Maurizio Bellina

INCIDENCE OF SKELETAL COMPLICATIONS IN PATIENTS WITH BONE METASTATIC PROSTATE CANCER AND HORMONE REFRACTORY DISEASE: PREDICTIVE ROLE OF BONE RESORPTION AND FORMATION MARKERS EVALUATED AT BASELINE

PURPOSE We evaluated the incidence of skeletal complications in patients with bone metastatic prostate cancer and hormone refractory disease. We also assessed the predictive role of bone turnover markers determined at baseline. MATERIALS AND METHODS A total of 112 patients were consecutively enrolled in our study from July 1990 to July 1998 and followed until death or the last followup. Bone pain, disease extent in bone, serum prostate specific antigen, hemoglobin, and a panel of bone formation and resorption markers were assessed at baseline before any second line treatment. RESULTS Skeletal complications in 34 patients (30.3%, estimated yearly incidence 12.3%) involved vertebral deformity or collapse requiring spinal orthosis in 20 (17.9%), spinal cord compression in 7 (6.2%), pathological bone fracture in 10 (8.9%), symptomatic hypercalcemia in 1 (0.9%) and symptomatic hypocalcemia in 1 (0.9%). Median time to the evidence of the initial skeletal complication was 9.5 months. These adverse events did not influence overall survival. At baseline patients with eventual skeletal complications had greater bone pain (p = 0.02), a heavier tumor load in bone (p = 0.005), lower performance status (p = 0.05), and higher serum alkaline phosphatase (p <0.02) and urinary deoxypyridoline (p <0.05) than their counterparts. Multivariate analysis revealed that only urinary deoxypyridinoline was independently associated with the onset of these events (p <0.02). The scatterplot of urinary deoxypyridinoline values in patients with and without skeletal complications enabled us to detect a cutoff of 38 pM./mM. for predicting 51% of skeletal events with only an 8% false-positive rate. CONCLUSIONS Skeletal complications are common in patients with prostate cancer and hormone refractory disease. Bone loss is the major cause of onset. Baseline deoxypyridinoline at the cutoff point noted had moderate sensitivity but high specificity for predicting these adverse skeletal events.

Circulating neuroendocrine markers in patients with prostate carcinoma.

Circulating neuroendocrine markers were measured in patients with prostate carcinoma (PC), prostatic intraepithelial neoplasia (PIN), and benign prostatic hypertrophy (BPH) with the goal to: 1) evaluate the differences in the expression of these markers in patients with benign, premalignant, and primary or metastatic PC; 2) evaluate their prognostic significance; 3) compare values in patients with hormone‐naive and hormone‐refractory disease; and 4) assess changes after androgen deprivation or chemotherapy.

Monoclonal Antibody Ki-67 in the Study of the Proliferative Activity of Bladder Carcinoma

We studied the proliferative activity of bladder carcinoma using monoclonal antibody Ki-67, which is able to stain a nuclear antigen exclusively present in cells in the cell cycle, that is with activated deoxyribonucleic acid (DNA). We used this immunohistochemical technique on neoplastic tissue removed by transurethral resection from 101 patients. A significant correlation was observed (p less than 0.003) between cells with activated DNA and histological grading, even though within the context of each grade we observed tumors with a different proliferation index. Furthermore, we studied the location of the activated cells in the context of the tumor. In invasive tumors (stages T1 to T4) cells with activated DNA were always present at the base of implant of the tumor and in the neoplastic tissue that infiltrates the bladder wall. In regard to noninvasive tumors (stage Ta), in 57% of the cases most cells with activated DNA were present in the vegetative portion of the tumor and there were no recurrences at followup, while in 43% of the cases such cells were present also or especially at the base of implant of the tumor, near the lamina propria. In the latter patients we observed a 94% recurrence rate. These results suggest that the immunohistochemical assessment of the proliferative activity of transitional tumors of the bladder, using monoclonal antibody Ki-67, and the evaluation of the location of stained neoplastic cells provide a more reliable estimate of biological aggressiveness than that obtained with histopathological patterns alone.

