von Hipple-Lindau基因突变与散发性肾透明细胞癌患者预后的关系

目的 探讨von Hippel-Lindau(VHL)抑癌基因突变与散发性肾透明细胞癌患者预后的关系. 方法应用聚合酶链反应(PCR)、PCR产物直接测序分析74例散发性肾透明细胞癌组织标本和相应远离肿瘤的正常组织标本中VHL基因突变情况.74例患者,病理分期为T1 51例(68.9%),T2 9例(12.2%),T3 14例(18.9%);病理分级为G1 15例(20.3%),G2 50例(67.6%),G39例(12.2%).随访其预后并进行统计学分析. 结果 VHL基因突变者40例(54.1%),不同病理分期和分级的肿瘤中VHL基因突变率差异无统计学意义(P值分别为0.915和0.237).随访34~107个月.平均71个月,因肿瘤死亡7例,出现远处肿瘤转移11例,5年无瘤生存率为78%.VHL基因突变组肿瘤死亡或转移等阳性事件发生率(15.0%,6/40)明显低于非突变组(35.3%,12/34,P=0.043).Logistic回归分析表明.患者预后与肿瘤病理分期、分级呈正相关,而与VHL基因是否突变呈负相关,三者的P值分别为0.016、0.024和0.033.对于T3和G3肿瘤患者,VHL基因突变者预后更好.P值分别为0.010和0.048. 结论 散发性肾透明细胞癌患者中VHL基因突变广泛,肾癌的病理分期和分级仍然是评估患者预后的有效指标.VHL基因突变失活可能提示肾透明细胞癌患者预后更好,尤其对于高分期和高分级肿瘤患者.     

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。     

肾细胞癌与VHL 基因

肾细胞癌是泌尿生殖系统最重要的肿瘤之一.其中约有4%为遗传性肾癌.肾癌中最常见的病理类型为透明细胞性肾细胞癌.几乎所有的遗传性肾癌和绝大多数的散发性透明细胞性肾细胞癌源于VHL 基因的失活.本综述主要关注于肾细胞癌和VHL 基因之间的联系.涉及肾细胞癌的遗传学分型、可能的发病机制、HIF 依赖途径的 VHL 功能、HIF 非依赖途径的 VHL 功能以及 VHL 基因失活的肾细胞患者预后.同时介绍针对VHL 其下游基因的分子靶向治疗药物及相关疗效.     

肾细胞癌与VHL 基因

肾细胞癌是泌尿生殖系统最重要的肿瘤之一.其中约有4%为遗传性肾癌.肾癌中最常见的病理类型为透明细胞性肾细胞癌.几乎所有的遗传性肾癌和绝大多数的散发性透明细胞性肾细胞癌源于VHL 基因的失活.本综述主要关注于肾细胞癌和VHL 基因之间的联系.涉及肾细胞癌的遗传学分型、可能的发病机制、HIF 依赖途径的 VHL 功能、HIF 非依赖途径的 VHL 功能以及 VHL 基因失活的肾细胞患者预后.同时介绍针对VHL 其下游基因的分子靶向治疗药物及相关疗效.     

肾细胞癌与VHL 基因

肾细胞癌是泌尿生殖系统最重要的肿瘤之一.其中约有4%为遗传性肾癌.肾癌中最常见的病理类型为透明细胞性肾细胞癌.几乎所有的遗传性肾癌和绝大多数的散发性透明细胞性肾细胞癌源于VHL 基因的失活.本综述主要关注于肾细胞癌和VHL 基因之间的联系.涉及肾细胞癌的遗传学分型、可能的发病机制、HIF 依赖途径的 VHL 功能、HIF 非依赖途径的 VHL 功能以及 VHL 基因失活的肾细胞患者预后.同时介绍针对VHL 其下游基因的分子靶向治疗药物及相关疗效.     

肾细胞癌与VHL 基因

肾细胞癌是泌尿生殖系统最重要的肿瘤之一.其中约有4%为遗传性肾癌.肾癌中最常见的病理类型为透明细胞性肾细胞癌.几乎所有的遗传性肾癌和绝大多数的散发性透明细胞性肾细胞癌源于VHL 基因的失活.本综述主要关注于肾细胞癌和VHL 基因之间的联系.涉及肾细胞癌的遗传学分型、可能的发病机制、HIF 依赖途径的 VHL 功能、HIF 非依赖途径的 VHL 功能以及 VHL 基因失活的肾细胞患者预后.同时介绍针对VHL 其下游基因的分子靶向治疗药物及相关疗效.     

