Kidney Cancer
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Renal cell cancer (kidney cancer) is a disease in which malignant cells arise from tissues of the kidney. This is one of the less common types of cancer and it occurs more frequently in men compared to women. The vast majority of renal cell cancers are histologically classed as adenocarcinomas, these may be subdivided into clear cell and granular cell types (in some cases the 2 types can occur together in the same tumour). There are other less common types of non-adenocarcinoma kidney cancers including transitional cell carcinoma of the renal pelvis. Wilms' tumour is another type of kidney cancer, which is almost exclusively found in children.

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Latest Research Publications
Transitional Cell Cancer of the Renal Pelvis and Ureter
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Urinary System Cancers

Information Patients and the Public (9 links)


Information for Health Professionals / Researchers (12 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Ozdemir AT, Altinova S, Asil E, Balbay MD
Robotic-assisted laparoscopic nephroureterectomy and bladder cuff excision.
JSLS. 2012 Apr-Jun; 16(2):320-4 [PubMed] Free Access to Full Article
BACKGROUND AND OBJECTIVES: Our aim was to show that bladder cuff excision and distal ureterectomy can be safely performed by using the LigaSure device during robotic-assisted laparoscopic nephroureterectomy.
METHODS: A 60-year-old man presented with gross hematuria. He was diagnosed with upper urinary tract transitional cell carcinoma (TCC) on the left side and was scheduled for robot-assisted laparoscopic surgery. Without changing the patient's position, sealing with the LigaSure atlas for bladder cuff excision and distal ureterectomy was performed.
RESULTS: The operating time was 140 minutes from the initial incision to skin closure of all incisions. The estimated blood loss during the surgery was 120 mL. There were no intraoperative or postoperative complications. The Foley drain was removed on day 3 after normal cystographic findings, and the patient was discharged from the hospital on the fourth postoperative day.
CONCLUSION: Robot-assisted nephroureterectomy with distal ureterectomy in the same position using a LigaSure device is a safe alternative for upper tract transitional cell carcinoma.


Sun Y, Sheng Q, Cheng Y, et al.
Zerumbone induces apoptosis in human renal cell carcinoma via Gli-1/Bcl-2 pathway.
Pharmazie. 2013; 68(2):141-5 [PubMed]
Renal cell carcinoma (RCC) is a malignant disease insensitive to conventional treatments such as radiochemotherapy and immunotherapy. Search for new approaches to induce cancer cell apoptosis will improve the management of RCC. Here, we reported that zerumbone, a monosesquiterpine, shows anticancer effects on human RCC cells via induction of apoptosis in vitro. Human renal clear cell carcinoma 786-0 and 769-P cell lines were used as the model system. Exposure of RCC cells to zerumbone resulted in cell viability inhibition, accompanied by DNA fragmentation and increased apoptotic index. Mechanically, treatment of RCC cells with zerumbone activated caspase-3 and caspase-9, and finally led to cleavage of PARR In addition, downregulation of Gli-1 and Bcl-2, which were closely related to the chemoresistance of RCC, was observed in zerumbone-treated RCC cells. Taken together, our study provided the first evidence that zerumbone imparted strong inhibitory and apoptotic effects on human RCC cells. The zerumbone-induced apoptosis might be related to the activation of the caspase cascade and deregulation of the Gli-1/Bcl-2 pathway. Our results suggest that zerumbone merit further investigation as an apoptosis inducer as well as a novel RCC chemotherapeutic agent in the clinical setting.


Beuselinck B, Karadimou A, Lambrechts D, et al.
Single-nucleotide polymorphisms associated with outcome in metastatic renal cell carcinoma treated with sunitinib.
Br J Cancer. 2013; 108(4):887-900 [PubMed] Article available free on PMC after 05/03/2014
BACKGROUND: There are no validated markers that predict response in metastatic renal cell cancer (RCC) patients treated with sunitinib. We aim to study the impact of single-nucleotide polymorphisms (SNPs) that have recently been proposed as predictors of outcome to anti-VEGF-targeted therapy in metastatic RCC in an independent cohort of patients.
METHODS: We genotyped 16 key SNPs in 10 genes involved in sunitinib pharmacokinetics, pharmacodynamics and VEGF-independent angiogenesis in patients with metastatic clear-cell RCC treated with sunitinib as the first-line targeted therapy. Association between SNPs, progression-free survival (PFS) and overall survival (OS) were studied by multivariate Cox regression using relevant clinical factors associated with PFS and OS as covariates.
RESULTS: In a series of 88 patients, both PFS and OS were associated significantly with SNP rs1128503 in ABCB1 (P=0.027 and P=0.025), rs4073054 in NR1/3 (P=0.025 and P=0.035) and rs307821 in VEGFR3 (P=0.032 and P=0.011). Progression-free survival alone was associated with rs2981582 in FGFR2 (P=0.031) and rs2276707 in NR1/2 (P=0.047), whereas OS alone was associated with rs2307424 in NR1/3 (P=0.048) and rs307826 in VEGFR3 (P=0.013).
CONCLUSION: Our results confirm former communications regarding the association between SNPs in ABCB1, NR1/2, NR1/3 and VEGFR3 and sunitinib outcome in clear-cell RCC. Prospective validation of these SNPs is now required.


Pietras W
Advances and changes in the treatment of children with nephroblastoma.
Adv Clin Exp Med. 2012 Nov-Dec; 21(6):809-820 [PubMed]
Wilms' tumor or nephroblastoma is the most common malignant tumor stemming from kidney cells and second only to neuroblastoma when it comes to extracranial solid tumors in children. The results of nephroblastoma treatment are a perfect example of therapeutic success resulting from an interdisciplinary approach to the problem and the cooperation of pediatric surgeons, pediatric oncologists, pathologists, radiologists and radiotherapists leading to precise diagnoses and the selection of the optimal treatment. At the end of the sixties, international research teams began studying the best treatment for this tumor in children. In Europe, it was the International Society of Paediatric Oncology (SIOP), which has used the working name SIOP- RTSG (Renal Tumor Study Group - Group for the Study of Kidney tumors) since 2008 and in North America NWTS (National Wilms' Tumor Study - The National Committee for Research on Wilms' tumor). Summarizing the experience and knowledge on the treatment of nephroblastoma, it should be noted that, despite years of research and information exchange, uniform guidelines have not yet been developed, and there are still differences in treatment of this tumor. The biggest differences are between the "American" treatment recommended by the NWTS and the "European" by SIOP. In the first it is recommended to start treatment from the surgical removal of the tumor, even in the case of disseminated disease with the presence of metastases in the lungs. The treatment method is chosen by the institution managing the patient; for this reason on the American continent in Brazil, Wilms' tumor is treated according to the recommendations of "European" protocols (SIOP) and some institutions in Europe, for example in Italy, treat patients with nephroblastoma according to the "American" protocols recommended by the NWTS; until recently, focal disease was treated with primary nephrectomy in the UK.


