care must be taken during division of the dorsal vein complex to avoid a positive margin on the anterior apex
of the prostate.
1. Takao T, Tsujimura A: Prostate stem cells: the niche and cell markers. Int J Urol. 2008; 15: 289-94.
2. Billis A, Meirelles L, Freitas LL: Mergence of partial and complete atrophy in prostate needle biopsies: a morphologic
and immunohistochemical study. Virchows Arch. 2010; 456: 689-94.
3. Rowley DR: What might a stromal response mean to prostate cancer progression? Cancer Metastasis Rev. 1998-1999;
Dr. Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil
The plasmacytoid carcinoma of the bladder - rare variant of aggressive urothelial carcinoma
Keck B, Stoehr R, Wach S, Rogler A, Hofstaedter F, Lehmann J, Montironi R, Sibonye M, Fritsche HM, Lopez-
Beltran A, Epstein JI, Wullich B, Hartmann A
Department of Urology, University Erlangen, Germany
Int J Cancer. 2010; 28. [Epub ahead of print]
The WHO classification of 2004 defines new histological and molecular variants of urothelial carcinoma.
However there are limited data available on the clinico-pathological characteristics or prognosis of these variants.
We present histopathological, molecular and clinical data of 32 plasmacytoid carcinomas of the bladder (PUC)
showing that PUC is a high-grade tumor with molecular features of aggressive urothelial carcinoma, usually
diagnosed in advanced pathological stage (64% pT3, 23% pT4) showing metastases in 60 % of the patients.
Average survival of our cohort of PUC treated with radical cystectomy and adjuvant chemotherapy was lower
than what is typically seen for comparable conventional urothelial carcinomas. 87% of the PUCs showed a
negative or strongly reduced membranous staining of E-cadherin. Beta-catenin staining was negative in 22.5%
and 16.7% of the remaining tumors showed nuclear accumulation. Aberrant CK20 expression (negative or >
10% of cells stained) and negative CK7 staining was found in 100% and 22.6%, respectively. 97% revealed
positive staining for PAN-CK. CD138 was positive in 78 %, whereas MUM-1 expression was negative in all
cases. Multi-target fluorescence in situ hybridization showed all PUCs to be highly aneuploid and polysomic.
Deletions on chromosome 9p21 seem to play an important role in this variant. FGFR3 and PIK3CA mutation
analyses yielded no mutations in any of the PUCs analyzed. TP53 mutation analysis showed mutations in 29%.
In summary, PUC is a aggressive variant of bladder cancer with molecular features of advanced bladder cancer
and evidence of WNT pathway activation in some of the cases.
The great majority of urinary bladder neoplasms derive from the urothelial (transitional) cells. Tumors
originating from the mesenchimal cells are rare. The most common tumors are benign or malignant conventional
clude several unusual histological variants. The importance of the recognition of these unusual forms is related
to: a) different prognosis; b) different therapeutic approach; and, c) the possibility of misinterpretation by the
An important example is the small cell carcinoma with neuroendocrine differentiation. The importance
of an accurate diagnosis of this variant of urothelial carcinoma is its response to newer chemotherapy protocols.
The histological variants of urothelial carcinoma includes: nested variant, urothelial carcinoma with small tu-
bules, microcystic urothelial carcinoma, micropapillary variant, lymphepithelioma-like, sarcomatoid carcinoma
(carcinosarcoma), small cell carcinoma, plasmacytoid carcinoma, urothelial carcinoma with rhabdoid features,
urothelial carcinoma with clear cytoplasm (glycogen-rich), urothelial carcinoma with trophoblastic differentia-
tion, urothelial carcinoma with unusual stromal reactions, osteoclast-rich undifferentiated carcinoma, and giant
cell carcinoma (1).
The study by Keck et al. based on a large series of plasmacytoid carcinoma showed that this tumor is
an aggressive variant of bladder cancer with molecular features of advanced bladder cancer and evidence of
WNT pathway activation in some of the cases.
