Urethroplasty performed with an autologous urothelium-vegetated collagen fleece to treat urethral stricture in the minipig model.

INTRODUCTION AND OBJECTIVE: Tissue-engineered materials in urethral reconstructive surgeries are a promising field for innovative therapy. Collagen matrices increase stability of cell-based implants and can promote viability and proliferation of urothelial cells. In this study, a collagen type I-based cell carrier (CCC) with stratified multi-layer autologous urothelium was used for urethroplasty after induction of urethral stricture in eight minipigs. MATERIALS AND METHODS: Minipigs underwent surgical procedures to induce urethral stricture by thermocoagulation. Simultaneously, bladder tissue was harvested. Urothelial cells were expanded, labeled with PKH26 and seeded onto CCC in high density. 3 weeks after strictures were induced and verified by urethrography, minipigs underwent urethroplasty using the seeded CCC. Two animals were euthanized after 1, 2, 4, and 24 weeks. Urethras were histologically examined for integration and survival of seeded CCC. In vivo phenotype of multi-layered urothelium matrix constructs was characterized via immunofluorescence staining with pancytokeratin, CK20, p63, E-cadherin and ZO-1. RESULTS: Seeded CCCs showed excellent stability and suturability after manipulation and application. Transplanted cells were detected using positive PKH26 fluorescence up to 6 months after labeling. Urothelium matrix implants integrated well into the host tissue without sign of inflammation. Animals showed no sign of rejection or stricture recurrence (urethrography) at any time during experimental period. Immunofluorescence analysis confirmed epithelial phenotype, junction formation and differentiation after 2 weeks. CONCLUSION: CCC can be suitable for urologic reconstructive surgeries and represents a promising option for clinical application. Longer follow-up results are required to exclude re-occurrence of stricture reformation.

Laparoscopic radical nephrectomy with inferior vena cava thrombectomy: highlight of key surgical steps.

OBJECTIVE: Vascular involvement in the form of renal vein (RV) or inferior vena cava (IVC) thrombus can be seen in 4-10% of patients presented with RCC. In patients without presence of metastasis, surgical treatment in the form of radical nephrectomy remains the treatment of choice with 5-year survival rates of 45-70%. Open surgery is still the first treatment option of choice at the moment for RCC patients with IVC thrombus. MATERIALS AND METHODS: In our study, we are reporting a case of patient with RCC and level I IVC thrombus treated with laparoscopy. Our patient is a 72 years old man with underlying co-morbidity of hypertension and chronic kidney disease (CKD) presented with right-sided RCC. The CT scan done showed a large right renal upper pole tumor measuring 8.4x5.2cm with level I IVC thrombus (Figure-1). There were no regional lymphadenopathy and the staging scans were negative. RESULTS: The operative time was 124 minutes and blood loss was minimal. The patient was progressed to diet on POD 1 with bowel movement on POD 2. There was no significant change in the pre and post-operative glomerular filtration rate (GFR). The surgical drain was removed on POD2. The patient was discharged well on POD 5. There were no perioperative complications. The pathology was pT3bN0M0 Fuhrman grade II clear cell RCC. CONCLUSIONS: As a conclusion, laparoscopic radical nephrectomy and IVC thrombectomy is a complex and technically demanding surgery. With advancement of surgical skills as well as technology, more cases of minimally invasive laparoscopic radical nephrectomy and IVC thrombectomy can performed to improve the perioperative outcomes of carefully selected patients in a high volume center.

[Laparoscopic partial nephrectomy for renal tumors. Time for a new standard?]. / Laparoskopische Nierenteilresektion bei Nierentumoren. Zeit für einen neuen Standard?

