Is There a Role for Functional MRI for the Assessment of Extracapsular Extension in Prostate Cancer?

BACKGROUND/AIM: Exctracapsular extension (ECE) in prostate cancer has a high impact on treatment decision. MRI might predict presence of ECE non-invasively. PATIENTS AND METHODS: Triplanar T2w-sequences, DWI (diffusion weighted imaging) and DCE (dynamic contrast-enhanced imaging) of 34 patients with PCa were analyzed to prior prostatectomy. Sensitivity (SS) and specificity (SP) of T2w, apparent diffusion coefficient (ADC), plasma flow (PF) and mean transit time (MTT) normalized by PCa/normal tissue ratio for prediction of CI (capsular infiltration)/ECE were determined by area-under-the-receiver-operating-characteristics analysis. RESULTS: SS/SP for detecting ECE was 29/85. AUC (area under the curve) of ECE cases was 0.98/0.92/0.69 (cut-off-ratios 3.2/0.51/0.46), SS 93/100/86% and SP 95/80/50% for PF-/MTT-/ADC-ratios, respectively. PF- and MTT-ratios between CI and without CI/ECE differed significantly (PF, p<0.0001; MTT, p=0.0134) with SS/SP 84/89% for PF and SS/SP 52/100% for MTT-ratios. No significant differences regarding ADC-ratios were identified. CONCLUSION: ECE/CI can be assessed by quantitative DCE analysis with great diagnostic confidence and higher specificity than ADC.

Microvascular invasion of testicular nonseminomatous germ cell tumors: implications of separate evaluation of lymphatic and blood vessels.

PURPOSE: We separately evaluated the lymphatic and blood vascular systems to assess the diagnostic accuracy of microvascular invasion and identify predictive markers for occult metastasis of testicular nonseminomatous germ cell tumors. MATERIALS AND METHODS: Tissue samples of 86 patients treated for testicular nonseminomatous germ cell tumors (stage 1 in 48 and stage greater than 1 in 38) were stained using the lymphatic endothelial cell specific marker LYVE-1 and the blood vessel endothelial cell marker von Willebrand factor. We assessed lymph vessel density in LYVE-1 stained sections and blood vessel density in von Willebrand factor stained sections. Lymphovascular invasion in LYVE-1 stained sections and blood vascular invasion in von Willebrand factor stained sections were documented. Parameters were correlated with standard clinicopathological data. RESULTS: Blood vessel density in von Willebrand factor sections was significantly greater than lymphatic vessel density in LYVE-1 sections (p<0.001). Peritumor and nontumor lymphatic vessel density in LYVE-1 sections was associated with metastasis at diagnosis (OR 1.277/U, p=0.020 and OR 1.113/U, p=0.095). Lymphovascular invasion in LYVE-1 sections was significantly associated with metastasis (OR=4.517, p=0.002) but blood vascular invasion in von Willebrand factor sections was only slightly significant (OR 2.261, p=0.071). Only lymphovascular invasion in LYVE-1 stained sections was significantly associated with metastasis in a multiple logistic regression model. Microvascular invasion in hematoxylin and eosin stained sections was not associated with metastasis but microvascular invasion evaluated in LYVE-1 and von Willebrand factor stained sections was associated with metastasis (OR 3.506, p=0.016). CONCLUSIONS: Lymphovascular invasion in LYVE-1 stained sections was the most important predictive parameter for metastasis at diagnosis, suggesting greater relevance of the lymphatic system in metastatic dissemination of testicular nonseminomatous germ cell tumors. Vascular endothelial cell specific markers provide higher diagnostic accuracy for microvascular invasion. Our results may impact the current concept of microvascular invasion used for risk stratification of clinical stage 1 testicular nonseminomatous germ cell tumors.

The role of lymph vessel density and lymphangiogenesis in metastatic tumor spread of nonseminomatous testicular germ cell tumors.

