Jason Hafron

Magnetic Resonance Imaging–Guided Transurethral Ultrasound Ablation of Prostate Tissue in Patients with Localized Prostate Cancer: A Prospective Phase 1 Clinical Trial

BACKGROUND Magnetic resonance imaging-guided transurethral ultrasound ablation (MRI-TULSA) is a novel minimally invasive technology for ablating prostate tissue, potentially offering good disease control of localized cancer and low morbidity. OBJECTIVE To determine the clinical safety and feasibility of MRI-TULSA for whole-gland prostate ablation in a primary treatment setting of localized prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS A single-arm prospective phase 1 study was performed at three tertiary referral centers in Canada, Germany, and the United States. Thirty patients (median age: 69 yr; interquartile range [IQR]: 67-71 yr) with biopsy-proven low-risk (80%) and intermediate-risk (20%) PCa were treated and followed for 12 mo. INTERVENTION MRI-TULSA treatment was delivered with the therapeutic intent of conservative whole-gland ablation including 3-mm safety margins and 10% residual viable prostate expected around the capsule. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary end points were safety (adverse events) and feasibility (technical accuracy and precision of conformal thermal ablation). Exploratory outcomes included quality of life, prostate-specific antigen (PSA), and biopsy at 12 mo. RESULTS AND LIMITATIONS Median treatment time was 36min (IQR: 26-44) and prostate volume was 44ml (IQR: 38-48). Spatial control of thermal ablation was ±1.3mm on MRI thermometry. Common Terminology Criteria for Adverse Events included hematuria (43% grade [G] 1; 6.7% G2), urinary tract infections (33% G2), acute urinary retention (10% G1; 17% G2), and epididymitis (3.3% G3). There were no rectal injuries. Median pretreatment International Prostate Symptom Score 8 (IQR: 5-13) returned to 6 (IQR: 4-10) at 3 mo (mean change: -2; 95% confidence interval [CI], -4 to 1). Median pretreatment International Index of Erectile Function 13 (IQR: 6-28) recovered to 13 (IQR: 5-25) at 12 mo (mean change: -1; 95% CI, -5 to 3). Median PSA decreased 87% at 1 mo and was stable at 0.8 ng/ml (IQR: 0.6-1.1) to 12 mo. Positive biopsies showed 61% reduction in total cancer length, clinically significant disease in 9 of 29 patients (31%; 95% CI, 15-51), and any disease in 16 of 29 patients (55%; 95% CI, 36-74). CONCLUSIONS MRI-TULSA was feasible, safe, and technically precise for whole-gland prostate ablation in patients with localized PCa. Phase 1 data are sufficiently compelling to study MRI-TULSA further in a larger prospective trial with reduced safety margins. PATIENT SUMMARY We used magnetic resonance imaging-guided transurethral ultrasound to heat and ablate the prostate in men with prostate cancer. We showed that the treatment can be targeted within a narrow range (1mm) and has a well-tolerated side effect profile. A larger study is under way. TRIAL REGISTRATION NCT01686958, DRKS00005311.

CD133 Staining Detects Acute Kidney Injury and Differentiates Clear Cell Papillary Renal Cell Carcinoma from Other Renal Tumors

CD133 has recently been characterized as a progenitor cell marker in the kidney. However, the expression of this marker has not been thoroughly investigated in kidney injury and variants of renal tumors for pathology practice. We quantified CD133 expression in kidney biopsies from patients with acute renal failure and compared staining intensity with serum creatinine levels. CD133 expression levels were also evaluated in several subtypes of renal neoplasms. Normal adult renal parenchyma showed CD133 expression in parietal epithelium and in less than 5% of the epithelial cells in proximal and distal nephron tubules. However, CD133 was diffusely upregulated in the injured proximal and distal tubular epithelium and the CD133 expression scores in renal tubules were significantly correlated with serum creatinine levels. Amongst the renal tumors, CD133 was diffusely expressed in clear cell papillary renal cell carcinoma but was only focally present in other types of renal tumors. In summary, CD133 is a useful marker to detect renal tubular injury and to differentiate clear cell papillary renal cell carcinoma from other tumor types.

Technical advances in urological laparoscopic surgery

Advances in laparoscopic techniques, technology and instruments have changed the face of urology to the extent that the laparoscopic approach has become the standard of care for many common urological procedures. The future of laparoscopy will build on incorporating additional technological innovations to improve surgical outcomes, advance surgical techniques and thereby decrease perioperative morbidity. Developments in laparoscopic imaging, laparoscopic instrumentation and novel surgical techniques will offer advantages to patients and urologists in the future.

Characterization of clear cell renal cell carcinoma by gene expression profiling.