PURPOSE: Our aim was to evaluate the laparoscopic partial nephrectomies (LPN) performed at our hospital and compare the results with those from other current studies on partial nephrectomy. PATIENTS AND METHODS: Between March 2006 and January 2014, 280 patients were treated with LPN in our hospital. We evaluated age, sex, and surgical parameters like operating time, warm ischemia time (WIT), hospital stay, complications, tumor staging, grading, and size RESULTS: The patients were 61.6±12.4 years old. The median operating time for LPN was 134±51 min. A total of 30% of the operations were treated using the zero ischemia technique. The WIT was 19.9±9.8 min. The WIT of the last 50 LPN performed was 13±7 min. Complications were documented in 15% of the LPNs. CONCLUSION: LPN is a curative treatment option for the renal cell carcinoma similar to open partial nephrectomy; however, laparoscopy is associated with lower morbidity.

[Treatment of invasive bladder cancer: robot-assisted radical cystectomy and intracorporeal urinary diversion]. / Therapie des invasiven Harnblasenkarzinoms : Roboterassistierte radikale Zystektomie und intrakorporale Harnableitung.

PURPOSE: Robot-assisted radical cystectomy (RARC) and intracorporeal urinary diversion are only performed in a few centers of excellence worldwide. Functional and oncologic outcomes are comparable. We report on our experience with RARC and intracorporeal diversion. PATIENTS AND METHODS: We retrospectively identified 86 RARCs in 72 men and 14 women (mean age 69.7 years). All patients underwent robot-assisted radical cystectomy and pelvic lymphadenectomy followed by intracorporeal urinary diversion using ileal conduit or neobladder. Of the 86 patients, 24 patients (28%) underwent intracorporeal ileal conduit and 62 patients (72%) underwent intracorporeal neobladder formation. A Studer pouch was created in all who underwent intracorporeal neobladder diversion. Cancer specific survival (CSS) and overall survival (OS) are reported. RESULTS: The mean operative time was 418.9 min (range 205-690 min) and blood loss was 380 ml (range 100-1000 ml). The mean hospital stay was 17.5 days (range 5-62 days). All the surgeries were completed with no open conversions. Minor complications (grade I and II) were reported in 23 patients, while major complications (grade III and above) were reported in 21 patients. The mean nodal yield was 20.3 (range 0-46). Positive margins were found in in 8%. The average follow-up was 31.5 months (range 3-52 months). Continence could be achieved in 88% of patients who received an intracorporeal neobladder. The cancer-specific survival (CSS) and overall survival (OS) were 80% and 70%, respectively. CONCLUSION: RARC with intracorporeal diversion seems to be safe and reproducible in tertiary centers with robotic expertise. Operative times are acceptable and complications as well as functional and oncologic outcomes are comparable. Further standardization of RARC with intracorporeal diversion may lead to a wider adoption of the approach.

[Complex residual tumors after chemotherapy of nonseminomatous germ cell tumors. Laparoscopic management - limits and chances]. / Komplexe Residualtumoren nach Chemotherapie bei nichtseminomatösen Keimzelltumoren. Laparoskopisches Management - Grenzen und Chancen.

PURPOSE: Laparoscopic retroperitoneal lymph node dissection (L-RPLND) is often required in patients with metastatic nonseminomatous germ cell tumors (NSGCT) and residual tumors after chemotherapy. Laparoscopy has become established as a safe procedure in the surgical management of these tumors. Due to the rapid development of laparoscopy, complex retroperitoneal and even intrathoracic residuals can also be treated in high volume centers. PATIENTS AND METHODS: This study included 21 retrospectively identified NSGCT and seminoma patients (mean age 29 years) with metastatic disease and clinical stage (CS) IIA-IIIB. A bilateral L-RPLND was performed in all male patients between 2009 and 2014. In 19 patients an infiltration of the great vessels was detected during surgery and vascular reconstruction was necessary. In 2 patients an intrathoracic residual 5.4 cm and 7 cm in size, respectively, was diagnosed during follow-up. Exclusion criteria for L-RPLND were positive tumor markers after chemotherapy, patients with local recurrence after previous open L-RPLND and patients with excessive vascular involvement. RESULTS: In this series no conversions to open surgery were necessary. The mean tumor size post-chemotherapy was 3.6 cm (range 1.5-9.7 cm). The mean measured blood loss was 294 ml (range 50-1000 ml). The mean hospitalization time was 6 days (range 3-9 days) and mean follow-up was 16 months (range 1-37 months). No complications higher than grade II (Clavien-Dindo classification) were registered in the immediate postoperative course. During the follow-up period no in-field recurrences were registered. CONCLUSION: The L-RPLND seems to be a safe alternative surgical procedure for certain complex residuals with vascular involvement after chemotherapy of testicular cancer. Bilateral L-RPLND is technically feasible and reproducible under guaranteed oncological principles. An infiltration of the great vessels and also intrathoracic residuals can be managed in selected patients without compromising the clinical and oncological course.

