Morbidity and clinical outcome of nephron-sparing surgery in relation to tumour size and indication

OBJECTIVE: To analyse through a large multicentre series, morbidity of nephron-sparing surgery (NSS) in relation to tumour size and surgical indication. METHODS: The study included patients from eight international academic centres. Age, sex, TNM stage, tumour size, Fuhrman grade, Eastern Cooperative Oncology Group performance status (ECOG-PS), surgical margins, local and distant recurrences, and overall and cancer-specific survival rates were collected and analysed. Indication for elective or mandatory NSS, medical and surgical complication rates, mean blood loss, blood transfusion, and length of hospital stay were specifically recorded for the purpose of this study. Groups were compared for qualitative and quantitative variables by using chi(2) (Fischer exact test) and Student t tests, respectively. RESULTS: A total of 1048 NSS procedures were included in this study. Mean tumour size was 3.4+/-2.1cm. In 730 elective procedures mean operative time (p=0.002), mean blood loss (p=0.01), the need for blood transfusion (p=0.001), and urinary fistula rate (p=0.01) were significantly increased for tumours >4 cm. However, these differences did not result in significantly increased medical (p=0.4), surgical complication rates (p=0.6), or length of hospital stay (p=0.9). Finally, in elective procedures for malignant tumours, positive surgical margins, local or distant recurrence rates, and cancer-specific survival were not significantly different in tumours < or =4 cm and >4 cm. CONCLUSION: Excellent cancer control and outcomes can be achieved with NSS in carefully selected patients with tumours >4 cm. Expanding the size indication of elective NSS results in an increased but acceptable morbidity.     

LABAZ1: A metastatic tumor model for renal cell carcinoma expressing the carbonic anhydrase type 9 tumor antigen

A metastatic renal cell carcinoma (RCC) tumor model xenograft that expresses the targetable, membrane-bound tumor-associated antigen carbonic anhydrase type 9 (CA IX) is described. The xenograft, established from a high-grade type-2 chromophil RCC (cRCC), has been serially transplanted in immune compromised mice, in which it grows orthotopically under the renal capsule, doubling its size every 9 weeks and sending metastases to the lung and liver at approximately 20 weeks. Tumors were capable of being imaged using a micro-PET (micro-positron emission tomograph) with an 18-fluorodeoxyglucose (18-FDG) tracer. Subsequent xenograft generations have conserved immunohistochemical and ultrastructural properties typical for malignant renal epithelium-derived neoplasia (vimentin+, CK-19+, CA IX+ with hypoxia-inducible factor (HIF)-1 alpha constitutive expression) and have demonstrated extensive proliferation, lack of apoptosis, severe genetic alterations, and molecular expression alterations; transforming growth factor beta 1 (TGF-beta 1), hepatocyte growth factor (HGF), proto-oncogene (c-met), matrix metalloproteinase (MMP)-1, and vascular endothelial growth factor (VEGF) C and D were overexpressed, whereas human epidermal growth factor receptor (HER)-2, MMP-2 and MMP-9, VEGF-R3, p53, and p27 were severely down-regulated, suggesting a proangiogenic environment, local invasiveness, and facilitated lymphatic metastasis. Altogether, LABAZ1 provides a relevant and flexible model to study the biology of cRCC, the role of CA IX in RCC tumorigenesis, progression, and metastasis, and a platform for testing new targeted therapeutic strategies.     

Intermittent androgen deprivation therapy: schedule modifications based on a novel in vivo human xenograft model

In most clinical trials of intermittent androgen deprivation (IAD), the decision to stop androgen withdrawal is based on monitoring PSA levels, waiting for its drop to nadir. Based on in vitro pre-clinical studies, a modified 'on-off' schedule of short intervals of androgen deprivation, designated pulsed androgen deprivation (PAD), is proposed to destroy androgen dependent (AD) cells more gradually and to conserve their androgen-independent (AI) inhibitory potential for longer periods, resulting in an overall prolongation of time to hormone resistant progression.Prostate Cancer and Prostatic Diseases (2000) 3, 280-282     

Angiographic management of pseudoaneurysm and arteriocalyceal fistula following blunt trauma: case report and review of the literature

We report a case of blunt trauma causing both a pseudoaneurysm and an arteriocalyceal fistula. These 2 lesions have not previously been reported occurring simultaneously as a complication of renal trauma. Pathophysiology, clinical presentation, and management options are discussed. Angiography in this case was both diagnostic and therapeutic. Selective and superselective gelfoam embolization led to immediate resolution of both injuries.     

Association between renal mass biopsy and upstaging to perinephric fat involvement in a contemporary cohort of patients with clinical T1a renal cell carcinoma

Background

Although tumor tract seeding from renal mass biopsy (RMB) is exceedingly rare, the possibility of tumor capsule violation from RMB leading to perinephric fat invasion has not been quantified. We evaluated the association between RMB and perinephric fat invasion in patients with clinical T1a renal cell carcinoma who underwent partial or radical nephrectomy.

