Renal cell carcinoma in the Canadian Indigenous population.

Background: Diagnosis and treatment of renal cell carcinoma (rcc) might be different in Indigenous Canadians than in non-Indigenous Canadians. In this cohort study, we compared rcc presentation and treatments in Indigenous and non-Indigenous Canadians. Methods: Patients registered in the Canadian Kidney Cancer Information System treated at 16 institutions between 2011 and 2018 were included. Baseline patient, tumour, and treatment characteristics were compared between Indigenous and non-Indigenous Canadians. The primary objective was to determine if differences in rcc stage at diagnosis were evident between the groups. The secondary objective was to determine if treatments and outcomes were different between the groups. Results: During the study period, 105 of the 4529 registered patients self-identified as Indigenous. Those patients were significantly younger at the time of clinical diagnosis (57.9 ± 11.3 years vs. 62.0 ± 12.1 years, p = 0.0006) and had a family history prevalence of rcc that was double the prevalence in the non-Indigenous patients (14% vs. 7%, p = 0.004). Clinical stage at diagnosis was similar in the two groups (p = 0.61). The disease was metastatic at presentation in 11 Indigenous Canadians (10%) and in 355 non-Indigenous Canadians (8%). Comorbid conditions that could affect the management of rcc-such as obesity, renal disease, diabetes mellitus, and smoking-were more common in Indigenous Canadians (p < 0.05). Indigenous Canadians experienced a lower rate of active surveillance (p = 0.01). Treatments and median time to treatments were similar in the two groups. Conclusions: Compared with their non-Indigenous counterparts, Indigenous Canadian patients with rcc are diagnosed at an earlier age and at a similar clinical stage. Despite higher baseline comorbid conditions, clinical outcomes are not worse for Indigenous Canadians than for non-Indigenous Canadians.

Fundamental mode operation of a ribbon fiber laser by way of volume Bragg gratings.

Selection of the fundamental mode of an active large mode area "ribbon" fiber laser with core dimensions of 107.8 µm by 8.3 µm was produced by a transmitting Bragg grating (TBG) in a free-space resonator. The multimode performance of the original laser was characterized to have an M2 of 11.3 with an absorbed power slope efficiency of 76%. With the TBG aligned to provide maximum diffraction efficiency for the fundamental mode, the M2 improved to 1.45 at an absorbed power slope efficiency of 54% and enhanced the brightness by 5.1 times.

An open-label, phase 2 trial of bicalutamide dose escalation from 50 mg to 150 mg in men with CAB and castration resistance. A Canadian Urology Research Consortium Study.

BACKGROUND: Bicalutamide is a widely used, relatively non-toxic anti-androgen, particularly when used in combination with androgen deprivation. In men on combined androgen blockade (CAB), the typical dose is 50 mg per day. For men receiving monotherapy with bicalutamide anti-androgen, the dose is 150 mg per day. The objective was to determine the PSA response rate to increasing bicalutamide to 150 mg per day in men who develop castrate-resistant prostate cancer (CRPC) on CAB with goserelin acetate and bicalutamide 50 mg per day. METHODS: A national, multicentre, phase 2, open-label study in men on CAB with a rising PSA>2.0. The primary end point of the trial was PSA response at 12 months, defined as a decline by 50% or more compared with baseline value. Partial response was defined as a PSA decline of 10-49%. Secondary end points were duration of PSA response, change in slope of serum PSA, change in ratio of free PSA: total PSA at 3 months, 6 months and 12 months as compared with baseline; duration of the bicalutamide withdrawal response after discontinuation; the rate of cardiovascular events; and toxicity. The study was initially planned to accrue 100 patients, but was closed early due to diminishing accrual. RESULTS: Sixty-four patients were accrued; 61 patients received trial treatment and constituted the intention-to-treat (ITT) cohort. 70% were M0. Among 59 evaluable ITT patients, 13 (22%) patients had a >50% PSA decline, 5 (8%) had a decline between 10 and 50%, 4 (7%) had stabilization and 37 (63%) had PSA progression. The median duration was 3.7 months (95% confidence interval of 0.92-6.21 months). CONCLUSION: In patients with early biochemical failure on CAB with bicalutamide 50 mg, an increase in dose to 150 mg of bicalutamide resulted in a PSA response of ⩾ 50% in 22% of patients. Toxicity was mild. Bicalutamide dose intensification may benefit a subset of patients with CRPC. We believe this relatively inexpensive approach warrants further evaluation.

