Combining PSA and PET features to select candidates for salvage lymph node dissection in recurrent prostate cancer.

Objective: To evaluate the relationship between pre-operative PSA value, 68Ga-prostate-specific-membrane-antigen (PSMA) PET performance and oncologic outcomes after salvage lymph node dissection (sLND) for biochemical recurrent prostate cancer (PCa). Patients and methods: The study included 164 patients diagnosed with ≤2 pelvic lymph-node recurrence(s) of PCa documented on 68Ga-PSMA PET scan and treated with pelvic ± retroperitoneal sLND at 11 high-volume centres between 2012 and 2019. Pathologic findings were correlated to PSA values at time of sLND, categorized in early (<0.5 ng/ml), low (0.5-0.99 ng/ml), moderate (1-1.5 ng/ml) and high (>1.5 ng/ml). Clinical recurrence (CR)-free survival after sLND was calculated using multivariable analyses and plotted over pre-operative PSA value. Results: Median [interquartile range (IQR)] PSA at sLND was 1.1 (0.6, 2.0) ng/ml, and 131 (80%) patients had one positive spot at PET scan. All patients received pelvic sLND, whereas 91 (55%) men received also retroperitoneal dissection. Median (IQR) number of node removed was 15 (6, 28). The rate of positive pathology increased as a function of pre-operative PSA value, with highest rates for patients with pre-operative PSA > 1.5 ng/ml (pelvic-only sLNDs: 84%; pelvic + retroperitoneal sLNDs: 90%). After sLND, PSA ≤ 0.3 ng/ml was detected in 67 (41%) men. On multivariable analyses, pre-operative PSA was associated with PSA response (p < 0.0001). There were 51 CRs after sLND. After adjusting for confounders, we found a significant, non-linear relationship between PSA level at sLND and the 12-month CR-free survival (p < 0.0001), with the highest probability of freedom from CR for patients who received sLND at PSA level ≥1 ng/ml. Conclusions: In case of PET-detected nodal recurrences amenable to sLND, salvage surgery was associated with the highest short-term oncologic outcomes when performed in men with PSA ≥ 1 ng/ml. Awaiting confirmatory data from prospective trials, these findings may help physicians to optimize the timing for 68Ga-PSMA PET in biochemical recurrent PCa.

Definition and Impact on Oncologic Outcomes of Persistently Elevated Prostate-specific Antigen After Salvage Lymph Node Dissection for Node-only Recurrent Prostate Cancer After Radical Prostatectomy: Clinical Implications for Multimodal Therapy.

BACKGROUND: The optimal definition and prognostic significance of persistently elevated prostate-specific antigen (PSA) after salvage lymph node dissection (sLND) for node-only recurrent prostate cancer (PCa) remain unknown. OBJECTIVE: To assess the definition and clinical implications of persistently elevated PSA after sLND for node-only recurrent PCa after radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: The study included 579 patients treated with sLND at 11 high-volume centers between 2000 and 2016. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed the linear relationship between the first PSA after sLND and death from PCa. Different definitions of PSA persistence were included in a multivariable model predicting cancer-specific mortality (CSM) after surgery to identify the best cutoff value. We investigated the association between PSA persistence and oncologic outcomes using multivariable regression models. Moreover, the effect of early androgen deprivation therapy (ADT) after sLND was tested according to PSA persistence status and estimated risk of CSM. RESULTS AND LIMITATIONS: We found an inverse relationship between the first PSA after sLND and the probability of cancer-specific survival. PSA persistence defined as first postoperative PSA ≥0.3 ng/ml provided the best discrimination accuracy (C index 0.757). According to this cutoff, 331 patients (57%) experienced PSA persistence. The median follow-up for survivors was 48 mo (interquartile range 27-74). After adjusting for confounders, men with persistently elevated PSA had higher risk of clinical recurrence (hazard ratio [HR] 1.61), overall mortality (HR 2.20), and CSM (HR 2.59; all p < 0.001) after sLND. Early ADT administration after sLND improved survival only for patients with PSA persistence after surgery (HR 0.49; p = 0.024). Similarly, when PSA persistence status was included in multivariable models accounting for pathologic features, early ADT use after sLND was beneficial only for patients with a predicted risk of CSM at 5 yr of >10%. CONCLUSIONS: PSA persistence after sLND independently predicts adverse prognosis, with the best discrimination accuracy for CSM provided by a definition of PSA ≥ 0.3 ng/ml. We showed that when stratifying patients by final pathology results and PSA persistence status, early ADT use after sLND was beneficial only for patients with PSA persistence or with a calculated 5-yr risk of CSM of >10%, which could be useful as we await results from ongoing prospective trials. PATIENT SUMMARY: We found that for patients with prostate cancer who had lymph nodes removed after their cancer recurred, persistently elevated prostate-specific antigen (PSA) levels predict poorer prognosis. We showed that a PSA level of ≥0.3 ng/ml provides the best accuracy in identifying patients with worse prognosis. This may help to improve risk stratification after lymph node removal and allow physicians to optimize treatment strategies after surgery.

