“effect of preoperative finasteride therapy on...
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“EFFECT OF PREOPERATIVE FINASTERIDE THERAPY ON PERIOPERATIVE BLOOD LOSS IN
TRANSURETHRAL RESECTION OF PROSTATE FOR BENIGN PROSTATIC HYPERPLASIA” – A PROSPECTIVE RANDOMIZED PLACEBO
CONTROLLED STUDY
Dissertation submitted to
THE TAMILNADU DR.M.G.R. MEDICAL UNIVERSITY CHENNAI - 32
in partial fulfillment of the requirements for
the award of the degree of
M.Ch (UROLOGY) BRANCH – IV
GOVERNMENT KILPAUK MEDICAL COLLEGE & HOSPITAL
CHENNAI – 600 010
AUGUST 2015
CERTIFICATE
This is to certify that this dissertation entitled “EFFECT OF
PREOPERATIVE FINASTERIDE THERAPY ON PERIOPERATIVE
BLOOD LOSS IN TRANSURETHRAL RESECTION OF PROSTATE
FOR BENIGN PROSTATIC HYPERPLASIA” A PROSPECTIVE
RANDOMIZED PLACEBO CONTROLLED STUDY submitted by Dr.
NEELAKANDAN R appearing for M.Ch UROLOGY degree examination
in August 2015 is an original bonafide record of work done by him during the
academic period of August 2012 to July 2015 under my guidance and
supervision in partial fulfillment of requirement of the Tamil Nadu Dr.
M.G.R. Medical University, Chennai. I forward this to the Tamil Nadu Dr.
M.G.R. Medical University, Chennai, Tamil Nadu, India.
Prof. Dr MUTHULATHA N M.S, M.Ch., Professor and Head Of the Department, Professor of Urology, Department of Urology, Kilpauk Medical college, , Chennai - 600 010.
Prof. Dr SARAVANAN K M.S, M.Ch., Professor of Urology, Department of Urology, Govt. Royapettah Hospital Chennai - 600 020.
Prof. Dr R. NARAYANA BABU M.D, D.C.H The Dean,
Government Kilpauk Medical College, Chennai- 10
CERTIFICATE
This is to certify that this dissertation entitled “EFFECT OF
PREOPERATIVE FINASTERIDE THERAPY ON PERIOPERATIVE
BLOOD LOSS IN TRANSURETHRAL RESECTION OF PROSTATE
FOR BENIGN PROSTATIC HYPERPLASIA” A PROSPECTIVE
RANDOMIZED PLACEBO CONTROLLED STUDY submitted by Dr.
NEELAKANDAN R appearing for M.Ch UROLOGY degree examination
in August 2015 is an original bonafide record of work done by him during the
academic period of August 2012 to July 2015 under my guidance and
supervision in partial fulfillment of requirement of the Tamil Nadu Dr.
M.G.R. Medical University, Chennai. I forward this to the Tamil Nadu Dr.
M.G.R. Medical University, Chennai, Tamil Nadu, India.
Guide Prof. Dr. MUTHULATHA N
Professor and Head Of the Department Professor of Urology
Department of Urology Government Kilpauk Medical College
Chennai – 600 010.
DECLARATION
I, Dr. NEELAKANDAN R solemnly declare that this dissertation
“EFFECT OF PREOPERATIVE FINASTERIDE THERAPY ON
PERIOPERATIVE BLOOD LOSS IN TRANSURETHRAL
RESECTION OF PROSTATE FOR BENIGN PROSTATIC
HYPERPLASIA” A PROSPECTIVE RANDOMIZED PLACEBO
CONTROLLED STUDY was done by me in the Department of Urology,
Government Kilpauk Medical College and Government Royapettah Hospital,
Chennai, under the guidance and supervision of Prof. MUTHULATHA N,
Professor and Head Of the Department, Department of Urology,Govt.
Kilpauk Medical College, Chennai-10.
This dissertation is submitted to the Tamil Nadu Dr. M.G.R. Medical
University, Chennai-600032 in partial fulfillment of the University
requirements for the award of the degree of M.Ch., Urology.
Place : Chennai Date : 28-03-15
Dr NEELAKANDAN R
ACKNOWLEDGEMENT
I owe my thanks to THE DEAN Prof. NARAYANA BABU R
Govt.Kilpauk Medical College, Chennai, for permitting me to utilize the
facilities and conducting this study and the members of Ethical Committee
for their role.
I am extremely thankful to Prof. MUTHULATHA N, Professor and
Head of Urology, Govt.Kilpauk Medical College Chennai, and my guide, for
devising this study, valuable guidance, motivation, expert advice and help
rendered during the procedures and throughout this study
I am extremely grateful to Prof. SARAVANAN K, Professor of
Urology, Department of Urology, Govt. Royapettah Hospital , Chennai, for
his constant encouragement and guidance throughout the study and periodic
reviews.
I am extremely thankful to Prof. ILANGOVAN M and Prof.
GOVINDARAJAN R for their constant encouragement, valuable guidance,
motivation, expert advice and help rendered during the procedures and
throughout this study.
I sincerely thank Prof THIYAGARAJAN K , Prof ILAMPARUTHI
C Prof PITCHAI BALASHANMUGAM K for helping me with his time
and advice during this study.
I am indebted to all my assistant professors Dr. LEELAKRISHNA P,
Dr JAYAGANESH R, Dr SENTHILVEL A, DR.JASON PHILIP D, DR.
EZHIL SUNDAR V AND Dr SIVASANKAR G for their support,
guidance and help without which it would had been difficult to carry out this
study. Help rendered by my senior and junior colleagues need special
mention.
I acknowledge the help by Mr EZHIL for the timely help rendered in
performing statistical analysis for this study.
The encouragement provided by my Late father and the support and
sacrifice of my mother and wife is inexplicable. The blessings of Almighty
without which this work would not have been possible is acknowledged with
humility and gratitude.
TABLE OF CONTENTS
SL. NO TITLE PAGE NO.
