Nejd F. Alsikafi

Immunohistochemical distinction between primary adenocarcinoma of the bladder and secondary colorectal adenocarcinoma.

Primary adenocarcinoma of the urinary bladder sometimes causes a diagnostic dilemma because it can be indistinguishable morphologically from adenocarcinoma of colorectal origin secondarily involving the bladder by metastasis or direct extension. It is much less well studied than conventional urothelial carcinoma and colorectal adenocarcinoma because of its rarity. The current study was specifically designed to investigate whether an important mechanism involved in the pathogenesis of colorectal adenocarcinoma, &bgr;-catenin dysregulation, was also important for the development of primary bladder adenocarcinoma and whether these two morphologically similar tumors could be distinguished immunohistochemically. Formalin-fixed, paraffin-embedded tissues from 17 primary adenocarcinomas of the urinary bladder, 16 colorectal adenocarcinomas involving the bladder, and 10 conventional urothelial (transitional) carcinomas were included in this study. Thirteen of the primary bladder adenocarcinomas were moderately to well differentiated (enteric type) and morphologically indistinguishable from colorectal cancers. The remaining four primary tumors were poorly differentiated (two cases) or of clear cell type (two cases). Immunohistochemical studies using a panel of monoclonal antibodies demonstrated positive nuclear staining for &bgr;-catenin expression in 13 of the 16 (81%) colorectal adenocarcinomas secondarily involving the bladder but in none of the primary adenocarcinomas or the urothelial carcinomas. Instead, positive membranous (and some cytoplasmic) staining was present in all primary bladder tumors with the exception of two poorly differentiated adenocarcinomas where no &bgr;-catenin staining was detected. All secondary colorectal adenocarcinomas stained negatively for CK7 and thrombomodulin (TM), whereas positivity for CK20 was observed in 15 (94%) cases. All urothelial carcinomas stained positively for CK7 and TM, and four of them also for CK20. Primary adenocarcinomas of the bladder showed mixed staining patterns for CK7, CK20, and TM with a positive rate of 65%, 53%, and 59%, respectively. These data indicate that dysregulation of &bgr;-catenin, an important aberration seen in colorectal carcinogenesis, does not appear to play a role in the pathogenesis of the bladder adenocarcinoma. In addition, our data demonstrate that a panel of immunostains, including CK7, CK20, TM, and &bgr;-catenin, is of diagnostic value in differentiating primary bladder adenocarcinoma from secondary adenocarcinoma of colorectal origin.

SURGICAL MODIFICATIONS OF RADICAL RETROPUBIC PROSTATECTOMY TO DECREASE INCIDENCE OF POSITIVE SURGICAL MARGINS

PURPOSE We sought to determine whether recent surgical modifications in the technique of radical retropubic prostatectomy decrease the incidence of positive surgical margins. MATERIALS AND METHODS We reviewed the records of 144 consecutive patients a mean of 60.8 years old who underwent radical retropubic prostatectomy using a modified surgical technique. Mean prostate specific antigen was 8.6 ng./ml. and mean Gleason grade was 5.8. Surgical modifications included division of the dorsal venous complex of the penis 10 to 15 mm. distal to the prostatic apex; transection of the urethra 3 mm. beyond the prostatic apex; division of the anterior aspect of the urethra, leaving the investing periurethral musculature intact, and division of the posterior aspect of the urethra en bloc with the striated urethral sphincter; sharp dissection of the rectourethralis muscle and remaining attachments of the prostate to the rectum; wide excision of the neurovascular bundle posterolateral to the prostate when adjacent induration or tumor is present, and division of the bladder neck, leaving a 5 mm. cuff of bladder tissue with the prostate. RESULTS Of 144 consecutive patients 16 (11.1%) had positive surgical margins at a total of 20 sites, including 7 (35%) at the apex, 8 (40%) posterolateral, 3 (15%) anterior and 2 (10%) at the bladder neck. These results compare favorably with the positive surgical margin rates after radical prostatectomy previously reported in the literature. CONCLUSIONS These surgical modifications appear to have decreased the incidence of positive surgical margins after radical retropubic prostatectomy.

Risk Factors for Erosion of Artificial Urinary Sphincters: A Multicenter Prospective Study

OBJECTIVE To evaluate the short- to medium-term outcomes after artificial urinary sphincter (AUS) placement from a large, multi-institutional, prospective, follow-up study. We hypothesize that along with radiation, patients with any history of a direct surgery to the urethra will have higher rates of eventual AUS explantation for erosion and/or infection. MATERIALS AND METHODS A prospective outcome analysis was performed on 386 patients treated with AUS placement from April 2009 to December 2012 at 8 institutions with at least 3 months of follow-up. Charts were analyzed for preoperative risk factors and postoperative complications requiring explantation. RESULTS Approximately 50% of patients were considered high risk. High risk was defined as patients having undergone radiation therapy, urethroplasty, multiple treatments for bladder neck contracture or urethral stricture, urethral stent placement, or a history of erosion or infection in a previous AUS. A total of 31 explantations (8.03%) were performed during the follow-up period. Overall explantation rates were higher in those with prior radiation and prior UroLume. Men with prior AUS infection or erosion also had a trend for higher rates of subsequent explantation. Men receiving 3.5-cm cuffs had significantly higher explantation rates than those receiving larger cuffs. CONCLUSION This outcomes study confirms that urethral risk factors, including radiation history, prior AUS erosion, and a history of urethral stent placement, increase the risk of AUS explantation in short-term follow-up.

