Aristotelis G. Anastasiadis

Radical retropubic versus laparoscopic prostatectomy: a prospective comparison of functional outcome

OBJECTIVES To evaluate and compare prospectively the functional results (urinary continence and erectile function) after retropubic and laparoscopic radical prostatectomy. METHODS From 1998 to 2001, 300 patients underwent radical prostatectomy, 70 by the retropubic and 230 by the laparoscopic approach. All of them completed a confidential, self-administered questionnaire regarding urinary continence and erectile function before and 1, 3, 6, and 12 months after surgery. The results were analyzed separately for day and nighttime urinary continence and by neurovascular bundle status and age for erectile function. RESULTS No differences were found between the two groups except for the duration of bladder catheterization (7.8 days for the retropubic and 5.8 for the laparoscopic approach, P = 0.0006). Before surgery, 296 patients (98.7%) were continent and 290 (96.6%) were potent. One year after surgery, diurnal urinary continence increased progressively to 66.7% and 71.6% (P >0.05), nocturnal continence to 66.7% and 87.1% (P = 0.008), and potency rates to 30% and 41% (P >0.05) for the retropubic and the laparoscopic approaches, respectively. After preservation of one and two neurovascular bundles, the potency rate increased to 27% and 46% and 44% and 53% for the retropubic and laparoscopic approaches, respectively (P >0.05). For patients younger than 60 years old with bilateral neurovascular bundle preservation, the potency rates were 72% and 81% (P >0.05). CONCLUSIONS The two approaches showed similar outcomes regarding continence and erectile function 1 year after surgery. However, the recovery of nocturnal continence seemed to occur earlier after the laparoscopic approach. It is necessary to conduct additional studies to determine the potential benefits of the laparoscopic approach regarding nocturnal continence.

Radical Prostatectomy by the Retropubic, Perineal and Laparoscopic Approach: 12 Years of Experience in One Center

OBJECTIVES We retrospectively evaluated the oncological outcome of radical prostatectomy performed by the retropubic, perineal and laparoscopic approaches. METHODS From 1988 to 2000, 401 patients underwent radical prostatectomy for localized prostate cancer by the retropubic, perineal or laparoscopic approach. Age, clinical stage, preoperative PSA and Gleason score of positive biopsies were noted. Operating time, complication rate, transfusion rate, length of hospital stay, catheterization time and pathological results were reviewed. Kaplan-Meier analysis was used to evaluate the likelihood of biochemical recurrence (PSA > or =0.2 ng/ml). RESULTS There were no significant differences between the three groups regarding preoperative characteristics, except for PSA (21.4 ng/ml, 13.2 ng/ml, and 11.6 ng/ml for the retropubic, perineal, and laparoscopic approach, p<0.05) and the frequency of stage T1c tumors (31.7%, 47.1% and 63.5%, respectively, p<0.05). The operating time was significantly longer in the laparoscopic approach (285 min) compared to the retropubic and perineal techniques (197 min and 178 min, respectively). The retropubic approach was associated with a higher transfusion rate (26.2% versus 15.9% and 2.9% with the perineal and laparoscopic approaches), longer bladder catheterization time (15.9 days versus 11.7 days and 6.8 days, respectively), and longer hospital stay (15.2 days versus 8.5 days and 7.4 days, respectively) (p<0.05 for each). With the retropubic, perineal and laparoscopic approaches, medical complication rates were 8.3%, 4.2% and 5.1%, and surgical complication rates were 16.5%, 12.7% and 13.1%, respectively. The rates of pathological stage pT2 tumors were 62.1%, 72.2% and 75.9%, in the retropubic, perineal and laparoscopic groups, respectively. Positive surgical margins in pT2 tumors were noted in 19%, 14% and 22%, respectively. The actuarial 3-year recurrence-free survival rates were not significantly different between the three techniques (75%, 85.2% and 84.1%, respectively; 91.7%, 95.8% and 90.4% among patients with organ-confined tumors). CONCLUSION Despite changes in patient selection criteria over time, and the relatively short follow-up, this study showed no significant difference in oncologic outcome between the retropubic, perineal and laparoscopic approaches to radical prostatectomy.