INTRAVESICAL BACILLUS CALMETTE-GUERIN (BCG) AS INDUCER OF TUMOR-SUPPRESSING PROTEINS P53 AND P21Waf1-Cip1 DURING TREATMENT OF SUPERFICIAL BLADDER CANCER

PURPOSE Previous in vitro investigations recorded an inhibition of cell proliferation by BCG when added to different cell cultures. The induction of apoptosis by BCG is controversial. Our study aimed to evaluate the influence of BCG on the expression of tumor suppressing proteins p53 and p21Waf1-Cip1 and apoptosis of the urothelial cells in vivo. MATERIALS AND METHODS Twenty-one cases of superficial bladder cancer, treated with TUR and subsequent intravesical BCG, were studied retrospectively. The assays evaluated the expression of p53 and p21Waf1-Cip1 by immunochemistry (IHC), and the presence of apoptosis by TUNEL assay. The estimates were performed, in each case, on the following specimens: one tumor sample and one non-neoplastic sample collected during the TUR which preceded the administration of BCG; one non-neoplastic sample collected 3 months after the diagnosis; and one non-neoplastic sample collected in the first 2 weeks after the completion of the treatment. Samples of 6 cancer recurrences detected during BCG were examined too. RESULTS As usual for non-neoplastic urothelium, the pre-BCG samples displayed poor p53 and p21Waf1-Cip1 immunoreactivity. By contrast, the samples collected during and in the aftermath of BCG showed an overall increase of the expression of both proteins. The rare occurrence of apoptosis proved to be chronologically unrelated to the BCG treatment. DISCUSSION The relationship between changes of the IHC features and BCG suggests that BCG, at least under some circumstances, can induce the activation of wild type p53 and p21Waf1-Cip1 in the urothelium. The mechanism of the BCG-p53 status interaction and its role in the antitumor activity of BCG remain to be clarified.

Seminal Monolateral Nerve-Sparing Radical Prostatectomy in Selected Patients

Introduction: In recent years there has been a shift in prostate cancer stage with the majority of patients nowadays being operated with cT1c disease, prostate-specific antigen levels of <10 ng/ml, and a decreased rate of seminal vesicle invasion. Recent data suggest the role of preservation of the seminal vesicle in improving continence and/or potency. We describe our preliminary experience with seminal-sparing, unilateral nerve-sparing retropubic radical prostatectomy. Patients and Methods: 21 selected patients with clinically localized prostate cancer underwent seminal unilateral nerve-sparing retropubic radical prostatectomy (seminal-sparing group, SSG). We compared the postoperative continence, erectile function and quality of orgasm results to those obtained in a control group (CG) of 21 patients who underwent unilateral nerve-sparing radical prostatectomy. Sexual function was evaluated preoperatively and 9 months postoperatively with the 5-item International Index of Erectile Function (IIEF-5) questionnaire and with oth er self-administered questionnaires. The quality of orgasm was evaluated 9 months postoperatively. Results: 1 month postoperatively, 95 and 28% of the patients in the SSG and CG were continent (p < 0.001). The median postoperative drop in IIEF-5 score was 5 points in SSG and 14.5 points in CG (p < 0.0001). Nine months postoperatively, 90 and 62% of the patients in SSG and CG, respectively (p = 0.05), maintained the ability to achieve orgasm. Conclusions: In our experience seminal-sparing radical prostatectomy showed good feasibility and improved early postoperative urinary continence, erectile function and quality of orgasm, without compromised cancer control.

Ectopic Adrenal Cortex Tissue in the Spermatic Cord in Association with Testicular Cancer

Ectopic adrenal cortex tissue is not an uncommon clinical finding, but the simultaneous occurrence with testicular cancer has not been reported. We describe a patient who had both pathologies.