1. INTRODUCTION 1
2. AIM OF THE STUDY 6
3. REVIEW OF LITERATURE 7
4. MATERIALS AND METHODS 25
5. RESULTS & ANALYSIS 39
6. DISCUSSION 81
7. CONCLUSION 93
8. BIBLIOGRAPHY
ANNEXURE
1. PLAGIARISM CERTIFICATE 2. ETHICAL COMMITTEE,
APPROVAL FORM 3. PROFORMA 4. RANDOM TABLE 5. IPSS CHART 6. MASTER CHART
ABBREVIATIONS
I-PSS – INTERNATIONAL PROSTATE SYMPTOM SCORE
TURP – TRANSURETHRAL RESECTION OF PROSTATE
AUA – AMERICAN UROLOGICAL ASSOCIATION
GA / SA – GENERAL ANAESTHESIA / SPINAL ANAESTHESIA
PVP - PLASMA VAPORIZATION TECHNIQUE
GnRH – GONADOTROPIN RELEASING HORMONE
AR – ANDROGEN RECEPTOR
PLESS - PROSCAR (FINASTERIDE) LONG-TERM EFFICACY AND SAFETY STUDY
AUR – ACUTE URINARY RETENTION
VEGF – VASCULAR ENDOTHELIAL GROWTH FACTOR
MVD – MICROVASCULAR DENSITY
DRE – DIGITAL RECTAL EXAMINATION
PSA – PROSTATE SPECIFIC ANTIGEN
OD – ONCE A DAY
SD – STANDARD DEVIATION
DF - DIFFERENCE
PRE OP – PREOPERATIVE
POST OP – POST OPERATIVE
INTRODUCTION
INTRODUCTION
Benign prostatic hyperplasia (BPH) is an abnormal stromal and
glandular proliferation of the prostate gland and is a common benign tumor
found in men above 50 years of age. Most men who reach their average
expectancy will experience this condition in their life time1.
Like prostate cancer, BPH also very often occurs in the West
compared to Eastern nations, such as Japan, China, and Asian countries
like India. They are more common in blacks1.
BPH is characterised by the proliferation of the prostatic epithelial
and stromal cells within the prostatic transition zone, which results in
enlargement of the prostate gland which in turn leads to compression of
the prostatic urethra, and restriction of urinary flow2.
The incidence of BPH also increases with age, being 50% at 60
years and around 90% at 80 years of age (2).The patho-physiology and
aetiology of BPH is multi factorial and they are yet to be known3.
However proliferation of prostatic stromal cells is dependent on
androgens, the most important being Dihydro-testosterone(DHT). This
androgen is essential for early embryological development and growth of
the prostate gland3.DHT is synthesized from testosterone by the isoenzyme
2
5α-reductase, which has two subtypes - type1 and 2. 5α-reductase type 2 is
the main enzyme in the prostatic stroma that is responsible for conversion
of testosterone to DHT and maintains intra prostatic dihydero-testosterone
in sufficient level to cause prostatic hyperplasia4.
Bladder outflow obstruction (BOO) due to benign prostatic
hyperplasia (BPH) is the commonest urological condition affecting men
over 50 years of age and may produce voiding symptoms like frequency,
urgency, nocturia with or without incontinence and storage symptoms like
intermittency, poor stream, hesitancy, post-void dribbling. These
symptoms are collectively known as lower urinary tract symptoms
(LUTS)5.
Apart from BPH, there are plenty of urological diseases that present
with LUTS. So complete assessment of patients with LUTS is essential,
and involves detailed patient history, clinical examination which includes
per-rectal examination of prostate and also subjective assessment of
symptoms in the form of various questionnaires (I-PSS), ultrasound
abdomen, pelvis and uroflowmetry.
Management of patients with BPH is based on the clinical
symptoms and complications associated with BPH. The absolute
indications for surgical treatment are history of refractory urinary
3
retention, recurrent urinary tract infection, hematuria, azotemia and vesical
stone formation6-7.
The different modalities of treatment for BPH are as follows8:
· watchful waiting,
· medical management with alpha blockers or 5 alpha reductase
inhibitors
· minimally invasive and endoscopic procedures like TURP,
Transurethral needle ablation of prostate (TUNA),transurethral
ultrasound–guided laser-induced prostatectomy (TULIP),
transurethral vaporization of the prostate (TUVP), transurethral
incision of prostate (TUIP) and
· Open prostatectomy.
The aim of surgical treatment is the removal of as much prostatic
tissue as possible, with minimal perioperative morbidity and shorter
hospitalization and catheterization6.
There has been a significant decrease in the complication rates
following endo-urological procedures, due to technical advancements, and
indications for open prostatectomy have become restricted. Though TURP
4
is considered the worldwide accepted gold standard tool in management of
BPH, it is associated with significant complications like intra op and peri-
operative bleeding, which maybe life threatening9.
The amount of intra-operative and postoperative bleeding depends
on the gland size, surgeon’s expertise and duration of surgery.
Intraoperative bleeding is usually controlled with electro-coagulation, but
excessive intra and perioperative blood loss can cause hemodynamic
instability, that may increase morbidity and mortality associated with the
procedure9.
Proliferation of the prostatic glandular tissue depends on the
androgen dihydrotestosterone, hence inhibition of 5α-reductase causes
reduction of gland volume, that will indirectly reduce the duration of
surgery and decrease the blood loss10. There have been few studies that
have suggested the 5α-reductase inhibitors finasteride and dutasteride to
have anti-angiogenic properties and cause reduction of intraprostatic and
suburethral microvessel density11.
Among 5α-reductase inhibitors finasteride inhibits only 5α-
reductase type 2, the main enzyme for development of BPH. Dutasteride
inhibits both 5α-reductase type1 and 2.Studies have reported that patients
5
treated with finasteride prior to surgery have lesser bleeding following
TURP than those who had been on dutasteride12.
Even though several studies have shown that preoperative short
course of finasteride for BPH reduces perioperative blood loss following
TURP, this is not practised routinely. The goal of this study is to evaluate
the effect of finasteride on intraoperative and postoperative blood loss
following TURP, which could resolve some of the controversies over the
use of this drug.
AIM OF THE STUDY
6
AIMS AND OBJECTIVES
AIM
· To assess the surgical blood loss in patients who undergo
transurethral resection of Prostate for BPH with and without
preoperative short course Finasteride therapy
OBJECTIVES
Primary objectives
· To assess the post-operative drop in Hemoglobin and PCV, and
intra-operative calculated blood loss in the two groups
· To assess the resected prostatic tissue micro vessel density,
resected tissue weight and operative time in the two groups
Secondary objectives
· To assess and compare the other postoperative complications like
clot retention, need for blood transfusion, failure to void after
catheter removal and post operative urinary tract infection in two
groups.
