von Hippel-Lindau病肾癌的诊治特点分析

目的 总结yon Hippel-Lindau(VHL)病肾癌的诊治经验. 方法 VHL肾癌患者28例.男16例,女12例.平均年龄45岁.双肾癌15例(同时11例、异时4例),单侧肾癌13例.行VHL基因检测25例.行保留肾单位手术或肾癌根治术24例,观察等待2例,保守治疗2例.结果 25例受检者均有VHL基因胚系突变,其中无症状患者14例.9例患者中有29个实性肿瘤曾被观察,平均44(12～86)个月,肿瘤平均生长速度0.531 cm/年;观察结束时,19个(65.5%)肿瘤生长>3 cm,仅1个肿瘤转移.24例手术切除实性肿瘤87个,其中肿瘤剜除术62个(71.3%)、肾下极切除1个、根治性肾切除术24个.术后病理报告24例均为肾透明细胞癌.TNM分期T1a8例、T1b7例、T2 8例、T3 1例.肿瘤86个,Fuhrman分级Ⅰ级73个、Ⅱ级12个、Ⅲ级1个,钙化结节1个.28例患者平均随访50(5～237)个月,存活26例,死亡2例,肿瘤局部复发4例. 结论 基因检测可早期发现无症状VHL患者;VHL病肾癌多生长缓慢,>3 cm的肿瘤多数不发生转移,可随访观察;保留肾单位手术是治疗VHL病肾癌安全有效的方法.     

小肾癌自然病程的相关风险因素研究

目的评估小肾癌自然病程及相关的风险因素。方法1995年至2005年收治偶发性肾癌患者21例,均经术后病理证实。男12例,女9例。平均年龄47（16～77）岁。肿瘤大小以CT或MRI肿瘤横断面最大径和体积计算。初诊时肿瘤平均直径1．92cm,平均体积4．38ml。平均随访时间22．9（14～42）个月,无远处转移患者。分析患者年龄、性别、病理分型、病理分级、初诊时肿瘤大小等风险因素与肿瘤自然生长速度的相关性。统计学方法采用Pearson相关分析。结果21例病理报告：透明细胞癌15例,乳头状细胞癌6例。肿瘤分级：G1 10例、G2 8例、G3 3例。肿瘤平均生长速度为0．56 cm/年和4．70ml/年。肿瘤平均生长速度与性别、病理类型无明显相关,但与年龄、病理分级和初诊时肿瘤大小相关。结论大多数小肾癌自然生长速率较缓慢,年龄、肿瘤病理分级和初诊时肿瘤大小为小肾癌自然病程相关风险因素。     

von Hippel-Lindau病肾肿瘤与散发性肾细胞癌临床比较分析

目的 探讨von Hippel-Lindau(VHL)病肾肿瘤的临床特征. 方法回顾性分析9例VHL病肾肿瘤患者资料,其中男6例,女3例.平均年龄51岁.双侧肾肿瘤7例,单侧多中心表现5例,囊实性表现6例.同期散发性肾细胞癌患者46例,其中男30例,女16例.平均年龄55岁.肿瘤均为单发,单侧多中心表现2例,囊实性表现1例.分析2组患者在发病人群、肿瘤表现、疾病生存等方面的差异. 结果 2组患者性别、年龄比较差异无统计学意义(P>0.05).2组肾肿瘤双侧性、多中心性和囊实性表现比较差异均有统计学意义(P<0.01).VHL组甲均随访54个月,死亡4例,死于远处转移3例、死十恶液质1例.VHL病肾肿瘤与散发性肾细胞癌患者中位生存时间分别为136、42个月,2组比较差异无统计学意义(P=0.251),但生存曲线显示VHL病肾肿瘤患者生存率呈现较高趋势. 结论 VHL病肾肿瘤临床表现与散发性肾细胞癌不同,临床上应根据临床特征正确诊断,避免肾切除术,采取保留肾单位手术结合严密影像学观察治疗策略.     