Vashistha V, Shabsigh A, Zynger DL
Utility and diagnostic accuracy of ureteroscopic biopsy in upper tract urothelial carcinoma.
Arch Pathol Lab Med. 2013; 137(3):400-7 [PubMed]
CONTEXT: Ureteroscopic biopsy is the gold standard for the histopathologic diagnosis of urothelial carcinoma of the upper urinary tract.
OBJECTIVE: To assess the accuracy of endoscopically obtained biopsy samples in diagnosing, grading, and staging urothelial carcinoma and correlate diagnostic findings to biopsy sample size.
DESIGN: We retrospectively reviewed endoscopic biopsies of the ureter, renal pelvis, and ureteropelvic junction from 2008 to 2011. Biopsy diagnoses that were discordant with follow-up pathology and/or ureteroscopic impression were re-reviewed and samples were immunohistochemically analyzed.
RESULTS: Endoscopic biopsies (n = 118) yielded a sensitivity of 85.4% for the ureter (n = 79), 77.8% for the renal pelvis (n = 37), and 100% for the ureteropelvic junction (n = 2). A specificity of 100% for all locations and a diagnostic accuracy of 98.3% were identified. The median sample size was 0.3 cm for true positives, 0.3 cm for true negatives, and 0.2 cm for false negatives with no statistical significance. We found that 87.1% of tumors diagnosed on biopsy had concordant grade and 60.0% had concordant pT stage with follow-up surgical resections (n = 43) and biopsies (n = 24). Biopsy samples with concordant tumor grades (mean = 0.6 cm) compared with follow-up resection were larger than biopsy samples with discordant grades (mean = 0.3 cm) (P = .04).
CONCLUSIONS: Though highly specific, endoscopic biopsy does provide a significant false-negative rate owing to both sampling and diagnostic errors when assessing the upper urinary tract for urothelial carcinoma. Tumor grading is accurate, particularly with larger tissue samples, but tumor staging is unreliable.


Noce A, Iaria G, Durante O, et al.
Bilateral native kidney neoplasia detected by ultrasound in functionning renal allograft recipient.
Arch Ital Urol Androl. 2012; 84(4):253-5 [PubMed]
We report the case of bilateral renal clear cell carcinoma in the native kidney, occurring fouryears after renal transplantation. Renal Doppler duplex sonography revealed large solid bilateral neoformation. Total-body computed tomography confirmed the presence of bilateral kidney lesions and also showed the presence of concomitant gross dyscariocinetic lesion of left hemotorax. The patient underwent bilateral native nephrectomy and the histological diagnosis was renal cell carcinoma. Subsequent left upper lobectomy revealed necrotic keratinizing squamous cell carcinoma. Then, the patients was switched tacrolimus to everolimus treatment and mycophenolate mofetil was reduced.


Diolombi M, Ross HM, Mercalli F, et al.
Nephrogenic adenoma: a report of 3 unusual cases infiltrating into perinephric adipose tissue.
Am J Surg Pathol. 2013; 37(4):532-8 [PubMed]
Nephrogenic adenoma of the urinary bladder, where they present most frequently, are typically confined to the lamina propria but can on occasion focally involve the superficial muscularis propria. Less commonly, nephrogenic adenoma involves the renal pelvis and ureter where again they almost always only involve the lamina propria. We identified 3 consult cases in which tubules of nephrogenic adenoma extensively involved the muscularis propria and focally infiltrated the perinephric adipose tissue, for which the contributing pathologists considered the diagnosis of adenocarcinoma. In 1 case, that of a 71-year-old man, the lesion was associated with a hemorrhagic renal cyst (3.0 cm) and a spontaneous retroperitoneal bleed (6.0 cm) of unknown origin. In the second case, that of a 73-year-old woman, 2 foci (2.2, 1.6 cm) were present in the renal pelvis. They developed after biopsy of a low-grade noninvasive papillary urothelial carcinoma in the same site complicated by perforation. The third case was that of a 20-year-old woman with ureteropelvic junction obstruction and severe hydronephrosis associated with renal calculi. In all cases, the lesions were positive for CK7 and PAX8. These 3 cases report the novel finding that nephrogenic adenoma can occasionally have a deep infiltrative pattern into perinephric adipose tissue, possibly as a result of either biopsy-associated perforation or extensive disruption due to hemorrhage or mechanical obstruction. Awareness of this worrisome infiltration pattern, although rare, can prevent a misdiagnosis of an infiltrating carcinoma.