Retroperitoneal Versus Transperitoneal Robotic Partial Nephrectomy: A Multicenter Matched-pair Analysis.

BACKGROUND: With increasing acceptance of robotic partial nephrectomy over the last decade, there is an ongoing discussion about the transperitoneal versus retroperitoneal access. OBJECTIVE: To report outcomes after transperitoneal (TRPN) versus retroperitoneal (RRPN) robotic partial nephrectomy. DESIGN, SETTING, AND PARTICIPANTS: A total of 754 patients were identified from the databases of three high-volume centers who underwent either TRPN (n = 551) or RRPN (n = 203). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Perioperative data were evaluated retrospectively. A propensity score matched-pair analysis was performed with the following variables: grade of renal insufficiency, age, body mass index, tumor diameter, and preoperative aspects and dimensions used for an anatomical (PADUA) score with a subsequent subgroup analysis for tumor location. For quality outcomes, the margin, ischemia, and complications (MIC) criteria were used (negative margins, ischemia time <20 min, and no major complications). Statistical analyses included chi-square and Mann-Whitney U tests. RESULTS AND LIMITATIONS: In all, 176 patients could be matched in each group. The median tumor diameter was 28 mm with a PADUA score of 9. In 11% of RRPN versus 44% of TRPN cases, an anterior tumor location was found, and in 55% versus 30%, a posterior lesion was found (p < 0.001). Operative time (119 vs 139 min, p < 0.001) and warm ischemia time (9 vs 10 min, p = 0.003) were significantly shorter for RRPN. No significant differences were observed between intra- and postoperative complication rates, with 8% major complications in TRPN versus 3% in RRPN (p = 0.06). The MIC criteria were achieved in 90% in the RRPN versus 88% in the TRPN group, without differences for tumor location. CONCLUSIONS: Significant differences between TRPN and RRPN could be found for intraoperative time, while complication rates and quality outcomes were comparable. RRPN can also be a considerable alternative for anterior tumors. PATIENT SUMMARY: In this study, we demonstrate that robotic partial nephrectomy is feasible with either a transperitoneal or a retroperitoneal surgical access. The posterior approach can also be used for anterior renal tumors and may result in shorter operative time.

Assessing the Best Surgical Template at Salvage Pelvic Lymph Node Dissection for Nodal Recurrence of Prostate Cancer After Radical Prostatectomy: When Can Bilateral Dissection be Omitted? Results from a Multi-institutional Series.