肾细胞癌与VHL 基因

肾细胞癌是泌尿生殖系统最重要的肿瘤之一.其中约有4%为遗传性肾癌.肾癌中最常见的病理类型为透明细胞性肾细胞癌.几乎所有的遗传性肾癌和绝大多数的散发性透明细胞性肾细胞癌源于VHL 基因的失活.本综述主要关注于肾细胞癌和VHL 基因之间的联系.涉及肾细胞癌的遗传学分型、可能的发病机制、HIF 依赖途径的 VHL 功能、HIF 非依赖途径的 VHL 功能以及 VHL 基因失活的肾细胞患者预后.同时介绍针对VHL 其下游基因的分子靶向治疗药物及相关疗效.     

肾细胞癌与VHL 基因

肾细胞癌是泌尿生殖系统最重要的肿瘤之一.其中约有4%为遗传性肾癌.肾癌中最常见的病理类型为透明细胞性肾细胞癌.几乎所有的遗传性肾癌和绝大多数的散发性透明细胞性肾细胞癌源于VHL 基因的失活.本综述主要关注于肾细胞癌和VHL 基因之间的联系.涉及肾细胞癌的遗传学分型、可能的发病机制、HIF 依赖途径的 VHL 功能、HIF 非依赖途径的 VHL 功能以及 VHL 基因失活的肾细胞患者预后.同时介绍针对VHL 其下游基因的分子靶向治疗药物及相关疗效.     

肾细胞癌与VHL 基因

肾细胞癌是泌尿生殖系统最重要的肿瘤之一.其中约有4%为遗传性肾癌.肾癌中最常见的病理类型为透明细胞性肾细胞癌.几乎所有的遗传性肾癌和绝大多数的散发性透明细胞性肾细胞癌源于VHL 基因的失活.本综述主要关注于肾细胞癌和VHL 基因之间的联系.涉及肾细胞癌的遗传学分型、可能的发病机制、HIF 依赖途径的 VHL 功能、HIF 非依赖途径的 VHL 功能以及 VHL 基因失活的肾细胞患者预后.同时介绍针对VHL 其下游基因的分子靶向治疗药物及相关疗效.     

肾细胞癌与VHL 基因

肾细胞癌是泌尿生殖系统最重要的肿瘤之一.其中约有4%为遗传性肾癌.肾癌中最常见的病理类型为透明细胞性肾细胞癌.几乎所有的遗传性肾癌和绝大多数的散发性透明细胞性肾细胞癌源于VHL 基因的失活.本综述主要关注于肾细胞癌和VHL 基因之间的联系.涉及肾细胞癌的遗传学分型、可能的发病机制、HIF 依赖途径的 VHL 功能、HIF 非依赖途径的 VHL 功能以及 VHL 基因失活的肾细胞患者预后.同时介绍针对VHL 其下游基因的分子靶向治疗药物及相关疗效.     

von Hippel-Lindau病肾癌的自然病程研究

目的 探讨von Hippel-Lindau(VHL)病肾癌的自然病程. 方法 初诊后未立即手术的VHL病肾癌患者11例,男5例,女6例,平均年龄45岁.共32个肿瘤,肿瘤直径平均2.5(0.5～6.2)cm.采用积极监测策略对其进行临床管理.对患者临床资料、随访结果及肿瘤生长速度进行分析. 结果 中位随访时间70(32～258)个月.双肾实性占位6例;行手术治疗8例,包括保留肾单位手术7次,根治性肾切除6次;肿瘤复发4例.死于肿瘤转移2例,死于非肿瘤因素1例.32个肿瘤中位随访时间51(19～106)个月.肿瘤平均生长速度0.55 cm/年;直径＞3 cm、≤3 cm肿瘤生长速度分别为0.55、0.44 cm/年,差异无统计学意义(P=0.40).肿瘤生长快3个(1.13～1.75cm/年),肿瘤生长慢29个(0.17～0.88 cm/年).肿瘤进展转移2例.随访结束时,肿瘤＞3 cm者27个(84%),直径≤4 cm肿瘤未发现转移.结论 多数VHL病肾癌生长缓慢,不发生转移;肿瘤直径≤4 cm者很少转移;对≤4 cm VHL病肾癌采用积极监测策略可行.     

Outcome of surgery in cystic renal cell carcinoma

OBJECTIVES: To review cases of cystic renal cell carcinoma treated surgically at our institution and define their clinical and histopathologic features. METHODS: Between 1986 and 1998, 21 patients with cystic renal cell carcinoma were treated surgically. Cystic renal cell carcinoma was categorized using Hartman's classification. RESULTS: Histopathologic examination demonstrated cystic necrosis in 11 patients, multilocular cystic renal cell carcinoma in 9, and unilocular cystic renal cell carcinoma in 1 patient. Tumors were incidentally found during an evaluation of unrelated disease or a general health checkup in 14 patients (67%). The mean tumor size was 5.6 cm (range 0.5 to 12) for cystic necrosis and 5.4 cm (range 2 to 9) for multilocular cystic renal cell carcinoma. All 9 cases of multilocular cystic renal cell carcinoma were of the clear cell type and tumor grade 1. The mean follow-up period was 65 months (range 9 to 141). The 5-year disease-specific survival rates for multilocular cystic renal cell carcinoma and cystic necrosis were 100% and 80%, respectively. CONCLUSIONS: The prognosis for patients with cystic renal cell carcinoma is better than that for patients with solid tumors. In particular, the prognosis of multilocular cystic renal cell carcinoma is excellent. Multilocular cystic renal cell carcinoma represents a distinct subtype of renal cell carcinoma that can be completely cured by surgery.     