Von Hippel—Lindau病肾癌的临床特征分析

目的 探讨Von Hippel-Lindau（VHL）病肾癌的临床特点。方法回顾分析28例VHL病肾癌患者的临床资料。就初诊年龄、肿瘤部位、同时或异时癌、肿瘤的组织病理等与散发性肾癌进行比较。结果VHL肾癌初诊年龄44．6岁，双肾癌15例、多灶性肾癌16例、伴双侧多发肾囊肿20例。共切除87个实性肿瘤。术后病理：透明细胞癌86个，Fuhrman分级Ⅰ级73个、Ⅱ级12个、Ⅲ级1个；钙化结节1个。TNM分期ⅠA期、ⅠB期、Ⅱ期、Ⅲ期分别为8例、7例、8例和1例。与散发性肾癌组相比，VHL病肾癌组患者发病年龄早（P〈0．05），双肾多灶性肾癌及伴双侧多发肾囊肿比例高（P〈O．001），高级别肿瘤比例低（P〈O．05）。结论VHL病肾癌不同于散发性肾癌，有其独特的临床病理特征，这对该病诊断治疗具有一定指导价值。     

von Hippel-Lindau综合征合并肾癌的TACE治疗:附2例报告

病例1,患者女,33岁,因“发现von Hippel-Lindau(VHL)综合征4月余”入院,无明显腹胀、腹痛、血尿等症状;2年前于外院接受延髓血管母细胞瘤切除术。CT:左肾见3.6 cm×3.5 cm囊实性病灶,增强扫描可见强化(图1A);胰腺弥漫囊实性病灶;诊断:VHL综合征合并肾癌。于DSA引导下行TACE,术中造影见左肾中上极团状肿瘤染色(图1B)。采用微导管超选供血动脉后,以超液态碘化油10 ml+盐酸吡柔比星20 mg混合乳剂栓塞,并以PVA颗粒(560~710μm)进行补充栓塞,复查造影,肿瘤染色基本消失(图1C)。术后按时随访,至术后42个月(2019年1月)复查CT示靶病灶控制良好(图1D)。     

von Hippel-Lindau综合征外科治疗

目的 探讨von Hippel-Lindau(VHL)综合征的外科治疗方法.方法 VHL综合征患者4例.例1,男,56岁.主诉乏力、心悸2 d.空腹血糖2.37 mmol/L.CT检查示左肾上、下极3个肿块,直径分别为8.0、7.0、4.0 cm.10年前行脑血管母细胞瘤切除术.例2,女,57岁.主诉左腰痛不适1个月.CT检查示左肾上腺、左肾、胰体肿物,直径分别为2.7、4.5、2.1 cm.例3,女,39岁.查体发现左肾上腺占位1个月.CT检查示左肾上腺3.0 cm×4.0 cm实性占位,增强后肿块明显强化.既往有小脑、脊髓血管母细胞瘤及双侧肾癌手术史.例4,女,41岁.B超发现双肾肿瘤1个月入院.CT检查示左肾、左肾上腺、右肾、胰腺肿物,直径分别为4.0、3.0、1.5、2.0 cm.1个月前行y刀治疗多发脑部肿瘤.结果 4例均手术治疗.例1行左肾根治性切除术,病理报告肾血管周细胞瘤,随访6个月右肾未见异常.例2行左肾、左肾上腺、胰体尾及脾切除,病理报告肾透明细胞癌、胰岛细胞瘤、肾上腺囊肿,随访3个月MRI检查发现脊髓肿瘤.例3行左肾上腺肿瘤摘除术,病理报告嗜铬细胞瘤,随访2年未见肿瘤复发.例4行左肾、左肾上腺切除,病理报告肾透明细胞癌、肾上腺嗜铬细胞瘤,3周后剜除右肾肿瘤,病理报告透明细胞癌,随访1年肿瘤未复发.结论 VHL可并发多器官肿瘤,较大中枢神经系统肿瘤可手术切除,多发较小的实性肿瘤可放疗.直径<3cm肾癌可密切随访、择期处理;直径>3cm肾癌首选保留肾单位手术.肾上腺肿瘤首选腺瘤摘除术,避免肾上腺全切术.腹部多器官肿瘤一期手术安全可行. 理报告肾透明细胞癌、胰岛细胞瘤、肾上腺囊肿,随访3个月MRI检查发现脊髓肿瘤.例3行左肾上腺肿瘤摘除术,病理报告嗜铬细胞瘤,随访2年未见肿瘤复发.例4行左肾、左肾上腺 除,病理报告肾透明细胞癌、肾上腺嗜铬细胞瘤,3周后剜除右肾肿瘤,病理报告透明细胞癌,随访1年肿瘤未复发.结论 VHL可并发多器官肿瘤,较大中枢神经系统肿瘤可手术切除,多发较小的实性肿瘤可放疗.直径<3cm肾癌可密切随访、择期处理;直径>3cm肾癌首选保留肾单位手术.肾上腺肿瘤首选腺瘤摘除术,避免肾上腺全切术.腹部多器官肿瘤一期手术安全可行. 理报告肾透明细胞癌、胰岛细胞瘤、肾上腺囊肿,随访3个月MRI检查发现脊髓肿瘤.例3行左肾上腺肿瘤摘除术,病理报告嗜铬细胞瘤,随访2年未见肿瘤复发.例4行左肾、左肾上腺 除,病理报告肾透明细胞癌、肾上腺嗜铬细胞瘤,3周后剜除右肾肿瘤,病理报告透明细胞癌,随访1年肿瘤未复发.结论 VHL可并发多器官肿瘤,较大中枢神经系统肿瘤可手术切除,多发较小的实性肿瘤可放疗.直径<3cm肾癌可密切随访、择期处理;直径>3cm肾癌首选保留肾单位手术.肾上腺肿瘤首选腺瘤摘     