The best surgical template for salvage pelvic lymph node dissection (sLND) in patients with nodal recurrence from prostate cancer (PCa) after radical prostatectomy (RP) is currently unknown. We analyzed data of 189 patients with a unilateral positive positron emission tomography (PET) scan of the pelvic lymph node areas, who were treated with bilateral pelvic sLND after RP at 11 high-volume centers. The primary endpoint was missed contralateral disease at final pathology, defined as lymph node positive for PCa in the side opposite to the positive spot(s) at the PET scan. Overall, 93 (49%) and 96 (51%) patients received a 11C-choline and a 68Ga prostate-specific membrane antigen (PSMA) PET scan, respectively, and 171 (90%) and 18 (10%) men had one and two positive spots, respectively. The rate of missed contralateral PCa was 18% (34/189), with the rates being 17% (29/171) and 28% (5/18) in men with one and two positive spots, respectively. While the rate of contralateral disease did not differ between 68Ga-PSMA and 11C-choline (29% and 27%, respectively) among men with two positive spots, the rate of contralateral PCa was only 6% with 68Ga-PSMA versus 28% with 11C-choline in patients with a single positive spot. This finding was confirmed at multivariable logistic regression analysis predicting missed disease at final pathology after accounting for confounders (odds ratio: 0.24; p = 0.001). However, in men with a single positive spot at 68Ga-PSMA PET/computed tomography, the rate of single confirmed lymph node metastasis at final pathology was only 33%, suggesting the need for extended template even if unilateral dissection is performed. Awaiting confirmatory studies, patients diagnosed with a single positive spot at the 68Ga-PSMA PET scan might be considered for unilateral extended pelvic sLND. PATIENT SUMMARY: We assessed the risk of missing contralateral disease in patients with a positron emission tomography (PET) scan suggestive of unilateral nodal recurrence from prostate cancer (PCa) after radical prostatectomy and who were treated with bilateral salvage lymph node dissection (sLND). Variability exists according to the number of positive spots and PET tracer, with the lowest rate of missed PCa in men diagnosed with a single positive spot at a 68Ga prostate-specific membrane antigen PET scan (6%). If replicated, our data suggest that these patients might be considered for unilateral extended pelvic sLND.

Long-term Outcomes of Salvage Lymph Node Dissection for Nodal Recurrence of Prostate Cancer After Radical Prostatectomy: Not as Good as Previously Thought.

BACKGROUND: Long-term outcomes of patients treated with salvage lymph node dissection (sLND) for nodal recurrence of prostate cancer (PCa) remain unknown. OBJECTIVE: To investigate long-term oncological outcomes after sLND in a large multi-institutional series. DESIGN, SETTING, AND PARTICIPANTS: The study included 189 patients who experienced prostate-specific antigen (PSA) rise and nodal-only recurrence after radical prostatectomy (RP) and underwent sLND at 11 tertiary referral centers between 2002 and 2011. Lymph node recurrence was documented by positron emission tomography/computed tomography (PET/CT) scan using either 11C-choline or 68Ga prostate-specific membrane antigen ligand. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome of the study was cancer-specific mortality (CSM). The secondary outcomes were overall mortality, clinical recurrence (CR), biochemical recurrence (BCR), and androgen deprivation therapy (ADT)-free survival after sLND. The probability of freedom from each outcome was calculated using Kaplan-Meier analyses. Cox regression analysis was used to predict the risk of prostate CSM after accounting for several parameters, including the use of additional treatments after sLND. RESULTS AND LIMITATIONS: At long term, 110 and 163 patients experienced CR and BCR, respectively, with CR-free and BCR-free survival at 10 yr of 31% and 11%, respectively. After sLND, a total of 145 patients received ADT, with a median time to ADT of 41 mo. At a median (interquartile range) follow-up for survivors of 87 (51, 104) mo, 48 patients died. Of them, 45 died from PCa. The probabilities of freedom from cancer-specific and all-cause death at 10 yr were 66% and 64%, respectively. Similar results were obtained in sensitivity analyses in patients with pelvic-only positive PET/CT scan, as well as after excluding men on ADT at PET/CT scan and patients with PSA level at sLND higher than the 75th percentile. At multivariable analyses, patients who had PSA response after sLND (hazard ratio [HR]: 0.45; p = 0.001), and those receiving ADT within 6 mo from sLND (HR: 0.51; p = 0.010) had lower risk of death from PCa. CONCLUSIONS: A third of men treated with sLND for PET-detected nodal recurrence of PCa died at long term, with PCa being the main cause of death. Salvage LND alone was associated with durable long-term outcomes in a minority of men who significantly benefited from additional treatments after surgery. Taken together, all these data argue against the use of metastasis-directed therapy alone for patients with node-only recurrent PCa. These men should instead be considered at high risk of systemic dissemination already at the time of sLND. PATIENT SUMMARY: We assessed long-term outcomes of patients treated with salvage lymph node dissection (sLND) for node-recurrent prostate cancer (PCa). In contrast with prior evidence, we found that the majority of these men recurred after sLND and eventually died from PCa. A significant survival benefit associated with the administration of androgen deprivation therapy after sLND suggests that sLND should be considered part of a multimodal approach rather than an exclusive treatment strategy.

