Gianluca Giannarini

Contemporary Role of Systematic Prostate Biopsies: Indications, Techniques, and Implications for Patient Care

CONTEXT Prostate cancer (PCa) screening to detect early stage PCa has resulted in increased identification of small-volume, low-grade PCa, many of which meet criteria for clinically indolent disease. Nevertheless, there remains some degree of underdetection of high-risk PCa in substantial numbers of men despite current diagnostic strategies. OBJECTIVE To discuss the contemporary role of prostate biopsy (PB), focusing on the indications, techniques, and limitations of current PB techniques and evolving techniques affecting patient care. EVIDENCE ACQUISITION A comprehensive Medline search was performed using the medical subject heading search terms prostate cancer, detection, prostate biopsy, significant cancer, and diagnosis, with restriction to the English language. Emphasis was given to publications within the past 5 yr. EVIDENCE SYNTHESIS Because abnormal digital rectal examination (DRE) and prostate-specific antigen (PSA) tests alone lack specificity for cancer, there is no universal indication for PB. This lack has inspired exploration for a cancer-specific biomarker and prediction tools such as risk calculators. Indication for biopsy should involve a balance between the underdiagnosis of high-risk cancers and the potential risks for the overdetection of clinically insignificant cancers as well as biopsy-related morbidity. Evidence supports the inclusion of laterally directed cores during transrectal ultrasound (TRUS) PB in addition to the traditional sextant pattern, which significantly improves cancer detection without a demonstrable increase in morbidity. These data indicate that such PB templates, typically 12 cores, represent the optimal template in initial PB. Optimised techniques and templates for repeat PB remain controversial. However, debate continues regarding indications, sampling number, and location as well as on the potential of modern image-guided approaches or three-dimensional (3D) mapping biopsy in this unique setting. Additional limitations of repeat PB techniques include associated procedural risks if general anaesthesia is required and inherent sampling errors of template-based techniques that are not targeted to the specific tumour site. CONCLUSIONS Current data support the utility of extended PB templates for initial TRUS PB intended to detect clinically significant PCa. Repeat PB in the setting of prior negative PB on the grounds of clinical suspicion or for risk-stratified approaches to management of low risk PCa requires balancing overdetection of low-risk cancer with the potential to miss significant cancer. Several options, including modern image-guided targeting, biomarker development, transrectal saturation PB, and 3D template mapping PB, are changing the clinical paradigms for evaluation and management. Evidence to support adopting approaches other than the current established standards should be tested through appropriately designed prospective studies.

Ureteroileal Strictures After Urinary Diversion with an Ileal Segment—Is There a Place for Endourological Treatment at All?

PURPOSE We compared the long-term results of minimally invasive endourological intervention and open surgical revision in patients with a nonmalignant ureteroileal stricture. MATERIALS AND METHODS We retrospectively evaluated the records of 74 patients (85 renal units) treated for unilateral or bilateral nonmalignant ureteroileal strictures. Overall, 96 endourological and 35 open surgical procedures were performed. Balloon dilatation and Acucise® or Ho:YAG laser endoureterotomy were used as minimally invasive endourological interventions. Open surgical revision with stricture resection and open ureteroileal end-to-side-reanastomosis was the alternate therapy. Treatment success was defined as radiological normalization or improvement of upper urinary tract morphology combined with absent flank pain, infection, ureteral stents or percutaneous nephrostomies. RESULTS Median followup was 29 months (range 2 to 177). The overall success rate was 26% (25 of 96 cases) for endourological intervention vs 91% (32 of 35) for open surgical revision (p <0.001). Subgroup analysis showed a significant difference in the success rate of minimally invasive endourological interventions vs open surgical revision for strictures greater than 1 cm (3 of 52 cases or 6% vs 19 of 22 or 86%, p <0.001). The success rate of endourological and open surgical procedures for strictures 1 cm or less was 50% (22 of 44 cases) and 100% (13 of 13), respectively. After adjusting for multiple preoperative stricture characteristics, only stricture length was strongly and inversely associated with a successful outcome (p <0.001). CONCLUSIONS Open surgical revision produces better results than minimally invasive endourological intervention for ureteroileal strictures, particularly those greater than 1 cm. The success rate of endourological intervention is acceptable only for ureteroileal strictures 1 cm or less. Therefore, ureteroileal strictures greater than 1 cm should be primarily managed by open surgical revision.

Elective management of transitional cell carcinoma of the distal ureter: can kidney‐sparing surgery be advised?