REVIEW OF
LITERATURE
7
REVIEW OF LITERATURE
Transurethral resection of prostate (TURP) is an endoscopic
procedure that has been accepted as the gold standard surgery of BPH for
decades. It is still considered the standard procedure by the Canadian
urological association13 and as the “benchmark to surgical treatment” by
the American Urological Association.14
Moreover, the European Urological Association considers TURP
“the procedure of choice for prostates between 30 to 80mL.”15
Inspite of the many challenges surrounding the procedure, TURP
still remains the gold standard with which others are compared. The
outcome of the procedure depends on factors like surgeon’s experience,
gland size and co-morbidities. Hence, in appropriately selected patients
TURP has a good track record of durability16.
MERITS OF TURP 17:
· Efficient
· Cost- effective
· Associated with reduced long term complications and recurrence
rates.
8
Wasson et al18 conducted a randomized study in the management of
BPH and compared watchful waiting with TURP (280 patients in surgery
group and 276 patients in watchful waiting group). Finally they concluded
that in men with moderate symptoms of BPH, surgery is the best modality
of treatment in view of reduced treatment failure and symptomatic
improvement.
In a study conducted by Pierre-Alain Hueber et al19, the results of
monopolar versus bipolar TURP were compared, and it was reported that
bipolar TURP has no clear advantage over monopolar TURP in BPH
management12.
COMPLICATIONS OF TURP:
1. Bleeding,
2. Transurethral resection syndrome,
3. Post -operative incontinence,
4. Failure to void
Jens Rassweiler et al20 retrospectively analysed 2800 studies on
TURP and they have given the incidence of post TURP complications in
early (1974-94), intermediate (1994-1999) and recent (2000-2005) years as
follows:
9
TABLE-I
Technical
Complications
Early Early Intermediate Intermediate Recent
Mebust17
1999
Doll21
1992 Haupt22 1997
Borboroglu23
1999
Kuntz24
2004
Bleeding &
blood
transfusion %
6.4 22 2.2 0.4 2
Clot retention
% 3.3 11 1.9 1.3 5
TUR syndrome
% 2 N.A 0.3 0.8 0
Capsule
perforation % 0.9 10 N.A 0 4
Hydronephrosi
s % 0.3 N.A 0.00.0 0 0
Faiure to void
% 6.5 3 N.A 7.1 5
Urosepsis % 0.2 3 0.2 0 0
10
TABLE – 2
N
Transfusi
on (%)
Revisi
on
(%)
Infecti
on (%)
TUR
Syndro
me
Early Zwergel 25
1979 232 21.2 N.A N.A N.A
Early Mebust71989 3885 6.4 N.A 2.3 2
Intermediate Zwergel1995 214 14.6 N.A N.A 0.8
Intermediate Hominger26 1996 1211 7.6 N.A N.A 2.3
Intermediate Haupt22 1997 934 2.2 N.A N.A 0.3
Intermediate Borboroglu199923 520 0.4 N.A 2.1 0.8
Recent Heilbron 2003 126 4.8 4.2 1.7 0.8
Recent Baden-wirttemb2 7717 3 5 3.5 0.8
Recent Kuntz 200424 100 2 3 4 0
Recent Muzzongro 200428 113 7.1 N.A N.A 0
Recent Berger 200427 271 2.6 N.A N.A 1.1
N.A = Not applicable
11
They concluded that bleeding was one of the most common intra-
operative complication and often required blood transfusion. Technical
advancements in the procedure have brought down the transfusion rate
from 21% in the earlier studies to 7% in recent studies24.
Arterial bleeding will be significant if patient has had preoperative
UTI due to congestion in the gland. Venous bleeding mainly occurs due to
sinusoidal opening and capsular perforation.
Mark Lynch et al29retrospectively reviewed 437 cases of TURP, and
found that 19 patients required immediate re-cystoscopy for persistent
postoperative hematuria, and one among them had to undergo exploration
and packing of prostatic fossa for control of bleeding. Their study
concluded that, though bleeding complications following TURP is reduced
with advanced endourological procedures, it could still be a major life
threatening event following TURP. When endoscopic methods fail to
control the bleeding, unnecessary delay to proceed for open exploration
should be avoided and all surgeons should be skilled in open exploration
and prostatic packing techniques in the event of post TURP catastrophic
bleeding.
Another study by Sristha BM et al30 assessed factors associated with
blood loss following TURP and reported that quantity of blood loss had no
12
association with type of anaesthesia (GA/SA), resection time and resected
gland weight.
Yet another study by Manish Banshali31 compared unipolar versus
bipolar TURP. It was concluded thateven though bipolar TURP had lesser
blood loss than monopolar TURP, it was not found to be statistically
significant31.
Bruyere F et al32 compared the blood loss following TURP and that
following Plasma Vaporization Technique (PVP- green light laser). It was
concluded that PVP technique has lesser blood loss than conventional
monopolar TURP and was found to be statistically significant.
Kirollos MM et al33 assessed important factors responsible for
postoperative blood loss in TURP. The weight of the resected prostatic
tissue and operative time more than 60 minutes were the most significant
predictors of blood loss and they found that resected tissue weight of <30 g
was associated with lesser bleeding. There was also lesser bleeding when
the procedure was performed under spinal anaesthesia.
Agarwal M19 retrospectively reviewed 87 cases of BPH managed by
TURP where the resected weight of gland was>80gms. The morbidity and
mortality rate of this study was 55% and 6% respectively. The final
conclusion of this study was that careful selection of patients prior to
13
surgery is of utmost importance for the reduction of morbidity and
mortality.
Walker EM at al24 evaluated effect of postoperative catheter traction
following TURP and found that catheter traction significantly reduces the
postoperative blood loss.
Role of Androgens in the development of BPH
Androgen stimulation is necessary for the initial growth and
development of the prostate and for the maintenance of its integrity. It also
plays a major role in the development of the obstructive urinary symptoms
associated with BPH21
Although the mechanisms underlying the development of BPH have
not been fully established, testicular androgens, particularly DHT, are
recognized as integral to the process. The influence of DHT in initial
prostatic development has been established, and the hormone has been
found to be responsible for the embryonic differentiation of the prostate
and the formation of external genitalia in the male35.
Fetal castration results in inhibited formation of the gland13, and the
continued role of testicular androgens in later life is evidenced by the
14
absence of BPH development among men who have undergone castration
prior to puberty23
DHT act by binding with androgen receptors contained within the
epithelium of the prostate36.These receptors are up regulated during
puberty, leading to increased androgen sensitivity.
These receptors may also bind with testosterone, but DHT has much
greater affinity, indicating that this hormone is the major influence on
subsequent genetic modulation in the prostate.