Automatic conformal prescription of very selective saturation bands for in vivo 1H-MRSI of the prostate.

An important step in the implementation of three-dimensional in vivo proton magnetic resonance spectroscopic imaging ((1)H-MRSI) of the prostate is the placement of spatial saturation pulses around the region of interest (ROI) for the removal of unwanted contaminating signals from peripheral tissue. The present study demonstrates the use of a technique called conformal voxel magnetic resonance spectroscopy (CV-MRS). This method automates the placement, orientation, timing and flip angle of very selective saturation (VSS) pulses around an irregularly-shaped, user-defined ROI. The method employs a user adjustable number of automatically positioned VSS pulses (20 used in the present study) which null the signal from periprostatic lipids while closely conforming the shape of the excitation voxel to the shape of the prostate. A standard endorectal coil in combination with a torso-phased array coil was used for all in vivo prostate studies. Three-dimensional in vivo prostate (1)H-MRSI data were obtained using the proposed semi-automated CV-MRS technique, and compared with a standard point resolved spectroscopy (PRESS) technique at TE = 130 ms using manual placement of saturation pulses. The in vivo prostate (1)H-MRSI data collected from 12 healthy subjects using the CV-MRS method showed significantly reduced lipid contamination throughout the prostate, and reduced baseline distortions. On average there was a 50 ± 17% (range 12% - 68%) reduction in lipids throughout the prostate. A voxel-by-voxel benchmark test of over 850 voxels showed that there were 63% more peaks fitted using the LCModel when using a Cramer-Rao Lower Bound (CRLB) cut-off of 40% when using the optimized conformal voxel technique in comparison to the manual placement approach. The evaluation of this CV-MRS technique has demonstrated the potential for easy automation of the graphical prescription of saturation bands for use in (1)H-MRSI.

Sci-Sat AM(2): Brachy-06: A Comparison of MR/CT fusion versus CT alone for assessment of implant quality in permanent prostate brachytherapy.

Low dose-rate permanent implant brachytherapy is widely used in the management of patients with early stage prostate cancer. An assessment of the implant quality is usually carried out 30 days after the implant is delivered, using computed tomography (CT) to identify the prostate and seeds. This is difficult due to poor contrast of the prostate and the superposition of seeds in the CT images. Magnetic resonance (MR) imaging offers superior contrast but inferior visualization of seeds. At our centre, patients are imaged using both CT and T2 weighted MR 30 days after an implant, and the image sets are fused using a commercial software package. The seeds are identified on CT and the prostate volumes are contoured on MR, with fusion performed by matching seeds on CT with seed signal voids on MR. The purpose of this study was to compare standard prostate post-implant dosimetric parameters (D90, V100, etc.) for prostates contoured on CT alone (MR blinded) versus MR/CT fusion. 25 patients were evaluated with all contouring performed by the same physician. We found that the prostate volume was overestimated using CT alone as compared to MR/CT fusion (mean: 37.2cc vs. 35.0cc respectively, p = 0.033). We also found that dosimetric parameters were underestimated for CT alone compared to MR/CT fusion, including D90 (mean: 144.3Gy vs. 150.8Gy respectively, p = 0.005) and V100 (mean: 89.2% vs. 91.0% respectively, p = 0.01). Centres using CT alone for post-implant dosimetry may therefore be underestimating their implant quality.

Retroperitoneoscopic-guided radiofrequency ablation of renal tumors.

