肾细胞癌的治疗进展

肾细胞癌（renal cell carcinoma,RCC）占成人恶性肿瘤的2％～3％,泌尿系恶性肿瘤的第二位,肾脏恶性肿瘤的80％~90％。随着影像技术的提高、检查的普及,早期肾癌检出率明显增加,但仍有20％-30％的肾癌患者在确诊时已有远处转移,超过40％的局限性肾癌患者术后发生复发或转移。根据肾脏肿瘤大小等自身特性及肿瘤侵袭范围等因素对患者预后的影响,2009年UICC／AJCC对TNM分期系统进行了明显修改,对选择RCC的治疗方式、评估预后有重要指导作用。手术是惟一可治愈的治疗手段,对于T1a期患者行肾部分切除术安全有效,对于T1b,保留肾单位手术和根治性肾切除术都是可选方案。对于远处转移的患者,减瘤手术作为内科系统治疗的辅助,效果确切。微创治疗、免疫治疗也取得了明显进步;放射治疗可用于mRCC患者以减轻痛苦和肾切除术后的局部复发。分子靶向药物改善了转移性肾癌患者的生存期和生活质量,成为mRCC的一线和二线治疗方案。     

Needling renal cysts and tumours: cytology and radiology.

Renal masses found by intravenous urography, ultra-sound scanning, and arteriography were needled in 102 patients. Simple renal cysts containing clear fluid and no cytological abnormalities were found in 85 patients. Two unsuspected renal cell carcinomas were found on puncture; cytological examination showed malignant cells in the aspirate. Another five renal tumours were needled deliberately before nephrectomy, and a firm preoperative diagnosis of renal cell carcinoma was made on aspiration cytology in three. Benign cysts which had bled were particularly hard to diagnose. With care, radiology and cytology in combination can provide the firm diagnostic base needed for sound clinical management. The radiology-cytology team must be alert to the unusual finding that indicates a complex lesion, such as an unsuspected renal tumour.     

Targeted-therapy in advanced renal cell carcinoma

Surgery has been the mainstay of renal cell carcinoma (RCC) treatment for resectable tumours. In stages I-III disease, nephrectomy is the standard of care and may be curative. Historically, patients presenting with stage IV disease may achieve improved survival with debulking nephrectomy, which is commonly performed prior to systemic therapy. The response rate of immunotherapy is low, with a smaller percentage exhibiting complete remission upon treatment. Therefore, new therapeutic approaches against metastatic RCC are necessary. Recently, molecular mechanisms responsible for the proliferation of RCC have been identified, and molecular targeted therapy has developed. Clear cell RCC commonly features mutation or inactivation of the von Hippel- Lindau (VHL) gene and resultant over-expression of vascular endothelial growth factor (VEGF). The first drug to validate VEGF as a target in the treatment of clear cell RCC was the monoclonal antibody bevacizumab. Sunitinib is now a standard first-line therapy for advanced disease and sorafenib is among the second-line treatment options. Mammalian target of rapamycin (mTOR) is a second validated therapeutic target as the mTOR inhibitor temsirolimus has been shown to prolong survival in first-line treatment of poor prognosis RCC of all histologies. Everolimus is an oral mTOR inhibitor and has been shown to prolong progression-free survival (PFS) when used in second-line treatment. This review describes recent advances in molecular targeted therapy for metastatic RCC, focusing on chemical structure and mechanism of action of VEGFR and mTOR inhibitors.     

A rare case of renal and uterine clear cell carcinoma: Which is the primary tumour?

Renal cell carcinoma to the uterus is rare. We describe a 52-year old lady who presented with progressive abdominal distension and computerized tomogram scan of the abdomen showing two pathologies; uterine and right renal tumour. It was initially thought to be two distinct tumours (double pathology). Radical nephrectomy and total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed concurrently. Histopathological evaluation of the uterine and right renal tumour however surprised us with a rare form of metastasis from a renal tumour to the uterus. The method of differentiating primary renal cell carcinoma with uterine metastasis, from primary uterine carcinoma with renal metastasis, via immunohistochemistry, is described.     