Underestimation of Positron Emission Tomography/Computerized Tomography in Assessing Tumor Burden in Prostate Cancer Nodal Recurrence: Head-to-Head Comparison of 68Ga-PSMA and 11C-Choline in a Large, Multi-Institutional Series of Extended Salvage Lymph Node Dissections.

PURPOSE: We compared the use of 11C-choline and 68Ga-prostate specific membrane antigen in men undergoing salvage lymph node dissection for nodal recurrent prostate cancer. MATERIALS AND METHODS: The study included 641 patients who experienced prostate specific antigen rise and nodal recurrence after radical prostatectomy and underwent salvage lymph node dissection. Lymph node recurrence was documented by positron emission tomography/computerized tomography using 11C-choline (407, 63%) or 68Ga-PSMA ligand (234, 37%). The outcome was underestimation of tumor burden (difference between number of positive nodes on final pathology and number of positive spots at positron emission tomography/computerized tomography). Multivariable analysis tested the association between positron emission tomography/computerized tomography tracer (11C-choline vs 68Ga-PSMA) and tumor burden underestimation. RESULTS: Overall the extent of tumor burden underestimation was significantly higher in the 11C-choline group compared to the 68Ga-PSMA group (p <0.0001), which was confirmed on multivariable analysis (p=0.028). Repeating these analyses according to prostate specific antigen, tumor burden underestimation was lower with 68Ga-PSMA only when prostate specific antigen was 1.5 ng/ml or less. Conversely, the underestimation of the 2 tracers became similar when prostate specific antigen was greater than 1.5 ng/ml. Furthermore, we evaluated the risk of underestimation by number of positive spots on positron emission tomography/computerized tomography. The higher the number of positive spots the higher the underestimation of tumor burden regardless of the tracer used (p=0.2). CONCLUSIONS: Positron emission tomography/computerized tomography significantly underestimates the burden of prostate cancer recurrence, regardless of the tracer used. 68Ga-PSMA was associated with a lower rate of underestimation in patients with a prostate specific antigen below 1.5 ng/ml and a limited nodal tumor load. In all other men there was no benefit from 68Ga-PSMA over 11C-choline in assessing the extent of nodal recurrence.

Identifying the Optimal Candidate for Salvage Lymph Node Dissection for Nodal Recurrence of Prostate Cancer: Results from a Large, Multi-institutional Analysis.

BACKGROUND: Salvage lymph node dissection (SLND) represents a possible treatment option for prostate cancer patients affected by nodal recurrence after local treatment. However, SLND may be associated with intra- and postoperative complications, and the oncological benefit may be limited to specific groups of patients. OBJECTIVE: To identify the optimal candidates for SLND based on preoperative characteristics. DESIGN, SETTING, AND PARTICIPANTS: The study included 654 patients who experienced prostate-specific antigen (PSA) rise and nodal recurrence after radical prostatectomy (RP) and underwent SLND at nine tertiary referral centers. Lymph node recurrence was documented by positron emission tomography/computed tomography (PET/CT) scan using either 11C-choline or 68Ga-labeled prostate-specific membrane antigen ligand. INTERVENTION: SLND. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The study outcome was early clinical recurrence (eCR) developed within 1 yr after SLND. Multivariable Cox regression analysis was used to develop a predictive model. Multivariable-derived coefficients were used to develop a novel risk calculator. Decision-curve analysis was used to evaluate the net benefit of the predictive model. RESULTS AND LIMITATIONS: Median follow-up was 30 (interquartile range, 16-50) mo among patients without clinical recurrence (CR), and 334 patients developed CR after SLND. In particular, eCR at 1 yr after SLND was observed in 150 patients, with a Kaplan-Meier probability of eCR equal to 25%. The development of eCR was significantly associated with an increased risk of cancer-specific mortality at 3 yr, being 20% versus 1.4% in patients with and without eCR, respectively (p<0.0001). At multivariable analysis, Gleason grade group 5 (hazard ratio [HR]: 2.04; p<0.0001), time from RP to PSA rising (HR: 0.99; p=0.025), hormonal therapy administration at PSA rising after RP (HR: 1.47; p=0.0005), retroperitoneal uptake at PET/CT scan (HR: 1.24; p=0.038), three or more positive spots at PET/CT scan (HR: 1.26; p=0.019), and PSA level at SLND (HR: 1.05; p<0.0001) were significant predictors of CR after SLND. The coefficients of the predictive model were used to develop a risk calculator for eCR at 1 yr after SLND. The discrimination of the model (Harrel'sC index) was 0.75. At decision-curve analysis, the net benefit of the model was higher than the "treat-all" option at all the threshold probabilities. CONCLUSIONS: We reported the largest available series of patients treated with SLND. Roughly 25% of men developed eCR after surgery. We developed the first risk stratification tool to identify the optimal candidate to SLND based on routinely available preoperative characteristics. This tool can be useful to avoid use of SLND in men more likely to progress despite any imaging-guided approach. PATIENT SUMMARY: The risk of early recurrence after salvage lymph node dissection (SLND) was approximately 25%. In this study, we developed a novel tool to predict the risk of early failure after SLND. This tool will be useful to identify patients who would benefit the most from SLND from other patients who should be spared from surgery.