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.     

上海仁济医院肾癌数据库资料分析

目的 探讨肾癌临床、病理、分期、分级与预后特征. 方法 分析2003年至2005年上海仁济医院泌尿科肾癌数据库435例患者临床和病理资料.采用WHO 1997年肾实质上皮性肿瘤组织学分类标准、2002年ATCC的TNM分期和临床分期、1982年Fuhrman病理分级.采用Kaplan-Meier法和Logrank检验对57例获随访的晚期患者行生存分析和预后因素判断. 结果 435例患者中,遗传性VHL病肾癌10例(2.4%)、散发性肾透明细胞癌372例(85.5%)、乳头状癌13例(3.0%)、嫌色细胞癌18例(4.1%)、集合管癌4例(0.9%)、嗜酸性细胞腺瘤4例(0.9 %)、未分类肾癌.14例(3.2%).行根治性肾切除术335例(77.0%),保留肾单位手术74例(17.0%),姑息性肾切除等手术26例(6.0%).遗传性VHL病肾癌均为双肾癌伴多发囊肿,临床分期Ⅰ期7例、Ⅱ期3例,病理分级Ⅰ级6例、Ⅱ级4例,基因测序均存在VHL基因突变,平均随访28.6个月,患者无肿瘤局部进展或转移,但4例患者出现同侧或双侧肿瘤再发.嫌色细胞癌临床分期均为Ⅰ期,病理分级Ⅰ级5例,Ⅱ级13例,平均随访19.8个月均存活,无肿瘤转移或复发.集合管癌临床分期均为Ⅰ期,病理分级均为Ⅲ级,平均生存时间11.3个月.肾透明细胞癌和乳头状癌临床分期Ⅰ期260例(67.6%)、Ⅱ期64例(16.6%)、Ⅲ期32例(8.3%)、Ⅳ期29例(7.5%),其中T1a 147例(38.2%)、T1b 113例(29.4 %);病理分级Ⅰ级124例(32.2%)、Ⅱ级219例(56.9%)、Ⅲ级40例(10.4%)、Ⅳ级2例(0.5%).57例晚期肾癌患者中位生存时间(16.0±1.3)个月,1年生存率55.0%,2年生存率31.0%.预后因素分析显示,临床分期、肿瘤大小、淋巴结转移、远处转移和病理分级是晚期肾癌解剖水平和组织学水平的预后影响因素. 结论 不同组织学亚型的肾癌生物学特征存在较大差异,遗传性VHL病肾癌存在基因突变,常为双侧、多中心、低Fuhrman分级透明细胞癌,易再发不易转移.肾嫌色细胞癌预后较好,而集合管癌预后差.在解剖水平和组织学水平,TNM分期、肿瘤大小、淋巴结转移、远处转移和肾癌病理分级是晚期肾癌的预后影响因素.     

Conservative therapy by percutaneous radiofrequency ablation of renal cell carcinomas--therapeutic experiments of four patients with seven renal tumors--

We report 7 renal cell carcinomas in 4 patients treated by percutaneous image-guided radiofrequency ablation (RFA). The mean age of the patients was 59 years (male: 2, female: 2). All 4 were imperative cases. Two patients (5 tumor) had hereditary multiple renal cell carcinomas with von Hippel-Lindau (VHL) disease. The other two patients had sporadic renal cell carcinomas. RFA was performed guided by computed tomography under conscious sedation with local anesthetics. The mean size of the treated tumors was 4.5 (1.8-8.1) cm. Impedance-regulated RF energy from a generator at 94 (45-130) watts was applied at 11 (8-14) min intervals. The average procedure time was 91 (45-165) minutes. The maximum tissue temperature reached 82 (56-91) degrees C immediately after ablation. Three of the 7 lesions (42.9 %) were locally well controlled during the mean follow-up period of 6.3 (4-9) months. The two patients with VHL disease developed visceral metastasis after There were no major complications. Minor complications encountered included flank pain, nausea, perinephritic hematoma and fever. Although percutaneous image-guided RFA showed limited success in large or central renal tumors, the therapy against small exophytic renal tumors would be well tolerable and successful.     

