The role of transarterial embolization in the treatment of renal cell carcinoma

OBJECTIVE: To review the role of transarterial renal embolization in our unit, assessing the indications, tolerability and efficacy of this technique for treating renal cell carcinoma (RCC). PATIENTS AND METHODS: Thirty patients undergoing transarterial embolization between 1991 and 1999 were identified and 25 case notes analysed retrospectively. RESULTS: Most patients (14 of 25) presented with less advanced (stage I-III) RCC who were unable or unwilling to undergo radical surgery; the remainder (11) presented with advanced (stage IV) disease. The embolizing agent was ethanol, usually combined with stainless steel coils (85% of cases). Procedural pain and fever was controlled successfully. The median hospital stay associated with the procedure was 4 days. At the time of analysis six of 11 stage IV and 11 of 14 stage I-III patients were alive (median follow-up 27 and 39 months, respectively). Symptoms from the primary tumour were well controlled. Overall, 17 of 25 (68%) of patients reported no problems while three (12%) required brief hospital admission for treatment of persistent haematuria. Fourteen patients were subsequently re-staged; the primary tumour in two had increased, in seven remained unchanged and in five it decreased. No patients without metastases developed them and metastases in two patients regressed. CONCLUSION: Transarterial embolization is associated with minimal morbidity and complications, and subsequent symptom control is good. The effect of palliative embolization on RCC progression is unknown and requires prospective investigation. Presently, there is no role for cytoreductive embolization; it should be included as a treatment option in clinical trials evaluating such options in patients with metastatic RCC.     

The role of embolization in radical surgery of renal cell carcinoma spinal metastases

Background  Radical surgery of renal cell carcinoma spinal metastases carries a high risk due to potentially life-threatening extreme blood loss. Radical preoperative embolization of renal cell carcinoma metastases alone is not necessarily a guarantee of extreme blood loss not occurring during operation. Methods  A retrospective analysis of 15 patients following radical surgery for a spinal metastases of a renal cell carcinoma was performed. Eight patients were embolized preoperatively and 7 were not. We analysed features influencing peroperative blood loss: size and extent of tumour, complexity of surgical approaches and radicality of embolization. Results  The embolized and non embolized groups were not comparable before treatment. They differed markedly in size of tumour as well as the complexity of approach. In the embolized group the size of the tumour was, on average, twice as large as that in non embolized patients and more complex approaches were used twice as frequently. Despite findings suggesting that embolization was effective, blood loss was greater in the embolized group of 8 patients (4750 ml), compared to the non-embolized group of 7 patients (1786 ml). Conclusion  Metastasis size, extent of tumour, technical complexity of surgery and the completeness of preoperative embolization had an important effect on the amount of peroperative blood loss. The evaluation of the benefits of preoperative embolization only on the basis of blood loss is not an adequate method.     

Role of targeted therapy in combination with surgery in renal cell carcinoma

Surgical complete resection is the only curative treatment of renal cell carcinoma including patients with locally advanced disease and those with limited metastatic disease. Patients at high risk of recurrence after complete resection might theoretically benefit from adjuvant and neoadjuvant systemic treatment strategies to prolong disease‐free survival and ultimately overall survival. Another rationale for using targeted therapy includes downsizing/downstaging of surgically complex locally advanced renal cell carcinoma to facilitate complete resection or primary tumors to allow for nephron‐sparing strategies. Unfortunately, a considerable percentage of patients are diagnosed with metastatic disease at first presentation. Although large population‐based studies consistently show a survival benefit after cytoreductive nephrectomy in the targeted therapy era, confounding factors preclude definite conclusions for this heterogeneous patient group until ongoing phase III trials are published. Presurgical targeted therapy has been proposed to identify patients with clinical benefit and potentially long‐term survival after cytoreductive nephrectomy. Recently, the use of targeted therapy before or after local treatment of metastases has been reported in small retrospective series. The present review revisits the current evidence base of targeted therapy in combination with surgery for the various disease stages in renal cell carcinoma.     