OBJECTIVE: Minimally invasive approaches to the management of renal tumors are being studied intensively in urology. Herein, we describe the use of multiple organ-sparing techniques for the management of tumors in a patient with von Hippel Lindau disease (VHL). MATERIALS AND METHODS: A 42 year-old woman with VHL underwent a right partial adrenalectomy and a left renal radiofrequency ablation (RFA) of two renal tumors. RESULTS: A 2.2 cm solitary right adrenal pheochromocytoma was resected using a transperitoneal approach. A retroperitoneal approach to the left kidney was performed and RFA of the two renal tumors completed using sonographic guidance. On the 5-month follow-up CT scan, there was no evidence of residual adrenal tumors and both renal lesions lacked contrast enhancement. No complications occurred during the post-operative recovery. CONCLUSIONS: Multiple organ-ablative laparoscopic procedures may be performed in a single sitting. Laparoscopic partial adrenalectomy is an effective technique in patients with bilateral tumors or a familial syndrome predisposing to multiple adrenal tumors. Further study of renal RFA is required to assess the long-term durability of the procedure.

Allogeneic stem cell transplantation for renal cell carcinoma.

Although the prognosis for patients with metastatic kidney cancer remains poor, a number of promising immunotherapeutic approaches for the treatment of metastatic disease have been developed over the past decade. The response of some patients to cytokines such as interleukin-2 and interferon-alpha, and more recently, vaccination with dendritic cell/tumor fusions has laid the ground work for ongoing immune-based investigational approaches. Allogeneic stem cell transplantation is a potent form of immunotherapy capable of delivering potentially curative immune-mediated anti-tumor effects against a number of different hematological malignancies. Knowledge of renal cell carcinoma's unusual susceptibility to immune attack has led to the hypothesis that tumor rejection, mediated through immunocompetent donor T-cells, might be generated against this solid tumor following the transplantation of an allogeneic immune system. Although clinical trials are early and ongoing, the recent observation of metastatic disease regression following non-myeloablative stem cell transplantation has identified renal cell carcinoma as being susceptible to a graft-versus-tumor effect. Disease responses following such therapy have ranged from partial to complete and have been observed even in patients who have failed conventional cytokine based strategies. This article reviews the design, methodology and early clinical results of studies investigating the use of allogeneic stem cell transplantation in metastatic renal cell carcinoma.

Treatment of prostate cancer: watchful waiting, radical prostatectomy, and cryoablation.

Current advances in diagnostic modalities and screening has lead to diagnosis of prostate cancer at an earlier stage (the so-called "stage shift" phenomenon), making primary treatments of localized disease of extreme importance in management. Therapeutic modalities include conservative management, radical prostatectomy, external beam radiotherapy, and newer techniques such as cryoablation surgery and brachytherapy. This review will focus on the non-radiation, non-hormonal primary treatment of localized prostate cancer and discuss the popularity and success of "watchful waiting," radical surgery, and cryoablation along with their advantages and disadvantages. These treatments will be compared to the qualities of an ideal treatment, which include cost effectiveness, efficacy, convenience of administration, tolerance by patients, low morbidity and mortality, and minimal impact on quality of life.

Circulating levels of interleukin-6 in patients with hormone refractory prostate cancer.