Ⅱ型von Hippel-Lindau病遗传学特点及外科处理

目的 提高von Hippel-Lindau (VHL)病的诊疗水平. 方法 ⅡB型VHL病家系1例.40岁男性患者1例,左上肢麻木6个月,发现腹腔多发占位3个月.头部MRI示脑部多发占位;腹部CT提示左肾下极肿瘤,胰尾部肿瘤,腹主动脉旁肿瘤,左肾上腺肿瘤;眼底检查提示视网膜多发成血管细胞瘤;PET-CT提示腹部多发高摄取病灶;系谱分析提示明确的家族史;基因检查提示VHL基因种系突变.行手术治疗,并对家族成员进行基因筛查. 结果 一期手术切除脑部肿瘤,二期后腹腔镜下切除腹主动脉旁肿瘤、左肾上腺肿瘤和左肾肿瘤.脑部肿瘤病理报告为成血管细胞瘤.腹膜后肿瘤分别为左肾透明细胞癌、副神经节瘤、左侧嗜铬细胞瘤.截至2012年6月,术后6个月复查未见明显异常.系谱分析提示4代30位成员中,发病者9例(30％).6位成员接受基因筛查,5例( 5/6)有基因突变.4例(4/5)突变位点为3处,3例(3/4)已经发病,1例(1/4)未发病成员经影像学检查发现脑部多发占位;另1例(1/5)突变位点仅1处,检查未见明确病变.4例有3个突变位点者,突变位点在3号染色体短臂25区1号外显子,均为杂合突变,分别为295位、337位核苷酸T→C、337位核苷酸T→A,导致第98位、第112位、第112位编码氨基酸分别由酪氨酸突变为组氨酸、由酪氨酸转变为组氨酸、由酪氨酸突变为天冬酰胺酸.仅有1个位点突变者,突变位点为VHL基因1号外显子的295位核苷酸T→C,导致第98位编码氨基酸由酪氨酸突变为组氨酸. 结论 VHL病为遗传性疾病,常呈家族性、多器官发病.基因诊断能够发现早期无症状患者,对有基因突变而未发病的家族成员,需要严密监测.外科治疗应在全面评估的基础上进行,可以一期切除多处病变.Ⅱ型VHL病多合并嗜铬细胞瘤,对此类患者,应首先处理嗜铬细胞瘤.     

von Hippel-Lindau病一例

von Hippel-Lindau（VHL）病是一组涉及多系统的常染色体显性遗传性、多器官受累的良恶性肿瘤征候群,肾癌和中枢神经系统成血管细胞瘤是导致死亡的主要原因[1].我们收治1例被误诊6年的少年VHL病患者,现报告如下.     

von Hippel-Lindau病家系调查及基因学研究(附二例报告)

目的探讨vonHippel-Lindau病(VHL)基因突变类型及改良的基因诊断方法。方法调查1例VHL病Ⅰ型家系及1例Ⅱ型家系,分别绘制树状图;抽取2个家族共8位成员的外周血,提取基因组DNA。改良方法进行3个外显子翻译区及剪接区的扩增,扩增产物经纯化后直接测序。将所得突变类型与人类基因突变数据库(HGMD)核对。结果VHL病I型家系4代12位家族成员中,有双肾透明细胞癌Ⅱ级合并视网膜血管母细胞瘤1例,中枢神经系统血管母细胞瘤合并视网膜血管母细胞瘤1例,突变基因携带者1例。Ⅱ型家系7位家族成员中,有双肾透明细胞癌Ⅱ级合并双肾多发囊肿1例,肾上腺嗜铬细胞瘤1例。Ⅰ型家系中,5例接受检测者中2例基因测序均见VHL基因第478位与479位核苷酸分别发生C→T及T→C突变,导致第89位编码氨基酸由亮氨酸转变为丝氨酸。Ⅱ型家系3例接受检测者中,2例基因测序见VHL基因第452位核苷酸发生G→T突变,导致第80位编码氨基酸由丝氨酸转变为异亮氨酸。测序获得突变类型与HGMD核对,发现I型家系中VHL基因第478位核苷酸与479位核苷酸的多点突变,为VHL基因第89位氨基酸位点未曾报道过的突变类型。2个家系的基因突变位点均...     

