Open Journal of Urology, 2013, 3, 227-231
http://dx.doi.org/10.4236/oju.2013.36043 Published Online October 2013 (http://www.scirp.org/journal/oju)
Bladder Neck Morphologic Changes and Clinical
Correlation of Smokers Submitted to Radical
Prostatectomy
L. C. N. Araujo1*, W. S. Costa2, F. O. Vilar1, S. V. C. Lima1, F. J. B. Sampaio2
1Urology Department, Hospital das Clinicas, Federal University of Pernambuco, PE, Brazil
2Urogenital Research Unit, State University of Rio de Janeiro, RJ, Brazil
Received August 18, 2013; revised August 30, 2013; accepted September 5, 2013
Copyright © 2013 L. C. N. Araujo et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Introduction: Smoking is an important risky factor to many diseases, affecting arterial system, skin and urogenital sys-
tem, including bladder neck stenosis. Its effect on bladder neck has not been described. Objective: Evaluate possible
morphological changes caused by nicotine in the bladder neck. Material and Method: Fragments of bladder neck of 16
patients were submitted to stereological analysis, and those patients are divided into two groups, one of smokers and the
other of non-smokers with 7 and 9 patients, respectively. After 90 days of surgery, they were submitted to free uro-
flowmetry and data analyzed by T test, having statistical significance with P < 0.05. Results: An increase of 63.26% in
the amount of fibers in the elastic system of the smokers group was observed, a reduction of 35.96% in the thickness of
arteries, as well as an increase of IPSS and decrease of maximum flow in uroflowmetry, all with statistical significance.
Discussion: Laboratorial changes are similar to those found in other studies with different tissues, such as skin, in
which those findings are related to premature ageing. Clinical results, though statistically significant, do not have clini-
cal consistence because the study was meant to morphological analysis. Conclusion: Smoking increases the amount of
fibers in the elastic system and decreases the thickness of bladder neck arteries.
Keywords: Smoking; Bladder Neck; Elastic Fibers; Uroflowmetry
1. Introduction
Smoking has been described as an important risky factor
to many diseases. It is closely linked to heart diseases,
affecting directly the arterial system and microvascula-
ture [1-4], and it also affects the distribution of extracel-
lular matrix related to early ageing of these tissues [5-7].
In urogenital tract, it is linked to the development of
bladder and prostate cancers and erectile dysfunction.
Epidemiologically, it is a risky factor to bladder neck
sclerosis following radical prostatectomy [1,8-14].
Morphological evaluation of bladder neck of smokers,
as well as its clinical repercussions, has not been de-
scribed yet.
2. Objective
The aim of this study is to analyze the possible morpho-
logical bladder neck changes of smokers and non-smok-
ers submitted to radical prostatectomy and compare those
findings with laboratorial and clinical data obtained.
3. Material and Method
The Project was submitted to the Ethics Committee of
the involved institution. Patients signed the form of free
and duly informed consent. The calculus of the number
of elements in the sample was done through standard
deviation and margin of error, considering P < 0.05, and
then obtaining the number of cases necessary to the com-
parison of two groups of patients, that had the amount of
6.65 for all parameters in each group.
Sixteen patients were selected, ages 62 to 69, all Navy
military retirees and residents in Rio de Janeiro without
prior prostate disease or vascular co-morbidities, which
were undergone to radical prostatectomy. During the
surgery fragments were taken from this group of patients,
measuring approximately 1 cm, from the anterior surface
of the bladder neck. The collection of material was done
*Corresponding author.
C
opyright © 2013 SciRes. OJU

L. C. N. ARAUJO ET AL.
228
after the prostate and the seminal vesicles were removed
and before vesicourethral anastomosis. Those patients were
split in two groups, smokers (7 patients) and non-smok-
ers (9 patients).
Patients that had surgical vesicle margin positive to
oncological impairment or those submitted to radiother-
apy as therapeutic complementation were excluded from
the sample.
The material obtained was fixed in formalin solution
(pH 7.2) and processed according to the histological rou-
tine stages to inclusion in paraffin. The material was cut
with a width of 5 µm.
The sections were stained by the following techniques:
hematoxylin and eosin to tissue integrity analysis and
arterial wall width measurement; oxidized Weigert’s re-
sorcin-fuchsin to characterize elastic system fibers and
Van Gieson’s to analyze collagen fibers and smooth mus-
cle cells. After histologic routine procedures, sections
were photographed in microscopic computerized system,
composed of optical microscope and camera (Olympus®).