Clinicopathological features and prognosis of synchronous bilateral renal cell carcinoma: an international multicentre experience

OBJECTIVE: To present a multicentre experience and the largest cohort to date of nonmetastatic (N0M0) synchronous bilateral renal cell carcinoma (RCC), as because it is rare the single-institutional experience is limited. PATIENTS AND METHODS: We retrospectively studied 10 337 patients from 12 urological centres to identify patients with N0M0 synchronous bilateral RCC; the clinicopathological features and cancer-specific survival were compared to a cohort treated for N0M0 unilateral RCC. RESULTS: In all, 153 patients had synchronous bilateral solid renal tumours, of whom 135 (88%) had synchronous bilateral RCC, 118 with nonmetastatic disease; 91% had nonfamilial bilateral RCC. Bilateral clear cell RCC was the major histological subtype (76%), and papillary RCC was the next most frequent (19%). Multifocality was found in 54% of bilateral RCCs. Compared with unilateral RCC, patients did not differ in Eastern Cooperative Oncology Group performance status (ECOG PS) and T classification, but bilateral RCCs were more frequently multifocal (54% vs 16%, P < 0.001) and of the papillary subtype (19% vs 12%), and less frequently clear cell RCC (76% vs 83%, P = 0.005). For the outcome, patients with nonmetastatic synchronous bilateral RCC and unilateral RCC had a similar prognosis (P = 0.63); multifocality did not affect survival (P = 0.60). Multivariate analysis identified ECOG PS, T classification, and Fuhrman grade, but not laterality, as independent prognostic factors for cancer-specific survival. CONCLUSIONS: Patients with N0M0 synchronous bilateral RCC and N0M0 unilateral RCC have a similar prognosis. The frequency of a familial history for RCC (von Hippel-Lindau disease or familial RCC) was significantly greater in bilateral synchronous than in unilateral RCC. The significant pathological findings in synchronous bilateral RCC are papillary subtype and multifocality.     

Unclassified renal cell carcinoma: an analysis of 85 cases

OBJECTIVES: To compare cancer-specific mortality in patients with unclassified renal cell carcinoma (URCC) vs clear cell RCC (CRCC) after nephrectomy, as URCC is a rare but very aggressive histological subtype. PATIENTS AND METHODS: Eighty-five patients with URCC and 4322 with CRCC were identified within 6530 patients treated with either radical or partial nephrectomy at 18 institutions. Of 85 patients with URCC, 55 were matched with 166 of 4322 for grade, tumour size, and Tumour, Node and Metastasis stages. Kaplan-Meier and life-table analyses were used to address RCC-specific survival. Subsequently, multivariate Cox regression analyses were used to test for differences in RCC-specific survival in unmatched samples. RESULTS: Of patients with URCC, 80% had Fuhrman grades III or IV, vs 37.8% for CRCC. Moreover, 36.5% of patients with URCC had pathologically confirmed nodal metastases, vs 8.6% with CRCC. Finally, 54.1% of patients with URCC had distant metastases at the time of nephrectomy, vs 16.8% with CRCC. Despite these differences in the overall analyses, after matching for tumour characteristics, the URCC-specific mortality rate was 1.6 times higher (P = 0.04) in matched analyses and 1.7 times higher (P = 0.001) in multivariate analyses. CONCLUSIONS: These findings indicate that URCC presents with a higher stage and grade, and even after controlling for the stage and grade differences, predisposes patients to 1.6-1.7 times the mortality of CRCC.     

Metastatic melanoma to the kidney presenting with renal vein tumor thrombus

We report on a patient with metastatic melanoma to the kidney who presented with a renal vein thrombus to the inferior vena cava. Three years after his initial lesion of the scalp, a 34-year-old Egyptian man was found to have two brain metastases and an 11-cm left renal metastasis with a tumor thrombus in the renal vein. After resection of the brain metastases, with no evidence of additional metastases, the patient underwent left radical nephrectomy and tumor venous thrombectomy. The patient later had tumor recurrence at multiple sites. He did not respond to systemic treatment and died 5 months later.     

Immunotherapy of prostate cancer

The realization that prostate cancer is an immunogenic tumor, in conjunction with the discovery of novel methods for priming the immune system to generate an antitumor response, has resulted in several new approaches for prostate cancer immunotherapy. Based on these various approaches, several human clinical trials have begun using immune-based therapies for prostate cancer. These approaches can be divided into cytokine-based therapies, tumor-associated antigen-based therapies, tumor vaccines, and dendritic cell-based therapies. This review summarizes the latest findings from each of these approaches and gives results from the few completed human clinical trials.