OBJECTIVES: To evaluate the role of lymph vessel density (LVD) and lymphangiogenesis in nonseminomatous testicular germ cell tumors (NSGCT) using the specific lymphatic endothelial cell (LEC) marker LYVE-1. MATERIALS AND METHODS: NSGCT specimens of 77 patients (32 with and 45 without metastases) were stained immunohistochemically using a LYVE-1 antibody. LVD was measured in different representative areas by the standardized "hot spot" method. Fluorescence double stainings for LYVE-1 and Ki-67 were performed. The median follow-up period was 46 (range 3-170) months. RESULTS: The mean peritumoral (2.16 ± 2.17) and nontumoral LVD (3.17 ± 3.24) were significantly higher than intratumoral LVD (0.16 ± 0.73) (both: P = < 0.001). In 5 patients proliferating LECs were observed. The peritumoral LVD was 2.66 (± 2.31) and 1.80 (± 2.02) in metastatic and nonmetastatic NSGCT, respectively. A higher peritumoral LVD was associated with the presence of metastases at the time of diagnosis (P = 0.087). The mean peritumoral LVD in tumors with and without lymphovascular invasion (LVI) was 3.33 (± 2.20) and 1.62 (± 1.95), respectively (P < 0.001). The presence of LVI detected by LYVE-1 (LVI-LYVE-1) was independently associated with metastatic disease (logistic regression; P = 0.045). CONCLUSIONS: The presence of a high peritumoral LVD and LVI-LYVE-1 are both associated with metastatic disease in NSGCT. LVI-LYVE-1 was independently associated with the presence of metastases at the time of diagnosis. Proliferating LECs are present, suggesting that lymphangiogenesis may promote metastatic dissemination of tumor cells in NSGCT.

During twenty years of Cisplatin-based therapy the face of nonseminomatous testicular germ cell tumors is still changing: an evaluation of presentation, management, predictive factors and survival.

PURPOSE: To assess the changing presentation and treatment of nonseminomatous testicular germ cell tumors (NSGCT) and to investigate predictive factors for the status of metastasis at diagnosis and on relapse and death. MATERIALS AND METHODS: Retrospective record review of 147 patients that underwent inguinal orchiectomy from 1987-2007. Follow-up data was available for 102 patients (median follow-up: 80 months (0-243); 96 patients alive). RESULTS: Mean patients age increased (p = 0.015) and more patients were diagnosed in clinical stage I (CSI) (p = 0.040). The fraction of yolk sac (YS) elements inclined (p = 0.030) and pT2 tumors increased (p < 0.001). Retroperitoneal lymph node dissection (RPLND) declined whereas more patients were treated with chemotherapy (p < 0.001; p = 0.004). There was an increase in relapse free (RFS) and cancer specific survival (CSS) due to an improvement in patients with disseminated disease (p = 0.014; p < 0.001). The presence of YS and teratoma elements showed a reduction in the odds ratio (OR) for metastasis at diagnosis (p = 0.002, OR: 0.262; p = 0.009, OR: 0.428) whereas higher pT-stage was associated to their presence (p = 0.039). Patients with disseminated disease (CS > I) showed a declined CSS compared to CSI patients (p = 0.055). The presence of YS elements was associated to an improved RFS (p = 0.038). CONCLUSIONS: In our single institution study the face of NSGCT markedly changed over 20 years even after the introduction of Cisplatin-based chemotherapy. These changes were accompanied by an improvement in RFS and CSS. When dealing with NSGCT patients such observations now and in the future should be taken into account.

During twenty years of Cisplatin-based therapy the face of nonseminomatous testicular germ cell tumors is still changing: an evaluation of presentation, management, predictive factors and survival