Kang WY, Sung DJ, Park BJ, et al.
Perihilar branching patterns of renal artery and extrarenal length of arterial branches and tumour-feeding arteries on multidetector CT angiography.
Br J Radiol. 2013; 86(1023):20120387 [PubMed] Article available free on PMC after 01/03/2014
OBJECTIVE: The purpose of our study was to assess the extrarenal length of renal arterial branches and tumour-feeding arteries on multidetector CT (MDCT) angiography, in addition to the perihilar branching patterns, with relevance to segmental artery clamping.
METHODS: MDCT angiograms of 64 patients with renal masses <4 cm were retrospectively reviewed by 2 radiologists. The perihilar branching patterns of the single main renal artery were assessed according to the number of pre-segmental and segmental arteries. The extrarenal lengths of segmental plus pre-segmental arteries and the tumour-feeding arteries, measured on volume-rendered images, were compared according to the vascular segmentation and the tumour location, respectively.
RESULTS: In the 116 kidneys, 1 pre-segmental plus 5 segmental arteries (n=48) was the most common branching pattern. The mean extrarenal length of the inferior segmental plus pre-segmental arteries (33.05 mm) and the posterior segmental plus pre-segmental arteries (32.30 mm) was longer than any of the other segmental plus pre-segmental arteries (apical, 23.87 mm; superior, 26.80 mm; middle, 29.23 mm) (p<0.05). The mean extrarenal length of the lower pole tumour-feeding arteries (35.94 mm) was longer than those of the upper and mid-pole tumour-feeding arteries (24.95 mm, 29.62 mm), with significant difference between the lower and the upper pole tumour-feeding arteries (p<0.05).
CONCLUSION: Tumours in the lower pole, supplied by the inferior or posterior segmental artery, may be more amenable to segmental artery clamping. Advances in knowledge: MDCT angiography with volume rendering can demonstrate the extrarenal length of tumour-feeding arteries and may help in determining the accessibility for segmental artery clamping.


Behrens G, Leitzmann MF
The association between physical activity and renal cancer: systematic review and meta-analysis.
Br J Cancer. 2013; 108(4):798-811 [PubMed] Article available free on PMC after 05/03/2014
BACKGROUND: Physical activity may decrease renal cancer risk by reducing obesity, blood pressure, insulin resistance, and lipid peroxidation. Despite plausible biologic mechanisms linking increased physical activity to decreased risk for renal cancer, few epidemiologic studies have been able to report a clear inverse association between physical activity and renal cancer, and no meta-analysis is available on the topic.
METHODS: We searched the literature using PubMed and Web of Knowledge to identify published non-ecologic epidemiologic studies quantifying the relationship between physical activity and renal cancer risk in individuals without a cancer history. Following the PRISMA guidelines, we conducted a systematic review and meta-analysis, including information from 19 studies based on a total of 2 327 322 subjects and 10 756 cases. The methodologic quality of the studies was examined using a comprehensive scoring system.
RESULTS: Comparing high vs low levels of physical activity, we observed an inverse association between physical activity and renal cancer risk (summary relative risk (RR) from random-effects meta-analysis=0.88; 95% confidence interval (CI)=0.79-0.97). Summarising risk estimates from high-quality studies strengthened the inverse association between physical activity and renal cancer risk (RR=0.78; 95% CI=0.66-0.92). Effect modification by adiposity, hypertension, type 2 diabetes, smoking, gender, or geographic region was not observed.
CONCLUSION: Our comprehensive meta-analysis provides strong support for an inverse relation of physical activity to renal cancer risk. Future high-quality studies are required to discern which specific types, intensities, frequencies, and durations of physical activity are needed for renal cancer risk reduction.


Piplani S, Kapur BN, Sandhu AS, et al.
Bilateral hybrid oncocytoma and renal cell carcinoma.
J Assoc Physicians India. 2012; 60:47-50 [PubMed]
A 26-year-old female presented with abdominal pain and distension in 2003. Clinical evaluation and imaging were suggestive of bilateral benign renal solid masses. Fine needle aspiration showed tubular cells only. Patient was kept under periodic follow up. She reported 4 years later with increase in pain and size of masses, and underwent bilateral staged nephron sparing surgery. The histopathology was reported as bilateral oncocytoma. Two years after surgery, she developed epidural spinal cord compression and liver metastasis. A decompression laminectomy and biopsy revealed conventional renal cell carcinoma (RCC). To our knowledge this is the first case report of sporadic bilateral synchronous hybrid RCC and oncocytoma in a young woman, with spinal epidural metastasis.


Stojanović N, Ignjatovic I, Kostov M, et al.
Giant renal oncocytoma.
Vojnosanit Pregl. 2013; 70(1):68-71 [PubMed]
BACKGROUND: Renal onkocytoma is a distinctive benign tumor derived from epithelial cells of the distal renal tubules. These tumors are often clinically asymptomatic, diagnosed accidentally and difficult to distinguish from renal cell carcinoma.
CASE REPORT: We presented a giant renal onkocytoma in a man aged 64, without any signs or symptoms of the urogenital system disorder. The preoperative diagnosis described the tumor mass of the right kidney, size 16 x 14 cm, and indicated a malignant tumor of kidney. The patient underwent radical nephrectomy. The tumor was encapsulated at the intersection with the characteristic central hyaline scar. Microscopically, it was built of uniform polygonal cells with abundant eosinophilic cytoplasm. Immunohystochemiclly, tumor cells were immunoreactive to CK AE1/AE3 and CD 117, but showed negative immunoreactivity to CK 7, RCC marker and Vimentin.
CONCLUSION: Giant renal oncocytomas are rare tumors with benign clinical course. As a rule, they are discovered by accident. Clinical differentiation from malignant tumors of the kidney is not possible. They are treated surgically, mainly by radical nephrectomy. A definitive diagnosis is made only by histopathological examination of tumors using immunohistochemical marker panels.


Buti S, Donini M, Lazzarelli S, Passalacqua R
A new modified schedule of sunitinib for metastatic renal cell carcinoma: a retrospective analysis.
Acta Biomed. 2012; 83(2):88-94 [PubMed]
BACKGROUND AND AIM OF THE WORK: Sunitinib 50 mg/day given for 4 weeks followed by 2 weeks off treatment (4+2 schedule) is a standard treatment for metastatic renal cell carcinoma, but several patients are forced to reduce the doses and/or had to discontinue therapy permanently due to toxicity. Recent data showed that increased exposure to sunitinib is associated with improved clinical outcome underlining the key role of dose-intensity in the efficacy/toxicity balance. We investigated the tolerability and efficacy of a modified schedule.
PATIENTS AND METHODS: This is a retrospective analysis which assessed consecutive non-progressive metastatic renal cell carcinoma patients admitted to our hospital who had at least a grade 2 toxicity during sunitinib therapy, and then switched to a modified schedule maintaining the same dose-intensity of 4+2 schedule: starting on Monday, 1 tablet/day for 5 consecutive days a week (days 6 and 7 off therapy) for 5 weeks and 1 tablet/day on days 1, 3 and 5 in the sixth week (days 2, 4, 6 and 7 off therapy) until disease progression. Primary end points were toxicity changes assessment and schedule feasibility.
RESULTS: Complete data from eight nephrectomized patients were collected: 6 males; median age 61; 3 pretreated patient. Median time from start therapy to switch was 7.4 months. After switch, treatment delays and dose reductions decreased from 50% to 25% and from 37% to 12% of patients respectively. Toxicity was reduced.
CONCLUSIONS: Even though no conclusions can be drawn about the actual effectiveness and toxicity of our schedule compared to the standard dosing schedule, it seems to be well tolerated and able to maintain a high adherence to therapy, resulting in maintenance of antitumour activity. This new modified schedule requires and deserves further studies.(www.actabiomedica.it).