The role of nephron sparing surgery for metastatic (pM1) renal cell carcinoma

PURPOSE: Studies have demonstrated increased time to progression when cytoreductive nephrectomy is performed for metastatic renal cell carcinoma. We evaluated the role of nephron sparing surgery in these patients. MATERIALS AND METHODS: We selected all patients with pM1 renal cell carcinoma treated with nephron sparing surgery or radical nephrectomy, and all patients with pM0 renal cell carcinoma undergoing nephron sparing surgery for solitary kidney from 1970 to 2002 from the Mayo Clinic Nephrectomy Registry. RESULTS: We identified 16 patients who underwent nephron sparing surgery for pM1 renal cell carcinoma. Solitary kidney was present in 12, 3 had bilateral synchronous disease and 1 had elective nephron sparing surgery. Cancer specific survival rates at 1, 3 and 5 years were 81%, 49% and 49%, respectively. We identified 404 patients who underwent radical nephrectomy for pM1 renal cell carcinoma. Cancer specific survival rates at 1, 3 and 5 years were 51%, 21% and 13%, respectively. The pM1 nephron sparing surgery for solitary kidney cases were more likely to have early (33% vs 10%, p = 0.009) or late (50% vs 19%, p = 0.018) complications compared with pM1 radical nephrectomy cases. There were no significant differences in early (p = 0.475) or late (p = 0.350) complications between pM1 nephron sparing surgery cases and 139 pM0 nephron sparing surgery cases. CONCLUSIONS: Cancer specific survival rates in pM1 nephron sparing surgery cases were comparable to pM1 radical nephrectomy cases. Although there were differences in early and late complications between the pM1 nephron sparing surgery and pM1 radical nephrectomy groups, there were no differences when compared with imperative pM0 nephron sparing surgery cases. This study demonstrates that nephron sparing surgery can achieve adequate cytoreductive therapy while preserving renal function, with postoperative complication rates similar to those of pM0 nephron sparing surgery cases.     

Cytoreductive surgery with liver-involved renal cell carcinoma

The purpose of this study was to demonstrate the benefits of cytoreductive surgery for renal cell carcinomas that also involve the liver. Between 1994 and 1997, four patients with renal cell carcinoma with liver involvement were surgically treated with nephrectomy and hepatectomy. Two of them underwent a simultaneous hepatectomy and nephrectomy (group 1), and the remaining two patients underwent a hepatectomy after a nephrectomy and had a diagnosis of postoperative recurrence (group 2). Two patients, one from each group, died of multiple bone metastasis and lung metastasis 30 months and 12 months after the hepatectomy; the second patient from group 1 died 40 months after the first operation due to gastrointestinal hemorrhaging. The second patient from group 2 displayed no evidence of recurrence 18 months after the second surgical procedure. The survival rates for these patients were 66% and 33% at 1 and 3 years, respectively. Autopsy studies revealed that one patient from group 2 had a local recurrence in the liver while the other two patients from group 1 did not. Our results suggested that a progressive approach may therefore be useful for patients demonstrating renal cell carcinoma where there is liver involvement.     

后腹腔镜保留肾单位手术治疗T1b期肾癌的疗效观察

目的：探讨后腹腔镜保留肾单位手术（NSS）治疗Tlb期肾癌（RCC）的手术方法及临床疗效。方法：2009年2月-2012年2月,对5例临床分期为T1b期RCC患者行后腹腔镜NSS,其中男3例,女2例,平均年龄（55．4±9．6）岁,左侧3例,右侧2例。肿瘤平均直径（5．7±1．3）cm。结果：所有手术均顺利完成,无中转开放,围手术期无严重并发症。平均手术时间（110．0±29．5）min,术中平均热缺血时间（24．2±5．1）min,术中平均出血量（42．2±13．1）ml,术后尿漏1例;术后平均住院时间（5．9±2．1）d,术后平均随访（25．3±11．1）个月,全部患者。肾功能正常且未见肿瘤局部复发及远处转移。结论：后腹腔镜NSS治疗Tlb期RCC创伤小、出血少、并发症少且近期疗效满意;但其远期疗效还需大样本对照研究和长期随访观察。     

Sunitinib relieves renal cell carcinoma spinal cord compression

A 66-year-old previously healthy female was diagnosed with renal cell carcinoma (RCC) metastic to the 4th, 6th and 12th thoracic vertebrae. Despite external beam radiotheraphy (20G in 5 fractions), she progressed to spinal cord compression within 4 weeks and was wheelchair bound. Radiation and surgery were not considered suitable, but sunitinib was initiated. After two 6-week sunitinib cycles, she is fully ambulatory. She reports grade I fatigue and occasional epistaxis, as sole side effects. This case demonstrates that despite the rapid progression of the disease, which escaped the effect of radiation within four weeks, sunitinib resulted in complete clinical symptom resolution, which was confirmed radiographically. Moreover, it appears that the novel therapies for metastatic RCC may restore quality and quantity of life to many of those, whose disease previously appeared too advanced to treat.     

