Oliver Engel

Outcomes of Ventral Onlay Buccal Mucosa Graft Urethroplasty in Patients after Radiotherapy

PURPOSE We evaluated stricture-free survival and functional outcomes of buccal mucosa graft urethroplasty in patients with urethral stricture disease after radiotherapy. MATERIALS AND METHODS We reviewed our urethroplasty database for patients with a radiotherapy history who underwent buccal mucosa graft urethroplasty between January 2009 and October 2013. We reviewed patient charts and the institutional, standardized, nonvalidated questionnaires administered to each patient postoperatively. Study end points included 1) the success rate, 2) continence status, 3) erectile function and 4) patient satisfaction postoperatively. Success was defined as stricture-free survival. RESULTS Of 38 men included in the study prostate cancer was the most common indication for radiotherapy in 35 (92.1%). External beam radiotherapy was performed in 24 cases (64.9%), brachytherapy was done in 8 (21.6%) and a combination of the 2 treatments was performed in 6 (13.5%). Strictures were in the bulbar/bulbomembranous urethra and had a median length of 3.0 cm (range 1.0 to 8.0). The overall success rate was 71.1% at a median followup of 26.5 months (range 1.0 to 50.0). Median time to stricture recurrence was 17.0 months (range 3.0 to 44.0). De novo urinary incontinence was observed in 4 patients (10.5%). Erectile function remained mostly unchanged compared to preoperative status. Study limitations include the small sample size and the lack of validated questionnaires. CONCLUSIONS At short-term to mid-term followup the success rate of ventral onlay buccal mucosa graft urethroplasty in patients with radiotherapy history seems acceptable. However, patients must be counseled about the increased risk of urinary incontinence. Longer followup is warranted to address long-term outcomes.

Does the extent of variant histology affect oncological outcomes in patients with urothelial carcinoma of the bladder treated with radical cystectomy

BACKGROUND To evaluate the effect of variant histology and its extent on oncological outcomes in patients with urothelial carcinoma of the bladder (UCB) who are treated with radical cystectomy. MATERIAL AND METHODS Data from 485 patients with UCB who were treated with radical cystectomy without neoadjuvant chemotherapy at a single academic center between 1996 and 2011 were collected retrospectively. All pathologic specimens were meticulously re-reviewed for the presence and extent of variant UCB histologies. Cox regression models were used to evaluate the association with disease recurrence and cancer-specific survival. RESULTS Variant histology was present in 96 patients (19.8%), with squamous cell differentiation (12.6%) being most common. In patients with variant histology, the median and mean extent was 70% and 60%, respectively. Variant histology was associated with female sex, advanced tumor stage, less presence of concomitant carcinoma in situ, and administration of adjuvant chemotherapy (P ≤ 0.001). The presence of variant histology and non-squamous cell differentiation was associated with cancer-specific mortality (pairwise P ≤ 0.02). Moreover, non-squamous cell differentiation was associated with disease recurrence (P = 0.002). The presence of variant histology, non-squamous cell differentiation, and the extent of variant histology were associated with cancer-specific mortality in univariable but not in multivariable analyses. CONCLUSIONS The presence of variant histology, particularly non-squamous cell differentiation, and its extent are associated with inferior survival. However, they are not independent predictors of outcomes. The association of variant histology with established predictors of aggressive tumor biology is likely impairing oncological outcomes and thus has to be considered in clinical decision making.

Gender-specific outcomes of bladder cancer patients: A stage-specific analysis in a contemporary, homogenous radical cystectomy cohort