The World Health Organization has expanded the microscopic forms of urothelial carcinomas to in-
1. Epstein JI, Reuter VE, Amin MB: Biopsy Interpretation of the Bladder, 2nd ed. Philadelphia, Lippincott Williams &
Dr. Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil
RECONSTRUCTIVE UROLOGY __________________________________________________
Volar onlay urethroplasty for reconstruction of female urethra in recurrent stricture disease
Gozzi C, Roosen A, Bastian PJ, Karl A, Stief C, Tritschler S
Department of Urology, Klinikum Großhadern, Ludwig Maximilians University of Munich, Munich,
BJU Int. 2010 Nov 17 [Epub ahead of print]
Objective: To report our experience with a new and simple method of urethral repair with a volar onlay of free
labium minus graft. Strictures of the female urethra are rare, and it is well accepted that the therapeutic options
of dilation and urethrotomy are not lasting solutions as a result of their high recurrence rates. However, there is
no consensus regarding the best way to reconstruct the female urethra in the case of stricture disease.
Patients and Methods: Four consecutive female patients with a long lasting history of recurrent urethral strictures
underwent open urethroplasty with a volar situated free split thickness epidermal graft from the labium minus.
The surgical technique is described and a short-term follow-up is presented.
Results: Operating time was 40–140 min (mean 105 min), and the graft measured between 2 × 1.5 cm and 3
× 2.5 cm. Follow-up time was 11–19 months. Maximum urinary flow rate could be improved from a baseline
of 9.4–11.2 mL/s (preoperatively, after intermittent use of dilation) to 19–23 mL/s. Postvoid residual urine
volume was 0-50 mL preoperatively and no postvoid residual urine volume postoperatively. Urinary catheters
were removed after 21 days. Urinary stress incontinence did not occur postoperatively. There were found no
complications related to the graft donor site.
Conclusions: The reported data concerning a new therapeutic approach for the treatment of recurrent female
urethral stricture show that a volar onlay urethroplasty represents a feasible, safe and simple surgical method.
Larger series with long-term follow-up are needed for further evaluation.
Vaginal flap urethroplasty for wide female stricture disease
Simonato A, Varca V, Esposito M, Carmignani G
Clinica Urologica L. Giuliani, Ospedale San Martino, Università degli Studi di Genova, Genova, Italy
J Urol. 2010; 184: 1381-5
Purpose: As in men, female urethral stricture disease is often treated with repeat urethral dilation or internal
urethrotomy but not always with good results. In nonresponsive cases surgical treatment may be useful but only
a few cases are reported in the literature. We present our single institution experience with urethral reconstruc-
tion in 6 patients using an alternative vaginal inlay flap technique inspired by the Orandi technique.
Materials and Methods: We treated 6 women with urethral stricture. In 5 patients stricture involved the entire
middle and distal urethra, and in 1 it also involved the proximal urethra with bilateral hydronephrosis. Patients
underwent urethral reconstruction using a vaginal flap with a lateral vascular pedicle that maintains the vascular
axis. The flap was partially de-epithelialized to favor tissue cicatrix formation where the sutures are placed and
avoid fistula formation.
Results: Mean followup was 70.8 months. Normal micturition was achieved after catheter removal in all pa-
tients. Post-void residual urine was measured postoperatively in 3 patients. One patient had significant post-void
residual urine and required intermittent self-catheterization. The remaining 5 patients required no additional
Conclusions: Using the vaginal wall to reconstruct large segments of the female urethra is simple and appears
to have good results. Our technique preserves the vascular axis of the flap and protects the sutures. More con-
tributions to the existing literature are needed before any further conclusions can be drawn.
Repair of female urethral stricture disease is difficult. First, the disease is less common than male urethral
stricture disease making the surgeon less familiar with the technique. Second, the shorter urethra and proximity
to the vaginal mucosa allows for little margin of error. Perhaps the multitude of surgical approaches described
attests to the quest to find a universally acceptable approach. Dividing the urethra along its volar aspect (the
vaginal rather than clitoral body side) is preferable for many reasons. First, it avoids the majority of the sphincter
fibers. These fibers follow an omega shape and are more prominent on the clitoral side. Second, a volar dissec-
tion is familiar to most urologists as the dissection for most anti-incontinence procedures is done in this area.