An J, Liu H, Magyar CE, et al.
Hyperactivated JNK is a therapeutic target in pVHL-deficient renal cell carcinoma.
Cancer Res. 2013; 73(4):1374-85 [PubMed]
Clear cell renal cell carcinomas (RCC), the major histologic subtype of RCC accounting for more than 80% of cases, are typified by biallelic inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. Although accumulation of hypoxia-inducible factor alpha (HIF-α) is the most well-studied effect of VHL inactivation, direct inhibition of HIFα or restoration of wild-type pVHL protein expression has not proved readily feasible, given the limitations associated with pharmacologic targeting of transcription factors (i.e., HIF-α) and gene replacement therapy of tumor suppressor genes (i.e., VHL). Here, we have established that phosphorylated c-Jun, a substrate of the c-Jun-NH(2)-kinase (JNK), is selectively activated in clear cell RCC patient specimens. Using multiple isogenic cell lines, we show that HIF-α-independent JNK hyperactivation is unique to the pVHL-deficient state. Importantly, pVHL-deficient RCCs are dependent upon JNK activity for in vitro and in vivo growth. A multistep signaling pathway that links pVHL loss to JNK activation involves the formation of a CARD9/BCL10/TRAF6 complex as a proximal signal to sequentially stimulate TAK1 (MAPKKK), MKK4 (MAPKK), and JNK (MAPK). JNK stimulates c-Jun phosphorylation, activation, and dimerization with c-Fos to form a transcriptionally competent AP1 complex that drives transcription of the Twist gene and induces epithelial-mesenchymal transition. Thus, JNK represents a novel molecular target that is selectively activated in and drives the growth of pVHL-deficient clear cell RCCs. These findings can serve as the preclinical foundation for directed efforts to characterize potent pharmacologic inhibitors of the JNK pathway for clinical translation.


Patatas K, Robinson GJ, Ettles DF, Lakshminarayan R
Patterns of renal angiomyolipoma regression post embolisation on medium- to long-term follow-up.
Br J Radiol. 2013; 86(1024):20120633 [PubMed] Article available free on PMC after 01/04/2014
OBJECTIVE: To assess the patterns of regression of renal angiomyolipoma (AML) post embolisation and report the outcomes related to the use of different embolic materials.
METHODS: A retrospective review of all patients who underwent embolisation for renal AML at our institution between January 2004 and April 2012.
RESULTS: 13 patients underwent 16 episodes of embolisation. Coils were used as the primary embolisation material in 10 episodes and microspheres in 6 episodes. The size reduction rate highly correlated on CT follow-up between the two groups, with 25.6% vs 22.7% reduction at 12 months, 27.5% vs 25.1% at 24 months, 35.0% vs 33.0% at 36 months and 35.0% vs 36.8% at 48 months. During follow-up, all tumours reduced in size with one patient requiring subsequent embolisation whose tumour reduced by only 6.5% after 1 year and subsequently exhibited regrowth after 4 years. Two patients presented with rebleeding and underwent repeat embolisation. Our overall retreatment rate (23%) is well within the literature range (up to 37%). None of the patients underwent surgery.
CONCLUSION: The majority of AML shrinkage occurs within the first year following embolisation and appears to plateau after 3 years, which could have an impact on follow-up strategy. The percentage reduction at 1 year may reflect the long-term effect of embolisation with tumours demonstrating minor size reduction more likely to relapse at long-term follow-up. Embolisation of renal AML produces durable long-term results regardless of the choice of embolic agent. ADVANCES IN KNOWLEDGE: These findings provide information to guide CT follow-up of renal AML post embolisation.


Nagashima Y, Kuroda N, Yao M
Transition of organizational category on renal cancer.
Jpn J Clin Oncol. 2013; 43(3):233-42 [PubMed]
The incidence of kidney cancer is gradually increasing, with a rate of 2-3% per decade. The kidney develops various kinds of neoplasms, some of which are associated with familial cancer syndromes. Such cases have provided clues to identify the cancer-responsible genes. In 2004, the World Health Organization published a new classification system of renal neoplasms, incorporating recent knowledge obtained in the cytogenetic and molecular biological fields, i.e. genes responsible for each histologic subtype (von Hippel-Lindau for clear cell renal cell carcinoma, c-met for papillary renal cell carcinoma type 1, etc.). Subsequently, the Japanese classification system in 'the General Rule for Clinicopathological Study of Renal Cell Carcinoma' has been revised as the 4th edition, according to the World Health Organization system. Several novel subtypes have been introduced, i.e. mucinous tubular and spindle cell carcinoma, and Xp11.2/TFE3 translocation-associated renal cell carcinoma. Even after the publication of the classification, other novel subtypes have emerged, i.e. acquired cystic disease-associated renal cell carcinoma and tubulocystic renal cell carcinoma. Additionally, some of the subtypes seem to form families based on morphological transition, immunohistochemical features and gene expression profile. In future, the classification of renal cell carcinoma should be reorganized on the basis of molecular biological characteristics to establish personalized therapeutic strategies.


Okur A, Pinarli FG, Karadeniz C, et al.
Familial synchronous bilateral teratoid Wilms tumor with elevated alpha-fetoprotein level.
Tumori. 2012; 98(6):179e-82e [PubMed]
Familial Wilms tumor is a rare entity that accounts for only 1-2% of all Wilms tumor cases, with an earlier age of onset and an increased frequency of bilateral tumors. Teratoid Wilms tumor is a variant of nephroblastoma with a predominance of heterologous tissues comprising more than 50% of the tumor volume. Wilms tumor does not usually secrete any specific tumor marker and all teratoid Wilms tumor cases previously reported were sporadic non-secreting neoplasms. Here we describe an infant with familial synchronous bilateral teratoid Wilms tumor whose serum alpha-fetoprotein level was elevated. To our knowledge, this extremely rare type of case is reported for the first time in the literature.