INTRODUCTION Controversial findings regarding gender-specific oncological outcomes of urothelial carcinoma of the bladder (UCB) have recently been reported. The aim of this study was to analyze gender-specific outcomes using a stage-adjusted approach in a homogenous, contemporary radical cystectomy (RC) cohort. MATERIAL AND METHODS We prospectively collected data of 517 UCB patients treated with RC and pelvic lymphadenectomy without neoadjuvant chemotherapy at our institution between 1996 and 2010. Stage-adjusted uni- and multivariable Cox regression models analyzed the association of gender with disease recurrence, cancer-specific mortality and overall survival. RESULTS In total, 398 (77%) patients were male and 119 (23%) were female. Compared to men, women were more likely to have advanced tumor stages (p = 0.017), nodal metastasis (p = 0.047) and received more frequently adjuvant chemotherapy (p = 0.009). At a median follow-up of 44 months, there was no statistical difference in disease recurrence, cancer-specific mortality and overall survival between both genders when analyzed as a group. In stage-adjusted analyses, only women with non-invasive UCB were more likely to die of UCB compared to the male counterparts (p = 0.013). In gender-specific multivariable analyses that adjusted for standard clinico-pathologic features, pathologic tumor stage was an independent predictor for disease recurrence (p-values ≤0.047) and cancer-specific mortality (p-values ≤0.049), respectively. CONCLUSION Women present with more aggressive tumor biologic features at RC, however this did not translate into inferior outcomes compared to men in stage-specific analyses in our cohort. Tumor stage is the most important factor influencing the course of disease in both genders. Validation of our findings is warranted in a larger cohort.

The Impact of Tumor Diameter and Tumor Necrosis on Oncologic Outcomes in Patients With Urothelial Carcinoma of the Bladder Treated With Radical Cystectomy.

OBJECTIVE To evaluate the influence of tumor diameter and tumor necrosis on oncologic outcomes in patients with urothelial carcinoma of the bladder treated with radical cystectomy (RC). MATERIALS AND METHODS We treated 517 consecutive patients with urothelial carcinoma of the bladder treated with RC without neoadjuvant chemotherapy at our institution between 1996 and 2011. All RC specimens were meticulously re-reviewed for the largest residual tumor diameter and for the presence and extent of tumor necrosis. Cox regression models evaluated the association with disease recurrence and cancer-specific survival. RESULTS At RC, 155 patients (30.0%) had a residual tumor diameter ≥3 cm and tumor necrosis was present in 156 patients (30.2%). Tumor diameter and necrosis were significantly correlated (P <.001). Both a tumor diameter ≥3 cm and the presence of tumor necrosis were associated with an older age, advanced tumor stage, higher tumor grade, lymph node metastasis, positive surgical margin status, lymphovascular invasion, and administration of adjuvant chemotherapy (P values ≤.009). A tumor diameter ≥3 cm and the presence of tumor necrosis were associated with disease recurrence and cancer-specific mortality in Kaplan-Meier analyses, respectively (pairwise P values <.001). In addition, a tumor diameter ≥3 cm was an independent predictor of cancer-specific mortality in multivariate analysis that adjusted for standard clinicopathologic features. CONCLUSION Tumor diameter and necrosis are closely correlated and associated with aggressive tumor features and inferior oncologic outcomes. A residual tumor diameter ≥3 cm is an independent predictor of cancer-specific mortality. This additional information should be considered to be reported in every pathology report for consideration in patient counseling and treatment decision making. In addition, these results underscore the importance of a thorough transurethral resection of the bladder tumor before RC.

Lymph node dissection during radical cystectomy for bladder cancer treatment: considerations on relevance and extent

Despite advances in the surgical and medical treatment for urothelial carcinoma of the bladder (UCB), there have only been limited improvements in disease-specific mortality rates over the past decades. Lymph node dissection (LND) during radical cystectomy is an integral part of the treatment for muscle-invasive and high-risk UCB. LND may detect and remove lymph node (LN) metastasis and thus guide patient counseling and decision making regarding additional treatment decisions. In addition, LND may improve survival in patients both with and without LN metastasis. In this non-systematic review article, we discuss benefits and risks of LND, the role of limited versus extended LND and the dilemma of preoperative LN staging.

Loss of SPINK1 expression is associated with unfavorable outcomes in urothelial carcinoma of the bladder after radical cystectomy