Randomized Prospective Trial Comparing Immediate Versus Delayed Ureteroscopy for Patients with Ureteral Calculi and Normal Renal Function Who Present to the Emergency Department

PURPOSE To compare the safety and efficacy of emergency vs scheduled ureteroscopy with a prospective study that included patients who presented to the emergency department (ED) with renal colic from ureteral stones. PATIENTS AND METHODS There were 271 consecutive patients who were enrolled in this prospective study. Patients were randomized to emergency ureteroscopy (group A) or delayed ureteroscopy (group B). All patients underwent helical unenhanced CT (HUCT). Stone-free status was defined as the complete absence of residual fragments at 1 week postoperatively, assessed with HUCT, with no need for ancillary interventions after ureteroscopy. RESULTS Group A included 139 assessable patients. The overall stone-free rate was 93%. Neither location nor size was a significant prognostic factor (P>0.05). Single-session ureteroscopy failed to clear nine ureteral stones. A Double-J stent was placed in 27/139 patients. Group B included 100 assessable patients. Patients in the control group were scheduled for ureteroscopy after their departure from the ED. The overall stone-free rate was 90%. Single-session ureteroscopy failed to clear 10 ureteral stones. A Double-J stent was placed in 80/100 patients. There were no statistical differences with regard to stone diameter and location, complications, and stone-free rate between group A and group B patients. The rate of Double-J stent positioning was significantly higher (P<0.05) in group B patients. CONCLUSIONS In our experience, emergency ureteroscopy showed equal efficacy and safety compared with the elective procedure. It has the main advantage of providing both immediate relief from pain and stone fragmentation.

Serum prostate-specific antigen determination in prostatic carcinoma.

Prostate-specific antigen (PSA) is a tissue-specific glycoprotein identified by Wang in 1979. It is synthesized in the prostate independently of prostatic acid phosphatase (PAP). A total of 199 subjects were divided into four groups: controls aged less than 50 years, controls aged more than 50 years, patients with benign prostatic hyperplasia (BPH) and patients with prostatic carcinoma. PSA cut-off value was set at 10 ng/ml (mean for the BPH group plus 2 SD). With this cut-off value PSA could not be used as an early predictor of prostatic carcinoma. The association of PSA and PAP in prostatic cancer increases the number of patients with positive biological markers.

MP24-12 A MODIFIED ILEO CONDUIT TECNIQUE TO AVOID URETEROENTERIC STRICTURE.

METHODS: Between January 1992 and April 2016, 51 children (27 boys and 24 girls) underwent a Mitrofanoff appendico-vesicostomy as external continent urinary diversion. we exclude at once those presented at end stage renal failure and required renal transplantation. The remaining (45) were aged between 5 and 15 years (mean 10.27); all of them underwent MAV in their right iliac fossa. Etiologies were dominated by neuropathic bladder (41 cases) ,mainly due to spina bifida defect with myelo-meningocele ; a posterior urethral valves causing altered bladder (2 cases) and complicated bladder exstrophy (2 cases). Diagnosis was established at advanced stage in all patients with mild renal failure (11) or moderate renal insufficiency in (34) with mean creatinine clearance of( 41 ml/min/1.73m2). RESULTS: The average follow-up was approximately 135 months (ranging from 12 to 256 months). All children became continent, 43 (95% ) after a single intervention. Minor complications consisted mainly on difficulties in intermittent catheterization (11.2%), they were treated merely by external stoma refection. The renal function deteriorated to severe renal failure (1 case), 6 years after surgery, then the patient underwent renal transplantation in his left iliac fossa; it remained stable at better levels with no need to dialysis, in 33 cases (average creatinine clearance of 58 ml/min/ 1.73m2), with mean follow up of 9 years; it returned to normal (11 cases). In addition, intermittent self-catheterization was well accepted by all children and their families, with complete readaptation to daily activities with good quality of life . CONCLUSIONS: The Mitrofanoff appendico-vesicostomy operation is usually associated to good results in children who suffer of some form of renal insufficiency. It ensures better continence status and a satisfactory educational rehabilitation. Our results demonstrate that it could also stabilize damaged renal function for quite a long time before renal replacement programmes if it was associated to mild or moderate renal failure.