The quantification of different elements analyzed was
done using ImageJ® program (Image Processing and
Analysis in Java).
All patients were clinically followed-up for 180 days
after surgery, filling up IPSS questionnaire (International
Prostate Score Symptoms) [15] and were submitted to
free uroflowmetry tests.
Results obtained were analyzed by statistical program
GraphPad Prism 4, through unpaired two-tailed Student’s
T test, as well as through Pearson correlation analysis
between gross amount results with calculus via confi-
dence interval. Results were considered significant when
P < 0.05.
4. Results
All data assumed normal distribution and the following
results were obtained: in the smokers’ group the amount
of collagen fibers was 22.70% (SD = 4.86), elastic sys-
tem fibers 13.29% (DP = 3.84) (Figure 1), smooth mus-
cle 23.97% (SD = 12.3), height of arterial wall was 16.52
μm (SD = 2.73) (Figure 2), while in the non-smoker’s
group was 21.20% (SD = 8.21) to collagen fibers, 8.14%
(SD = 3.54) to elastic system fibers, 23.97% (SD = 8.01)
(Figure 3) to smooth muscle fibers and 25.80 μm (SD =
7.18) to height of arterial wall (Figure 4).
As for the parameters of clinical analysis, smokers’
IPSS had an average of 18.40 (SD = 5.58), and non-
smokers’ was 9.39 (SD = 3.73), maximun flow obtained
in free uroflowmetry (Qmax) had an average of 4.80 ml/s
(DP = 1.72), and 9.60 ml/s (SD = 3.20) for non-smokers.
Statistical analysis showed that the increase in the
amount of collagen fibers and the decrease of smooth
muscle fibers had no statistical significance (P > 0.05).
However the increase of the amount of elastic system
Figure 1. Photomicrography smoker group Weigert’s re-
sorcin-fuchsin, 400×.
Figure 2. Arterial Wall, smoker Group, Van Gieson, 400×.
Figure 3. Photomicrography nonsmoker group Weigert’s
resorcin-fuchsin, 400×.

L. C. N. ARAUJO ET AL. 229
Figure 4. Arterial Wall, non-smoker Group, H & E, 400×.
fibers and the decrease of height of arterial wall in the
same group had P < 0.05.
Through clinical analysis it was perceived increase of
IPSS and decrease of Qmax, both with statistical signifi-
cance (P < 0.05), in the smokers group.
Correlation analysis showed R = −0.67 (P < 0.05) be-
tween the amount of elastic system fibers and height of
arterial wall, R = 0.55 (P < 0.05) between amount of
elastic system fibers and IPSS, R = −0.54 (P < 0.05) be-
tween elastic system fibers and Qmax, R = −0.59 be-
tween height of arterial wall and IPSS, R = 0.47 (P =
0.06) between height of arterial wall and Qmax, and R =
−0.94 (P < 0.05) between IPSS and Qmax.
Four patients in each group developed cardiovascular
diseases, but no statistical difference was found when
compared with the averages of the group that did not
developed obstructive pathology.
Numerical results of different parameters can be seen
on Tables 1 to 3.
5. Discussion
Effects of tobacco consumption on bladder neck circula-
tion had not been previously characterized in literature.
Borboroglu in 2000 evaluated patients that had sclerosis
of bladder neck anastomosis among those risky factor
groups: chronic obstructive lung disease (COLD), coro-
nary arterial disease (CAD), Diabetes Mellitus (DM),
smoking, pre-operative blood loss, surgical time and pre-
vious history of transurethral prostate resection (TURP)
and concluded that smoking is an important factor to the
development of sclerosis of bladder neck anastomosis,
suggesting that it is originated from micro vascular changes
[10]. Mack et al. (2003) observed a decrease of thickness
of carotid artery as consequence of chronic use of nico-
tine [4].
Table 1. Morphometry of smooth muscle collagen, elastic
system fibers and width of arterial wall—average ± stan-
dard deviation. Arterial wall width in μm.
smoking non-smokingP
Collagen % 22.70 ± 4.86 21.20 ± 8.210.904
Smooth Muscle % 23.97 ± 12.31 27.97 ± 8.020.338
Elastic Fiber % 13.29 ± 3.85 8.14 ± 3.54 0.020
Arterial Wall (μm) 16.52 ± 2.73 25.80 ± 7.190.005
Table 2. Clinical analysis. IPSS (International Prostate
Score Symptoms) and Qmax (maximum flow).
smoking non-smoking
P
IPSS 18.40 ± 5.59 9.67 ± 3.73 0.004
Qmax 4.80 ± 4.72 9.45 ± 3.20 0.040
Table 3. Analysis of Pearson correlation. Morphometry and
Clinical Analysis. International Prostate Score Symptoms
(IPSS); Free Uroflowmetry (Qmax).
