Neoadjuvant treatment in advanced renal cell carcinoma: current situation and future perspectives

Neoadjuvant approaches in renal cell carcinoma are currently under investigation, following the demonstration of targeted therapy efficacy in the metastatic setting. It raises the issues of downsizing locally advanced or nonresectable tumor and offering organ-sparing surgery, saety and its potential role in early micrometastatic disease. Relevant studies of the neoadjuvant setting in renal cell carcinoma with targeted therapies were identified from the literature, clinical trial databases and conference abstracts. To date, a neoadjuvant approach appears feasible in terms of saety. Currently available drugs do not achieve major tumor downsizing with primary tumor diameters response rate of 10%. Neoadjuvants should only be considered in clinical trials or as a litmus test in locally advanced patients.     

Current role,techniques and outcomes of percutaneous biopsy of renal tumors

The use of percutaneous biopsy of renal masses has not been traditionally widely used because of concerns about safety, accuracy and sampling errors. The current gold standard of treatment for localized renal tumors is partial or radical nephrectomy. However, many small masses are benign tumors or low-grade renal cell carcinomas (RCCs). In selected cases, RCCs can be managed with active surveillance or with minimally invasive ablative technologies. In the setting of metastatic disease, the histological characterization of a renal tumor may also be helpful to select the most suitable targeted treatment. With the development of new and improved techniques and increasing expertise, percutaneous needle core biopsy of renal masses is a safe and accurate diagnostic procedure. Clinically significant bleeding is very rare and no case of RCC seeding along the needle tract has been observed in the last decade. Percutaneous biopsy should have an increasing role in the diagnostic management of renal masses, particularly in elderly or unfit patients diagnosed with small incidental masses or in patients with metastatic disease being considered for cytoreductive surgery and/or therapy with biological modifiers.     

Percutaneous radiofrequency ablation: minimally invasive therapy for renal tumors

Currently, up to 60% of renal tumors are detected incidentally by abdominal imaging. Most of these tumors are small and localized to the kidney. Owing to the shift to lower stage at diagnosis, radical nephrectomy has fallen out of favor and has been replaced by nephron-sparing surgery. Currently, partial nephrectomy is the treatment of choice for patients with small renal tumors. As the trend towards less invasive therapy continues, laparoscopic and percutaneous ablation techniques have gained popularity for the treatment of renal tumors in patients who are high-risk surgical candidates, or have a solitary kidney, limited renal function or multifocal disease. Percutaneous radiofrequency ablation is a safe, minimally invasive treatment option for those patients.     

Percutaneous radiofrequency ablation of renal tumours: Case series of 11 tumours and review of published work

Detection of renal cell carcinoma (RCC) is increasing with the greater use of cross‐sectional imaging and up to two‐thirds of RCCs are discovered incidentally in asymptomatic patients. The traditional option of nephrectomy or partial nephrectomy may not always be appropriate. A minimally invasive treatment alternative is radiofrequency ablation (RFA). We retrospectively reviewed the RFA cases for renal tumours at our institution between January 2004 and June 2006. Thirteen RFA treatment sessions were conducted for 11 neoplasms in 11 patients. Mean patient age was 74.4 years (61–88 years). Imaging was carried out after ablation with a mean follow up of 8.0 months (2–26 months). No residual tumour was observed after the first RFA treatment in 82% of patients (nine of 11). Two patients required a second RFA treatment for residual (one) or recurrent tumour (one). RFA is emerging as a useful technique for treatment of small renal tumour. A number of short‐term studies reflect this, however, long‐term findings are still lacking.     