To determine the long‐term oncological outcome of patients with primary transitional cell carcinoma (TCC) of the distal ureter electively treated with either kidney‐sparing surgery (KSS) or radical nephroureterectomy (RNU) in a retrospective, non‐randomized, single‐centre study.

Diffusion-Weighted Magnetic Resonance Imaging Detects Local Recurrence After Radical Prostatectomy: Initial Experience

Current conventional cross-sectional imaging techniques, such as contrast-enhanced computed tomography and magnetic resonance imaging (MRI), are largely inaccurate in detecting local recurrence after radical prostatectomy. We report on five patients with biochemical recurrence after radical retropubic prostatectomy and pelvic lymph node dissection for whom local recurrence could only be detected with diffusion-weighted (DW) MRI. Prior to DW-MRI, all patients had negative digital rectal examinations, negative or equivocal conventional cross-sectional imaging, and negative bone scans. All suspicious lesions on DW-MRI imaging were histologically proved to be local recurrences of prostate cancer after either transrectal ultrasound-guided or transurethral biopsy. These results should encourage other centres to test our findings.

Will Focal Therapy Remain Only an Attractive Illusion for the Primary Treatment of Prostate Cancer

Focal therapy is an emerging treatment modality for clinically localized prostate cancer (PCa). It was introduced with the aim of reducing the morbidity associated with standard whole-gland therapy, such as radical prostatectomy (RP) and external beam radiation therapy, without jeopardizing cancer control. In particular, following the organ-preservation approach adopted for several other solid tumors, focal therapy strategies in PCa were conceived in an attempt to destroy the tumor while minimizing damage to noncancerous tissue and sparing key structures, such as the neurovascular bundles and the external urinary sphincter. Another advantage of this approach is that any future tumor lesions diagnosed at a later stage of the disease after the initial treatment are still amenable to re-treatment. Despite a dramatically increasing interest among clinicians and investigators, focal therapy is still in its infancy and should thus be regarded as an experimental approach. How long it will remain an investigational therapy is difficult to predict. However, we believe that several misconceptions and intrinsic limitations of this approach may prevent its further development as a possible treatment option for men with clinically localized PCa.

Bacillus Calmette-Guérin Failure in Patients with Non–Muscle-invasive Urothelial Carcinoma of the Bladder May Be Due to the Urologist's Failure to Detect Urothelial Carcinoma of the Upper Urinary Tract and Urethra

BACKGROUND Various reasons exist for so-called bacillus Calmette-Guérin (BCG) failure in patients with non-muscle-invasive urothelial bladder carcinoma (NMIBC). OBJECTIVE To explore whether urothelial carcinoma of the upper urinary tract (UUT) and/or prostatic urethra may be a cause for BCG failure. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of 110 patients with high-risk NMIBC repeatedly treated with intravesical BCG, diagnosed with disease recurrence, and followed for a median time of 9.1 yr. INTERVENTION Two or more intravesical BCG induction courses without maintenance. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary outcome was pattern of disease recurrence (BCG failure) within the urinary tract categorised into UUT and/or urethral carcinoma (with or without intravesical recurrence), and intravesical recurrence alone. Secondary outcome was survival. Predictors of UUT and/or urethral carcinoma and the effect of pattern of disease recurrence on cancer-specific survival were assessed with multivariable Cox regression analysis adjusting for multiple clinical and tumour characteristics. RESULTS AND LIMITATIONS Of the 110 patients, 57 (52%) had UUT and/or urethral carcinoma (with or without intravesical recurrence), and 53 (48%) had intravesical recurrence alone. In patients with UUT and/or urethral carcinoma, bladder carcinoma in situ (Tis) before the first and second BCG course was present in 42 of 57 (74%) and 47 of 57 (82%) patients, respectively. On multivariable analysis, bladder Tis before the first and/or second BCG course was the only independent predictor of UUT and/or urethral carcinoma. Of the 110 patients, 69 (63%) were alive at last follow-up visit, 18 (16%) had died due to metastatic urothelial carcinoma, and 23 (21%) had died of other causes. Pattern of disease recurrence within the urinary tract was not an independent predictor of cancer-specific survival. Main study limitations were retrospective design and limited power for survival analysis. CONCLUSIONS In our patients with high-risk NMIBC failing after two or more courses of intravesical BCG, UUT and/or urethral carcinoma was detected in >50% of the cases during follow-up. The vast majority of these patients had bladder Tis before the first and/or second BCG course. In patients experiencing the so-called BCG failure, a diagnostic work-up of UUT and prostatic urethra should always be performed to exclude urothelial carcinoma before additional intravesical therapy or even a radical cystectomy is considered.