Pearson Correlation R P
Elastic X Arterial Wall −0.67 <0.05
Elastic X IPSS 0.55 <0.05
Elastic X Qmax −0.52 <0.05
Arterial Wall X IPSS −0.57 <0.05
Arterial Wall X Qmax 0.44 >0.05 (p = 0.06)
In this study, there were no findings of significant dif-
ferences between the two groups when compared the
amount of collagen and smooth muscle fibers. The re-
ports of changes in synthesis and deposit of collagen from
instillation of 7H-dibenzol (c, g) carbazole, that is a com-
ponent of tobacco, represent specific changes of the res-
piratory tract, trachea and bronchi, in progressive neo-
plasia during the process of tumoral induction [16]. In
this case tobacco action is not direct and, therefore, the
effects are presented in a different way of those found in
lungs, which explains conflicting results with previous
studies.
The decrease of bladder neck arterial wall thickness in
35.96% (Figures 3 and 4) is conformed to literature, in
which nicotine consumption is risky factor to atheroscle-
rosis, thrombosis, tissue injury, superoxide ions and free
radicals formation, reducing production and availability
of Nitric Oxide, increasing the production of endothelin,
leading to endothelial dysfunction, thrombosis, athero-
sclerosis and other endothelial diseases [3,17,18], de-
creasing elasticity of large arteries [4,17,19], with con-
sequent organization disturbances, stiffness, calcification
and vasomotor dysfunction [20], which are directly re-
lated to decrease of tissue oxygenation [21]. Even though
Raveendran et al, 2004, have related these changes to
collagen metabolism [22], our results indicate that there
is a change in elastic system fibers metabolism through

L. C. N. ARAUJO ET AL.
230
changes in the production and metabolism of metallo-
proteinase [5,6], confirmed by statistical correlation be-
tween thickness and amount of bladder neck elastic fi-
bers (Table 3).
In vitro studies indicate that tobacco consumption pre-
vents collagen production and increases tropoelastin pro-
duction and activation of metalloproteinase, causing a
degradation of matrix proteins and a abnormal produc-
tion of elastic material, in its morphology and amount,
having as a consequence the increase of the number of
elastic system fibers in the skin [4-6]. In our results we
have seen an increase of 62.36% of elastic system fibers
in bladder neck tissue in smokers group when compared
to non-smokers (Figures 1 and 2). Morita, associated
these findings to early skin ageing [6].
Effect of smoking on the arterial system and conse-
quent formation of elastic system fibers may not be lim-
ited to bladder neck, being distributed in all bladder, with
an increase of elastic system fibers in all bladder wall
and its repercussions, being able to cause early ageing,
but there are no ways of getting definitive conclusions,
once there are no previous data in the literature on blad-
der ageing.
Not with standing the results in clinical data have been
statistically significant, they should be viewed with re-
strictions mainly by the number of participants and the
absence of data related to detrusor function provided by
uroflowmetry, once the study design was not meant to
morphological evaluation only, and as such there are no
previous data of bladder function in smokers. Gathered
data may be, in spite of statistical significance, a coinci-
dence, and are necessary future clinical studies to con-
firm the present findings. Results will be discussed only
in order to be compared to further.
Results found on clinical data supposedly indicated an
impact related to tobacco consumption both in IPSS re-
sult, with an increase of approximately 93%, as in Qmax
reduction, with a decrease of about 51%, which was re-
flected in a reduction of voiding function statistically
significant in smokers when compared to those that were
not exposed to nicotine.
Correlation analysis between quantitative data and clini-
cal results shows that there can be a strong connection
between clinical changes related to amount of elastic
system fibers. Even though there is a great limitation of
data, which leads to absence of definitions regarding de-
trusor behavior, as for number of specimens, there should
be a supposed early ageing that can happen to bladder
tissue as well as skin [6], which should explain the
changes that were found, with a probable reduction in
detrusor contractility, as results are related to smoking
and not with existence of cardiovascular diseases. But
stating a definitive conclusion will only be possible with
studies that evaluate detrusor function.
6. Conclusions
In the present study, smoking modified bladder neck ex-
tra-cell matrix of patients submitted to radical prostatec-
tomy with an increase of the amount of elastic system
fibers (P < 0.05).
It is also observed a decrease of arterial wall height in
the same group with statistical correlation (P < 0.05).
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