Dendritic cell immunotherapy for patients with metastatic renal cell carcinoma: University of Tokyo experience

BACKGROUND: Dendritic cells (DC) are the most potent antigen-presenting cells and induce host antitumor immunity through the T-cell response. A clinical study of immunotherapy using cultured DC loaded with tumor antigen, for patients with metastatic renal cell carcinoma (RCC) was performed. METHODS: Dendritic cells were generated by culturing monocytes from peripheral blood for 7 days in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. On day 6 the DC were pulsed with lysate from autologous tumor as the antigen and with keyhole limpet hemocyanin (KLH) as immunomodulator. The patients were given four doses of lysate-pulsed DC by intradermal injection with a 2-week interval between doses. Clinical effect and immune response were, respectively, evaluated by radiological examination and delayed-type hypersensitivity (DTH) test. RESULTS: Three patients were enrolled and the immunotherapy was well tolerated without significant toxicity. The vaccination induced a positive DTH reaction to tumor lysate in two patients and to KLH in all patients. Clinical responses consisted of one case of no change and two cases of progression of disease. However, we did not see a significant reduction of tumor volume in any case. CONCLUSION: Dendritic cell vaccination can safely induce an immunological response against RCC. Further trials are needed to fully evaluate its efficacy.     

Parenchymal sparing surgery in patients with hereditary renal cell carcinoma: 10-year experience

PURPOSE: von Hippel-Lindau disease, hereditary papillary renal cell carcinoma, the Birt-Hogg-Dubé syndrome and familial renal oncocytoma are familial renal tumor syndromes. These hereditary disorders are noteworthy for the development of multiple bilateral renal tumors and the risk of new tumors throughout life. One management strategy is observation of solid renal tumors until reaching 3 cm, then performing parenchymal sparing surgery. We present a 5-year update on our experience. MATERIALS AND METHODS: From May 1988 to October 1998, 49 patients with hereditary renal cell carcinoma, including von Hippel-Lindau disease in 44, hereditary papillary renal cell carcinoma in 4 and the Birt-Hogg-Dubé syndrome in 1, and 1 with familial renal oncocytoma underwent exploration to attempt renal parenchymal sparing surgery. Patients were followed prospectively with periodic screening for recurrence, metastasis and loss of renal function. Median followup was 79.5 months (range 0.7 to 205). RESULTS: A total of 50 patients underwent 71 operations resulting in unilateral nephrectomy in 6, bilateral nephrectomy in 1 and partial nephrectomy in 65, with 1 to 51 tumors removed from each kidney (mean 14.7). Mean patient age was 39.5 years (range 18 to 70). Of the 65 (40%) partial nephrectomies 26 were performed with cold renal ischemia. Mean blood loss was 2.9 +/- 0.5 l (range 0.15 to 23). Postoperative complications included renal atrophy in 3 patients. Mean preoperative serum creatinine was 1.05 +/- 0.03 mg/dl (range 0.6 to 1.8), and postoperative creatinine was 1.06 +/- 0.04 mg/dl (range 0.6 to 2.0). No patient who underwent renal parenchymal sparing surgery required renal replacement therapy. Metastatic disease developed in 1 patient with a 4.5 cm renal tumor. CONCLUSIONS: Parenchymal sparing surgery with a 3 cm threshold in patients with hereditary renal cancer appears to be an effective therapeutic option to maximize renal function while minimizing the risk of metastatic disease.     

Prognostic factors and risk classifications for patients with metastatic renal cell carcinoma

The introduction of molecular‐targeted therapy has made dramatical changes to treatment for metastatic renal cell carcinoma. Currently, there are four vascular endothelial growth factor receptor‐tyrosine kinase inhibitors and two mammalian target of rapamycin inhibitors in Japan. For the appropriate clinical use of these molecular‐targeted drugs, the identification of prognostic and/or predictive factors in patients who received these drugs is required. Although molecular biological and genetic factors that determine the prognosis of patients with metastatic renal cell carcinoma have been reported, most of these factors are problematic in that the number of patients analyzed was small. In contrast, clinicopathological prognostic factors, including the practice of cytoreductive nephrectomy, pathological findings, metastatic sites and metastasectomy, and abnormal inflammatory response, have been identified by analyzing a relatively large number of patients. Several prognostic classification models that were developed by combining these clinicopathological factors are widely used in not only clinical trials, but also routine clinical practice. However, the quality of these prognostic models is considered to be insufficient regarding prognostic prediction of metastatic renal cell carcinoma patients and, thus, requires further improvements. Recently, basic and clinical studies have been extensively carried out for the identification of promising informative markers and for understanding molecular mechanisms of resistance to molecular‐targeted drugs in metastatic renal cell carcinoma patients. The present review considers ongoing translational research efforts on clinicopathological, molecular biological, and genetic prognostic and/or predictive factors for metastatic renal cell carcinoma patients in the era of molecular‐targeted therapy, and discusses the clinical implications of these findings.     