Third, it avoids dissection of the urethra off the clitoral bodies – a dissection unfamiliar to urologists.
These two articles present descriptions of modifications of the volar urethroplasty in women. In Gozzi
et al, the authors describe a suburethral incision followed by dissection of the vaginal flap off the urethra, a
volar urethrotomy and excision of all scarred tissue. A labia minora graft is then harvested, thinned, and grafted
ventrally, using the periurethral tissue as a graft bed. The vaginal flap is closed. In contrast, the Simonato et al
group describes an approach that borrows heavily from the Orandi urethroplasty well-known in reconstruction
of penile urethral stricture disease. A laterally-based vaginal flap is created and the middle portion is de-epithe-
lialized. This essentially creates a medially located island flap which is then rolled onto the ventral urethrotomy.
The remaining (lateral) vaginal flap is closed over the urethra.
Both of these approaches are attractive in the fact that they use a volar approach and borrow from
reconstructive principles used in male urethral stricture surgery. Both approaches are most appropriate in the
distal to middle third of the urethra. The proximal third remains a higher risk area due to the deeper dissection
and the prominence of bladder neck sphincter fibers. Small patient numbers and limited follow-up may limit
the external validity of the results of these two series.
Dr. Sean P. Elliott
Department of Urology Surgery
University of Minnesota
Minneapolis, Minnesota, USA
UROLOGICAL ONCOLOGY _____________________________________________________
Clinical outcome in a contemporary series of restaged patients with clinical T1 bladder cancer
Dalbagni G, Vora K, Kaag M, Cronin A, Bochner B, Donat SM, Herr HW
Division of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Eur. Urol. 2009; 56: 903-910
Objectives: To evaluate the indications for early and deferred cystectomy and to report the impact of this tailored
approach on survival.
Design, Setting, and Participants: We retrospectively studied 523 patients seen at our institution who were
initially diagnosed with T1 disease between 1990 and 2007.
Measurements: Variables analyzed included age, gender, multifocality, multifocal T1 disease, carcinoma in situ,
grade, recurrence rate, and restaging status. End points were overall and disease-specific survival.
Results and Limitations: A restaging transurethral resection (TUR) was performed in 523 patients. Of the pa-
tients who underwent restaging, 106 (20%) were upstaged to muscle-invasive disease and 417 patients were
considered true clinical T1 (cT1); 84 of the latter group underwent immediate cystectomy. The median follow-up
for survivors was 4.3 yr. The cumulative incidence of disease-specific death at 5 yr was 8% (95% confidence
interval [CI], 5-13%), 10% (95% CI, 5-17%), and 44% (95% CI, 35-56%) for those restaged with lower than
T1, T1, and T2 disease, respectively. Immediate cystectomy was more likely in patients with cT1 disease at
restaging than in those with disease lower than cT1, but there were no other obvious differences in clinical
characteristics between those with and without immediate cystectomy. Survival was not statistically different
for patients who underwent an immediate cystectomy versus those who were maintained on surveillance with
deferred cystectomy if deemed appropriate. Of 333 patients who did not undergo immediate cystectomy, 59
had a deferred cystectomy, and the likelihood of deferred cystectomy was greater in those with T1 disease on
restaging TUR (hazard ratio: 2.40; 95% CI, 1.43-4.01; p=0.001).
Conclusions: Restaging TUR should be performed in patients diagnosed with cT1 bladder cancer to improve
staging accuracy. Patients with T1 disease on restaging are at higher risk of progression and should be consi-
dered for early cystectomy.