Cost effective laparoendoscopic single-site surgery with a reusable platform.

BACKGROUND AND OBJECTIVES: Many disposable platforms have been applied in laparoendoscopic single-site surgery (LESS). Besides technical issues, cost is one of the limiting factors for its widespread acceptance. The current study describes the first completely reusable LESS-platform. METHODS: We performed LESS-procedures in 52 patients including nephrectomy (18), adrenalectomy (2), partial nephrectomy (3), pyeloplasty (4), renal cyst ablation (4), pelvic lymphadenectomy (15), and lymphocele ablation (6). All procedures were conducted using a novel reusable single-port device (X-Cone, Karl-Storz) with a simplified set of instruments. We obtained perioperative and demographic data, including a visual analogue pain scale (VAS), and a complication reporting system based on Clavien grading. RESULTS: Mean age was 50.04 y. Conversion to standard laparoscopy was necessary in 3 cases and addition of a needlescopic instrument in 6 cases. There was no open conversion. Intra- and postoperative complications occurred in 3 (Clavien II in 2 and III in 1) cases. Mean operative time was 110, 90, and 89 min, and hospital stay was 4.9, 3.1, and 3.6 d for nephrectomy, pelvic lymphadenectomy, and pyeloplasty, respectively. Mean VAS was 2.13, 1.07, and 1.5 while blood loss was 81.3 mL, 25.67 mL, and 17.5 mL, respectively. Mean lymph node yield was 15 (range, 8 to 21). CONCLUSIONS: A completely reusable LESS-platform is applicable to various uses in urology, yielding favorable functional and cosmetic results. Reusable materials are useful to reduce the cost of LESS, further increasing its acceptance. LESS with a completely reusable platform is more cost effective than standard laparoscopy.

[Post-chemotherapy laparoscopic retroperitoneal lymph node dissection in low volume residual germ cell cancer: a technique to reduce morbidity]. / Laparoskopisch retroperitoneale Lymphadenektomie bei Low-volume-Keimzelltumoren nach Chemotherapie : Ein Verfahren zur Verringerung der Morbidität.

PURPOSE: Retroperitoneal lymph node dissection (RPLND) is the most appropriate method for the detection of residual tumor tissue and mature teratoma after chemotherapy in patients with advanced nonseminomatous (NSGCT) or seminomatous (SGCT) germ cell tumors in clinical stage II-III. Open surgical procedures are associated with higher morbidity rates and laparoscopic RPLND offers a minimally invasive procedure with equivalent oncological safety and low morbidity. METHODS: In 39 patients laparoscopic RPLND (L-RPLND) after platinum-based chemotherapy for clinical stage IIa-III NSGCT was performed unilaterally as well as bilaterally by two surgeons. Patients with retroperitoneal residual tumor >1 cm and normalization of tumor markers after chemotherapy were included. Bilateral L-RPLND was performed with complete contralateral nerve sparing while the decision for ipsilateral nerve preservation was based on the volume of the residual mass in the respective standard field. RESULTS: The L-RPLND was completed in all patients without conversion. Median operation time was 248 min (range 95-397 min) and mean hospitalization time was 5 days (range 3-14 days). Furthermore, there was no difference in recurrence rate of the disease (p=0.45) between patients with unilateral or bilateral dissection. The postoperative ejaculatory function was normal in 37 out of 39 patients. The median follow-up period was 18.5 months (range 3-38 months) and 3 out of 39 patients developed recurrence (7.69 %). CONCLUSIONS: Post-chemotherapy L-RPLND is feasible with a lower complication rate and an adequate oncological safety and functional outcome. Due to the complexity of L-RPLND the procedure remains limited to institutions with extensive laparoscopic experience.