von Hippel-Lindau综合征一例报告

目的提高对von Hippel-Lindan（VHL）综合征的认识,探讨其诊治方法。方法患者,女,40岁。头晕、下肢麻木、行走易向右侧跌倒,CT检查见小脑肿瘤,高位颈髓病变,于1997年入院。9年中以小脑、脊髓血管母细胞瘤,胰腺囊肿、双侧肾脏肿瘤、右侧肾上腺嗜铬细胞瘤等疾病诊治。对该患者进行家系调查,连续随访。结果依肿瘤发生部位,先后行单纯肿瘤切除术,手术效果良好,未见局部复发。家系调查仅见先证者之子（17岁）为双肾多发小囊肿患者。结论手术切除是治疗VHL综合征肿瘤的有效方法,应重视对VHL综合征患者的家系调查,以积累更多的临床资料。     

Natural history and growth kinetics of clear cell renal cell carcinoma in sporadic and von Hippel-Lindau disease

BackgroundTo evaluate and compare the natural history and growth kinetics of sporadic clear cell renal cell carcinoma (ccRCC) with those of ccRCC in von Hippel-Lindau disease (VHL).MethodsSixty patients in the sporadic group with 61 tumors and 15 patients in the VHL group with 30 tumors whom all underwent delayed surgery after at least 12 months of active surveillance (AS) were enrolled to conduct a retrospective cohort study. The growth rate was calculated, and the growth kinetics between the sporadic and VHL groups were compared. The patient and tumor characteristics were reviewed, and their correlation with growth rate was analyzed.ResultsThe mean growth rate of sporadic ccRCC was 0.91 cm/year (ranging from 0–4.74 cm/year) and that of VHL ccRCC was 0.47 cm/year (ranging from 0.04–1.89 cm/year). The growth rate of sporadic ccRCC showed a tendency of being faster than that of VHL ccRCC but did not reach statistical significance (P=0.07). The factors affecting the growth rate were different between the two groups. For VHL ccRCC, the only factor that correlated with growth rate was initial tumor diameter (P<0.001), but for sporadic ccRCC, the only factor was pathological nuclear grade (P<0.001).ConclusionsThe growth rate of VHL-associated ccRCC might be slower than that of sporadic ccRCC. Furthermore, we identified a disparity in growth kinetics between sporadic and VHL-associated ccRCC.     

多房囊性肾细胞癌的临床分析及其与vonHippel-Lindau基因突变的相关性研究

目的 提高对多房囊性肾细胞癌(MCRCC)的认识及诊治水平,分析MCRCC中von Hippel-Lindau(VHL)基因的作用.方法 回顾性分析2000-2010年17例MCRCC患者资料,占同期收治512例肾癌的3.32%.男11例,女6例.年龄37～61岁,平均46岁.术前常规行B超、CT等检查,误诊为肾盂旁囊肿1例.应用PCR、PCR产物直接测序等方法分析11例MCRCC组织和相应远离病灶的正常组织中VHL基因突变的情况.结果 17例患者行根治性肾切除术14例,其中1例先行囊肿去顶术,术中囊壁组织冰冻病理检查提示透明细胞癌,改行根治性肾切除术;行肾部分切除术3例.肿瘤直径2.2～6.0 cm,平均(3.6±1.2)cm.术后病理均为MCRCC,镜下主要表现为纤维囊壁组织内衬单层或数层肿瘤细胞,核小致密,胞质透亮.TNM分期均为T1N0M0,病理分级G1 14例,G2 3例.术后随访9～36个月,平均12个月,均未见复发及转移.11例MCRCC组织中7例(64%)存在VHL基因突变,而正常组织标本均未发现VHL基因突变.结论 MCRCC作为肾细胞癌的一种少见的独立亚型,病理及临床上易漏诊或误诊.CT等影像学检查有助于术前诊断,因其预后良好,手术方式推荐保留肾单位手术.VHL基因突变与MCRCC的发生存在一定关系.