凝血功能与肾癌肿瘤分期及转移的相关性研究

目的探讨凝血功能与肾癌肿瘤分期及转移的关系。方法回顾性分析我院2011～2012年收治的150例肾癌患者的临床资料。男95例,女55例。平均年龄（51．41±19．68）岁。病理类型：透明细胞癌120例、乳头状癌11例、嫌色细胞癌6例、囊性肾癌8例,其他类型5例。TNM分期：Ⅰ期87例（T1a45例,T1b42例）,Ⅱ期24例、Ⅲ期22例、Ⅳ期17例。N0111例、N1 17例、N2 22例,M0 133例、M1 17例。病理明确诊断为肾良性肿瘤132例纳入对照组。比较两组患者术前纤维蛋白原（Fib）、凝血酶原时间（PT）、部分活化凝血酶原时间（APTT）及国际标准化比值（INR）水平。结果肾癌组患者术前Fib值（4．08±1．12）g／L,对照组（3．23±0．52）g／L,两组比较差异有统计学意义（P〈0．01）;肾癌组PT（10．65±1.38）s、APTT（31．11±3．56）s、INR（0．95±0．72）,对照组分别为（11．02±7．44）s、（31．24±3．05）s、（O．96士o．64）,两组比较差异均无统计学意义（P〉0．05）。肾癌5个亚组术前Fib分别为（3．75±0．59）g／L、（3．31±0．64）g／L、（4．34±0．52）g／L、（4．99±0．38）g／L、（6．04±1．06）g／L,其中T1a、T1b组与对照组比较差异无统计学意义（P〉0．05）,其余组与对照组比较差异有统计学意义（P〈0．01）。肾癌组高纤维蛋白原血症（Fib＞4．0g／L）者68例（24．1％）。结论肾癌伴淋巴结及远处转移者血清Fib升高,肿瘤分期为Ⅱ期、Ⅲ期、Ⅳ期发生转移的可能性较大。血清Fib对肾癌预后具有独特的预测价值。     

舒尼替尼治疗转移性肾癌的初步评价

目的 评价舒尼替尼治疗转移性肾癌的疗效和安全性. 方法转移性肾癌患者31例.男23例,女8例.中位年龄55(25～75)岁.31例中行原发肿瘤切除30例,仅行活检术1例,病理证实为肾细胞癌,并至少有1处可测量的转移病灶.初始患者均口服舒尼替尼50 mg/d,用药4周、间歇2周为1个周期,每2个周期行CT扫描以评价疗效. 结果全组可评价疗效24例,无完全缓解病例,部分缓解5例、疾病稳定15例、疾病进展4例,其中死亡1例.中断治疗4例,其中因高龄、全身情况差、不能耐受服药1例,因经济困难停药2例,因肝功能损害停药1例.3例因治疗时间短而未评价.全组客观反应率21%(5/24),疾病控制率83%(20/24),中位无疾病进展生存时间11个月,1年无进展生存率80%.常见不良反应是手足皮肤反应、腹泻、食欲差、口腔炎、出血倾向和血液学毒性,分别通过外敷、口服药物和补液治疗得到及制. 结论舒尼替尼对转移性肾癌的病情控制有显著效果,也存在一定不良反应,通过及时干预和处理,患者大多可以耐受其不良反应.     

Solitary, late metastatic recurrence of renal cell carcinoma: Two extraordinary cases

Late recurrence of renal cell carcinoma (RCC) has been well documented in the literature. We present two extraordinary cases of solitary, late metastatic recurrence of RCC. The first is a case of a solitary, adrenal metastasis excised 38 years after nephrectomy and the second is a case in which two solitary metastatic deposits were resected 14 and 26 years after excision of the primary tumor. In each of these patients the solitary metastases were initially believed to be primary tumors at other sites; however, on histological examination they were found to be metastatic RCC recurrences. In patients with a previous history of RCC presenting with apparently new solitary lesions, metastatic RCC must first be excluded.     