[Laparoendoscopic single-site surgery in urology using reusable systems]. / Laparoendoskopische Single-site-Chirurgie in der Urologie durch Einsatz eines wieder verwendbaren Systems.

PURPOSE: Many disposable platforms have been available for laparoendoscopic single-site surgery (LESS) for a long time. Besides technical challenges cost remains the limiting factor for the widespread use of LESS. We present our experiences with the first completely reusable LESS platform. METHODS: We performed LESS procedures in 52 patients, including nephrectomy (n=18), adrenalectomy (2), partial nephrectomy (3), pyeloplasty (4), renal cyst ablation (4), pelvic lymphadenectomy (15) and lymphocele ablation (6). All procedures were carried out using a novel reusable single-port device (X-ConeR, Karl-Storz) with a simplified combination of standard and preformed instruments. Perioperative and demographic data including a visual analogue pain scale (VAS) were obtained. Complications were recorded using the Clavien classification. RESULTS: The mean age of the patients was 50.04 years. Conversion to standard laparoscopy was necessary in 3 cases and the additional use of a 3 mm needle instrument in 6 cases. There were no open conversions. Intraoperative and postoperative complications occurred in 3 (Clavien II in 2 and III in 1) cases. Mean operating time was 110, 90, and 89 min and hospital stay was 4.9, 3.1 and 3.6 days for nephrectomy, pelvic lymphadenectomy, and pyeloplasty, respectively. The mean VAS was 2.13, 1.07 and 1.5 while blood loss was 81.3 ml, 25.67 ml and 17.5 ml, respectively. CONCLUSIONS: The LESS technique with a completely reusable platform is applicable to various indications in urology yielding favorable functional and cosmetic results. This novel simplified combination of instruments facilitates handling and shortens the learning curve. Reusable materials may help to reduce cost leading to a wider acceptance of LESS.

Influence of age on false positive rates of urine-based tumor markers.

INTRODUCTION: Several influencing factors on false positive rates (FPRs) of urine-based tumor markers in the detection of urothelial cancer (UC) have been identified. We evaluated age as a possible influencing factor. METHODS: Urinary cytology (Cyt), UroVysion (FISH), ImmunoCyt (uCyt+) and NMP22 were determined in 1,554 patients suspicious for UC of the bladder before cystoscopy and in case of cancer detection before TURB. Additionally, upper urinary tract imaging was performed. Maker sensitivity, specificity and FPRs were evaluated in the entire cohort and in subgroups divided by age into <50, ≥ 50-70 and ≥ 70 years. Contingency tables and the Cochrane Armitage tests were used for statistical comparisons. RESULTS: UC was found in 377 and no UC in 1,177 (75 %) patients. A total of 336 patients were diagnosed with UC of the bladder and 41 with UC of the upper urinary tract. Overall sensitivity and specificity for Cyt were 82 and 82 %: for FISH, 73 and 79 % and for uCyt+, 79 and 75 %, respectively. For NMP22, regardless of the exclusion criteria they were 72 and 34 % and after exclusion of urinary tract infection (UTI) or prior to manipulation 46 and 86 %, respectively. Significantly higher FPRs were found with increasing age for Cyt (p = 0.001), a trend to higher FPRs for uCyt+ (p = 0.11) and almost no difference for FISH (p = 0.63). For NMP22, differences became significant after exclusion of patients with UTI or prior manipulation (p = 0.02). CONCLUSIONS: The results of the present study give evidence that false positive rates of Cyt and NMP22 increase with age indicating that age should be respected for their correct interpretation.