Urinary continence and erectile function: A prospective evaluation of functional results after radical laparoscopic prostatectomy

OBJECTIVES To evaluate prospectively functional results (urinary continence and erectile function) after laparoscopic radical prostatectomy. METHODS From 1998 to 2001, 235 patients underwent laparoscopic radical prostatectomy for localized prostate cancer. All of them completed a confidential, self-administered questionnaire regarding urinary continence and erectile function before, and 1, 3, 6, and 12 months after surgery. Results were analyzed separately for day and night for urinary continence and status of neurovascular bundles as well as age for erectile function. RESULTS To date, 100 consecutive patients have completed all questionnaires. Diurnal and nocturnal urinary continence have increased to 90% and 97% one year after surgery. Overall, 49.3% of the 77 patients, who were potent preoperatively, and did not receive any form of adjuvant therapy, had erections sufficient for intercourse one year after surgery. Potency rates were 38.4%, 53.8% and 58.8% after no, unilateral, and bilateral nerve bundle preservation, respectively. For younger patients (<60 years) with unilateral and bilateral neurovascular bundle preservation, potency rates were 75% and 83.3%, respectively. CONCLUSION One year after laparoscopic radical prostatectomy, urinary continence rate is 90% during the day and 97% during the night. Overall potency rates after bilateral preservation of neurovascular bundles are 58.8% and 83.8% for the subgroup of younger patients (<60 years).

Erectile dysfunction is a marker for cardiovascular complications and psychological functioning in men with hypertension.

The aim of this study was to investigate the incidence of cardiovascular complications in hypertensive patients with erectile dysfunction (ED). An anonymous questionnaire was mailed to 467 and received from 104 hypertensive male patients. Despite the low response rate of 22%, the following interesting findings could be observed: 70.6% of the patients who responded suffered from ED. The hypertensive patients with ED had significantly higher prevalence of cardiovascular complications (P<0.05). The correlation between depression and low quality of life as well as between ED and low sexual satisfaction was also statistically significant (P=0.05). ED in hypertensive patients can be considered as a marker for cardiovascular complications in this patient group.

Location of positive surgical margins after retropubic, perineal, and laparoscopic radical prostatectomy for organ-confined prostate cancer

OBJECTIVES To evaluate and compare the location of positive surgical margins after retropubic, perineal, and laparoscopic radical prostatectomy for organ-confined prostate cancer (pT2). METHODS From 1988 to 2001, 538 patients underwent radical prostatectomy for clinically localized prostate cancer. Patient age at surgery, clinical stage, preoperative prostate-specific antigen, and Gleason score of positive biopsies were noted. Postoperatively, specimen weight, final Gleason score, and capsular, seminal vesicle, and lymph node status, as well as tumor volume, were studied. The incidence and location of positive margins and the pathologic stage were noted according to the surgical approach. RESULTS A total of 371 patients (69.5%) had organ-confined tumors. Of the 371 patients, 116 underwent the retropubic, 86 the perineal, and 169 the laparoscopic approach, and positive surgical margins were noted in 22 (18.9%), 12 (13.9%), and 32 (18.9%) patients, respectively. Positive surgical margins were reported in 72 specimen locations, 32 (44.4%) at the apex, 17 (23.6%) at the bladder neck, and 29 (31.9%) posterolaterally. The distribution for the retropubic, perineal, and laparoscopic approaches was apex in 50%, 33.3%, and 44.4%, bladder neck in 29.1%, 41.7%, and 13.9%, and posterolaterally in 20.8%, 25%, and 41.6%, respectively. CONCLUSIONS In our series, each approach had a specific high-risk location of positive margins: the apex for the retropubic, the bladder neck for the perineal, and posterolaterally for the laparoscopic approach. Improvements in the surgical techniques should take these specific locations under consideration to decrease the incidence of positive surgical margins.

Prognostic Significance of Tumor Volume after Radical Prostatectomy: A Multivariate Analysis of Pathological Prognostic Factors