Long-Term Efficacy of Distal Penile Circular Fasciocutaneous Flaps for Single Stage Reconstruction of Complex Anterior Urethral Stricture Disease

PURPOSE We determined the overall efficacy and predictors of success of the distal penile circular fasciocutaneous flap in the management of complex anterior urethral stricture disease not due to lichen sclerosus. MATERIALS AND METHODS We performed a retrospective review of all patients undergoing reconstruction of complex anterior urethral strictures without lichen sclerosus repaired from 1985 to 2006. Primary and overall stricture-free survival curves were estimated using the Kaplan-Meier method. Cox proportional hazards regression analysis was used to identify univariate and multivariate predictors of flap success. RESULTS A total of 124 patients met the inclusion and exclusion criteria. Median patient age was 48 years (range 16 to 83). Median followup was 7.3 years (range 1 month to 19.5 years). Median stricture length was 8.2 cm (range 0.5 to 24). At 1, 3, 5 and 10 years the overall estimated stricture-free survival rates were 95%, 89%, 84% and 79%, respectively. On multivariate analysis smoking (HR 4.0, 95% CI 1.2-12.9, p = 0.02), history of hypospadias repair (HR 4.4, 95% CI 1.3-14.6, p = 0.01) and stricture length 7 to 10 cm (HR 7.0, 95% CI 1.4-34.7, p = 0.02) were predictive of failure. CONCLUSIONS Fasciocutaneous flap urethroplasty has good and durable success rates in the treatment of complex anterior urethral strictures. Predictors of failure included smoking, history of hypospadias repair and longer stricture length.

Impact of surgical margin status on long-term cancer control after radical prostatectomy.

To determine whether previously described technical modifications that significantly decreased the positive surgical margin (PSM) rate have translated into improved long‐term cancer control, as SM status is generally recognized as an independent risk factor for biochemical recurrence (BR) after radical retropubic prostatectomy (RRP), and is the only factor that can be modified by surgical technique.

High-grade prostatic intraepithelial neoplasia with adjacent atypia is associated with a higher incidence of cancer on subsequent needle biopsy than high-grade prostatic intraepithelial neoplasia alone

OBJECTIVES High-grade prostatic intraepithelial neoplasia (HGPIN) is often considered a premalignant lesion of the prostate. Its incidence ranges from 0.7% to 20% in all prostate biopsies, and patients with HGPIN on initial biopsy are reportedly found to have a higher risk of cancer on subsequent biopsy. The purpose of our study was to determine the incidence of HGPIN in our patients who underwent prostate biopsy and to determine whether a further pathologic subclassification of HGPIN between HGPIN alone and HGPIN with adjacent atypical glands has any prognostic value in predicting the rate of prostate cancer on subsequent prostate biopsy. METHODS A total of 485 patients who underwent prostate biopsy between January 1998 and October 1999 were included in the study. Each set of slides was reviewed by a single urologic pathologist to determine the presence of HGPIN alone or HGPIN with adjacent atypical glands. If any HGPIN was identified, a repeat biopsy was performed, and the presence of cancer was recorded. RESULTS The overall incidence of HGPIN alone and HGPIN with adjacent atypical glands on initial biopsy was 33 (6.8%) of 485. Of these 33 patients, 21 (64%) had HGPIN alone and 12 (36%) had HGPIN with adjacent atypical glands. Three (14%) of 21 patients with HGPIN alone were found to have cancer on subsequent biopsy compared to 9 (75%) of 12 patients with HGPIN with adjacent atypia on initial biopsy. This difference is statistically significant (P <0.005). CONCLUSIONS The incidence of HGPIN alone in our experience is 4.3% (21 of 485). Patients with HGPIN with adjacent atypical glands suspicious for cancer have a significantly higher incidence of cancer on subsequent biopsy than patients with HGPIN alone.