Prevalence of Nephrolithiasis in Patients with Ileal Bladder Substitutes

OBJECTIVES To assess the effect of ileal bladder substitutes with preservation of the ileocecal valve and distal 25 cm of ileum on nephrolithiasis. METHODS We reviewed a consecutive series of 518 patients (44 women and 474 men) with ileal orthotopic bladder substitution in whom 55 to 65 cm of ileum was resected but with preservation of the ileocecal valve and distal 25 cm of ileum, to determine prevalence of nephrolithiasis as well as bicarbonate, base excess, creatinine levels, and urinary pH at time of stone diagnosis and 2 years before it. RESULTS Four male patients with a median age of 66 years (range, 50 to 70 years) developed nephrolithiasis after ileal bladder substitute, for a total of five calculi. The prevalence of nephrolithiasis in this retrospective cohort is thus 1% (5 of 518). They developed the calculi after a median follow-up of 8 years (range, 4 to 17 years). The four patients were diagnosed with calculi at 2.3, 3, 10, 10.3, and 14 years after bladder substitute. Two of the stones were uric acid calculi; the remaining three were calcium oxalate. None of our patients were acidotic or had elevated serum creatinines at time of stone formation. Urinary pH determined once in spontaneously voided urine at the time of stone diagnosis was pH 6.0 for the two uric acid calculi and pH 7.0 for the remaining calculi. CONCLUSIONS The present study demonstrates a low prevalence of calculi in our cohort.

Functional Multiparametric Magnetic Resonance Imaging of the Kidneys Using Blood Oxygen Level Dependent and Diffusion-Weighted Sequences

PURPOSE Little data are available on noninvasive magnetic resonance imaging based assessment of renal function during upper urinary tract obstruction. We determined whether functional multiparametric kidney magnetic resonance imaging could monitor the treatment response in cases of acute unilateral upper urinary tract obstruction. MATERIAL AND METHODS Between January 2008 and January 2010, 18 patients with acute unilateral upper urinary tract obstruction due to calculi were prospectively enrolled to undergo kidney magnetic resonance imaging with conventional, blood oxygen level dependent and diffusion-weighted sequences upon emergency hospital admission and after release of obstruction. We assessed functional imaging parameters of obstructed and contralateral unobstructed kidneys derived from blood oxygen level dependent (apparent spin relaxation rate) and diffusion-weighted (total apparent diffusion coefficient, pure diffusion coefficient and perfusion fraction) sequences during acute upper urinary tract obstruction and after its release. RESULTS During acute obstruction the apparent spin relaxation rate and perfusion fraction were lower in the cortex (p=0.020 and 0.031) and medulla (p=0.012 and 0.190, respectively) of obstructed kidneys compared to contralateral unobstructed kidneys. After obstruction release the apparent spin relaxation rate and perfusion fraction increased in the cortex (p=0.016 and 0.004) and medulla (p=0.071 and 0.044, respectively) of formerly obstructed kidneys to values similar to those in contralateral kidneys. Total apparent diffusion coefficient and pure diffusion coefficient values did not significantly differ between obstructed and contralateral unobstructed kidneys during or after obstruction. CONCLUSIONS In our patients with acute unilateral upper urinary tract obstruction due to calculi functional kidney magnetic resonance imaging using blood oxygen level dependent and diffusion-weighted sequences enabled us to monitor pathophysiological changes in obstructed kidneys during obstruction and after its release.

Will Active Surveillance for Clinically Localized Prostate Cancer Survive in the Era of Individualized Medicine

The challenge for the next few years will be to individualize prostate cancer treatment and to determine whether or not a cancer will be lethal based on molecular characteristics at the time of diagnosis. In this view, the need for active treatment would represent a failure of any conservative approach.

A Diagnostically Challenging Case of Ureterovaginal Fistula After Laparoscopic Hysterectomy

A complicated case of iatrogenic ureterovaginal fistula in a 56-year-old woman after laparoscopic-assisted vaginal hysterectomy, which persisted after several attempts of repair including ureterocystoneostomy, is presented. Accurate radiologic work-up enabled us to identify a refluxing ureteral stump, which was not ligated at the time of ureterocystoneostomy, as the origin of urinary leakage. Surgical principles that should be adhered to when managing such complex cases to obtain successful long-lasting outcome are described.