Down regulation of many androgen receptors occurs after puberty at
other sites, but this is not seen in the prostatic epithelium. The growth
promoting properties of DHT and the DHT- receptor complex can be
explained by the fact that DHT levels remain constant after puberty, even
when testosterone levels decline37.
Two isoezymes38 of the highly lipophilic enzyme 5α-reductase have
been identified so far. These isoezymes are encoded by different genes,
with the gene for type I being located on chromosome 5 and that for type II
on chromosome 2.
The isoezyme 5 alpha reductase type I is predominantly found in the
liver, scalp, and skin, with low levels found in the prostate, whereas type II
15
mainly occurs in the prostate and other genital tissues and is found to a
lesser extent at other sites35.
MECHANISM OF DHT SYNTHESIS WITH THE PROSTATIC
STROMAL & EPITHELIAL CELLS
Role of anti-androgens in BPH management
Numerous medical therapies have been extensively evaluated in the
management of BPH. They include α-adrenergic blockers, 5α-reductase
inhibitors, aromatase inhibitors, and various plant extracts.
Currently α-adrenergic blockers39and 5α-reductase inhibitors are
commonly used for medical management of BPH. Patients who lack
16
absolute indications for surgery are mostly managed medically with either
α-adrenergic blockers or 5α-reductase inhibitors either separately or in
combination of both.
An ideal candidate for medical therapy must have bothersome
LUTS that significantly affects the quality of life and they must be
committed to lifelong use of medical therapy39.
The rationale behind medical management with anti androgens in
BPH is that prostatic growth and development is an androgen dependent
process. So androgen suppression causes reduction prostatic volume.
But it also must be kept in mind that the bothersome symptoms in
BPH are not always related to glandular size. Even small prostates may
have obstructive LUTS39.
TABLE - 3
GnRH analogues Leuprolide,Nafarelin acetate and certralix
Progestational Agents 17 hydroxy cortisone, megestral
Antiandrogens Flutamide ,bicalutamide
5α-reductase
inhibitors Finasteride and dutasteride
17
The above table shows the various agents that were used in the
medical management of BPH. Of the above drugs, 5 alpha reductase
inhibitors are widely used now.
Feneley et al40 assessed the long term effects of anti androgens in
the treatment of BPH and he concluded maximal glandular size reduction
was achieved by 6 months of anti androgen therapy. Presently 5α-
reductase inhibitors are the only anti androgens that are extensively used in
treatment of BPH.
MECHANISM OF ACTION OF 5 Α REDUCTASE INHIBITORS
18
Finasteride
Finasteride37 is a 5α-reductase inhibitor, which mainly acts on
intraprostatic region and blocks the conversion of testosterone to
dihydrotestosterone(80-95%). DHT is the main androgen responsible for
development of BPH. It does not interfere with the actions of testosterone
hence secondary sexual characters are not affected37. After 2 weeks of
Tab.Finasteride therapy up to 90% of the intraprostatic DHT levels are
reduced. There is 30% prostatic glandular volume reduction after 6 months
of finasteride therapy37.
The above diagram depicts the mechanism of action of finasteride.
(T-testosterone, AR – androgen receptor.)
Feneley et al40 conducted a study in BPH patients and he observed
that finasteride predominantly blocks type 2 (more than 90%), than type 1
5α-reductase (70%).
Finasteride inhibiting intra nuclear enzyme 5α reductase
19
The Proscar (finasteride) Long-term Efficacy and Safety Study
(PLESS)5 was a large randomized study conducted in BPH patients, where
one arm received tab. Finasteride 5 mg once a day and other arm received
placebo. The final results revealed that the finasteride group had a 55-65%
reduction rate for surgery for BPH and acute urinary retention. The bar
diagram show reduced risk of AUR and need for surgery in finasteride
group.
BAR DIAGRAM -1
3
5
4
7
10
2
0
2
4
6
8
10
12
AUR% SURGERY% DECREASE IN IPSS SCORE
finasteride placebo
20
A similar study was conducted by Marberger41 and co-workers. This
was a two-year randomized, placebo-controlled trial of 3270 men
receiving finasteride versus placebo. The results showed that the mean
baseline prostatic volumes in the placebo and finasteride groups were 39.2
and 38.7 cm3, respectively. Again AUR incidence in placebo and
finasteride group was 2.5 and 1%.
Another study by Gormley GJ et al42 assessed the long term efficacy
of finasteride therapy in BPH patients who underwent more than 3 years of
treatment and concluded that finasteride had long term durable response
and lesser complications.
Dutasteride inhibits both 5α- reductase types 1 and 2 and greatly
reduces the serum DHT levels. Clark et al43 conducted a randomized trial
between placebo and tab. Dutasteride 0.5 mg once a day in medical
management of BPH. The Dutasteride arm showed 90% serum DHT
reduction, 24% additional symptoms score improvement, 45% AUR risk
reduction and more than 2.2ml/sec qmax improvement over the baseline
values suggesting that long treatment with dutasteride results in significant
as well as durable response in the medical management of BPH.
21
Nickel JC et al44 conducted a comparative study between finasteride
and dutasteride for the management of BPH. The primary objectives
assessed in this study were prostatic volume, AUA symptom score and
qmax changes. It was concluded that the efficacy and safety of both drugs
in BPH management were similar.
In a study by prabakar et al, the safety and efficacy of tamsulosin
0.4mg once a day and finasteride 5 mg once a day given in a short course
treatment for symptomatic BPH patients was evaluated. They concluded
that while tamsulosin had better symptoms score improvement; finasteride
had a higher glandular volume reduction.
Another study by Mohanty et al45 compared finasteride with
tamulosin and dutasteride with tamulosin in the management of BPH. In
their study dutasteride with tamsulosin arm showed early symptomatic
relief, but the overall long term results were similar among both the
groups.
Role of antiandrogens in post TURP blood loss
Anti androgens have potential anti-angiogenic effects in prostatic
tissue and these properties have been evaluated for clinical application in
the prevention of hematuria following TURP. The main reason for this
reduced blood loss is due to down regulation of vascular endothelial
22
growth factors (VEGF) in those patients treated with anti-androgens. The
resected prostatic tissue from these patients revealed reduced micro
vascular density in the sub-urethral prostatic tissue.
Donohue et al11 evaluated the effects of pre operative finasteride for
a short course of two weeks in BPH patients planned for TURP. He found
that finasteride significantly reduced prostatic microvascular
density(MVD) and VEGF which in turn casued reduced post operative
hematuria following surgery.