The timing of cystectomy in T1 bladder cancer is a matter of debate since years. Here, the authors from
a tertiary referral center present their series of 523 patients and analyze variables which may help with the deci-
sion to remain conservatively, or proceed with radical surgical therapy. Interestingly, re-TUR was performed in
all patients and yielded a high rate of 20% upstaging to muscle-invasive disease. If true T1 was considered, the
disease-specific mortality at 5 years was 10%, with no survival differences between those patients undergoing
early cystectomy versus those with no or deferred cystectomy. Clearly, these data support an initial conservative
approach in select patient with true pT1. In any case, a re-TUR is mandatory.
Dr. Andreas Bohle
Professor of Urology
HELIOS Agnes Karll Hospital
Bad Schwartau, Germany
Outcome predictors of radical prostatectomy in patients with prostate-specific antigen greater
than 20 ng/ml: A European multi-institutional study of 712 patients
Spahn M, Joniau S, Gontero P, Fieuws S, Marchioro G, Tombal B, Kneitz B, Hsu CY, Van Der Eeckt K, Bader
P, Frohneberg D, Tizzani A, Van Poppel H
University Hospital Würzburg, Department of Urology and Pediatric Urology, Germany; Community Hospital
Karlsruhe, Department of Urology, Karlsruhe, Germany
Eur. Urol. 58: 1-7, 2010
Background: Prostate cancer (PCa) patients with pretreatment prostate-specific antigen (PSA) >20 ng/ml have
a high risk of biochemical and clinical failure and even cancer-related death after local therapy. Pretreatment
predictors of outcome after radical prostatectomy (RP) in this patient group are necessary.
Objective: Our aim was to assess how the use of additional high-risk factors (biopsy Gleason score [bGS] >/=8
or clinical stage 3-4) can improve prediction of treatment failure and cancer-related death after RP in patients
with PSA >20.
Design, Setting, and Participants: In a retrospective multicentre cohort study from six European centres between
1987 and 2005, 712 patients with PSA >20 ng/ml underwent RP and bilateral pelvic lymphadenectomy.
Measurements: Subgroups were analysed to determine the relationship between the number of high-risk factors
and histopathology, biochemical progression-free survival, clinical evidence of progressive disease, prostate
cancer-specific mortality (PCSM), and overall mortality. Kaplan-Meier analysis with log-rank test and Cox
multivariable analysis were applied.
Results and Limitations: Median follow-up was 77 mo. The number of high-risk factors was significantly asso-
ciated with unfavourable histopathology. Among patients with only PSA >20 ng/ml, 33% had pT2 PCa, 57.9%
had bGS <7, 54% had negative surgical margins, and 85% were lymph node negative (pN0), whereas among
patients with all three high-risk factors, 4.5% had pT2 PCa, 2.3% had bGS <7, 20.5% had negative margins,
and 49% were pN0 (p<0.001). The strongest predictor of progression and mortality was bGS. PSA >20 ng/ml
associated with bGS </=7 resulted in 10-yr PCSM of 5%; when associated with bGS >/=8, PCSM was 35%.
The main limitations of the study were retrospective design and varying treatment modalities.
Conclusions: PCa patients with PSA >20 ng/ml have varying risk levels of disease progression and PCSM.
Considering additional risk factors further stratifies this group into four subgroups that can guide the clinician
in preoperative patient counselling.
Surgical therapy in patients with prostate cancer and a PSA >20 ng/ml is a matter of debate. Most patients
are considered high-risk and receive either hormonal therapy alone or are referred to external beam radiation
therapy. The authors from this multi-institutional study analyze their 712 patients with PSA >20 ng/ml who
underwent radical prostatectomy. Of this group, roughly 40% had Gleason score > 7, 50% had positive surgical
margins and 15% were node-positive. The combination of these factors was predictive for patient’s outcome.
Interestingly, even in this special group of patients death of disease was a rare event, with high cancer-
specific survival rates of 90% and 85% after 5 and 10 years, respectively, whereas biochemical progression-free
rates in the same group were as low as 65% at 5 years and 52% at 10 years.
The combination of several risk factors, expectedly, led to reduced progression-free and survival rates.
In summary, radical prostatectomy is a viable option even for high-risk patients.