Identification and validation of an eight‐gene expression signature for predicting high Fuhrman grade renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is a malignancy with heterogeneous outcomes. Currently, renal mass biopsies are commonly employed to extract disease characteristics and aid prognosis. Although the pathological diagnosis of malignant disease is accurate in contemporary reports, the classification of Fuhrman grade using biopsy specimens remains far from promising. To generate a gene signature to distinguish high‐grade ccRCC, we used the cancer genome atlas (TCGA) database to develop a gene expression signature for distinguishing high‐grade (G3/4) from low‐grade (G1/2) disease. The expression profile was further validated for performance and clinical use in 283 frozen renal cancer samples and 127 ex vivo renal mass biopsy samples, respectively. The area under curve (AUC) was used to quantify discriminative ability and was compared using the De‐long test. Using the discovery dataset, we identified a 24‐gene signature for high‐grade disease with an AUC of 0.884. After applied to the development dataset, an eight‐gene profile was defined and achieved an AUC of 0.823. Accuracy of eight‐gene panel was maintained in the renal mass biopsies (RMB) samples (AUC = 0.821). In summary, using three‐stage design, we validated an eight‐gene expression signature for predicting high Fuhrman grade of ccRCC. This tool may help to reveal the characteristics of ccRCC biopsy specimens.     

Sex and the clinical value of body mass index in patients with clear cell renal cell carcinoma

Background:

An increased body mass index (BMI) is significantly associated with favourable prognosis in renal cell carcinoma (RCC). This study investigated the associations among sex, BMI, and prognosis in clear cell RCC patients.

Methods:

We retrospectively analysed 435 patients with clear cell RCC who underwent a nephrectomy. The associations among sex, BMI, clinicopathologic factors, and cancer-specific survival (CSS) were analysed.

Results:

As a continuous variable, increased BMI was associated with higher CSS rate by univariate analysis in the whole population (hazard ratio, 0.888 per kg m^–2; 95% confidence interval, 0.803–0.982; P=0.021). A sub-population analysis by sex demonstrated that BMI was significantly associated with CSS in men (P=0.004) but not in women (P=0.725). Multivariate analysis revealed BMI to be an independent predictor of CSS in only men.

Conclusion:

Body mass index was significantly associated with clear cell RCC prognosis. However, the clinical value of BMI may be different between men and women.     

Percutaneous microwave ablation of renal cell carcinoma is safe in patients with renal dysfunction

Objectives: To present the clinical effect of microwave ablation (MWA) on renal cell carcinoma (RCC) of the patients with renal dysfunction, mainly focussing on the extent of renal tumour control and damage to the residual kidney function.

Methods and materials: From 2006 to 2014, 19 tumours of 18 patients with renal dysfunction underwent percutaneous ultrasound-guided MWA in our institution. The tumour diameters range from 1.9 to 5.0?cm. The serum creatinine and urea levels of each patient pre-MWA, one?day after MWA and the most recent occasion on record at our institution were collected. After MWA all the patients were followed up using contrast enhanced ultrasound (CEUS) and computed tomography (CT) or magnetic resonance imaging (MRI) at the first 1, 3 and 6 months and every six months thereafter. Patients were available for clinical and laboratory evaluations at a median follow-up time of 24.9 months (range from 3.5 to 85.9 months). The technical success, survival rates and complications were accessed.

Results: Complete ablation was achieved in 19/19 (100%) lesions after 1 or 2 MWA sessions; 2/18(11.1%) patients died of other diseases. No severe complications occurred during MWA. After MWA no significant elevation of renal function was observed either in patients of CKD stage 1–3 or in patients of CKD stage 4–5.

Conclusions: MWA is an effective and relatively safe treatment option for patients with renal tumour who also suffered from renal dysfunction. The complication rate is low, and excellent tumour control can be achieved with acceptable loss of residual renal function.     

Treatment of renal cell carcinoma: Current status and future directions

Answer questions and earn CME/CNE Over the past 12 years, medical treatment for renal cell carcinoma (RCC) has transitioned from a nonspecific immune approach (in the cytokine era), to targeted therapy against vascular endothelial growth factor (VEGF), and now to novel immunotherapy agents. Multiple agents—including molecules against vascular endothelial growth factor, platelet‐derived growth factor, and related receptors; inhibitors of other targets, such as the mammalian target of rapamycin and the MET and AXL tyrosine‐protein kinase receptors; and an immune‐checkpoint inhibitor—have been approved based on significant activity in patients with advanced RCC. Despite these advances, important questions remain regarding biomarkers of efficacy, patient selection, and the optimal combination and sequencing of agents. The purpose of this review is to summarize present management and future directions in the treatment of metastatic RCC. CA Cancer J Clin 2017;67:507‐524. © 2017 American Cancer Society.     