Intralesional Injection of Mitomycin C at Transurethral Incision of Bladder Neck Contracture May Offer Limited Benefit: TURNS Study Group

PURPOSE Injection of mitomycin C may increase the success of transurethral incision of the bladder neck for the treatment of bladder neck contracture. We evaluated the efficacy of mitomycin C injection across multiple institutions. MATERIALS AND METHODS Data on all patients who underwent transurethral incision of the bladder neck with mitomycin C from 2009 to 2014 were retrospectively reviewed from 6 centers in the TURNS. Patients with at least 3 months of cystoscopic followup were included in the analysis. RESULTS A total of 66 patients underwent transurethral incision of the bladder neck with mitomycin C and 55 meeting the study inclusion criteria were analyzed. Mean ± SD patient age was 64 ± 7.6 years. Dilation or prior transurethral incision of the bladder neck failed in 80% (44 of 55) of patients. Overall 58% (32 of 55) of patients achieved resolution of bladder neck contracture after 1 transurethral incision of the bladder neck with mitomycin C at a median followup of 9.2 months (IQR 11.7). There were 23 patients who had recurrence at a median of 3.7 months (IQR 4.2), 15 who underwent repeat transurethral incision of the bladder neck with mitomycin C and 9 of 15 (60%) who were free of another recurrence at a median of 8.6 months (IQR 8.8), for an overall success rate of 75% (41 of 55). Incision with electrocautery (Collins knife) was predictive of success compared with cold knife incision (63% vs 50%, p=0.03). Four patients experienced serious adverse events related to mitomycin C and 3 needed or are planning cystectomy. CONCLUSIONS The efficacy of intralesional injection of mitomycin C at transurethral incision of the bladder neck was lower than previously reported and was associated with a 7% rate of serious adverse events.

Multi-institutional 1-Year Bulbar Urethroplasty Outcomes Using a Standardized Prospective Cystoscopic Follow-up Protocol

OBJECTIVE To evaluate multi-institutional outcomes of bulbar urethroplasty utilizing a standardized cystoscopic follow-up protocol. METHODS Eight reconstructive surgeons prospectively enrolled urethral stricture patients in a multi-institutional study and performed postoperative cystoscopy at 3 and 12 months. Anatomic failure was defined as the inability to pass a flexible cystoscope without force. Functional failure was defined as the need for a secondary procedure. Men not compliant with the 12-month cystoscopy were called and asked if any interval secondary procedures had been performed. Patients with bothersome voiding complaints at cystoscopy were considered symptomatic. RESULTS Of 213 men in study, 136 underwent excisional urethroplasty (excision and primary anastomosis [EPA]) and 77 underwent repair with buccal grafts. Cystoscopy compliance was 79.8% at 3 months and 54.4% at 12 months. Anatomic success rates were higher at 3 vs 12 months for EPA repairs (97.2% [106 of 109] vs 85.5% [65 of 76; P=.003] but not buccal repairs (85.5% [53 of 62] vs 77.5% [31 of 40]; P=.30). Functional success rates at a year were higher but statistically similar to anatomical success rates (EPA-90.3% [93 of 103]; P=.33; buccal-87% [47 of 54]; P=.22). Of the 20 anatomic recurrences, only 13 (65%) were symptomatic at the time of cystoscopic diagnosis. CONCLUSION Rates of success are lower when using the anatomic vs traditional definition. Of recurrences found by cystoscopy, only 65% were symptomatic. One-year patient cystoscopy compliance was poor and its ability to be used as the gold standard screening methodology for recurrence is questionable.

Intravesical valrubicin in the treatment of carcinoma in situ of the bladder.

The propensity of patients with carcinoma in situ (CIS) of the bladder to progress to invasive and metastatic disease is clearly established. Today, the standard therapy in treating patients with CIS of the bladder is intravesical bacillus Calmette-Guerin (BCG). Nevertheless, patients who fail intravesical BCG have few viable options except to undergo a radical cystectomy. Valrubicin (N-trifluoroacetyladriamycin-14-valerate) is a new semisynthetic derivative of the anthracycline antibiotic doxorubicin that has been shown to benefit patients with BCG-refractory CIS of the bladder. Intravesical instillation of valrubicin is well-tolerated, safe and can be durable. Early non-randomised studies show promise and the current utilisation of this drug is limited to patients with BCG-refractory CIS of the bladder who are not good surgical candidates. Randomised studies of intravesical valrubicin for the treatment of superficial bladder cancer are ongoing.

Internet Survey of Management Trends of Urethral Strictures

Objectives: The management of urethral stricture is often complex and the decision to proceed to urethroplasty may be difficult. A variety of factors are used by urologists to help guide this decision. We sought to conduct a survey to define current management trends and referral patterns in the treatment of urethral stricture disease. Methods: An internet survey was conducted using the email directory for the AUA North Central Section. Survey design focused on urologist demographics and practice type, practice trends for treating urethral strictures, and referral patterns. Results were analyzed to assess for demographic parameters influencing management and referral trends. Results: Responses were received from 84/600 (14%) urologists. Despite 95% of respondents reporting the recent treatment of urethral stricture, the majority of urologists reported performing no urethroplasties within the same time period. Complicated repairs (posterior, buccal) were performed by only a few of the respondents. A variety of factors were used by urologists to help decide at what point urethroplasty should be pursued. However, the importance of these factors varied significantly. Conclusions: Our data suggest that the treatment algorithm for urethral strictures is complex and varies considerably between urologists. The decision to perform urethroplasty may be particularly difficult. Finally, patient referral appears to play a significant role in stricture management. Treatment guidelines based on objective data are needed.