Sarcomatous dedifferentiated renal cell carcinoma mimicking a severe purulent kidney infection

Sarcomatous renal cell carcinomas (SRCCs) originate from a dedifferentiation of renal cell carcinoma (RCC). They are characterized by an aggressive course and very poor prognosis. Less known is their ability to imitate inflammatory diseases of the kidney. The aim of the study was to outline the less usual symptoms of SRCCs in a retrospective analysis of 180 patients operated for RCC in 1997-2001. In 11 (6.1%) patients (8 men and 3 women, age 40-76 years, mean age 60 years) SRCC was present. The pTNM classification, results of histological examination, the stage of RCC dedifferentiation and survival after the operation are presented. In almost every patient SRCC was diagnosed at a late stage with combined histological variants of RCC. Survival of the patients after the operation ranged from 1 to 19 (average 8.8) months. In 2 patients an atypical clinical picture imitated abscess of the kidney and calculous pyonephrosis. The authors warn that in spite of the clinical signs of inflammatory disease of the kidneys, a tumorous origin should be excluded. In doubtful cases a quick peroperative biopsy and histology should be performed. Sometimes only a definitive histological examination can reveal the tumorous origin of the disease.     

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.     

Somatic mutations of the von Hippel-Lindau disease gene in renal carcinomas occurring in patients with long-term dialysis.

BACKGROUND: Renal cell carcinoma (RCC) frequently occurs in patients with long-term dialysis. Long-term dialysis causes distinctive pathological changes in the kidney, which is known as acquired cystic disease of the kidney (ACDK). It is of great interest to know whether RCCs occurring in the dialytic kidneys harbour the same or similar mutations of the von Hippel-Lindau (VHL) gene as conventional dialysis-unrelated clear cell RCCs so often do. METHODS: Renal cancer tissues (eight clear cell, two papillary, one Bellini duct and three of the so-called dialysis-specific renal carcinomas) from 13 patients undergoing long-term dialysis were examined for somatic mutations of the VHL disease gene. By means of laser capture microdissection, cancerous and surrounding non-cancerous renal tissues from dialytic patients were subjected to PCR-based direct sequencing of the VHL gene. RESULTS: Direct forward and reverse sequencing showed that three tumours possessed VHL gene mutations (713delG, 500-504del5-bp and 709A>G). These three mutations were identified in clear cell carcinomas occurring in association with end-stage renal disease undergoing dialysis for 194, 147 and 125 months. None of the non-tumour tissues or other carcinoma tissues analysed, including dialysis-specific carcinoma, possessed VHL gene mutations. CONCLUSION: These results indicate that VHL tumour-suppressor gene mutation is involved in clear cell carcinoma in association with long-term dialysis. Mutation of the VHL gene was not found in any of the dialysis-specific RCCs studied herein.     

小肾癌76例临床分析

目的　探讨小肾癌 (SRCC)的临床症状、影像学特征、分级分期与预后的关系。　方法　选择直径≤ 3cm的小肾癌患者 76例。其中有血尿、腰痛的 17例计为症状组 (2 2 .4 % ) ,健康体检或因其它疾患就诊偶然发现的 5 9例 (77.6 % )计为无症状组。 6 9例行B超检查 ,诊断率 84 .1% ;76例行CT检查 ,诊断率 94 .7%。　结果　 76例患者均行经腰部斜切口根治性肾切除术 ,病理诊断均为透明细胞癌。术后随访 32～ 87个月 ,平均 6 2 .7个月。症状组和无症状组术后 1、3、5年无瘤生存率分别为 10 0 .0 %、5 3.3%、33.3%和 10 0 .0 %、90 .6 %、77.4 % ,两组 3年和 5年生存率差异均有显著性意义 (P <0 .0 5 )。　结论　小肾癌的早期诊断主要依赖B超和 (或 )CT等影像学检查。无症状患者的远期无瘤生存率显著高于有症状患者。     

Nephron-sparing surgery for renal cell carcinoma with venous involvement

A nephron-sparing operation recently has been shown to provide extended survival free of disease in selected patients with localized renal cell carcinoma, particularly for tumors of lower stage. To define better the role of conservative surgical treatment in more locally advanced renal cell carcinoma we reviewed 9 patients with venous tumor involvement in solitary functioning kidneys who underwent a nephron-sparing operation. Complete tumor resection with adequate preservation of renal function was accomplished in all cases. Of the 9 patients 5 had no evidence of disease 7 to 93 months (mean 33.2 months) postoperatively. The remaining 4 patients died of metastatic renal cell carcinoma 17 to 47 months (mean 35.5 months) postoperatively, 2 of whom had concomitant local recurrences in the renal remnant. Based on previously reported results of total nephrectomy for renal cell carcinoma with venous involvement and the morbidity associated with renal replacement therapy, we believe that a nephron-sparing operation is a viable option in the management of these patients.