Purpose: To assess the changing presentation and treatment of nonseminomatous testicular germ cell tumors (NSGCT) and to investigate predictive factors for the status of metastasis at diagnosis and on relapse and death. Materials and Methods: Retrospective record review of 147 patients that underwent inguinal orchiectomy from 1987-2007. Follow-up data was available for 102 patients (median follow-up: 80 months (0-243); 96 patients alive). Results: Mean patients age increased (p = 0.015) and more patients were diagnosed in clinical stage I (CSI) (p = 0.040). The fraction of yolk sac (YS) elements inclined (p = 0.030) and pT2 tumors increased (p < 0.001). Retroperitoneal lymph node dissection (RPLND) declined whereas more patients were treated with chemotherapy (p < 0.001; p = 0.004). There was an increase in relapse free (RFS) and cancer specific survival (CSS) due to an improvement in patients with disseminated disease (p = 0.014; p < 0.001). The presence of YS and teratoma elements showed a reduction in the odds ratio (OR) for metastasis at diagnosis (p = 0.002, OR: 0.262; p = 0.009, OR: 0.428) whereas higher pT-stage was associated to their presence (p = 0.039). Patients with disseminated disease (CS > I) showed a declined CSS compared to CSI patients (p = 0.055). The presence of YS elements was associated to an improved RFS (p = 0.038). Conclusions: In our single institution study the face of NSGCT markedly changed over 20 years even after the introduction of Cisplatin-based chemotherapy. These changes were accompanied by an improvement in RFS and CSS. When dealing with NSGCT patients such observations now and in the future should be taken into account. .

Lymph vessel density in seminomatous testicular cancer assessed with the specific lymphatic endothelium cell markers D2-40 and LYVE-1: correlation with pathologic parameters and clinical outcome.

OBJECTIVES: To evaluate the role of lymph vessel density (LVD) and lymphangiogenesis in seminomatous testicular cancer (STC) by using the lymphatic endothelial cell (LEC) markers LYVE-1 and D2-40. METHODS AND MATERIALS: Paraffin embedded tumor specimens from 40 patients with STC were stained by specific D2-40 and Lyve-1 antibodies. LVD was measured in different representative and standardized areas. Fluorescence double immunostaining for Lyve-1 and Ki-67 was performed and results were correlated with clinicopathologic data. The median follow-up period was 55 (range 10-135) months. RESULTS: Mean intratumoral LVD (D2-40: 1.30 ± 1.99; Lyve-1: 1.82 ± 2.34) was significantly lower than peritumoral LVD (D2-40: 4.94 ± 2.58; Lyve-1: 4.62 ± 2.73) and LVD in nontumoral areas (D2-40: 4.81 ± 3.79; Lyve-1: 4.22 ± 3.19). There was no significant difference between LVD measures when using D2-40 or LYVE-1. Detection rates of lymphatic vascular invasion (LVI) were significantly higher than in conventional HE-stained sections (77.5% vs. 52.5%). No proliferating lymphatic vessels were found. CONCLUSIONS: We found that LVD is decreased within tumor areas of STC. Despite a higher peritumoral LVD, no signs of proliferating endothelial cells were observed, suggesting a lack of lymphangiogenesis in STC. Detection of LVI can be optimized by specific D2-40 or LYVE-1 staining.

Initial experience with a newly developed antirefluxive ureter stent.

The objective of this study was to assess the functional efficacy of newly developed antirefluxive ureter stents (DJ), by performing immediate post-stenting cystograms on patients with acute ureteral obstruction requiring a DJ stent, and assessing stent-related symptoms by means of ureteral stent symptoms questionnaire (USSQ). Patients with acute hydronephrosis requiring internal drainage were randomized to receive either an antirefluxive DJ or a conventional DJ (7 Fr., 26 cm, polyurethane, Urovision(®), Germany). Mean stone size was 6.64 ± 3.33 and 6.5 ± 3.54 mm. Immediately after correct placement of the DJ, 200 ml of diluted contrast media was introduced into the bladder under fluoroscopic control to detect vesicoureteral reflux (VUR). Patients completed German versions of the USSQ on days 2 and 7 following stent placement, and 1 week after stent removal. The results were analyzed. 13 conventional and 16 antirefluxive stents were placed in 29 patients. Reflux was documented in eight conventionally stented patients (62.5%). Two of the 16 patients with antirefluxive stents (22%) presented reflux. 1 week after stent implantation, the mean pain value was 1.1 in the antirefluxive group and 3 in the standard group (p < 0.062). Flank pain during micturition occurred after 2 days in seven patients (58%) with standard stents and in three patients (33%) with antirefluxive stents (p < 0.23). 1 week after stent insertion, flank pain had dropped to 40% in the standard group and 11% in the antirefluxive group (p < 0.3). Our initial experience showed that the antirefluxive system might be effective in terms of reflux prevention and reduction of stent related symptoms especially during sexual intercourse.