OBJECTIVES To analyze the association between Gleason score, stage and status of surgical margins with tumor volume in prostate cancer progression after radical prostatectomy. METHODS 200 consecutive radical prostatectomy specimens were analyzed. Preoperative clinical stage, PSA, results of prostate biopsies as well as pathological results were noted. A biochemical recurrence was defined as a single, postoperative detectable PSA level (>0.2 ng/ml). Tumor volume was compared to postoperative staging, Gleason score, and surgical margin status to predict tumor progression. Univariate and multivariate analysis using stepwise logistic regression were used to identify parameters with additional prognostic value. RESULTS Pathological results of the prostatectomy specimens showed 149 (74.5%) pT2a-b, 29 (14.5%) pT3a and 22 (11%) pT3b tumors. Tumor volume was 0.57 cc for pT2a, 1.2cc for pT2b, 1.7cc for pT3a and 2.9cc for pT3b, respectively (p<0.05). Taken together, mean volume for pT2 and pT3 were 1.06 and 2.2 cc, respectively (p<0.0001). Five-year progression-free actuarial survival was 69.7%. Using univariate analysis, tumor progression correlated with final Gleason score (p<0.0007), positive surgical margins (p=0.02), tumor volume (p=0.009) and stage (p<0.0001). In a multivariate analysis, tumor progression correlated only with the final Gleason score (p=0.04) and stage (p=0.0002). CONCLUSION Gleason score and pathological stage are independent factors to predict prostate cancer progression after radical prostatectomy. When these parameters are known, tumor volume does not provide additional information.

Hypoxia and an angiogenic response in the partially obstructed rat bladder

Previous molecular and blood flow studies performed on animal models of partial bladder outlet obstruction (PBOO) caused us to propose that bladder hypoxia/ischemia was a significant effector of the cellular and functional changes that occur in the bladder as a result of this condition. To confirm the occurrence of hypoxia in the partially obstructed bladder, we obtained rat bladders at increasing intervals following PBOO and measured biomarkers of hypoxia (intracellular formation of hypoxyprobe-1 adducts and expression of hypoxia inducible factor-1α [HIF-1α] protein) and whether such hypoxia might elicit an angiogenic response in the tissue. Rats receiving PBOO or controls were treated with hypoxyprobe-1 at increasing intervals subsequent to surgery and their bladders were sectioned and immunostained using an antibody that detects hypoxyprobe-1 adducts. Control rat bladders were unstained, whereas intense, but regionally restricted, hypoxyprobe-1 immunostaining was detected in all obstructed bladders in a unique pattern that changed over time. Proteins were extracted from bladders removed from similarly treated rats and were analyzed for the expression of the HIF-1α protein as well as for expression of angiogenic regulatory factors (vascular endothelial growth factor, angiopoietin-1, and endostatin) using Western blotting techniques. HIF-1α protein was not expressed in control bladders, however, the protein was highly up-regulated over the 2-week period after PBOO. Likewise, the expression of vascular endothelial growth factor (a downstream target of HIF-1α action) and angiopoietin-1 was also up-regulated in obstructed bladders confirming an angiogenic response to this hypoxia. Enigmatically, however, expression of the antiangiogenic molecule endostatin was also up-regulated by chronic PBOO. These results further support the concept that hypoxia is involved in the cellular remodeling as well as in the progressive functional impairment exhibited by the urinary bladder after PBOO.

Seminal vesicle involvement after radical prostatectomy: predicting risk factors for progression

OBJECTIVES To evaluate and study the factors for progression after radical prostatectomy with seminal vesicle invasion in a cohort of European and American patients. METHODS The data of 137 patients with isolated seminal vesicle invasion who underwent radical retropubic prostatectomy between 1988 and 2001 were analyzed. The Gleason score of the specimen, presence of capsular invasion, and surgical margin status were noted. Follow-up data were obtained through routine serum prostate-specific antigen (PSA) assays and digital rectal examinations. A defining criterion for progression was a postoperative serum PSA level greater than 0.2 ng/mL or any postoperative radiotherapy or hormonal treatment. Kaplan-Meier analysis was used to determine the actuarial biochemical recurrence-free likelihood, and the log-rank test was used to compare these results. Differences were considered statistically significant when the P value was less than 0.05. RESULTS After a mean follow-up of 4.9 years (range 0.9 to 13.4), 70 patients (51.9%) had progression. The biochemical 5-year progression-free survival rate was 33.8%. In univariate and multivariate analyses, only preoperative PSA level (P = 0.001) and Gleason score of the specimen (P = 0.01) were independent predictors of progression. Neither capsular invasion nor positive surgical margins predicted progression. When an analysis was performed according to the major Gleason grade of the radical prostatectomy specimen, Gleason grade 5 was associated with a worse prognosis compared with Gleason grade 3 and 4 (P = 0.01). The mean time to progression was 20.5, 17.1, and 10.1 months for Gleason grade 3, 4, and 5, respectively. CONCLUSIONS Seminal vesicle invasion after radical prostatectomy has historically been associated with a poor prognosis. However, in the present study, seminal vesicle invasion was associated with a 34% rate of freedom from progression at 5 years after surgery alone. Preoperative PSA and Gleason score of the radical prostatectomy specimen were independent factors for progression in the present study, which described the largest patient group to date. The Gleason grade of the radical prostatectomy specimen distinguished among different times to progression.