Pichler M, Hutterer GC, Stoeckigt C, et al.
Validation of the pre-treatment neutrophil-lymphocyte ratio as a prognostic factor in a large European cohort of renal cell carcinoma patients.
Br J Cancer. 2013; 108(4):901-7 [PubMed] Article available free on PMC after 05/03/2014
BACKGROUND: The neutrophil-lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response. Several studies suggest a negative impact of increased NLR for patient's survival in different types of cancer. However, previous findings from small-scale studies revealed conflicting results about its prognostic significance with regard to different clinical end points in non-metastatic renal cell carcinoma (RCC) patients. Therefore, the aim of our study was the validation of the prognostic significance of NLR in a large cohort of RCC patients.
METHODS: Data from 678 consecutive non-metastatic clear cell RCC patients, operated between 2000 and 2010 at a single centre, were evaluated retrospectively. Cancer-specific, metastasis-free, as well as overall survival (OS) were assessed using the Kaplan-Meier method. To evaluate the independent prognostic significance of NLR, multivariate Cox regression models were applied for all three different end points. Influence of the NLR on the predictive accuracy of the Leibovich prognosis score was determined by Harrell's concordance index.
RESULTS: Multivariate analysis identified increased NLR as an independent prognostic factor for overall (hazard ratio (HR)=1.59, 95% confidence interval (CI)=1.10-2.31, P=0.014), but not for cancer-specific (HR=1.59, 95% CI=0.84-2.99, P=0.148), nor for metastasis-free survival (HR=1.39, 95% CI=0.85-2.28, P=0.184). The estimated concordance index was 0.79 using the Leibovich risk score and 0.81 when NLR was added.
CONCLUSION: Regarding patients' OS, an increased NLR represented an independent risk factor, which might reflect a higher risk for severe cardiovascular and other comorbidities. Adding the NLR to well-established prognostic models such as the Leibovich prognosis score might improve their predictive ability.


Ehrlich PF, Anderson JR, Ritchey ML, et al.
Clinicopathologic findings predictive of relapse in children with stage III favorable-histology Wilms tumor.
J Clin Oncol. 2013; 31(9):1196-201 [PubMed] Article available free on PMC after 20/03/2014
PURPOSE: Stage III designation in NWTS-5 (National Wilms Tumor Study-5) was determined by four pathologic criteria: positive lymph nodes (LNs), peritoneal implants, residual disease, and tumor rupture. The objective of this study was to determine the prognostic significance of each of the stage III criteria.
PATIENTS AND METHODS: Children with stage III Wilms tumor (WT) treated in NWTS-5 were assessed for event-free (EFS) and overall survival (OS). Sites of relapse and molecular status of tumors are reported. EFS and OS are reported 8 years after diagnosis.
RESULTS: There were 569 patients with local stage III favorable-histology (FH) WT in this analysis, of whom 109 had overall stage IV disease. LN involvement alone was the most frequent criterion for stage III designation (38%), followed by microscopic residual disease alone (20%), microscopic residual disease and LN involvement (14%), and spill or soilage alone (9%). The 8-year EFS and OS estimates for all patients with local stage III FHWT were 82% and 91%, respectively. Multivariate analysis demonstrated that both LN involvement (relative risk, 1.89; P = .005) and microscopic residual disease (relative risk, 1.87; P = .007) were predictive of EFS, and OS results were similar. There was no apparent difference in pattern of relapse according to stage III subtype. The rate of loss of heterozygosity was higher (6%) for those with positive LNs than for those without (2%; P = .05).
CONCLUSION: LN involvement and microscopic residual are the stage III criteria highly predictive of EFS and OS for patients with stage III FHWT. It is possible that in future studies, patients with different stage III criteria may receive different therapies.


O'Mahony FC, Nanda J, Laird A, et al.
The use of reverse phase protein arrays (RPPA) to explore protein expression variation within individual renal cell cancers.
J Vis Exp. 2013; (71) [PubMed]
Currently there is no curative treatment for metastatic clear cell renal cell cancer, the commonest variant of the disease. A key factor in this treatment resistance is thought to be the molecular complexity of the disease. Targeted therapy such as the tyrosine kinase inhibitor (TKI)-sunitinib have been utilized, but only 40% of patients will respond, with the overwhelming majority of these patients relapsing within 1 year. As such the question of intrinsic and acquired resistance in renal cell cancer patients is highly relevant. In order to study resistance to TKIs, with the ultimate goal of developing effective, personalized treatments, sequential tissue after a specific period of targeted therapy is required, an approach which had proved successful in chronic myeloid leukaemia. However the application of such a strategy in renal cell carcinoma is complicated by the high level of both inter- and intratumoral heterogeneity, which is a feature of renal cell carcinoma as well as other solid tumors. Intertumoral heterogeneity due to transcriptomic and genetic differences is well established even in patients with similar presentation, stage and grade of tumor. In addition it is clear that there is great morphological (intratumoral) heterogeneity in RCC, which is likely to represent even greater molecular heterogeneity. Detailed mapping and categorization of RCC tumors by combined morphological analysis and Fuhrman grading allows the selection of representative areas for proteomic analysis. Protein based analysis of RCC is attractive due to its widespread availability in pathology laboratories; however, its application can be problematic due to the limited availability of specific antibodies. Due to the dot blot nature of the Reverse Phase Protein Arrays (RPPA), antibody specificity must be pre-validated; as such strict quality control of antibodies used is of paramount importance. Despite this limitation the dot blot format does allow assay miniaturization, allowing for the printing of hundreds of samples onto a single nitrocellulose slide. Printed slides can then be analyzed in a similar fashion to Western analysis with the use of target specific primary antibodies and fluorescently labelled secondary antibodies, allowing for multiplexing. Differential protein expression across all the samples on a slide can then be analyzed simultaneously by comparing the relative level of fluorescence in a more cost-effective and high-throughput manner.