Standardized comparison of prostate morcellators using a new ex-vivo model.

BACKGROUND AND PURPOSE: Transurethral laser enucleation of the prostate is a common therapeutic option for the treatment of benign prostate enlargement. Evacuation of the enucleated tissue from the bladder is usually performed by electric morcellators. Until now, a standardized evaluation of the different morcellator settings does not exist. Therefore, we developed an ex-vivo model to find the best settings for four different morcellators. MATERIALS AND METHODS: We morcellated pieces of a prostate adenoma after an open adenomectomy. The same speed settings were used to morcellate commercially available minced meat, fine pork sausage meat, and bovine heart, all of which had been cooked for 10 minutes using a Piranha Morcellator. We also morcellated raw pig perirenal fat tissue, raw pig liver, and raw bovine heart. The pieces were morcellated at different speed settings in an open water tank filled with saline. Because raw bovine heart showed to be the most equivalent tissue, we morcellated five pieces with four different settings of four different morcellators: The Piranha, the VersaCut, and two morcellator prototypes. RESULTS: The median retrieval rate for the prostate adenoma was 14.02 (3.7-19.8) g/min. The retrieval rate for raw bovine heart was 13.75 (5.66-20) g/min. The maximum morcellation rates of the morcellators were: Piranha 20 (19.3-21.4) g/min, VersaCut 10.8 (8.2-13.1) g/min, Karl Storz prototype 9.8 (7.9-10.76) g/min, and Richard Wolf prototype 38.6 (35.3-42.9) g/min. CONCLUSION: Raw bovine heart tissue is suitable for ex-vivo testing of prostate morcellators and can replace human prostate tissue in this standardized setting. In our ex-vivo study, the morcellation rates of the different morcellators increased with optimized oscillation speed and suction power settings. This needs to be confirmed in clinical studies.

Changes of stage, predictive factors and adjuvant treatment modalities in seminomatous testicular cancer from 1987 to 2007 and their impact on the status of metastasis, recurrence-free and overall survival: a single-center analysis.

INTRODUCTION: To observe the changing presentation of seminomatous testicular cancer (STC), placing particular emphasis on predictive factors with a view to evaluating their impact on the status of metastasis, recurrence-free survival (RFS) and overall survival (OAS). MATERIALS AND METHODS: 180 patients with STC were evaluated retrospectively. Four study periods were generated and compared for changes. The data were analyzed for predictive factors for metastasis. Mean follow-up was 83 months (range 10-246, patients alive = 146). RESULTS: The number of STC patients increased constantly throughout 2007. From 1992 onwards, significantly more patients were diagnosed as being in CS1 (p = 0.001). The odds ratio (OR) of metastasis was significantly higher for pT3 than pT2 STC (OR 12.4 vs. 1.7; p = 0.003); pT1 tumors showed a lower risk factor. The 10- and 15-year RFS were 91 and 85%, respectively. Patients in clinical stages higher than CS1 (CS>1) had significantly reduced RFS (p < 0.001). The 5- and 10-year OAS were 97 and 96%, respectively. Patients in CS>1 had significantly reduced OAS rates (p = 0.013). CONCLUSIONS: The number of STC cases is increasing, particularly in the case of patients in CS1. This emphasizes the need for surveillance regimens and makes the evaluation of predictive factors for metastasis, recurrence and survival essential.

Thulium:YAG laser enucleation (VapoEnucleation) of the prostate: safety and durability during intermediate-term follow-up.