Current status of cytoreductive nephrectomy in metastatic renal cell carcinoma

The incidence of metastatic renal cell carcinoma (mRCC) continues to rise. While treatment options have increased dramatically in the last few years, few patients achieve a cure. The standard of care for mRCC in cytokine-eligible candidates is nephrectomy followed by high-dose IL-2. High-dose IL-2 can induce durable complete remissions, but only select patients can enjoy its benefits owing to toxicities. While not curative, the newer targeted therapies offer a broader patient population the chance for treatment response and prolonged survival. This review highlights the historical background of cytoreductive nephrectomy in mRCC, discusses the available treatment options and considers alternative treatment paradigms, such as the integration of the targeted agents with nephrectomy and the use of systemic therapy as medical selection for determining appropriate nephrectomy candidates.     

Body mass index and survival in patients with renal cell carcinoma: A clinical‐based cohort and meta‐analysis

Growing evidence suggests that obesity, an established cause of renal cell cancer (RCC), may also be associated with a better prognosis. To evaluate the association between RCC survival and obesity, we analyzed a large cohort of patients with RCC and undertook a meta‐analysis of the published evidence. We collected clinical and pathologic data from 1,543 patients who underwent nephrectomy for RCC between 1994 and 2008 with complete follow‐up through 2008. Patients were grouped according to BMI (kg/m²): underweight <18.5, normal weight 18.5 to <23, overweight 23 to <25 and obese ≥25. We estimated survival using the Kaplan–Meier method and Cox proportional hazard models to examine the impact of BMI on overall survival (OS) and cancer‐specific survival (CSS) with adjustment for covariates. We performed a meta‐analysis of BMI and OS, CSS and recurrence‐free survival (RFS) from all relevant studies using a random‐effects model. The 5‐year CSS increased from 76.1% in the lowest to 92.7% in the highest BMI category. A multivariate analysis showed higher OS [hazard ratio (HR) = 0.45; 95% CI: 0.29–0.68) and CSS (HR = 0.47; 95% CI: 0.29–0.77] in obese patients than in normal weight patients. The meta‐analysis further corroborated that high BMI significantly improved OS (HR = 0.57; 95% CI: 0.43–0.76), CSS (HR = 0.59; 95% CI: 0.48–0.74) and RFS (HR = 0.49; 95% CI: 0.30–0.81). Our study shows that preoperative BMI is an independent prognostic indicator for survival among patients with RCC.     

Tumor enucleation: a safe treatment alternative for renal cell carcinoma

The treatment of renal cell carcinoma has evolved tremendously over the years. Initially the entire kidney was removed along with the renal tumor despite the size or extent of the mass. Early attempts to remove tumors with a normal surrounding parenchymal margin showed equivalent oncologic results in small renal masses. Attempts to preserve more renal parenchyma in patients with compromised renal function led to the enucleation of renal masses by blunt dissection following the natural plane between the peritumor pseudocapsule and the renal parenchyma. Enucleation of renal tumors has been especially useful for renal preservation in patients with preoperative renal insufficiency, solitary kidneys, multiple renal lesions and hereditary renal cell carcinoma syndromes. Comparable long-term progression and cancer-specific survival has been shown with tumor enucleation and standard partial nephrectomy. However, there has been considerable controversy regarding the safety of renal tumor enucleation due to histopathologic findings of pseudocapsule tumor invasion. Current data suggest that tumor enucleation is a safe alternative for small renal masses that are locally confined on preoperative imaging, easily delineated intraoperatively and do not appear to grossly invade beyond the pseudocapsule.     