肾脏不典型良性肿块与肾癌的多层螺旋CT鉴别诊断

目的 提高肾脏良恶性肿块的诊断与鉴别诊断水平,降低误诊率,避免误切肾脏.方法 肾良性肿块患者9例,男6例,女3例,年龄30～76岁,平均56岁.肾癌患者52例,男性40例,女性12例,其中透明细胞癌37例,乳头状癌10例以及嫌色细胞癌5例.术前均行CT平扫及三期增强扫描,比较肾脏良性肿块与肾癌的CT影像学特点.结果 所有肾肿块性病变均经手术及病理证实.9例患者中8例按肾癌行根治术,1例行肿瘤剜除术,术后病理均为肾脏良性病变.其中少脂肪血管平滑肌脂肪(AML)4例、嗜酸细胞瘤2例、平滑肌瘤、炎性假瘤和囊肿伴血肿机化各1例.52例肾癌平扫呈均匀或不均匀的等、稍低、稍高或混杂密度;增强扫描肿瘤呈不均匀、均匀明显或不明显强化.结论 CT是肾脏良恶性肿块诊断与鉴别诊断中一种重要的影像学手段,对于影像学表现不典型良性肿块病变者,术前穿刺病理活检或术中冰冻病理切片是避免误诊及误切肾脏的关键,从而选择合适的治疗方案,避免不必要的肾根治性术.     

肾透明细胞癌膀胱转移1例报告并文献复习

目的探讨肾癌膀胱转移的临床特点、可能转移途径、治疗方案的选择。方法报道1例肾癌转移至膀胱的临床病例的详细资料,并复习相关文献。结果肾癌发生膀胱转移极为罕见,只有膀胱发生转移的更为少见,膀胱转移常伴其他多器官转移。结论肾癌可能通过血行、淋巴、腔内种植途径发生膀胱转移,对单独膀胱转移应积极手术治疗。     

局限性肾癌保留肾单位手术治疗的预后影响因素

目的 探讨局限性肾癌保留肾单位手术治疗的预后影响因素.方法 我院2000年10月至2009年9月采用保留肾单位手术治疗肾细胞癌患者80例,对侧肾功能良好者68例为相对适应证组,孤立肾肾癌或对侧肾功能较差者12例为绝对适应证组.应用SPSS 17.0统计软件,采用Kaplan-Meier模型进行生存分析,Log rank检验和Cox比例风险模型对生存的影响因素进行单因素和多因素分析,计算肿瘤特异性生存率并分析预后影响因素.结果 肿瘤直径平均3.5(1.2～7.0)cm,≤4 cm 68例(85.0％),＞4 cm 12例(15.0％);病理分期采用UICC2002TNM分期法,T1a期68例(85.0％),T1b期12例(15.0％).80例患者随访12～ 107个月,平均49.8个月,随访期间8例(10％)死于复发和(或)转移,3、5年肿瘤特异性生存率分别为95.0％、83.9％.相对适应证组3、5年肿瘤特异性生存率分别为:97.1％ (66/68)、95.6％ (65/68),绝对适应证组3、5年肿瘤特异性生存率分别为:83.3％ (10/12)、58.3％ (7/12),组间比较差异均有统计学意义(Log-rank P ＜0.01).多因素分析显示,手术适应证(相对/绝对)是惟一影响肿瘤特异性生存率的独立因素(P=0.030,RR=0.033).结论 保留肾单位手术治疗肾细胞癌具有良好的临床疗效,但因术前对侧肾功能差或孤立肾肾癌而行NSS的患者,预后相对较差.     

32例小肾癌诊治分析

目的：探讨小肾癌的诊断和治疗。方法：对32例直径小于3cm的小肾癌的临床资料进行回顾性分析。结果：32例中因体检或其他疾病检查时发现15例（46．8％）,腰痛6例（15．6％）,血尿2例（6．2％）,腰痛伴血尿3例（9．3％）,无症状6例（18．7％）。行根治性肾切除术12例,行保留肾单位手术20例。术后均经病理证实,术中快速冰冻切片证实2例。结论：小肾癌多为偶然发现．其早期诊断主要依靠B超、CT、肾血管造影等影像学检查：手术视患者具体情况行根治性肾切除术或保留肾单位手术：小肾癌病理分期低,肿瘤体积小,预后较好,生存率高。     

囊性肾癌5例诊治体会

目的探讨囊性。肾癌（RCC）的诊断与治疗。方法复习文献对例5囊性肾癌的临床、超声及CT的特点以及手术方式和预后进行回顾性分析。结果术前超声诊断囊性肾癌2例;CT诊断囊性肾癌3例,2例诊断肾囊肿,肿瘤不能除外。术后病理回报均为透明细胞癌。5例均行根治性肾切除术。随访1～5年无复发。结论熟悉囊性肾癌的影像学特点是提高囊性肾癌诊断率的关键。     

肾细胞癌PCNA表达与CT征象关系的探讨

目的：研究肾细胞癌相关NPCNA与CT征象的关系。方法：用免疫组化染色（S—P法）检测40例经手术切除、病理证实且CT资料完整的肾细胞癌和10例正常肾组织的PCNA阳性表达率。结果：（1）PCNA阳性表达率与肿瘤直径，肿瘤强化，肾周脂肪浸润有关，P〈0．05；而与瘤体内坏死、液化，淋巴结肿大，静脉侵犯，邻近器官侵犯或（和）远处转移无关，P〉0．05；（2）肿瘤病理分级增加，PCNA阳性表达率升高，P〈0．05。结论：RCC的CT表现与PCNA的表达存在内在关系，据此可术前评价其生物学行为与恶性程度。     