PURPOSE: Thulium:YAG (Tm:YAG) VapoEnucleation has been introduced and relief of obstruction was demonstrated. The aim of this study was to proof durability of the outcomes in patients with an postoperative follow-up >12 month. METHODS: VapoEnucleation was performed using a 70 Watt continuous-wave-laser. After enucleation tissue was morcellated within the bladder. Patients were followed in terms of improvement of uroflow, intra- and postoperative course and for occurring complications. RESULTS: 88 consecutive patients with prostatic enlargement underwent our initial series of VapoEnucleation. Prostatic volume was 61.3 +/- 24.0 cc (30-160). OR-time was 72 min +/-26.6 (35-144) and laser-time 32.4 +/- 10.1 min (16.3-59.3). Applied laser energy was 123.7 +/- 40.6 kJ (67.8-240.9). Foley catheter-time was 2.1 +/- 1.06 days on average. In 79/88 patients the postoperative period extended 12 month (mean: 16.5 month). 2 patients deceased during the follow-up, 15 patients did not respond. Therefore, 62/77 patients were available for follow-up. Flow-rate and post-voiding residual urine improved significantly [3.5 vs. 23.3 ml/s (p < 0.001); 121.3 vs. 33.4 ml (p < 0.05)]. IPSS decreased from 18.4 to 6.8, QoL dropped from 4.6 to 1.4. Early complications were urinary tract infection (n: 6/6.8%), bleeding (n: 5/5.6%) and immediate re-treatment (n: 2/2.2%), as well as urethral stricture (n: 1/1.6%) during follow-up. Postoperative short-term dysuria was recorded in 27% of the patients. CONCLUSION: VapoEnucleation is a safe and effective minimal invasive treatment modality for BPO. The improvement in voiding and bother is durable in patients with a postoperative period extending 12 month.

Thulium:yttrium-aluminium-garnet laser prostatectomy in men with refractory urinary retention.

OBJECTIVE: To evaluate the feasibility and efficacy of thulium:yttrium-aluminium-garnet (YAG) laser prostatectomy in patients with an indwelling transurethral catheter due to recurrent urinary retention secondary to benign prostatic obstruction. PATIENTS AND METHODS: Preoperative data and postoperative outcome, as well as complications, were recorded in 65 patients with a history of recurrent urinary retention before surgery (group A), who were compared with a group of 143 men with no recurrent urinary retention (group B). RESULTS: The mean (sd) volume of the prostate was 45.6 (22.5) and 43.1 (24.5) mL in groups A and B, respectively. The respective preoperative prostate-specific antigen levels were 3.6 (7.8) and 2.8 (6.4) ng/mL, the surgical duration 72.4 (28.9) and 65.6 (28.6) min, the mean laser time and energy 32.5 (11.8) min/140.7 (42.1) kJ and 29.4 (11.6) min/117.6 (11.6) kJ, the maximum urinary flow rate after surgery 19.6 (11.2) and 19.1 (9.6) mL/s, and the postvoid residual urine volume 26.7 (36.3) and 20.6 (27.3) mL. Recorded complications were: bleeding, at 3% in group A and 1.4% in group B; urinary tract infection 15.4% and 4.2%; and a second procedure, 3% and 2.3%. Overall, complications were more frequent in group A (P = 0.02). CONCLUSION: Thulium:YAG prostatectomy is feasible and effective, even in patients with potentially impaired detrusor function. The long-term durability of these promising results has yet to be confirmed.

[The influence of "differentiated trandurethral resection" in the recurrence and progression of superficial bladder cancer]. / La influencia de la "resección transuretral diferenciada" en la recurrencia y progresión en cáncer vesical superficial.

OBJECTIVES: Experimental data show the relationship between the area of injured urothelium and recurrence rates in superficial bladder cancer. Tumor cell adherence is increased by the exposure to the extracellular matrix (ECM). Transurethral resection uncovers the ECM and might lead to recurrent tumors. The question if recurrences are increased by enlarged urothelium resection areas is difficult to answer because there will be no prospective studies available. We investigated if deeper and larger urothelial injuries, which are caused by differentiated resections lead to higher recurrence and progression rates than regular resections of bladder tumors. METHODS: 163 patients with superficial bladder cancer were retrospectively evaluated. Sixty-six received a differentiated resection and 97 a regular one. We analyzed the recurrence and progression rates over a minimum of 48 months as well as tumor persistence in the second resection. RESULTS: Patients with differentiated resections of bladder tumors were found to have no higher incidence of tumor recurrence and progression but showed a significantly higher percentage of tumor free second resections. CONCLUSIONS: As a model of enlarged urothelial lesions the differentiated resection technique for superficial bladder cancer has no negative influence on recurrence or progression rates. It seems unlikely that the extracellular matrix uncovered by resection is the main reason for the high recurrence rates. The significantly lower incidence of tumor persistence in the second resection favors the differentiated resection technique in the transurethral treatment.