Shu X, Lin J, Wood CG, et al.
Energy balance, polymorphisms in the mTOR pathway, and renal cell carcinoma risk.
J Natl Cancer Inst. 2013; 105(6):424-32 [PubMed] Article available free on PMC after 20/03/2014
BACKGROUND: The interplay between obesity, physical activity, weight gain, and genetic variants in the mTOR pathway has not been studied in renal cell carcinoma (RCC). We examined the associations between obesity, weight gain, physical activity, and RCC risk. We also analyzed whether genetic variants in the mTOR pathway could modify the association.
METHODS: Incident RCC case subjects and healthy control subjects were recruited from the University of Texas MD Anderson Cancer Center in Houston, Texas. Case subjects and control subjects were frequency matched. Epidemiologic data were collected by in-person interview. One hundred ninety single nucleotide polymorphisms (SNPs) from 22 genes in the mTOR pathway were extracted from previous genome-wide association studies. Logistic regression and regression spline were performed to obtain odds ratios (ORs). All statistical tests were two-sided.
RESULTS: A total of 577 non-Hispanic white case subjects and 593 healthy control subjects were included. Obesity at age 20 years (OR = 1.92, 95% confidence interval [CI] = 1.05 to 3.50; P = .03) and age 40 years (OR = 2.03, 95% CI = 1.38 to 2.98; P < .001) and moderate (OR = 1.46, 95% CI = 1.02 to 2.09; P = .04) and massive weight gain (OR = 1.62, 95% CI = 1.10 to 2.39; P = .01) from age 20 to 40 years were each statistically significantly associated with increased RCC risk. Low physical activity was associated with a 4.08-fold increased risk. Among 190 SNPs in the mTOR pathway, six SNPs located in the AKT3 gene were statistically significantly associated with increased risk, and those with three or more unfavorable genotypes had a 1.72-fold increased risk of RCC.
CONCLUSION: Obesity, weight gain, physical activity, and genetic variants in the mTOR pathway may individually and jointly influence susceptibility to RCC.


Emerling BM, Benes CH, Poulogiannis G, et al.
Identification of CDCP1 as a hypoxia-inducible factor 2α (HIF-2α) target gene that is associated with survival in clear cell renal cell carcinoma patients.
Proc Natl Acad Sci U S A. 2013; 110(9):3483-8 [PubMed] Article available free on PMC after 26/08/2013
CUB domain-containing protein 1 (CDCP1) is a transmembrane protein that is highly expressed in stem cells and frequently overexpressed and tyrosine-phosphorylated in cancer. CDCP1 promotes cancer cell metastasis. However, the mechanisms that regulate CDCP1 are not well-defined. Here we show that hypoxia induces CDCP1 expression and tyrosine phosphorylation in hypoxia-inducible factor (HIF)-2α-, but not HIF-1α-, dependent fashion. shRNA knockdown of CDCP1 impairs cancer cell migration under hypoxic conditions, whereas overexpression of HIF-2α promotes the growth of tumor xenografts in association with enhanced CDCP1 expression and tyrosine phosphorylation. Immunohistochemistry analysis of tissue microarray samples from tumors of patients with clear cell renal cell carcinoma shows that increased CDCP1 expression correlates with decreased overall survival. Together, these data support a critical role for CDCP1 as a unique HIF-2α target gene involved in the regulation of cancer metastasis, and suggest that CDCP1 is a biomarker and potential therapeutic target for metastatic cancers.


Rowe RG, Thomas DG, Schuetze SM, et al.
Ewing sarcoma of the kidney: case series and literature review of an often overlooked entity in the diagnosis of primary renal tumors.
Urology. 2013; 81(2):347-53 [PubMed]
OBJECTIVE: To evaluate our own experience with primary Ewing sarcoma family tumors (ESFTs) of the kidney and to review cases of this in published reports.
MATERIALS AND METHODS: Institutional cases of renal ESFT were identified in our pathology database. The retrieved records were reviewed for relevant data. Published cases of renal ESFTs were identified from the National Library of Medicine Medline database and restricted to English language studies. The factors associated with initial surgical management (diagnostic biopsy vs surgical resection) were analyzed using chi-square analysis.
RESULTS: We diagnosed and treated 10 cases of renal ESFT from 2002 to 2011 and identified an additional 97 published cases describing this tumor. A review of these 107 cases revealed that renal ESFTs more often presented with distant metastases than did ESFTs of the bone or soft tissue. Moreover, patients rarely received preoperative (neoadjuvant) chemotherapy, the current standard of care for ESFT, often because of early total tumor resection without diagnostic biopsy. Younger patients and patients with distant metastases were more likely to undergo diagnostic biopsy as initial management (P <.0001), allowing for use of neoadjuvant chemotherapy.
CONCLUSION: ESFTs of the kidney should be considered in the differential diagnosis of renal masses. Preoperative biopsy should be considered to identify these tumors to allow for delivery of neoadjuvant chemotherapy.


O'Hara JF, Mahboobi R, Novak SM, et al.
Fenoldopam and renal function after partial nephrectomy in a solitary kidney: a randomized, blinded trial.
Urology. 2013; 81(2):340-5 [PubMed]
OBJECTIVE: To test the hypothesis that fenoldopam administration ameliorates ischemic injury, preserving the glomerular filtration rate and serum creatinine postoperatively after partial nephrectomy in patients with a solitary kidney.
MATERIALS AND METHODS: Fenoldopam is a short-acting dopamine-1 receptor agonist that might provide renal protection during ischemic stress. A total of 90 patients with a solitary functioning kidney who were undergoing partial nephrectomy were randomized to fenoldopam or placebo in a double-blind protocol. The patients assigned to fenoldopam received an infusion rate of 0.1 μg/kg/min for 24 hours. The effect of fenoldopam on renal function was assessed by comparing the groups on the change in glomerular filtration rate from baseline to the third postoperative day (primary outcome) and on the change in serum creatinine over time (secondary outcome).
RESULTS: Of the 90 enrolled patients, 77 provided analyzable data (43 in fenoldopam and 44 in placebo group). Fenoldopam (vs placebo) did not reduce the mean percentage of change in the glomerular filtration rate from baseline to the third postoperative day (P = .15), with an estimated ratio of means of 0.89 (95% confidence interval 0.69-1.09) for fenoldopam vs placebo. The postoperative serum creatinine in the 2 groups changed at comparable rates from postoperative day 1 to 4 (group-by-time interaction, P = .72) after adjusting for baseline creatinine, with no difference in the mean serum creatinine over time (P = .78).
CONCLUSION: Fenoldopam administration did not preserve renal function in the clinical setting of renal ischemia during solitary partial nephrectomy, as evidenced by changes in the glomerular filtration rate or serum creatinine.