Similarly Jae-Ho Hyun et al46 studied the effect of finasteride on
MVD reduction and VEGF expression in BPH patients. But contrary to the
above mentioned study by Donohue et al, he concluded that administration
of preoperative finasteride had no clear effect on VEGF reduction in BPH.
However it showed reduction of MVD in prostatic tissue.
Another study by Foley et al47 compared short term finasteride
therapy with placebo and reported that the finasteride group had 86%
reduction in postoperative bleeding and did not require blood transfusion
when compared with the placebo group.
23
TABLE - 4
Study No of
patients
Mean resected
weight (gm) Blood loss
Microvessel density
Ozdal et al48
2005
Finasteride arm-20 pts
23 g 173ml -
Placebo -20 pts
19 235 ml -
Donohue et al49
Finasteride -33 pts
18 g - 60
Placebo – 30 pts
19 g - 71
Sandfeldt et al50
2001
Finasteride -29 pts
20 g 175 ml 40
Placebo – 26 pts
17.5 g 220 ml 65
(Pts. – Patients )
The above given table depicts the efficacy of finasteride in reducing
the perioperative blood loss and reduction of micro-vascular density.
24
R.G.Hahn51 et al assessed the effect of preoperative dutasteride on
surgical blood loss and postoperative complications following TURP. He
reported that even though there is reduction of serum DHT levels in the
dutasteride arm, there was no significant effect on blood loss following
TURP for BPH.
Similarly another French study by Boccon Gibod L52 et al assessed
the effect of preoperative dutasteride therapy on postoperative blood loss
in patients undergoing TURP. The results showed less blood loss in
dutasteride group but the data was not fund to be statistically significant.
Shanmugasundaram53 et al conducted the same study with
dutasteride in management of BPH, and it was agreed that dutasteride had
no clinically significant effect on postoperative bleeding following TURP.
MATERIALS &
METHODS
25
MATERIALS AND METHODS
Study Design
Prospective Randomized placebo Controlled Study
Patient Population
The study was conducted in the Department of Urology,
Government Kilpauk Medical College and Government Royapettah
Hospital, Chennai. One hundred patients who underwent TURP for
symptomatic BPH from AUGUST 2013 to February 2015 fulfilling the
inclusion and exclusion criteria were included in the study. They were
subsequently followed up for one month. These patients were randomized
into two groups using computer generated random numbers table (Odd
numbers –group A, Even numbers – group B). The ethical committee of
our hospital approved the current study and informed consent was signed
properly by all the patients.
Group A (Test Group): Symptomatic BPH patients received 2 weeks
Tab. Finasteride 5 mg OD dose prior to Surgery (TURP).
Group B (Placebo Group); Symptomatic BPH patients received 2 weeks
placebo prior to surgery
26
Inclusion Criteria
1. Men with enlarged prostate and associated lower urinary tract
symptoms
2. Patient’s age should be more than 40 years
3. USG prostate weight should be more than 30 grams
4. Patients with no psychological or clinical contraindications to
anaesthesia or surgery
5. Able to understand and give written consent for the study
6. Patients who have comprehension and commitment to follow up.
Exclusion criteria
1. Previous history of prostatic surgery
2. Suspected prostatic carcinoma or prostatic diseases other than
BPH
3. Patients who already received long term 5 alpha reductase
inhibitors or alpha blockers
4. Patients who are on anti coagulants, aspirin or NSAIDS
5. Patients with bleeding diathesis or liver disease
27
6. Patients who are high risk for surgery (ASA iv)
7. Patients who refused to consent for the study
Preoperative evaluation
I. Counselling
All patients were initially counselled regarding
· The natural course of the disease
· The need for surgery (TURP)
· About the procedure (TURP)
· Risks about surgery including post operative bleeding/ need for
return to OT in the event of persistent hematuria
· Counselling regarding the study and randomization
· Need for regular one month follow-up.
II. Detailed patient interview to include the following
Patient’s detailed medical and previous surgical history especially
· H/O Diabetes Mellitus, Hypertension or Tuberculosis and any
H/O drug intake in the present or past.
· Any H/O previous urethral instrumentation/ catheterisation.
28
· H/O LUTS and duration / h/o hematuria.
III. CLINICAL EXAMINATION
In addition to routine general and systemic examination the
following additional examination was carried out:
· External genitalia and urethral meatus status
· Digital Rectal examination (DRE) – Rectal Tone, Prostatic
enlargement grade, consistency.
· Serum PSA for variable prostatic consistency/prostate volume
more than 50 grams.
DRE GRADING SYSTEM FOR BPH
TABLE - 5
GLAND SIZE DRE
NORMAL
PROSTATE
Up to one cm rectal luminal encroachment
GRADE I Up to two cm encroachment
GRADE II 2 to three cm encroachment
GRADE III 3 to four cm encroachment
GRADE IV More than four cm
29
This grading system mainly depends on the intra rectal luminal
encroachment of the prostate gland.
International prostatic symptom score(I-PPSS) assessment
Preoperative IPSS symptoms score assessment was done for all
patients with the AUA – IPSS chart (annexure).In each group, according to
their score they were divided as grade I, II or III
GRADE I – score 0 to 7; Grade II - 8 TO 19; Grade III – 20 TO 35
Laboratory Investigations
Before proceeding for TURP the following laboratory investigations
were routinely done for all of our patients.
· Complete blood count (CBC) with platelets
· Random blood sugar with renal function test (RFT)
· Serum electrolytes ( Na+, K+)
· FBS, PPBS for diabetic patients
· Urine routine examination
· Urine Culture and sensitivity
30
Radiological Investigations
· Ultra sound KUB: was done for all our study group patients, in
our hospital Radiology Department by the Senior Radiologists.
Patients underwent trans abdominal USG with 3.5 HZ probe. The
volume of the prostate was calculated by the formula for ellipsoid
prostate
Prostate volume in grams = (Π/6 x AP diameter of prostate x transverse diameter x sagittal diameter)
USG KUB- AP,TRANSVERSE AND SAGITTAL DIMENSIONS.
31
After prostatic volume estimation, the post void residual urine was
also calculated as a routine. Bladder wall thickness was measured if found
significant. Upper tracts was screened concomitantly to rule out features of
bladder outlet obstructive changes and to assess the cortico-medullary
differentiation.
Uroflowmetry –Qmax estimation
In our study population we compared the maximum urine flow rate
(Qmax) before and after TURP procedure in both the groups. This test is
done in our departmental uroflowmetry machine, with full bladder. We
measured Qmax, and all the parameters were recorded in our computer
database.