肾细胞癌相关分子标志物研究现状及进展

近年,有关肾细胞癌病理学、遗传性及分子生物学方面的研究取得显著进展,这对提高肾细胞癌早期诊断、预后判断及治疗水平有重要意义。目前研究的多个肾细胞癌相关分子标志物(如CAⅨ、B7-H1等)对于肾细胞癌患者的预后判断有一定意义。本文总结了近年来与肾细胞癌患者有关的肿瘤标志物,分析其与肾细胞癌的诊断、治疗和预后方面关系。     

红色胶状肾透明细胞癌的临床及病理特点——附2例报告

目的探讨大体标本为红色胶状肾透明细胞癌的临床特点。方法报告2例临床发现的特殊肾透明细胞癌的诊治情况,并回顾肾癌相关文献。结果临床2例肾透明细胞癌大体标本表现为均一红色,质软,胶状的特殊特点,其影像学及病理表现为典型肾透明细胞癌。结论在肾透明细胞癌大体标本可以表现为特殊的均一红色特点,其影像学为典型肾癌,大体标本与病理分期关系不明显。     

Liquid biopsy in cholangiocarcinoma: Current status and future perspectives

Cholangiocarcinoma (CCA) are a heterogeneous group of tumors in terms of aetiology, natural history, morphological subtypes, molecular alterations and management, but all sharing complex diagnosis, management, and poor prognosis. Several mutated genes and epigenetic changes have been detected in CCA, with the potential to identify diagnostic and prognostic biomarkers and therapeutic targets. Accessing tumoral components and genetic material is therefore crucial for the diagnosis, management and selection of targeted therapies; but sampling tumor tissue, when possible, is often risky and difficult to be repeated at different time points. Liquid biopsy (LB) represents a way to overcome these issues and comprises a diverse group of methodologies centering around detection of tumor biomarkers from fluid samples. Compared to the traditional tissue sampling methods LB is less invasive and can be serially repeated, allowing a real-time monitoring of the tumor genetic profile or the response to therapy. In this review, we analysis the current evidence on the possible roles of LB (circulating DNA, circulating RNA, exosomes, cytokines) in the diagnosis and management of patients affected by CCA.     

New entities,new technologies,new findings: A review of the cytologic features of recently established subtypes of renal cell carcinoma

Several new renal tumor types with distinctive pathologic, epidemiologic, and genetic signatures have recently been adopted in the fourth edition of the World Health Organization classification. In succeeding years, the cytologic features of most of these new types have been described, adding to the trend of increasing diagnostic accuracy for most common renal cell carcinoma subtypes and the important diagnostic role of cytologic sampling in the management and personalization of therapy. The current article reviews the cytologic findings from these recently established renal cell carcinoma subtypes. Emphasis is placed on cytologic diagnostic clues, confirmatory ancillary testing, salient differential diagnoses, and challenges that can be encountered in an attempt to render accurate interpretations in small samples.     

非小细胞肺癌联合治疗的现状与展望

对T1、T2期没有淋巴结受侵的NSCLC患者只要能耐受手术、肺叶切除术应作为首选。对Ⅰ、Ⅱ、ⅢA期符合手术指征的患者单纯手术是不够的,必须进行辅助化疗并从中受益,但辅助放疗因显著的副作用,使Ⅰ、Ⅱ期患者反而有害。对ⅢA期NSCLC患者术后使用放化疗,亦无益于改善局控率和延长生存期。关于可切除的Ⅰ、Ⅱ、ⅢA期NSCLC的新辅助化疗尚有争议。一项RTOG和SWOG的Ⅲ期随机对照临床试验(ⅢA期NSCLC患者先联合放化疗,后行手术和化疗)以评估ⅢANSCLC患者的预后已启动。本文综述了一系列重要文献及临床试验。讨论了各期NSCLC联合治疗的现状及展望未来的发展方向。