囊性肾细胞癌18例诊治分析

目的提高囊性肾细胞癌的诊治水平。方法回顾性分析2004年2月至2011年5月收治的18例囊性肾细胞癌患者临床资料,包括临床特点、影像学表现、术式选择、病理结果和随访情况。结果行根治性肾切除11例,保留肾单位肾切除7例,术后病理报告均为囊性透明细胞癌。所有患者术后恢复平稳,随访2～87(平均36)个月均无瘤生存,未发现淋巴结及远处转移。结论囊性透明细胞癌是肾细胞癌的一种少见亚型,恰当的外科治疗后预后好。鉴于其相对低度恶性的生物学行为表现,推荐行保留肾单位肾部分切除术治疗。     

Therapy for non-clear cell histologies in renal cancer

The advent of targeted systemic therapies has significantly improved treatment options for patients with metastatic renal cell carcinoma (RCC). Multiple agents that inhibit angiogenesis cell growth and proliferation via the VEGF and mTOR (TORC1) pathways have been USFDA-approved for locally advanced or metastatic renal cell carcinoma in recent years although the majority of clinical trials have focused only on clear cell RCC. While clear cell RCC is the most common histologic subtype nearly 25% of RCC cases are histologic variants representing a diverse group of diseases with different prognoses underlying biology and molecular targets and therapies. This review will focus on the incidence clinical and pathologic features pathogenesis and treatment strategies of non-clear cell RCC in both the adjuvant and metastatic setting. These non-clear cell subtypes include papillary type 1 and type 2 chromophobe translocation carcinoma and collecting duct RCC. Controlled studies in these relatively rare subgroups are needed to inform upon clinical practice which is currently based on small series of uncontrolled studies. Ongoing clinical trials and areas of future research will be discussed.     

5-Aza-2'-deoxycytidine suppresses human renal carcinoma cell growth in a xenograft model via up-regulation of the connexin 32 gene

BACKGROUND AND PURPOSE: The connexin (Cx) 32 gene, a member of the gap junction gene family, acts as a tumour suppressor gene in human renal cell carcinoma (RCC) and is down-regulated by the hypermethylation of CpG islands in a promoter region of the Cx gene. The current study investigated whether the restoration of Cx32 silenced by hypermethylation in RCC by a DNA demethylating agent could be an effective treatment against RCC. EXPERIMENTAL APPROACH: Using nude mice bearing Caki-1 cells (a human metastatic RCC cell line), the effects of 5-aza-2'-deoxycytidine (5-aza-CdR), a DNA demethylase inhibitor, on Cx32 mRNA expression and tumour growth were examined by RT-PCR, and by measuring tumour weight and volume. Cx32 expression in Caki-1 tumours was inhibited by Cx32 short interfering (si) RNA, and the effect of siRNA on 5-aza-CdR-dependent suppression of tumour growth in nude mice was evaluated. KEY RESULTS: 5-aza-CdR treatment inhibited the growth of Caki-1 cells in nude mice by 70% and increased 7-fold the level of Cx32 mRNA. The intratumour injection of Cx32 siRNA almost totally inhibited the expression of Cx32 mRNA and significantly reduced the suppression of tumour growth in 5-aza-CdR-treated nude mice. CONCLUSIONS AND IMPLICATIONS: 5-aza-CdR suppressed the growth of Caki-1 tumours in a xenograft model, by restoring Cx32 expression. This finding suggests that treatment with 5-aza-CdR could be a new effective therapy against human metastatic RCC and that Cx32 could be a potential target for the treatment of RCC.     

保留肾单位肾癌切除术的近期疗效观察

目的 探讨保留肾单位肾癌的手术疗效.方法 18例行保留肾单位肾癌切除术的患者,男12例,女6例,平均年龄50岁.肿瘤直径1.5～4.0 cm,平均3.6 cm.先天性孤立左肾肾下极肿瘤1例,双肾肿瘤1例.透明细胞癌16例,肾细胞癌1例,颗粒细胞癌1例.T1 15例,T2 3例.结果 18例手术均成功.术后平均随访36个月,1例先天性孤立左肾肾下极肿瘤术后30个月肺转移外,余17例均无瘤生存至今.结论 保留肾单位肾癌切除术安全有效,适合于肿瘤直径≤4.0 cm早期肾癌.     