OBJECTIVES Use global gene expression to characterize differences between high-grade and low-grade clear cell renal cell carcinoma (ccRCC) compared with normal and benign renal tissue. METHODS Tissue samples were collected from patients undergoing surgical resection for ccRCC. Affymetrix gene expression arrays were used to examine global gene expression patterns in high- (n = 16) and low-grade ccRCC (n = 13) as well as in samples from normal kidney (n =14) and benign kidney disease (n = 6). Differential gene expression was determined by analysis of variance with a false discovery rate of 1% and a 2-fold cutoff. RESULTS Comparing high-grade ccRCC with each of normal and benign kidney resulted in 1,833 and 2,208 differentially expressed genes, respectively. Of these, 930 were differentially expressed in both comparisons. In order to identify genes most related to progression of ccRCC, these differentially expressed genes were filtered to identify genes that showed a pattern of expression with a magnitude of change greater in high-grade ccRCC in the comparison to low-grade ccRCC. This resulted in the identification of genes such as TMEM45A, ceruloplasmin, and E-cadherin that were involved in cell processes of cell differentiation and response to hypoxia. Additionally changes in HIF1α and TNF signaling are highly represented by changes between high- and low-grade ccRCC. CONCLUSIONS Gene expression differences between high-grade and low-grade ccRCC may prove to be valuable biomarkers for advanced ccRCC. In addition, altered signaling between grades of ccRCC may provide important insight into the biology driving the progression of ccRCC and potential targets for therapy.

Cone beam computed tomography: an assessment of renal image quality and applicability for percutaneous renal cryotherapy in a swine model.

OBJECTIVES To assess cone bean computed tomography (CBCT) for renal imaging in a phantom model, ex vivo kidney and an in vivo porcine percutaneous renal cyroablation (PRC). CBCT provides 3-dimensional sectional imaging without the space requirements, repositioning, and expenditure of computed tomography (CT). METHODS CBCT was focused on a radiological phantom with electron density of renal tissue and visualization was recorded. The ability of CBCT to image an ex vivo kidney in a water bath, with and without contrast, was then evaluated. An in vivo porcine animal model was then used to perform PRC and the scanner was evaluated in regard to image of the kidneys, a fiber-agarose pseudotumor, and guidance of the cryoprobe. RESULTS Qualitative assessment of phantom images revealed sufficient contrast between the renal tissue and water densities. Images of the ex vivo porcine kidneys without contrast revealed limited renal architecture, whereas retrograde contrast revealed 3D images of renal shape and vascular/collecting system architecture visible in axial and sagittal planes. Noncontrast imaging facilitated precise needle guidance but was inadequate to consistently visualize ice-ball formation during cryoablation. At necropsy, all tumors were encompassed by the cryolesion with >1-cm margins, except for 1 pseudotumor that had been placed extracapsularly. CONCLUSIONS CBCT is an imaging modality capable of excellent spatial resolution and soft-tissue sensitivity in a radiographic phantom and ex vivo and in situ porcine renal models. Based on our preliminary results, further refinements in image quality are required to improve soft tissue visualization to be applied to percutaneous renal cryoablation.

Localised prostate cancer treated with MRI-guided transurethral ultrasound ablation: phase I trial results

Purpose Purpose of this prospective, multi-institutional Phase I clinical study was to investigate whether MRI-guided transurethral ultrasound ablation (MR-TULSA), a novel minimally-invasive technology to treat organ-confined prostate cancer (PCa), is safe, feasible and effective. It employs directional plane-wave high-intensity ultrasound, which ablates prostate tissue using real-time thermometry with active temperature feedback control.

Diagnosis and Management of Localized Prostate Cancer

Objectives 1. Discuss the diagnosis and incidence of localized prostate cancer. 2. Review screening and staging of prostate cancer. 3. Discuss treatment options in localized prostate cancer.

MRI-guided transurethral ultrasound prostate ablation: midterm outcomes of a phase I clinical trial

MRI-guided transurethral ultrasound ablation (TULSA) is a new minimally-invasive modality for the treatment of prostate cancer, which aims to provide local disease control with low morbidity. A transurethral ultrasound device generates a continuous volume of thermal coagulation that is shaped precisely to the prostate using real-time MR thermometry and active temperature feedback control. The aim of this multi-center, prospective Phase I clinical study is to determine the safety and feasibility of MRI-guided TULSA, and to assess initial efficacy for treatment of localized prostate cancer.

Progenitor/stem cells in renal regeneration and mass lesions

Abstract Adult kidneys have limited regenerative capacity following a prominent acute kidney injury. As understanding regenerative mechanisms is the key to discovering therapeutic strategies for preventing and treating renal diseases, in recent years, researchers have hotly debated whether progenitor/stem cells offer a support system for renal repair. The Romagnani-led group identified CD133 stem cells in the parietal epithelium and renal tubules, and their data indicate that these progenitor/stem cells support renal repair in the glomeruli and renal tubules. The Humphreys and Bonventre group used the lineage-tracing technique. They observed no contribution of progenitor cells to tubular repair, but they later reported that the differentiated tubular cells responsible for tubular repair actually gained some characteristics of progenitor cells. This review article will focus on major updates regarding the controversial progenitor/stem cells in renal regeneration and highlight some new progenitor cell issues in renal mass lesions.