Xu B, Zhang Q, Jin J
Laparoscopic aspiration for central renal angiomyolipoma: a novel technique based on single-center initial experience.
Urology. 2013; 81(2):313-8 [PubMed]
OBJECTIVE: To report on the novel technique of laparoscopic aspiration for central renal angiomyolipoma (RAML) in a series of patients treated in our institution and summarize our single-center initial experience.
METHODS: We retrospectively reviewed the clinical data of 10 patients (4 men and 6 women) with pathologically confirmed central RAML who underwent laparoscopic aspiration between August 2010 and May 2012. Indications for surgical intervention included 8 (80%) tumors of >4 cm and 2 (20%) symptomatic RAMLs. Patient demographics, intraoperative variables, and postoperative outcomes were reported and analyzed. Follow-up was performed by serum creatinine and imaging techniques.
RESULTS: All patients were diagnosed with sporadic central RAML. None was affected by tuberous sclerosis. All operations were performed successfully by laparoscopic aspiration without conversion to partial nephrectomy, enucleation, or even open surgery. One complication of perirenal fluid collection occurred but finally recovered only with conservative treatment. No other complication or transfusion was observed. The mean tumor size was 5.1 cm (range 3.2-7.7 cm). The mean operative time was 92.1 minutes (range 67-140). The mean warm ischemia time was 27.5 minutes (range 20-30). The mean estimated blood loss was 53.5 mL (range 10-150). The mean retroperitoneal drainage was 2.3 days (range 1-3). The mean postoperative hospital stay was 4.3 days (range 3-8). The level of serum creatinine were all within normal limits with mean preoperative and postoperative 0.85 mg/dL (range 0.55-1.07) and 1.11 mg/dL (range 0.71-1.26), respectively. No recurrence or new lesions occurred in these patients at a mean follow-up of 7.7 months.
CONCLUSION: Our initial experience suggests that the novel technique of laparoscopic aspiration is a feasible, safe, and effective minimally invasive procedure for the treatment of RAML, especially the central RAML. It can be a nephron-sparing alternative and recommended in well-selected patients that might prove to be safer, with equal efficacy, and should be further explored.


Abaza R, Shah K
A single overnight stay is possible for most patients undergoing robotic partial nephrectomy.
Urology. 2013; 81(2):301-6 [PubMed]
OBJECTIVE: To evaluate establishment of overnight stay only as sufficient after robotic partial nephrectomy (RPN).
METHODS: Stated benefits of minimally invasive surgery include reduced hospitalization, but published hospital stays after laparoscopic or robotic partial nephrectomy are not significantly less than with open surgery. We developed a clinical pathway targeting discharge on postoperative day (POD) 1 after RPN of any complexity. We reviewed all RPNs by a single surgeon since instituting our clinical pathway, including ambulation and diet the night of surgery, avoidance of intravenous narcotics and drains, and catheter removal on POD 1 before discharge. Targeted discharge was not modified regardless of RPN complexity.
RESULTS: A total of 150 consecutive patients underwent 160 RPNs with 35 hilar tumors and 26 with segmental, and 33 with no artery clamping. Three had solitary kidneys, and 8 underwent multiple (range, 2-4) RPNs. Mean patient age was 57 years (range, 22-89 years), and body mass index was 32 kg/m(2) (range, 18-54 kg/m(2)). Mean tumor size was 3.6 cm (range, 1.0-11.0; median, 3.2 cm), and the RENAL (radius, exophytic/endophytic, nearness to collecting system, anterior/posterior, and location) nephrometry score was 8 (range, 4-12; median, 8). Mean warm ischemia time was 12.1 minutes (range, 0-30.0 minutes). Mean preoperative and discharge creatinine were 0.9 mg/dL (range, 0.43-2.79 mg/dL) and 1.13 mg/dL (range, 0.56-2.93 mg/dL). All patients ambulated on POD 0. One patient required one dose of intravenous narcotic. Mean length of stay was 1.1 days, with 145 (97%) discharged on POD 1, of which only 4 (2.7%) were readmitted within 30 days.
CONCLUSION: Discharge on POD 1 is feasible in most RPN patients regardless of complexity. Readmission rate was low, indicating that longer admissions may not prevent complications when patients meeting discharge criteria go home on POD 1.


Smaldone MC, Churukanti G, Simhan J, et al.
Clinical characteristics associated with treatment type for localized renal tumors: implications for practice pattern assessment.
Urology. 2013; 81(2):269-75 [PubMed]
OBJECTIVE: To determine the associations between the pretreatment characteristics and treatment selection in patients presenting with clinical stage I renal masses.
MATERIALS AND METHODS: Using institutional data, patients presenting with clinical stage I (≤ 7 cm) renal tumors that were managed with active surveillance (AS), tumor ablation (ABL), partial nephrectomy (PN), or radical nephrectomy (RN) from 2005 to 2011 were identified. The associations between the pretreatment characteristics and the selected treatment strategy were assessed using multinomial regression models, with RN as the reference group.
RESULTS: A total of 969 patients (mean age 61.9 ± 12.8 years) with 1034 clinical stage I lesions (mean tumor size 3.3 ± 1.5 cm) met the inclusion criteria. The patients were initially treated with RN (29.4%), PN (38.8%), ABL (6.1%), and AS (25.7%). Traditionally captured covariates, including older age (PN, odds ratio [OR] 0.96, 95% confidence interval [CI] 0.94-0.99]) and decreasing tumor size (PN, OR 0.2, 95% CI 0.1-0.4; ABL, OR 0.01, 95% CI 0.0-0.1; AS, OR 0.2, 95% CI 0.1-0.3) were associated with alternative treatment types compared with RN. However, the characteristics associated with treatment type that are not included in traditional registry or administrative data included the presence of a solitary kidney (PN, OR 11.9, 95% CI 2.9-48.9; ABL, OR 15.5, 95% CI 2.5-98.1; AS, OR 7.1, 95% CI 1.3-39.3) and high complexity nephrectomy score (PN, OR 0.1, 95% CI 0.1-0.3; ABL, OR 0.1, 95% CI 0.0-0.6; AS, OR 0.1, 95% CI 0.03-0.3).
CONCLUSION: Pretreatment characteristics associated with treatment type in our series, including the presence of a solitary kidney and anatomic complexity, are poorly captured using administrative and registry data. Observational studies investigating the variations in practice patterns for stage I renal masses require improved integration of clinical and tumor characteristics to reduce selection biases.