Abstract：

Objective To discuss the diagnosis and surgical management of multilocular cystic renal cell carcinoma (MCRCC) and to evaluate the gene function of the mutation of von Hippel-Lindau (VHL) gene in MCRCC. Methods Seventeen MCRCC cases (11 men and 6 women) out of 512 cases of renal cell carcinoma from 2000 to 2010 were retrospectively analyzed. The mean age of the 17 patients was 46 years (37-61 years). Ultrasonography and CT were available in all 17 cases, and 1 case was misdiagnosed as parapelvic renal cyst. The mutation of VHL gene was detected by PCR in the specimens of can-cerous tissue and adjacent normal tissue from 11 cases of MCRCC. Results Three of 17 cases underwent nephron sparing surgery, the others underwent radical nephrectomy. One case underwent unroofing of parapelvic renal cyst, but the rapid frozen pathology of the cyst wall showed renal cell carcinoma of clear type. As a result, radical nephrectomy was eventually performed. All 17 cases were confirmed as MCRCC by eva-luating pathological characteristics, such as the cyst wall lined by single or several layers of clear tumor cells and the nuclei which were small and anachromasis. Clinical stages of all cases were T1N0M0, in which there were 14 cases with pathological T1G1 and 3 cases with pathological T1G2. All patients underwent a follow-up of 9 to 36 months (mean, 12 months) without recurrence or metastasis. Mutation of VHL gene was detected in 7 of 11 cases (64%), but all adjacent normal tissues were negative. Conclusions As a rare subtype of renal cell carcinoma, MCRCC is difficult to diagnose. CT is an essential measure in diagnosis of MCRCC preoperatively. Because of the good prognosis of reported cases, nephron sparing surgery for the treatment of MCRCC is recommended. VHL gene mutations may play an important role in the carcinogenesis of MCRCC.     

Percutaneous renal cryoablation of renal tumors in patients with von Hippel-Lindau disease

PURPOSE: We determine the feasibility and safety of performing percutaneous cryoablation of renal tumors in patients with von Hippel-Lindau disease. MATERIALS AND METHODS: We selected 2 men and 2 women with von Hippel-Lindau disease and radiographic determined solid renal tumors were selected to undergo percutaneous cryoablation. All patients underwent standard preoperative evaluation. An interventional magnetic resonance imaging unit was used for probe guidance and ice ball monitoring. The cryoablation procedure was performed with a 2 or 3 mm. cryoprobe using a pressurized argon gas system for ice ball formation. The patients were hospitalized overnight for observation and discharged home the following day. A followup computerized tomogram or magnetic resonance imaging scan was performed at 1 week, 1, 3, 6 and 12 months and every 6 months thereafter, along with physical examination, urinalysis, serum blood urea nitrogen and creatinine. RESULTS: A total of 5 tumors were treated ranging from 2.8 to 5.0 cm. in diameter. All patients underwent the procedure without difficulty with 2 requiring re-treatment due to residual tumor for a total of 7 treatments. At followup from 2 to 23 months there has been no radiographic evidence of recurrence at the cryoablated areas. CONCLUSIONS: Percutaneous cryoablation of renal tumors in patients with von Hippel-Lindau disease proved to be successful in this initial series. Although 2 patients had residual tumor after the initial cryoablation procedure re-treatment was performed with no adverse sequela. This minimally invasive therapy may allow patients with von Hippel-Lindau disease to avoid the necessity of multiple open surgical procedures.     

von Hippel-Lindau disease with bilateral multiple renal cell carcinoma managed by right radical nephrectomy and left repeat partial nephrectomy

von Hippel-Lindau (VHL) disease is an autosomal dominant disorder characterized by cysts and cystadenoma in the kidney, pancreas and epididymis and angiomas of the central nervous system and retina as well as renal cell carcinoma (RCC), phaeochromocytoma, islet tumors of the pancreas, and endolympatic sac tumors. VHL for its multicentric-characteristic and bilateralism often puts the surgeon in challenging situation. We present a case of VHL with bilateral RCC and retinal angiomas managed with right radical nephrectomy and left repeat partial nephrectomy.     

遗传性肾癌11例临床分析

目的 探讨遗传性肾癌的诊断和治疗方法.方法 回顾性分析11例遗传性肾癌患者的临床资料,其中男8例、女3例,年龄32～67岁,平均48岁;4例为双侧肾癌,4例为多发肾癌.2例诊断为希佩尔-林道病综合征,6例诊断为家族性肾透明细胞癌,3例诊断为遗传性乳头状肾癌.10例患者行保留肾单位的手术和（或）肾癌根治术,1例未手术.结果 随访12～114个月,4例发生肿瘤复发,1例死于肿瘤转移,2例死于其他原因,4例无瘤生存.结论 遗传性肾癌发病年龄较早,肿瘤双侧、多中心发病率较高,应尽量行保留肾单位手术.