Interstitial high-dose-rate brachytherapy as salvage treatment for locally recurrent prostate cancer after definitive radiation therapy: Toxicity and 5-year outcome.

PURPOSE: We report our results with interstitial high-dose-rate brachytherapy (HDR-BT) as a salvage therapy option after external beam therapy with or without BT. Emphasis was put on toxicity and 5-year outcome. METHODS AND MATERIALS: From 2003 to 2011, 29 patients with local failure after previous radiotherapy for prostate cancer were treated with salvage interstitial HDR-BT. The diagnosis of local recurrence was made on the basis of choline positron emission tomography. Salvage HDR-BT was given in three fractions with a single dose of 10 Gy per fraction and weekly. The target volume covered the peripheral zone of the prostate and the positron emission tomography-positive area. Acute and late toxicities were documented according to common terminology criteria for adverse events (CTCAE v 4.0). RESULTS: Twenty-two patients with minimum followup of 60 months were analyzed. The 5-year overall survival was 95.5% with a disease-specific survival of 100%. The 5-year biochemical control was 45%. Late grade 2 gastrointestinal toxicities were observed in two patients (9%). No grade 3 or higher gastrointestinal late toxicities were observed. Urinary incontinence found in 2 patients (9%) and grade 2 obstruction of urinary tract occurred in one patient (4%). CONCLUSIONS: Interstitial HDR-BT was feasible and effective in the treatment of locally recurrent prostate cancer after definitive radiotherapy. The long-term toxicity was low and acceptable.

Barry shunt for treatment of a 76-hour stuttering priapism without subsequent erectile dysfunction.

INTRODUCTION: This paper reports treatment of a 76-hour low-flow priapism with a shunting procedure that was first described by Barry in 1976. We were able to observe the preservation of erectile function despite the long period of ischemia. A review of the literature shows that there are few reports of erectile function recovery after a priapism of similar duration. MATERIALS AND METHODS: A 42-year-old patient presented with a 76-hour priapism, probably caused by consumption of alcohol and illegal drugs. A Barry Shunt procedure was performed. The erectile function of the patient was assessed by means of International Index of Erectile Function score over a follow-up period of 30 months. Moreover, we reviewed different surgical options for treatment of priapism in the literature. RESULTS: Partial return of erection without sexual arousal occurred on two occasions during the 10-day hospitalization, but was treated by manipulation of the penis, ie, by milking the tumescence into the shunt. After 3 months, the shunt was still palpable as a subcutaneous swelling. Six months postoperatively, the residual swelling had disappeared. The International Index of Erectile Function score was of 21 without phosphodiesterase type 5 inhibitors after a follow-up of 2.5 years. CONCLUSION: Barry shunt is an effective alternative surgical option for the treatment of low-flow priapism. In the case of our patient, it was also effective after a 76-hour-lasting priapism.

Sensitivity and specificity of PET/CT regarding the detection of lymph node metastases in prostate cancer recurrence.