BACKGROUND We assessed the association of serine protease inhibitor Kazal type I (SPINK1) expression with clinicopathologic outcomes in urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC). MATERIALS AND METHODS Tissue microarrays comprising 438 consecutive UCB patients treated with RC between 1988 and 2003 and 62 cases of normal urothelium controls were evaluated for SPINK1 protein expression by immunohistochemistry (IHC). Semiquantitative evaluation was performed by 2 pathologists blinded to clinical outcomes (loss of expression: <50% cells or intensity 0-2). RESULTS In normal urothelium, SPINK1 expression was noted in umbrella cells of 32 of 62 controls (52%); 254 RC patients (57.9%) exhibited loss of SPINK1 expression. Loss of SPINK1 expression was significantly associated with higher pathologic stages (P = 0.002) and presence of lymph node metastasis (P = 0.04). At a median follow-up of 130 months (IQR: 98.4), loss of SPINK1 expression was associated with an increased risk of disease recurrence (P = 0.02) and cancer-specific mortality (P = 0.03). On multivariable analysis that adjusted for the effects of standard clinicopathologic parameters, SPINK1 was not an independent predictor of disease recurrence (P = 0.09) or cancer-specific mortality (P = 0.12). CONCLUSIONS Over half of UCB patients treated with RC exhibit loss of SPINK1 expression. Loss of SPINK1 correlates with features of biologically aggressive UCB. Although SPINK1 expression did not have independent prognostic value in RC patients, it may serve as a biomarker for tumor staging and may be useful as an adjunct in clinical decision-making.

Short-Term Outcome and Morbidity of Different Contemporary Urethroplasty Techniques—A Preliminary Comparison

BACKGROUND AND PURPOSE Only few comparative reports about different urethroplasties have been published, addressing success rate (SR), adverse events (AE), and quality of life (QoL). Our purpose was to evaluate SR, AE, and QoL in a contemporary cohort of patients undergoing urethroplasty in the short-term follow-up (FU). PATIENTS AND METHODS Between December 2008 and June 2010, 205 patients underwent urethroplasty for anterior urethral strictures at our institution. A standardized questionnaire was sent to all patients. The primary end point was SR. Secondary end points were AE and QoL. To assess the risk of SR, the Kaplan-Meier method and log-rank test were used. To assess risk factors for urethral stricture recurrence (SRec), univariable Cox regression analysis was used. RESULTS Overall, 140 (68%) patients responded to our questionnaire and were used for analysis. Of these 9%, 85%, and 6% were treated by excision and primary anastomosis (EPA), buccal mucosa graft urethroplasty (BMGU), and mesh graft urethroplasty (MGU), respectively. At 10 months of FU, SR was 87.5%. SRs of EPA, BMGU, and MGU were 100% (n=13/13), 85.7% (n=102/119), and 87.5% (n=7/8), with no significant differences between the groups. In univariable analysis, ≥ 2 vs 1 previous urethroplasties showed a trend toward a reduced SR (hazard risk 2.95; P=0.057). Streaking the urethra (P=0.024) and penile curvature (P=0.026) were significantly more often associated with MGU compared with EPA and BMGU. Postoperative total median (mean) scores were 3.5 (4.8) for the International Consultation on Incontinence Questionnaire Male lower urinary tract symptoms, 15 (15.2) for the International Index of Erectile Function, and 80 (73) for EuroQol visual analogue score; there was no difference between urethroplasty types. CONCLUSION In the short-term FU, urethroplasty demonstrates an excellent SR. Specific SRs of EPA, BMGU, and MGU seem comparable. Despite significant differences in AE, patient reported QoL is high with no difference between the applied techniques.

A non-randomized, prospective, clinical study on the impact of circulating tumor cells on outcomes of urothelial carcinoma of the bladder patients treated with radical cystectomy with or without adjuvant chemotherapy.

To investigate outcomes of urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC) according to the presence of circulating tumor cells (CTC) and the administration of adjuvant chemotherapy (AC). We prospectively enrolled 226 UCB patients treated with RC without neoadjuvant chemotherapy at our institution between 2007 and 2013. Blood samples were obtained from all patients preoperatively and analyzed for CTC using the CellSearch® system. Platinum‐based AC was administered in 50 patients (27.0%). Cox regression models evaluated the association of CTC with disease recurrence, cancer‐specific and overall mortality according to AC administration. 185 patients were available for analyses. CTC were present in 41 patients (22.2%). Patients with presence of CTC received AC more frequently, compared to patients without CTC (p = 0.027). At a median follow‐up of 31 months, the presence of CTC was associated with disease recurrence, cancer‐specific and overall mortality (p‐values < 0.001) in patients without AC administration. In patients who received AC, there was no difference in either endpoint between patients with or without presence of CTC. In multivariable analysis of patients without AC administration, the presence of CTC was an independent predictor for disease recurrence (HR: 4.9; p < 0.001), cancer‐specific (HR: 4.2; p = 0.003) and overall mortality (HR: 4.2; p = 0.001). The CTC status may be implemented in decision‐making regarding AC administration in UCB patients following RC. CTC measurement should be implemented in future UCB studies on systemic chemotherapy to validate our findings.