32
Comprehensive Multidisciplinary Evaluation
· Cardiology evaluation including ECG and ECHO was done for all
patients.
· Routine Chest X-ray and chest medicine clearance for all patients.
· Nephrology opinion for patients with raised renal parameters.
· Preoperative physiotherapy counselling
Peri-operative preparation
· Patient comprehension was reviewed and all patients’ questions
were answered to their satisfaction.
· Study procedure was explained to the patients and their relatives
· An informed consent was taken for the study.
· Post procedural surgical risks and need for follow up were
thoroughly explained to the patients.
· Patients were randomly assigned to group A& B by the
computerized random table (odd number – group A, even number
– group B).
33
· For Group A we Started on tab.finasteride 5 mg od- 2 weeks and
for group B placebo was given.
· In both the Groups patients were called for surgery after 2 weeks
of drug therapy.
TECHNIQUES OF THE PROCEDURE (TURP)
In our Hospital Transurethral resection of prostate was done under
spinal anaesthesia and our entire study group cases were operated by the
senior consultants in our department. Initially Cystoscopy was done.
Anterior and posterior urethra, grade of prostate gland, bladder status, and
presence/absence of growth, stone, diverticulum was assessed. Instruments
used for TURP includes 24 – Fr. KarlStorz intermittent flow sheath with
blind and visual obturator, TUR resectoscope, monopolar electric loop,
high frequency cord, 30 degree telescope and monopolar diathermy. Sterile
water was used as irrigation fluid. We followed the Mauermayer technique
for prostate resection. Dissection was begun from the median lobe,
followed by 5 and 7 o clock position and then lateral lobes. Apical lobe
was the last one to be resected. Complete hemostatsis was achieved with
electro-coagulation.
34
TURP TECHNIQUE
The main principles for TURP procedure were followed for our entire
study population. They are
· Slow and controlled resection
· Resection was limited proximal to verumontanum
· Only adenoma component to be removed
· Surgical capsule not to be violated
· No bladder neck undermining
The resection time was measured from starting of prostatic resection
to the removal of resectoscope and all resected prostatic chips at the end of
the procedure. 3- Way Foleys catheter and bladder irrigation was started
routinely for all our study population and was continued for 24 hours
postoperatively.
35
FOLEYS CATHETER TRACTION AFTER TURP
Foleys catheter traction was also given for all and was released after
24 hours of surgery. But some patients may not need irrigation after few
hours of surgery due to clear urine. Total volume of irrigating fluid used
for surgery was measured. After stirring the irrigating fluid 5 ml of
irrigation fluid sample was sent to the laboratory for estimation of
calculated blood loss. The blood loss was calculated by the given formula
Calculated intraoperative blood loss67 (ml)
= Hemoglobin in irrigating fluid (g/L) × volume of irrigating fluid ×1000
Preoperative hemoglobin (gms/dl) × 5.2
All patients were shifted to our surgical intensive care ward. All
intra and immediate post operative complications were recorded.The
resected prostatic tissue was dried and weight in grams was recorded. The
36
resected tissue from suburethral portion and glandular portions were fixed
with formalin and sent in a separate containers for Microvessel density
assessment. This MVD11 was assessed in the pathological department with
immunohistochemical staining with CD 34 that stains the blood vessels.
The density of microvessels in ten high power field regions were counted
by light microscopy with 200 times of magnification, from which MVD
was calculated11.
During the immediate postoperative period all patients were
intensively monitored by our duty urology resident. Need for blood
transfusion, severity of hematuria, clot retention,vital parameters and
altered sensorium if present, were recorded. Bladder irrigation was stopped
24 hours after surgery. Estimation of hemoglobin and PCV was done on
postoperative day1 and day 4. Mean hemoglobin and PCV values were
estimated. Preoperative values were compared with postoperative values
HISTOPATHOLOGY - MVD. PLACEBO GROUP. INCREASED MVD
HISTOPATHOLOGY- MVD FINASTERIDE GROUP.
REDUCED MVD
37
and need for blood transfusion assessed. Foleys catheter was removed on
post operative day 4. Intravenous antibiotics were administered for three
days. Patients who failed to void were recatheterized and catheter
removed after one week. Patients who had persistent hematuria were
immediately shifted to the operation theatre after hemodynamic
stabilization. Under anaesthesia immediate cystoscopy was done. After
clot evacuation, bleeding from the prostatic fossa was assesed under direct
vision.Acive bleeders were controlled with TUR electrocoagulation.
Patients with diffuse ooze or loss of endoscopic vision were immediately
explored and transvesical prostatic fossa packing done.
DIAGRAMACTIC REPRESENTATION OF PROSTATIC
FOSSA PACKING
38
The pack was removed after 24 to 48 hours. Postoperative followup
was done at one month period with TURP biopsy report. Uroflowmetry
was repeated at one month and Qmax was compared with preoperative
Qmax. Postoperative IPSS score was assessed. Repeat urine culture was
done. Symptomatic culture positive patients were treated with with oral
antibiotics. Ultrasound KUB repeated and residual prostatic weight and
postvoid residual volume also assessed.
STATISTICAL ANALYSIS
Descriptive statistical analysis has been carried out in the present
study. Results on continuous measurements are presented on Mean ± SD
and results on categorical measurements are presented in percentage. (%).
Chi-square test has been used to find the significance of study parameters
on categorical scale between two groups. Student ‘t’ test has been used to
determine the significance between two group means. All analyses were
two tailed and p <0.05 was considered significant. SPSS version 16.0 was
used for data analysis.
RESULTS &
ANALYSIS
39
RESULTS
This study was undertaken in the Department of Urology at
Government Kilpauk medical college hospital and Government
Royapettah hospital, Chennai between March 2014 and February 2015.A
total number of 100 patients who underwent TURP for symptomatic BPH
at our hospital were included in this study.
They were randomized in to group A (received 2 weeks of
preoperative tab. Finasteride 5 mg OD) and group B (placebo group), with
a total of fifty patients in each group. Randomization was done by
computer derived randomization table.