[Primary treatment for localized prostate cancer: evaluation of patients' quality of life]. / Patienten nach Primärtherapie eines klinisch lokal begrenzten Prostatakarzinoms: Evaluation der Lebensqualität.

BACKGROUND: Radical prostatectomy (RP) and percutaneous radiotherapy (RT) are viable options for the primary treatment of localized prostate cancer (PC). Given the comparable efficacy of both modalities quality of life (QOL) has been suggested as an additional decision criterion. In recent years several validated instruments have been introduced to assess QOL. Most of them allow for patient-based rating of QOL. AIM: Herein, we aim to compare QOL after RP and RT in our own cohort of patients in Tübingen using validated questionnaires. METHODS: In total, 165 patients who had been treated for PC in Tübingen were enrolled. Of those 100 men had RP and 65 had RT. The validated QOL questionnaires EORTC QLQ-C30 and EORTC QLQ-PR 25 were used for assessment. Statistical analyses focused on analyses of variance. RESULTS: Concordant to previous studies it could be shown that RP mainly creates voiding problems most importantly urinary incontinence but also erectile dysfunction. After RT, patients mainly complained about disturbed bowel function including diarrhea and proctitis as well as about urgency and frequency. RP patients had better PF2 Scale values than RT patients (p= 0.00357143). On DI scales RT patients yielded significantly poorer values than the RP group (p= 0.003333). CONCLUSION: Our data comply well with those from other international centers. QOL is an important yet underestimated variable in oncological research. Our investigations underline the importance of an interdisciplinary approach for the successful management of PC.

Evidence for PTEN-independent Akt activation and Akt-independent p27(Kip1) expression in advanced bladder cancer.

In the treatment of advanced bladder cancer (BC), attention has recently focused on small molecule therapy concerning EGFR and the downstream Akt signalling pathway. Cellular deregulation processes are poorly understood, and biological determinants for the selection of therapy and monitoring are currently not available. The proteins PTEN, p-Akt and p27(Kip1) are suggested to be potentially significant biomarkers of Akt signalling. In this study, we investigated the expression of these proteins in advanced BC. PTEN, p-Akt and p27(Kip1) expression was determined immunohistochemically in 86 T2-4 BC specimens using a tissue microarray technique. Staining was documented with regard to intensity, cellular frequency and a multiplied staining score. Staining characteristics of the three proteins were correlated by regression analysis with the parameters of tumour stage and grade. A positive correlation was observed in the expression scores of PTEN and p-Akt, p-Akt and p27(Kip1) as well as PTEN and p27(Kip1) (p<0.02 for all combinations). The positive correlation between PTEN and p-Akt resulted mainly due to the strong correlation of PTEN intensity with p-Akt (p=0.0003 and p=0.0006 to p-Akt frequency and intensity, respectively). A positive correlation between p-Akt and p27(Kip1) was noted for p-Akt frequency as well as intensity (p<0.05 for all combinations). The positive correlation between PTEN and p27(Kip1) resulted due to the correlation of PTEN intensity alone with p27(Kip1) (p<0.03 for p27(Kip1) frequency and intensity), whereas no significance was noted for PTEN frequency. No correlation was found between T or G and expression of the proteins. However, activation of Akt in BC is known to occur independently of PTEN protein loss and appears not to cause a decrease of p27(Kip1). However, a direct regulatory impact of PTEN on p27(Kip1) was found. PTEN intensity, rather than frequency, appears to be a superior biomarker. These results may provide information to support research into protein profiling-predicted targeted therapy for BC. Correlations to benign urothelium, superficial BC specimens and follow-up data remain to be investigated.