Adjuvant and neoadjuvant therapy in renal cell carcinoma

Nephrectomy continues to be the cornerstone of treatment for localized renal cell carcinoma (RCC). Despite undergoing nephrectomy, recurrence of disease remains a concern in many patients, and different medical therapies are being investigated as means to decrease this risk. The use of the traditional immunotherapy options has not provided benefit as adjuvant treatment in this disease state. Recently, the treatment of metastatic RCC has experienced key advances with the introduction of targeted agents against the vascular endothelial growth factor (VEGF) molecule and related pathways as well as inhibitors of the mammalian target of rapamycin (mTOR), in addition to improvements in surgical technique. Additionally, there are questions about the optimal timing of systemic therapy in the context of high risk non-metastatic disease. There is optimism that locally advanced RCC might benefit from adjuvant or neoadjuvant treatment with these therapies. Ongoing clinical trials are addressing the role of targeted agents in this disease state.     

Primary renal carcinoid: report of a case

A 28 year old female presented with a right renal mass. She was treated with a radical nephrectomy. Histologically the tumour revealed the classical appearance of a carcinoid. The opposite kidney contained a multilocular cystic renal cell carcinoma. The histogenesis of a renal carcinoid is discussed.     

经后腹腔镜肾切除术的临床应用

目的探讨后腹腔镜肾切除术的技术要点和临床效果。方法2005年5月～2010年5月采用后腹腔镜行单纯肾切除10例,肾癌根治术9例,肾全输尿管切除6例,结石梗阻致肾积水无功能肾10例,肾癌9例,肾盂癌6例。术前均行B超、IVU、CT或MRI检查．健侧肾功能正常,肾脏良性病变提示患肾无功能,肾脏恶性病变选择T1。T2NOM0病例,肿瘤局限于肾包膜内,肾周无肿大淋巴结。观察手术时间、术中出血量、术中术后并发症及手术效果。结果手术均一次成功,手术时间90-150min,平均110min,术中出血80～160ml,术中术后均未输血,引流管拔除时间24～72h,肠功能恢复时间24-48h,下床活动时间36-72h。15例肾脏恶性肿瘤病人已随访6～36个月．无肿瘤复发及切口种植转移。结论后腹腔镜肾切除术具有创伤小、恢复快、疗效可靠的优点。     

保留肾单位手术治疗局限性肾癌的临床价值

目的评价保留肾单位手术治疗局限性肾癌的疗效与安全性。方法回顾分析64例采用保留肾单位手术治疗局限性肾癌患者的临床资料。观察手术时间、肾蒂阻断时间、出血量、并发症及肿瘤控制情况。结果 64例手术均顺利完成。平均手术时间（125±35）min,平均肾蒂阻断时间（27±3）min,术中平均出血（245±65）ml。术后继发出血3例,经选择性肾动脉栓塞后治愈。1例并发尿瘘经充分引流后治愈。随访18～52月,局部复发2例而行根治性手术,无肿瘤远处转移。结论保留肾单位手术治疗局限性肾癌安全、有效,可在不降低复发率的前提下保留患肾功能。     

肾嗜酸细胞腺瘤的诊断与治疗(附11例报道及文献复习)

目的探讨肾嗜酸细胞腺瘤的诊断与治疗方法。方法报道11例确诊病例及复习相关文献,总结肾嗜酸细胞腺瘤的诊疗经验。结果 6例行肾部分切除术,5例行根治性肾切除术。病理结果均为肾嗜酸细胞腺瘤,其中3例合并肾透明细胞癌。随访时间1～10年,肿瘤无转移或复发。结论肾嗜酸细胞腺瘤是一种肾脏的良性倾向肿瘤,术前诊断较困难。治疗首选保留肾单位手术,但因其易合并肾恶性肿瘤,术后应密切随访。     

Phase II trial of irofulven (6-hydroxymethylacylfulvene) for patients with advanced renal cell carcinoma

The aim of this study was to determine the antitumor activityof irofulven (6-hydroxymethylacylfulvene) in patients withadvanced renal cell carcinoma (RCC). Eligible patients hadadvanced renal cell carcinoma with bidimensionally measurabledisease, a Karnofsky performance status of at least 70, lifeexpectancy of greater than three months, no prior treatmentwith chemotherapy, and no evidence of brain metastases.Irofulven was administered at a dose of 11 mg/m² by 5-minintravenous infusion, on 5 consecutive days. Cycles wererepeated every 28 days. Thirteen patients were enrolled inthis study and 12 were evaluable for response. Of the twelveevaluable patients, no major responses were achieved. Eightpatients had stable disease as best response. Toxicityincluded myelosuppression and gastrointestinal side effects.At the dose and schedule used in this trial, irofulven did notproduce clinical response in RCC.