Comparative analysis of comorbidity and performance indices for prediction of oncological outcomes in patients with upper tract urothelial carcinoma who were treated with radical nephroureterectomy

OBJECTIVE Comorbidity and performance indices (CPIs) are useful tools to evaluate patients risk of comorbidities and thus may guide clinical decision making regarding surgery or multimodal therapy approaches. Hence, the aim of the current study was to assess the predictive capacity of CPIs comprising the American Society of Anaesthesiologists (ASA)-score, the Charlson comorbidity index (CCI), the age-adjusted CCI (ACCI), and the Eastern Cooperative Oncology Group performance status (ECOG-PS) in patients with upper tract urothelial carcinoma (UTUC) who were treated with radical nephroureterectomy (RNU). METHODS AND MATERIALS A total of 242 patients with UTUC underwent RNU without neoadjuvant chemotherapy between 1992 and 2012 at 3 German academic centers. Patients were stratified according to the pre-RNU CPIs dichotomized as ASA 1/2 vs .≥ 3, CCI 0 to 2 vs. > 2, ACCI 0 to 5 vs. > 5, and ECOG-PS 0 to 1 vs. > 1. We assessed the associations of CPIs with clinicopathologic features, as well as the prognostic effect on recurrence-free survival, cancer-specific survival (CSS), overall survival, and cancer-independent mortality (CIM), using univariable and multivariable Cox regression analyses. RESULTS Sixty-two patients (25.6%) had an ASA-score ≥ 3, 71 patients (29.3%) a CCI>2, 50 patients (20.7%) an ACCI > 5, and 122 (50.4%) patients an ECOG-PS > 1. The ASA-score (P = 0.001), CCI (P = 0.029), and the ECOG-PS (P < 0.001) were significantly associated with age. In addition, the ECOG-PS was associated with pelvicalyceal tumors (P = 0.012), and the CCI with preoperative hydronephrosis (P = 0.026). The median follow-up was 30 months. In Kaplan-Meier analyses, ACCI > 5 (P ≤ 0.025) and ECOG-PS > 1 (P ≤ 0.042) were associated with recurrence-free survival, CSS, and overall survival, and ASA-score ≥ 3 (P = 0.011) and ACCI > 5 (P = 0.006) with CIM. In multivariable analysis that adjusted for standard clinicopathologic parameters, an ECOG-PS > 1 was an independent predictor for CSS (hazard ratio = 1.89, P = 0.019), and an ASA-score ≥ 3 (hazard ratio = 1.86, P = 0.026) was a predictor for CIM. CONCLUSION CPIs are easy assessable predictors for outcome in patients with UTUC who were treated with RNU. CPIs have carefully to be taken into account in patient counseling regarding operative decision making and multimodal treatment.

Management of iatrogenic ureteral injury and techniques for ureteral reconstruction.

Purpose of review Ureteral reconstruction is still a sophisticated approach. Because of an increase in endoscopic procedures for kidney and ureteral stone treatment, radiation therapy and pelvic surgery, ureteral strictures are more frequently observed. Short proximal and distal strictures can be reconstructed by using the renal pelvis or urinary bladder. New techniques are needed for reconstruction of long strictures as well as those located in the middle ureter. Recent findings This article summarizes very recent studies from 2014, investigating new techniques and their functional outcome of procedures for ureteral reconstruction. In an open reconstruction, some new techniques to reconstruct full-length ureter defects using bladder flaps or by intestinal onlay techniques were described. In addition, laparoscopic and robotic reconstruction methods as well as single site procedures demonstrated feasibility. Visualizing the ureter using near-infrared fluorescence techniques for prevention of ureteral injuries is also a new aspect. Future targets focus on the development of artificial transplants by tissue engineering for ureteral reconstruction. Summary Novel open and minimally invasive techniques for reconstruction of full-length and middle ureter strictures demonstrated feasibility in the past year. Although reasonable outcomes were reported, current results are significantly compromised by short-term follow-up. To date, artificial transplants remain experimental.