Biomarker analysis demonstrates a hypoxic environment in the castrated rat ventral prostate gland.

Within the first 24 h after castration of an adult male rat, the vascular system of the ventral prostate gland undergoes a degenerative process that drastically reduces blood flow to the tissue. Since the vascular degeneration precedes the loss of the prostatic epithelium (by apoptosis), we have proposed that the onset of epithelial cell apoptosis in this tissue is caused by an ischemic/hypoxic environment resulting from the loss of blood flow. In order to further evaluate the extent to which ischemia/hypoxia might be a factor in apoptosis of the prostate epithelium after castration, we analyzed for biomarkers of cellular hypoxia in rat ventral prostates during the first 3 days following castration. Ventral prostate tissues removed from hypoxyprobe‐1‐treated adult male rats (uncastrated controls; surgically castrated for 24, 48 or 72 h, or sham‐castrated for equivalent times) were directly analyzed for evidence of hypoxia by in situ immunohistochemical evaluation of hypoxyprobe‐1 adduct formation in the prostate cells. Protein extracts from these tissues were also tested for expression of the 120 kDa hypoxia‐inducible factor‐1‐α (HIF‐1‐α) protein as well as for expression of mitogen‐activated protein kinase (MAPK) and c‐Jun N‐terminal kinase (JNK) proteins using a Western blot assay. The tyrosine phosphorylation status of the latter signaling molecules was also evaluated by Western blotting using anti‐tyrosine phosphate antibodies. Our results showed that epithelial cells of the rat ventral prostate stained positively for hypoxyprobe‐1 adducts at all times after castration, whereas cells in control tissues were unstained by this procedure. In addition, the prostatic expression of HIF‐1‐α protein was increased approximately 20‐fold at 48 h after castration compared to control tissues. Finally, although prostatic MAPK and JNK protein expression was unaltered during the early period after castration, phosphorylation of the JUN kinase protein was significantly elevated, indicating that this stress‐activated cellular signaling pathway becomes more active subsequent to castration. These results support our proposal that early castration‐induced degeneration and constriction of the vascular system of the rat ventral prostate gland leads to reduced oxygenation of prostatic epithelial cells and the activation of hypoxic cellular signaling in these cells through upregulation of HIF‐1‐α expression and stimulation of the JUN kinase signaling pathway. J. Cell. Biochem. 81:437–444, 2001.

Magnetic resonance-guided percutaneous radiofrequency ablation of renal cell carcinomas: a pilot clinical study.

Objective:The objective of this study was to assess the feasibility and efficacy of magnetic resonance imaging-(MRI) guided percutaneous radiofrequency (RF) ablation of renal cell carcinomas (RCC). Subjects and Methods:Twelve patients with RCC (63 to 82 years old) were treated with RF ablation in an interventional 0.2-Tesla open MR unit. Tumor sizes varied from 1.6 cm to 3.9 cm in maximum diameter (tumor volumes 1.9 cm3 to 28.7 cm3). RF procedures were entirely performed in the MR suite. For positioning of the MR-compatible RF-electrode, near real-time MR fluoroscopy by means of rapid gradient echo sequences (acquisition time approximately 2 seconds) was used. Monitoring of ablation was obtained by intermittent imaging with T1- and T2-weighted spin echo sequences. Results:Accurate placement of the RF electrodes was possible in all cases using near real-time MR fluoroscopy. Eleven of 12 patients were successfully treated within 1 single session; 1 patient had to be retreated for tumor relapse at 13 months follow up. Mean number of electrode repositionings under MR guidance during 1 session was 1.7; ablation time ranged between 12 and 28 minutes. Mean duration of 1 treatment session was 5 hours. Coagulation volumes ranged from 7.3 cm3 up to 30.2 cm3. All patients now appear to be disease-free with a mean follow up of 10.3 months (range, 3–23 months). Conclusion:MRI-guided RF ablation of RCC in an interventional MR unit is safe and feasible. Fast MR imaging is a convenient method for rapid positioning of MR-compatible RF electrodes. MR monitoring of ablation procedure with T2-weighted imaging allows for immediate assessment of coagulation extent.