Dr. Andreas Bohle
Professor of Urology
HELIOS Agnes Karll Hospital
Bad Schwartau, Germany
NEUROLOGY & FEMALE UROLOGY ____________________________________________
Functional results after tape removal for chronic pelvic pain following tension-free vaginal tape
or transobturator tape
Rigaud J, Pothin P, Labat JJ, Riant T, Guerineau M, Le Normand L, Glemain P, Robert R, Bouchot O
Urology Clinic, Hôtel-Dieu, Nantes University Hospital Centre, Nantes, France
J Urol. 2010; 184: 610-5
Purpose: The incidence of pelvic pain after placement of a suburethral sling for incontinence ranges between
0% and 30%. The management of this chronic pain after suburethral sling placement is complex and to our
knowledge no consensus has been reached. We evaluated the functional results after removal of the suburethral
tape responsible for chronic pelvic pain.
Materials and Methods: From November 2004 to August 2009, 32 patients undergoing removal of suburethral
tape causing chronic pelvic and perineal pain at our department were prospectively followed. Patients were
divided according to the type of suburethral sling into the transobturator tape group (15 patients) and the ten-
sion-free vaginal (retropubic) tape group (17 patients). In the TVT group tape removal was performed using
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transperitoneal laparoscopy in every patient. In the TOT group tape removal was performed via a transvaginal
approach possibly associated with a unilateral or bilateral incision in the proximal part of the thigh. Pain was
evaluated by a visual analogue scale from 0-no pain to 10-maximal pain.
Results: The surgical exploration of suburethral tape responsible for chronic, treatment refractory pelvic pain
revealed in most cases an abnormal tape position or excessive tape traction. In the overall population tape
removal provided improvement of pain (at least 50% improvement of the visual analogue scale score) in 68%
with a mean followup of 10 months. Mean visual analogue scale score was 7.3 +/- 1.5 before surgery and 3.4
+/- 3 after surgery. However, recurrence of incontinence was observed in 22% of cases. No significant differ-
ence was demonstrated in terms of functional results according to the type of tape insertion.
Conclusions: The surgical removal of suburethral tape improved pain in 68% of patients but with a risk of
recurrence of urinary incontinence in 22%.
The authors review their experience in addressing chronic pelvic pain following the placement of a
tension free vaginal tape or transobturator tape. Notable findings included that only approximately two-thirds
of the patients were able to have a > 50% improvement in their pain control with resection of the tape. In ad-
dition, 1 in 5 patients had a return of their incontinence.
The physicians noted that the onset of pain after the placement of the tape was exceedingly rapid thus
assisting the reader in linking the rapid temporal nature of this iatrogenic pain to the surgery. Of interest, is that
cystoscopy, CT scan, and MRI’s were all normal and thus are of potentially little assistance in evaluating this
pain syndrome. For the TVT tapes, the authors utilized laparoscopy while for anatomic reasons with the tran-
sobturator tape, removals were performed transvaginally. Upon examination of the cause of pain with the TOT
tape, it was noted that this was most likely to be secondary to a myofascial syndrome from muscle response to
the tape passing through the body of the muscle.
Important take home messages include that the rapid appearance of pain after the placement of a
suburethral tape should embolden the surgeon to promptly proceed with removal prior to the period of tissue
ingrowth and that imaging studies with this temporal associated pain are of limited value. That the authors
found that they had approximately 20% recurrence of incontinence after tape removal is understandable in view
of similar findings of a very similar incontinence rate after simple sling incision for relief of urinary retention
following pubovaginal slings (1). Strong consideration for long term physical therapy may be of value in view
of the identified myofascial component and the less than 100% response to surgery for the pain.
1. Thiel DD, Pettit PD, McClellan WT, Petrou SP: Long-term urinary continence rates after simple sling incision for
relief of urinary retention following fascia lata pubovaginal slings. J Urol. 2005; 174: 1878-81.
Dr. Steven P. Petrou
Professor of Urology, Associate Dean
Mayo School of Graduate Medical Education
Jacksonville, Florida, USA