Kryvenko ON, Roquero L, Gupta NS, et al.
Low-grade clear cell renal cell carcinoma mimicking hemangioma of the kidney: a series of 4 cases.
Arch Pathol Lab Med. 2013; 137(2):251-4 [PubMed]
CONTEXT: Clear cell renal cell carcinoma (CCRCC) has a rich, sinusoid-like vascularity frequently used as a diagnostic criterion. CCRCC with predominantly vascular architecture has not been described.
OBJECTIVE: To describe 4 unusual CCRCC cases, primarily presenting with hemangioma-like morphologic pattern.
DESIGN: Clinicopathologic and selected immunohistochemical analysis of 4 cases of CCRCC mimicking hemangioma.
RESULTS: Cases were seen in 1 woman and 3 men (average age, 48.8 years; range, 40-66 years). Grossly, tumors were red-brown (3 of 4) with scant bright-yellow foci in 1. The average tumor size was 4 cm (range, 2.5-5.5 cm). Microscopically, all were composed of varying proportions of a rich, arborizing, sinusoid-like vasculature with focal hobnail appearance of endothelial cells. Entrapment of renal tubules between blood vessels was seen at the periphery of the tumors. This morphology was reminiscent of anastomosing hemangioma. Isolated tumor cells resembling lymphocytes with clear halos were sparsely interspersed between vessels. Cytokeratin immunostain confirmed the diagnosis of CCRCC.
CONCLUSION: Extensive sampling and immunohistochemical workup of what is deemed to be a benign vascular neoplasm of the kidney is needed to rule out the presence of individual carcinoma cells or small viable carcinoma cell clusters.


Javaid MM, Chowdhury S, Henderson A, Olsburgh J
Advanced native kidney renal cell carcinoma in renal transplant recipients: role of sirolimus as dual anti-cancer and anti-rejection agent.
Clin Nephrol. 2013; 79(2):154-60 [PubMed]
The incidence of native kidney renal cell carcinoma (RCC) in renal transplant recipients is 15 times higher than the general population. These tumors are often found incidentally when imaging is performed for another indication. At that stage tumors are usually small and asymptomatic but it is possible that they may escape detection until a more advanced stage. Early stage RCC can be treated with radical nephrectomy but the treatment of advanced RCC may be more complicated and is associated with a poorer prognosis. RCC in context of renal transplant presents a special therapeutic challenge; balancing treatment of a potentially lethal malignancy in a redundant organ whilst maintaining good allograft function.We describe 2 cases of advanced renal cell carcinoma of native kidneys in renal transplant recipients and present our experience with sirolimus as a dual immunosuppressive and anti-tumor agent.


Jain D, Chopra P
Metastatic renal cell carcinoma of gall bladder.
Saudi J Kidney Dis Transpl. 2013; 24(1):100-4 [PubMed]
Renal cell carcinoma (RCC) is well known for its propensity to metastasize to unusual sites. Metastasis to the gall bladder (GB) has been reported in the literature rarely. We herein report an interesting case of metastatic RCC, which presented with cholecystitis. Gall bladder is a rare site of metastasis of RCC. Polypoid lesions of the GB in patients who have a synchronous or a prior history of RCC should be considered as metastatic lesions. It needs to be differentiated from primary clear cell carcinoma of the GB with the help of immunohistochemistry.


Liu Xl, Zhou Jj, Zeng MS, et al.
Homogeneous high attenuation renal cysts and solid masses--differentiation with single phase dual energy computed tomography.
Clin Radiol. 2013; 68(4):e198-205 [PubMed]
AIM: To assess the feasibility of using single-phase dual-energy computed tomography (DECT) to differentiate between homogeneous high attenuation renal cysts and solid renal masses.
MATERIALS AND METHODS: Twenty-nine pathologically proven solid renal masses in 29 patients and 14 high attenuation renal cysts from 11 patients were evaluated retrospectively. Two readers independently measured CT values from each lesion using both unenhanced single-energy phase and nephrographic dual-energy phase scans. Enhancement was defined as the attenuation difference between average-weighted 120 kV images and unenhanced images. Diagnostic sensitivity, specificity and accuracy based on enhancement, D-value (CT: 80 kV-140 kV) and DE-ratio (CT: 80/140 kV) were compared by the receiver operator characteristic (ROC) curves.
RESULTS: Using 17.6 HU as the cutoff value for enhancement, resulted in a sensitivity, specificity and accuracy of 96.6%, 100% and 97.7%, respectively. Corresponding values were 100%, 92.9% and 97.7% using a D-value cutoff of 15.6 HU, and 100%, 85.7% and 95.3% using a DE-ratio cutoff of 1.3. There were no significant differences in the AUCs obtained from the ROC curves for enhancement, D-value or DE-ratio. The mean effective radiation dose was 6.04 mSv with biphasic scanning compared with 2.91 mSv for single dual-energy nephrographic phase scanning.
CONCLUSION: Single-phase dual-energy CT is able to differentiate high attenuation renal cysts and solid renal masses with high sensitivity, specificity and accuracy, based on either D-value or DE-ratio. Omitting unenhanced scanning reduces the radiation dose by more than 50%.


This page last updated: 15th May 2013
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