Cytoreductive nephrectomy for metastatic renal cell carcinoma with nonclear cell histology

PURPOSE: To our knowledge the benefit of cytoreductive surgery for patients with metastatic renal cell carcinoma with nonclear cell histology is unknown. In this retrospective study we report our experience with cytoreductive nephrectomy for nonclear cell metastatic renal cell carcinoma at M. D. Anderson Cancer Center. We compared the outcomes with those in patients with clear cell metastatic renal cell carcinoma. MATERIALS AND METHODS: From 1991 to 2006, 606 patients with metastatic renal cell carcinoma underwent cytoreductive nephrectomy and they formed the basis of this report. Of these patients 92 had nonclear cell metastatic renal cell carcinoma. The remaining 514 patients had clear cell metastatic renal cell carcinoma and they formed a comparative group. Multivariate Cox regression analysis was performed to evaluate the relationship between clinical variables and histology (clear cell vs nonclear cell) on disease specific survival. RESULTS: Compared with patients with clear cell histology those with nonclear cell metastatic renal cell carcinoma were younger (p = 0.0001), and more likely to have nodal metastases (p <0.0001) and sarcomatoid features (23% vs 13%, p = 0.026). On multivariate analysis median disease specific survival in patients with nonclear cell histology was significantly worse than that in patients with clear cell metastatic renal cell carcinoma (9.7 vs 20.3 months, p = 0.0003) even after adjusting for T stage, grade, performance status, age and sarcomatoid features. Sarcomatoid features were a predictor of poor outcome in cases of clear and nonclear cell histology, although even in the absence of sarcomatoid features nonclear cell histology was associated with worse disease specific survival (p = 0.017). Interestingly although there was a significantly higher incidence of positive nodes in patients with nonclear histology (p <0.0001), this phenotype was not associated with a worse disease specific survival, as it was in those with clear cell histology (p = 0.0001). In fact, patients with node negative disease with nonclear cell histology had the worst prognosis overall in the entire group. CONCLUSIONS: Patients with nonclear cell metastatic renal cell carcinoma were younger and had a higher incidence of nodal metastases, a higher incidence of sarcomatoid features and a worse prognosis than those with clear cell histology who underwent cytoreductive surgery.     

舒尼替尼在晚期肾细胞癌治疗中的运用

目的：探讨苹果酸舒尼替尼对晚期肾细胞癌治疗的安全性和有效性。方法：晚期肾细胞癌患者22例,男18例,女4例,平均年龄56岁,均为转移性或难以手术的肾细胞癌患者。采用舒尼替尼治疗,其中18例为一线治疗,4例为二线治疗。均为单一服药,口服50mg／d,每4周停药2周者16例;口服37．5mg／d,连续服药者6例。持续用药至肿瘤进展或出现不可耐受的并发症。以6周为1个治疗周期,至少每2个治疗周期进行疗效评价。结果：1例患者服药不足2周期内死亡,可评价病例21例。部分缓解6例（28．6％）,疾病稳定13例（61．9％）,疾病进展2例（9．5％）,无完全缓解病例。常见的不良反应包括手足皮肤反应、皮疹、疲劳乏力、骨髓抑制、味觉变化等。结论：舒尼替尼治疗晚期肾癌患者效果确切,不良反应多数可控制,但对于KPS评分较低,一般情况差,肿瘤负荷大的患者,运用时需慎重。     

Hepatocellular carcinoma with adjacent organ extension: The enhancement of preoperative transcatheter arterial embolization and the results of surgical resection

A review was conducted on 93 patients with hepato-cellular carcinoma (HCC) who underwent a collective total of 98 resections. A total of 24 hepatic resections were performed on 22 patients who had a serosa-exposed tumor (group A), for which combined resection of the adjacent organs was also required due to gross tumor invasion. The tumors of the group A patients were larger, had a higher incidence of intrahepatic vascular involvement, and were in a more advanced stage than those of the other patients (group B). Nevertheless, there were no differences in operative morbidity and mortality between the two groups. Only ten of the group A patients, who each underwent one operation, had concomitantly resected adjacent organs histologically invaded by HCC, while histological examination revealed adhesions in the remaining surgical specimens of concomitantly resected adjacent organs. More of the group A patients had undergone a preoperative transcatheter arterial embolization (TAE), which may enhance the histological invasion of HCC to the adjacent organs. The median survival times of the group A and B patients were 15.3 months and 40.1 months, respectively (P < 0.05), although whether the concomitantly resected organs were truly invaded by HCC did not influence the prognosis. Thus, en bloc combined resection of HCC-invaded adjacent organs is still advocated even for recurrent tumors; however, for serosa-exposed HCC after TAE, earlier resection is recommended whenever possible to avoid invasion of the adjacent organs.