical nephrectomy.The tumor thrombus of Mayo gradeⅠwas removed after IVC was partially blocked by Satinsky′s forceps.The MayoⅡtumor thrombus was removed,after blocking the distal vena cava,the contralateral renal vein and the proximal vena cava.Mayo gradeⅢtumor thrombus needed pringer's method to block the first porta hepatis.For gradeⅣtumor thrombus the diaphragm could be cut directly,or the thrombus could be removed by cardiopulmonary bypass.Laparoscopic surgery was performed in 22 cases(39.3%)and open surgery in 30 cases(53.6%).Six cases(10.7%)underwent IVC wall resection because of tumor invasion.32 cases(57.1%)underwent ipsilateral adrenalectomy because of tumor invasion or adrenal metastasis,and 23 cases(41.1%)underwent ipsilateral lymphadenectomy.In this study,there were 11 cases of solitary metastasis,8 cases of which were operated on and 3 cases of which were not operated on.Forty-three patients were treated with sunitinib after palliative nephrectomy,9 patients were treated with pazopanib,3 patients were treated with acitinib,and 1 patient was treated with sorafenib.Results The operations were successfully completed in 56 patients.Four cases(7.1%)changed from laparoscopic surgery to open surgery.The operation time was(326.8±114.9)(108-589)min.Intraoperative hemorrhage was(1435.2±1513.4)(20-6000)ml,intraoperative red blood cells transfusion was(1456.7±832.8)(400-3600)ml in 30 cases,and intraoperative plasma transfusion was(700.0±473.6)(200-1800)ml in 15 cases.The postoperative hospital stay was(10.6±4.6)(5-26)days.The serum creatinine one week after operation was(109.5±98.7)(47-772)μmol/L.There were 46 cases(82.1%)of renal clear cell carcinoma,7 cases(12.5%)of papillary renal cell carcinoma and 3 cases(5.4%)of unclassified renal cell carcinoma.One case was WHO/ISUP 2016 nuclear grade 1(1.8%),20 cases(36.4%)was grade 2,18 cases(32.7%)was grade 3,and 16 cases(29.1%)was grade 4.Early postoperative complications occurred in 22 cases(39.3%).Among them,1 case of Clavien gradeⅠwas wound infection.There were 16 cases with Clavien gradeⅡ,including 5 cases who received blood transfusion due to anemia,3 cases with chylous fistula,4 cases with postoperative pulmonary infection,2 cases with postoperative lower extremity venous thrombosis,1 case with atrial fibrillation and 1 case with epididymitis.Clavien gradeⅢa was found in 1 case with pneumothorax.Clavien gradeⅣwas found in 2 cases,including 1 case of acute cerebral infarction and 1 case of renal insufficiency.There were 2 cases with Clavien gradeⅤwith perioperative death.Among the 56 patients,5 lost the follow-up,2 died during the perioperative period,and the other 49 patients were followed up for 1-39 months,with a median follow-up of 14 months.The mean survival time was(25.6±2.5)months,and the median survival time was 25 months.Conclusions It was relatively safe and effective to perform cytoreductive nephrectomy and tumor thrombectomy in patients with metastatic renal cancer with tumor thrombus.For the patients with clinical symptoms,IMDC prognosis score model medium risk group,and strong desire for surgery,the combination of cytoreductive nephrectomy with tumor thrombectomy and postoperative targeted medical therapy was recommended.