TABLE - 6
GROUP NO OF
PATIENTS
MEAN AGE – Std Std.
error
of
Mean
AGE
(YEARS)
RANGE
YEARS
Deviatio
n
Group A 50 65.74 56 to 82 8.789 1.6321
Group B 50 65.08 52 – 80 8.432 1.5987
40
Patient Demographics –Age Group
TABLE – 7
Age group
Total <60yrs 60-69 >=70 yrs
Group
Group-A
Count 12 20 18 50
%
Within
group
24.00% 40.00% 36.00% 100.00%
Group-B
Count 11 22 17 50
% Within
group
22.00% 44.00% 34.00% 100.00%
Total
Count
%
Within
group
23 42 35 100
23.00% 42.00% 35.00% 100.00%
Chi square test = 0.167 p= 0.299. Not significant
41
BAR DIAGRAM - 2
Chi square test = 0.167 p= 0.299. Not significant
Mean age in group A & B was 65.74, 65.08 years and minimum and
maximum age of the patients in group A was 56 and 82 years, in group B,
52 &80 years respectively. In both the groups more than 40% of the
patients belonged to the age group 60 to 70 years. From table no 3, age
distributions in both groups were comparable.
<60yrs 60-69 >=70 yrs
Group-A 24.0% 40.0% 36.0%Group-B 22.0% 44.0% 34.0%
24.0%
40.0%36.0%
22.0%
44.0%
34.0%
0.0%5.0%
10.0%15.0%20.0%25.0%30.0%35.0%40.0%45.0%50.0%
% o
f pat
ient
s
Age distribution by group
42
Digital Rectal Examination(DRE) – Grade Distribution
TABLE – 8
DRE GRADING - PROSTATE Total
1 2 3
Group
Group-A
Count 11 36 3 50
% within group
22.00% 72.00% 6.00% 100.00%
Group-B
Count 10 37 3 50
% within group
20.00% 74.00% 6.00% 100.00%
Total
Count 21 73 6 100
% within group
21.00% 73.00% 6.00% 100.00%
The p value here is 0.123(not significant).
DRE GRADING SYSTEM
Grade 0 - Normal DRE (0-1 CM);
Grade 1 - 1-2cm prostatic encroachment in to rectal lumen;
Grade 2 - 2-3 cm enlargement;
Grade 3- 3-4 cm enlargement;
43
BAR DIAGRAM - 3
In both the groups most patients belonged to grade 2, i.e around
73% of the patients were in grade 2 category of digital rectal examination.
Grade distributions were equal and comparable between these two groups
and there was no statistical significance as far as DRE grading was
concerned. The p value here is 0.123(not significant).
Only 3 patients in each group fell in the grade 3 of the DRE grading
system.
0
10
20
30
40
50
60
70
80
GRADE 1 GRADE 2 GRADE 3GROUP A 11 36 3GROUP B 10 37 3ENTIRE STUDY GROUP 21 73 6
11
36
310
37
3
21
73
6
NO
OF
PATI
ENTS
DRE GRADE DISTRIBUTION
44
Preoperative trans-abdominal ultrasound(USG) prostate weight
TABLE -9
USG PROSTATE
WEIGHT ( Grams )
LESS
than
40Gms
40 To 60
Gms
More than
60 Gms
Total
patients
GROUP A (no of
patients) 6 34 10 50
GROUP B ( no of
patients) 5 36 9 50
Total study group 11 70 19 100
In 70% of the patients in this study group, the prostatic weight was
between 40 to 60 grams. 10 out of 50 patients in group A and 9 out of 50
patients in group B had prostatic weight of more than 60 grams.
45
TABLE - 10
USGPROSTATE WEIGHT-
RANGE ( GRAMS )
MEAN
WEIGHT
(gms )
STANDARD
DEVIATION
GROUP A 30.5 to 75 45.5 10.241
GROUP B 30 to 72 46.01 10.432
TOTAL
MEAN
WEIGHT
30 to 75 45.75 10.336
BAR DIAGRAM 4
USG PREOPERATIVE PROSTATIC WEIGHT DISTRIBUTION
05
10152025303540
PROSTATE WEIGHT LESS THAN
40 gms
40 TO 60 gms More than 60gms
GROUP A 6 34 10
GROUP B 5 36 9
6
34
105
36
9
NO
OF
PATI
ENTS
PROSTATE WEIGHT DISTRIBUTION
46
The above tables and graphs shows that USG prostate volumes were
equally distributed in both the groups and were comparable, with p value
of 0.234.USG prostate volume in group- A ranges from 30.5 to 75 grams
with mean volume of 45.5 grams, and in group B the volume ranged from
30 to 72 grams with a mean volume of 46.1 grams. In each group 70% of
the patients had 40 to 60 grams of prostatic weight.
Preoperative Haemoglobin Distribution
TABLE - 11
Preoperative Haemoglobin
( grams/dl ) Range Mean
Standard Deviation
Group A(grams/dl) 10 to 12.5 11.7 0.3469
Group B((grams/dl) 10.1 to
12.7 12 0.5559
Total Study group ( grams/dl) (10 to 12.7)
12.05 0.4587
From the above table it can be inferred that the mean haemoglobin
for group A was 11.7 grams/dl and the range was 10 to12.5 grams. The
mean haemoglobin for group B was 12.0 grams and the range was 10.1 to
12.7 grams/dl. The p value for this table was 0.114, hence statistically not
significant. Therefore both the groups were comparable.
47
Comparison of preoperative packed cell volume
TABLE -12
Preoperative packed cell
volume(PCV)% Range Mean
Standard Deviation
Group A % 29.5 to 33 31.51 1.814
Group B % 29 to 33.5 31.54 1.055
Total Study Group %
29 to 33.5 31.52 0.876
Mean preoperative PCV for group A was 31.5% and the range was
29.5 to 33%.Similarly the mean PCV for group B was 31.5 and the range
was 29 to 33.5. So PCV values were similar and p value is 0.83 that is not
statistically significant.
48
BAR DIAGRAM -5
This Bar diagram shows preoperative haemoglobin and PCV for
both group A and B. Since p value is not significant these groups are
comparable. This preoperative haemoglobin and PCV values in our study
group were lower than the normal levels.
PRE OP MEAN HB(gms) PRE OP PCV %
11.7
31.54
Preoperative HB and PCVGROUP AGROUP B
12
31.51
49
10 g
9.2 g
GROUP A
GROUP B
post op HB(G)post op HB(G)
BAR DIAGRAM -6
Comparison of postoperative haemoglobin between the groups
TABLE -13
Post Operative
Hemoglobin( gms/dl ) Range Mean
Standard
Deviation
Group A ( gms/dl ) 8 to 11.0 10 0.5049
Group B ( gma/dl ) 8.2 to
10.7 9.2 0.5148
BAR DIAGRAM -6
There is significant haemoglobin drop difference between the
groups. p=0.001.it’s statistically significant.