BACKGROUND: The aim of the study is to assess the efficacy of choline PET/CT regarding the detection of lymph node (LN) metastases in recurrent prostate cancer (PCa). METHODS: 49 patients with a biochemical recurrence of PCa (PSA >0.2 ng/ml) were included in the study. All patients were selected for further diagnostics with a choline-PET/CT. All patients underwent salvage extended lymphadenectomy. The PET/CT result and the histological findings were analyzed regarding the specificity and sensitivity and with respect to the localization of the metastases. The detection rate of LN metastases was analyzed with respect to interdependencies between the pre-PET/CT PSA-value as well as the role of prior ADT. RESULTS: 41 out of 49 (83.6%) patients showed positive PET/CT results. Positive LNs were found in 27 out of 49 patients (55.1%). 48.9% of the PET-CT-findings proved true positive, 36.7% were found to be false positive. 8.1% proved true negative and 8.1% false negative. This results in a specificity of 22.7% and a sensitivity of 85.1%. Out of the true positive PET/CT scans, 61.9% were not congruent regarding the localization of positive LNs. In patients with PSA [greater than or equal to] 5 ng/ml, the sensitivity of the PET/CT result was 93.7%, while specificity was 0%. In 24 patients who underwent ADT prior to the PET/CT diagnostics, the sensitivity was 84.6% and specificity 9.0%. CONCLUSIONS: The reliability of PET/CT imaging for detection of LN metastases is limited by a high false-positive rate. The influence of ADT further diminishes the PET/CT reliability. Sensitivity of the PET/CT is highest in patients with a PSA of [greater than or equal to] 5 ng/ml. Based on our results, we propose the following conclusions: 1. There is no well-established diagnostic alternative to Choline-PET/CT Scan. Therefore this method may continue to be performed in patients with BCR. 2. It is not sufficient to remove only those LNs that show up in the PET/CT. 3. Salvage extended lymphadenectomy should follow a predefined template (e.g. the "Kiel template") and not just the PET/CT scan results.

Experience with botulinum toxin type A in the treatment of neurogenic detrusor overactivity in clinical practice.

Control of the lower urinary tract is a complex, multilevel process that involves both the peripheral and central nervous system. Neurogenic lower urinary tract dysfunction (LUTD) is a widespread chronic illness that impairs millions of people worldwide. Neurogenic LUTD has a major impact on quality of life, affecting emotional, social, sexual, occupational and physical aspects of daily life, and in addition to the debilitating manifestations for patients, it also imposes a substantial economic burden on every healthcare system. First-line treatment for neurogenic LUTD includes antimuscarinics and some form of catheterization, preferably intermittent self-catheterization. However, the treatment effect is often unsatisfactory, so that other options have to be considered. Moreover, neurogenic LUTD is a challenge because all available treatment modalities (i.e. conservative, minimally invasive and invasive therapies) may fail. In recent years, botulinum neurotoxin type A (BoNT/A) treatment has been shown to be an effective pharmacological therapy option in patients refractory to antimuscarinic and neurogenic detrusor overactivity (NDO). Several studies have shown that BoNT/A injection significantly reduces detrusor muscle overactivity. Also BoNT/A treatment of NDO has revealed a significant improvement of lower urinary tract function with regard to reduced urinary incontinence, reduced detrusor pressure, increased bladder capacity and improved quality of life in NDO.

Extended lymphadenectomy "step by step" in patients undergoing radical prostatectomy.

OBJECTIVES: To describe a surgical technique of pelvic lymph node dissection (PLND) in prostate cancer patients. The idea was to standardize the procedure of PLND and to increase the significance of lymphadenectomy as a part of radical prostatectomy (RP). The best ways to achieve this are (1) to describe the surgical procedure in detail, (2) to improve the knowledge of metastatic spread, and (3) to improve the management of complications. METHODS: One-hundred six patients with localized prostate carcinoma were treated with RP, including extended PLND. The number of removed lymph nodes (LNs) was correlated with histology and compared with that reported in the literature. Our aim was to observe technical differences that probably accrue in clinical outcomes. We proposed a conceptual schema of PLND. RESULTS: LN metastases were detected in 15 of 106 patients (14.15%). Positive sentinel LNs were detected in 11 of these 15 patients (73.3%). The average number of removed LNs was 20.5 (range +5). In 4 of 15 patients (26.5%), positive LNs were found in the fossa obturatoria; in 4 patients (26.5%) in the region of the external iliac artery; in 3 patients (20%) in the internal LN region; in 2 patients (13%) in the region of the common iliac artery; in 1 patient (7%) in the presciatic area; and in 1 patient (7%) in the sacral region. CONCLUSIONS: The standard routine was: (1) dissection of LN tissue along the common iliac artery, (2) dissection of LN tissue in the presciatic area, (3) dissection of LN tissue parasacral, and (4) peritoneal fenestration.