BACKGROUND: Interleukin-6 (IL-6) is a cytokine that plays a central role in host defense due to its wide range of immune and hematopoietic activities. It is found in high levels in human ejaculate, and has recently been found to regulate prostate-specific protein expression in prostate cancer cells through nonsteroidal activation of the androgen receptor. IL-6 may be a candidate mediator of morbidity in patients with metastatic disease. We attempted to evaluate the potential of circulating IL-6 levels as a marker of disease progression. MATERIALS AND METHODS Serum IL-6, prostate specific antigen (PSA), percent free PSA (%fPSA), and prostate-specific membrane antigen (PSMA) were measured using commercially available assays in 407 men, including 15 controls. The rest of the study population had clinical or histologic evidence of prostate diseases, including 41 patients with chronic prostatitis, 167 with benign prostatic hyperplasia (BPH), 8 with high-grade prostatic intraepithelial neoplasia (PIN), 88 with localized prostate cancer, 22 with local recurrence after treatment of primary tumor, 4 with advanced untreated disease (nodal or bony metastases), 23 with advanced hormone dependent disease, and 39 with advanced hormone refractory disease (PSA > 1.0 ng/ml while on hormone treatment and/or evidence of disease progression). None had history of concurrent malignancy or acute inflammatory condition. Kruskal-Wallis analysis of variance and Spearman's correlation analysis were used for statistical analyses. RESULTS: Serum levels of IL-6 were significantly elevated in patients with clinically evident hormone refractory disease (5.7 +/- 1.9 pg/ml) and statistical significance was seen when comparing the elevated serum IL-6 levels to those in normal controls, prostatitis, BPH, and localized and recurrent disease, (P values < 0.01). Compared to serum levels of controls and BPH, PSA was significantly elevated in advanced untreated disease and hormone refractory groups (P < 0.05). Percent fPSA was significantly lower in all cancer patients but the hormone refractory. Serum PSMA was elevated in advanced untreated prostate cancer. Serum IL-6 showed positive correlation with PSMA and negative correlation with serum PSA but did not attain statistical significance. CONCLUSIONS: Serum IL-6 levels are significantly elevated in hormone-refractory prostate cancer patients and may be a surrogate marker of the androgen independent phenotype.

Penile entrapment injury: a case report.

Penile incarceration is a rarely seen injury that requires urgent medical attention and may provide a challenge to even the most experienced emergency and urologic personnel. Described is a novel method of liberating the penis from a nonexpandable metal ring through a combination of multiple puncture wounds and manual compression after failure of other well-described techniques. Included is a treatment algorithm to guide progression of management options in difficult cases.

Ability of serum prostate-specific antigen levels to predict normal bone scans in patients with newly diagnosed prostate cancer.

OBJECTIVES: To determine whether pretreatment serum prostate-specific antigen (PSA) levels in newly diagnosed prostate cancer patients can identify a group with a low probability of osseous metastasis and safely eliminate the need for a bone scan as a routine part of the staging evaluation. METHODS: We retrospectively reviewed 683 patients with prostate cancer between 1990 and 1993. Patients with prior therapy or serum PSA levels obtained longer than 3 months prior to bone scan were excluded. Bone scans were reviewed by two nuclear medicine physicians with a third deciding equivocal cases. RESULTS: Only 6% of 490 evaluable patients had a positive bone scan on initial evaluation. Scans were positive in 0 of 290 (0%) with PSA levels below 10 micrograms/L, 4 of 88 (4.5%) with PSA levels between 10 and 20 micrograms/L, and 24 of 112 (21%) with PSA levels above 20 micrograms/L. Although the risk of a positive bone scan increased with increasing PSA levels, PSA is a poor positive predictor of positive bone scans. The risk of a positive bone scan was 8% (5 of 64 patients) when PSA was between 20 and 50 micrograms/L, and increased to 40% (19 of 48 patients) for PSA levels greater than 50 micrograms/L. In contrast, serum PSA levels below 10 micrograms/L are strong negative predictors of positive bone scans, with no positive scans in 290 patients with PSA levels below 10 micrograms/L. Although the risk of a positive bone scan increased with increasing stage and grade, tumor stage and grade were poor negative predictors of positive bone scans. Up to 4% of patients with clinically confined or well-differentiated to moderately differentiated tumors had positive scans. Scans were positive in 12% of poorly differentiated tumors, but all these patients had PSA levels above 10 micrograms/L. CONCLUSIONS: Our data support the elimination of routine bone scintigraphy in patients with newly diagnosed prostate cancer and PSA levels below 10 micrograms/L. Bone scans are indicated when PSA levels are above 10 micrograms/L, or with T3 or poorly differentiated disease.