5-year-follow-up of patients with clinically insignificant residual fragments after extracorporeal shockwave lithotripsy.

OBJECTIVES: After SWL treatment, many patients have residual fragments in the kidney or ureter. Fragments 2 stones episodes. These patients and their referring urologist received follow-up questionnaires which contained questions about stone clearance, late complications, auxillary measures and dietary or drug metaphylaxis. RESULTS: Most residual stone fragments were located within the lower calyx (17%) and the renal pyelon (14%). Stone analysis was available in 142 patients with CIRF and revealed calciumoxalate calculi in 93.6% of the cases. In 78.6%, CIRF cleared spontaneously within few weeks and did not recur within 5 years. However, residual stones led to stone recurrence and need of re-treatment in 21.4%. Renal pyelon (23%) and calices showed comparable growth of former CIRF (lower calices 26.5%, middle calices 27%, upper calices 26%). Only 48% of the patients with recurrent stone formation followed dietary metaphylaxis. However, a significant correlation between a general or specific metaphylaxis and stone growth of CIRF could not be demonstrated. CONCLUSIONS: Most of the CIRF after SWL pass spontaneously without any complications. But considering that one fifth of the patients developed new stones at the side of residual fragments, it is obvious that close follow-up is required. Although we could not demonstrate a relation between metaphylaxis and stone re-growth, it is conceivable that adequate metaphylaxis can reduce stone recurrences.

Validation of computer-based training in ureterorenoscopy.

OBJECTIVES: To evaluate the outcome of training both urological novices and experts, using the recently developed UroMentor (Simbionix Ltd, Israel) trainer, that provides a realistic simulation of rigid and flexible ureterorenoscopy (URS). SUBJECTS AND METHODS: Twenty experienced urologists (total number of previous flexible URSs 21-153) were monitored during simulated flexible URS for treating a lower calyceal stone, and the outcome was correlated with individual experience. A score was compiled based on the variables recorded, including total operation time, stone contact time, complications such as bleeding or perforation, and treatment success. A further five urological residents with no endourological experience were trained on the UroMentor in rigid URS for ureteric stone treatment. Their acquired clinical skills were subsequently compared to those of five urological residents who received no simulator training. RESULTS: All 20 experienced urologists disintegrated the stone on the simulator, and the score achieved was related to their personal experience; there was a significant difference in performance in those with < 40 and > 80 previous flexible URSs. For the five urological residents with no endourological experience, simulator training improved their skills, and comparison with urological residents who had received no simulator training showed advantages for the trained residents. After being trained on the simulator, the group performed better in the first four URSs on patients. CONCLUSIONS: Individual experience correlates with individual performance on the simulator. Simulator training was helpful in improving clinical skills. Although the distribution of computer-based simulators is limited by high prices, virtual reality-based training has the potential to become an important tool for clinical education.

Diverticular carcinoma of the urinary bladder: diagnosis and treatment problems. A case report.

OBJECTIVES: To report a case of a primary carcinoma arising in a vesical diverticulum. CLINICAL PRESENTATION AND INTERVENTION: A 59-year-old male patient presented with painless macrohematuria. A primary carcinoma arising in a vesical diverticulum was detected with cystoscopy and confirmed with rectal endosonography and computer tomography. and radical cystoprostatovesiculectomy with ileal conduit was performed. Chemotherapy with cisplatin and methotrexate followed. The patient died of an acute cardiac event in the 4th postoperative month. CONCLUSION: This report illustrates that in a case of a closed opening of a bladder diverticulum, rectal endosonography and computer tomography do provide additional support for making a diagnosis of a hidden tumor in the diverticulum.