Lymphatic spread in squamous cell carcinoma of the penis is independent of elevated lymph vessel density.

OBJECTIVE: To examine the potential effect of tumour-induced lymphangiogenesis in squamous cell carcinoma of the penis as a possible mechanism responsible for lymphatic spread. PATIENTS AND METHODS: Specimens from 65 patients with invasive tumours (31 with and 34 without metastases) were evaluated for lymphatic vessel density (LVD) by the 'hot-spot' method as the density of lymphatic endothelium hyaluronan receptor (LYVE-1)-positive lymphatic vessels per unit area of tissue. LVD was examined in peritumoral, intratumoral and normal tissue areas. The LVD of each tumour in these locations was calculated as the mean of the three highest lymph vessel counts in three to five hot-spots. The nodal status was based on histopathological examination or an uneventful follow-up of >or=2 years. RESULTS: In all patients the mean (SD) peritumoral LVD of 8.05 (3.14)/0.75 mm(2) was significantly higher than for intratumoral and normal tissue, of 4.67 (2.58) and 5.20 (1.87), respectively (P < 0.001). The slightly lower intratumoral LVD than in normal tissue was not significant. The peritumoral LVD was 8.07 (3.29) in metastatic and 8.03 (3.03) in non-metastatic carcinomas. The intratumoral LVD was 5.13 (3.01) in node-positive carcinomas and 4.28 (2.15) in tumours with no lymphatic node metastasis (LNM). Comparing tumours with and without LNM, there was no statistically significant difference between intra- and peritumoral LVD. CONCLUSION: Increased LVD does not significantly affect the lymphatic spread in penile carcinomas, indicating that there must be alternative mechanisms that selectively enable tumour cells to invade lymph vessels and to metastasize into the lymph nodes.

Lymph-node metastases in intermediate-risk squamous cell carcinoma of the penis.

OBJECTIVE: To evaluate the metastatic risk of pT1 G2 squamous cell carcinoma (SCC) of the penis. PATIENTS AND METHODS: We retrospectively reviewed 20 patients with pT1 G2 penile SCC and determined their groin status at first presentation, their nodal status after inguinal lymph node dissection and their follow-up for at least 18 months. RESULTS: Four of the 20 patients had a clinically positive groin; three of these were found to have lymph node metastases. Among the 16 patients with a clinically negative groin, one of five who had surgical lymph node staging had lymph node metastases. During surveillance six of 11 patients developed lymph node metastases. There was lymphovascular invasion in three of 10 patients with lymph node metastases. CONCLUSIONS: As the metastatic risk of pT1 G2 penile SCC was 50% in this series of patients, and 44% in those with an initially negative groin, surgical staging of inguinal lymph nodes is recommended in patients with pT1 G2 penile SCC.

Conditioning stimulus can influence an external urethral sphincter contraction evoked by a magnetic stimulation.

AIMS: To study the effect of a conditioning stimulus on an external urethral sphincter (EUS)contraction evoked by a magnetic stimulation at different time intervals. METHODS: Seven healthy male volunteers underwent EUS pressure measurement. At baseline, magnetic stimulation of the lumbosacral spinal cord above the motor threshold was performed and evoked EUS pressure responses were recorded. The lumbosacral magnetic stimulation was repeated with same intensity, while a selective electrical dorsal penile nerve stimulation below the bulbocavernosus reflex (BCR) threshold was preceding at five different intervals (10, 20, 30, 50, 100 msec). The protocol was performed with empty and full bladder (BLA), and baseline responses were statistically compared to those with combined stimulation. RESULTS: When the dorsal penile nerve electrical stimulation preceded the lumbosacral magnetic stimulation by 20 msec (P=0.0048), 50 msec (P=0.0039), or 100 msec (P=0.0002), the amplitudes of the EUS pressure response with empty BLA were significantly reduced compared to lumbosacral magnetic stimulation alone. With a filled BLA, the amplitudes of the EUS were significantly reduced only at an interval of 50 msec (P<0.0001). CONCLUSIONS: A conditional sensory pudendal stimulation seems to have the capacity to inhibit the external urethral sphincter contraction induced by a magnetic stimulation. The inhibitory effect seems to depend on the latency between the peripheral and lumbosacral stimulation as well as on the degree of BLA filling. It remains to be proved if the neuromodulative effect of the conditional stimulus occurs at a spinal or supraspinal level.

Penile carcinoma (pT1 G2): surveillance or inguinal lymph node dissection?

BACKGROUND: Due to the low incidence of squamous cell penile cancer and lack of well-designed studies, controversies persist over the therapeutic approach in patients with pT1 G2 carcinoma. PATIENTS AND METHODS: Between 1992 and 2003, 16 patients with T1 squamous penile cancer were treated in our institution either by surveillance or by inguinal lymph node dissection (ILND). RESULTS: A total of 8 primary lesions were classified as pT1 G2 carcinoma with 4 tumors developing early or delayed inguinal metastatic disease. CONCLUSIONS: The natural behavior of pT1 G2 squamous penile carcinoma and its metastatic potential has been underestimated in recent literature. Since morbidity after early ILND has markedly decreased and its superiority over delayed ILND has been shown, we advocate the early modified inguinal lymph node dissection until strong prognostic factors for positive inguinal lymph nodes have been validated.

Immunocyt and the HA-HAase urine tests for the detection of bladder cancer: a side-by-side comparison.

OBJECTIVES: The reliable detection of bladder cancer from urine specimen remains an unsolved problem. Especially superficial bladder cancer can be missed with urine tests. We assessed the sensitivity and specificity of the commercial Immunocyt test in a side-by-side comparison with the HA-HAase urine test and cytology. The Immunocyt test measures the immunocytological expression of sulfated mucin-glycoproteins and glycosylated forms of the carcinoembryonic antigen in urine. With the HA-HAase urine test the level of hyaluronic acid (HA) and its degrading enzyme hyaluronidase (HAase) are measured in an ELISA-like test. METHODS: A total of 94 consecutive patients were studied and among these 30 patients had bladder cancer and 64 were controls. Among bladder cancer patients, there were 14 pTa, 9 pT1, 5 pT2 and 2 carcinoma in situ (CIS) transitional cell carcinoma of the bladder, respectively. The controls consisted of 55 patients with a history of bladder cancer but no evidence of tumor at the follow-up cystoscopy and 9 benign prostatic hyperplasia (BPH) patients. The 30 transitional cell cancer specimens had 4 (13%) grade 1 tumors, 15 (50%) grade 2 tumors and 11 (37%) grade 3 tumors. Sensitivity and specificity as well as the positive and negative predictive values of each test were evaluated. RESULTS: The sensitivity of the HA-HAase urine test (83.3%; 25/30) was significantly higher than the Immunocyt at 63.3% (19/30) (p = 0.038, McNemar test) and cytology (73%; p < 0.05). The specificity of the HA-HAase test (78.1%; 50/64), Immunocyt (75%; 48/64) and cytology (79.7%; 51/64) were comparable. The prevalence of bladder cancer in our study was 31%. The positive predictive value (PPV) of the HA-HAase test (64.1%) was significantly higher than the Immunocyt test (54.3%). The negative predictive value (NPV) of the HA-HAase test (90.9%) was also higher than the Immunocyt test (81.3%). The PPV and NPV values for cytology were 62.9% and 86.4%, respectively. False negative patients in the HA-HAase urine test were 5 pTa tumors (2 G1, 2 G2 and 1 G3). False negative patients in the Immunocyt test were 7 pTa tumors (1 G1 and 6 G2), 3 pT1 (2 G2, 1 G3) and 1 pT2 G3, respectively. CONCLUSIONS: The sensitivity of the HA-HAase urine test is significantly higher than that of the Immunocyt test to detect bladder cancer. Specificity, as well as the PPV and NPV of the HA-HAase test were higher than that of the Immunocyt test. With a prevalence of 31% bladder cancer patients in all hematuria patients studied, a typical distribution of patients in a urological clinic is presented. Longer follow up of the study patients will give more information on the value of these tests in the detection of bladder cancer.

Effect of subthalamic deep brain stimulation on the function of the urinary bladder.

Detrusor hyperreflexia is a relevant clinical symptom for patients suffering from Parkinson's disease. In a series of 16 patients, we demonstrated that subthalamic deep brain stimulation has a significant and urodynamically recordable effect leading to a normalization of pathologically increased bladder sensibility.