50
POST OP HB(gms) POST OP PCV%
10 G
30 %
9.2 G
POST OPERATIVE HB AND PCVGROUP A GROUP B
28%
Comparison of postoperative PCV between the groups
TABLE -14
Postoperative packed
cell volume(PCV)% Range Mean
Standard
Deviation
Group A % 28.2 to 30.5 29.6 1.013
Group B 27.1 to29.1 28 1.029
In group A the packed cell volume ranges from 28.2% to30.5%.in
group B it was 27.1 % to 29.1 %.
The mean PCV in group A was 29.6 % and in group B 28%. When
comparing in between the groups there was clinically significant fall in
group B PCV.
BAR DIAGRAM -7
51
The above tables and bar diagram show that postoperative mean
haemoglobin in group A & B were 10 grams and 9.4 grams/dl
respectively. Postoperative mean PCV in both group A& B were 30 and
28%.
Comparison of pre and postoperative Hemoglobin
TABLE -15
Mean
Preoperative
Haemoglobin
( Gms/dl )
Mean post op
Haemoglobin
( Gms/dl)
Mean HB
loss(g/dl)
Group A (gms/dl) 11.7 10 1.7
Group B (gms/dl) 12 9.2 2.8
Total Study Group
( gms/dl ) 11.95 9.7 2.3
It can be inferred from the above table pre and postoperative mean
haemoglobin in group A were 11.7 & 10 grams and mean haemoglobin
loss after TURP in this group was 1.7 grams/dl and p value is 0.112. In
group B pre and post operative haemoglobin were 12.0 & 9.2 grams and
mean haemoglobin loss in group B was 2.8 grams and p value is 0.000. So
52
there is significant post operative haemoglobin drop in group B and that is
statistically significant.
BAR DIAGRAM -8
P value for group B is 0.000 that is statistically significant. So
patients on preoperative short course finasteride therapy show less post
operative haemoglobin drop than those directly undergoing TURP without
any preoperative treatment with finasteride.
11.712.0
10.0
9.2
8.5
9.0
9.5
10.0
10.5
11.0
Group-A Group-B
Pre and post mean Hb by group
Pre_op Post_op
53
Comparison of pre and postoperative PCV
TABLE -16
Mean
Preoperative
PCV %
Mean post
op PCV%
Mean PCV
loss %
Group A % 31.5 29.6 1.9
Group B % 31.5 28 3.5
Total Study Group % 31.5 28.8 1.028
11.710
12.0
9.2
0
5
10
15
20
25
Pre op HB (g) Post op HB(g)
Group B
Group A
HEMOGLOBIN DROP CURVE
54
Pre operative PCV of our entire study group patients was 31.5%. After
TURP there was a fall in PCV seen in both groups. Mean fall in PCV in
group A was 1.9 % and for GROUP B, 3.5%. Over all for the entire study
population, the mean fall in PCV after TURP was 1.028.
BAR DIAGRAM -9
The above depicted table and bar diagram show that following
TURP, there was a significant fall in PCV in group B when compared to
group A. The student T test p value is 0.000, which is statistically
significant.
31.51 31.54
29.6
28.0
26.0
27.0
28.0
29.0
30.0
31.0
32.0
Group-A Group-B
Pre and post mean PCV by group
Pre_op Post_op
55
Comparison of Turp Resection Time
TABLE - 17
RESECTION Time( Minutes )
Range
Mean Resection
Time(minutes)
Standard Deviation
Group A 35 to 65 46.6 7.63
Group B 40 to 70 52.8 8.56
Total Study Group 35 to 70 49.7 8.21
Transurethral prostate resection time was calculated from the start of
resection of prostate up to withdrawal of resectoscope from the urethra. In
group A the resection time varies from thirty five minutes to maximum of
sixty five minutes with a mean resection time of 46.6 minutes. For group B
31.5 29.6
31.5
28
0
10
20
30
40
50
60
70
GROUP A GROUP B
POST OP PCV DROP
POST OP PCV %
PRE OP PCV %
56
this time varies from minimum of forty minutes with maximum resection
resection time of up to 70 minutes. Mean resection time for group B was
52.8 minutes.
Average resection time for the entire study group population was
49.7 minutes with standard deviation of 8.27 minutes.
BAR DIAGRAM - 10
The difference in the average resection time between the two groups
was six minutes, with group B having increased resection or operative time
than group A. Students T test p value is p=0.004 and it is statistically
significant.
44 46 48 50 52 54
GROUP A
GROUP B
47
53
RESECTION TIME (MINUTES)
RESECTION TIME (MINUTES)
57
Comparison of Resected Prostatic Tissue Weight
TABLE - 18
Resected Prostatic
tissue weight (gms) RANGE
Mean resected tissue Weight
( gms)
Standard Deviation
Group A 15.0 - 50 27.7 7.058
Group B 15 - 45 24.14 8.681
Total Study group
15 - 50 25.92 7.86
From this table it is inferred that the mean resected prostatic weight
in group A ranged from 15 to 50 grams. Similarly for group B the resected
prostatic tissue weight varied from 15 to 45 grams. The average resected
weight for group A and B were 27.7 g & 24.1 g respectively.
58
BAR DIAGRAM - 11
The above table and bar picture shows that the difference in mean
resected prostatic tissue weight between group A & B is (27.7 – 24.1 = 3.6
g) around 3.6 grams. When student’s T test was applied to these values, it
show statistical significance with p value of 0.024 (<0.05 is significant).
Therefore resected tissue weight is significantly higher in BPH patients
who were on preoperative short course finasteride therapy.
27.7 G
24.1 G
25.9 G
22
23
24
25
26
27
28
GROUP A GROUP B MEAN WEIGHT OF TOTAL GROUP
TURP TISSUE WEIGHT
59
Comparison of Post OP USG PROSTRATE WEIGHT
TABLE – 19
USG PROSTATE
WEIGHT- RANGE
( GRAMS )
MEAN
WEIGHT
( GRAMS )
STANDARD
DEVIATION
GROUP A 15 - 24 18.3 6.241
GROUP B 15 - 24.5 19.9 5.432
TOTAL
MEAN
WEIGHT
15 - 24.3 19.1 5.336
BAR DIAGRAM – 12
GROUP A GROUP B TOTAL MEAN
18.3g
19.9 g
18.6 g
USG POST TURP PROSTATE WEIGHT
60
45.5 46.01
18.3 19.9
0.0
5.0
10.0
15.0
20.0
25.0
30.0
35.0
40.0
45.0
50.0
Group-A Group-B
Pre and post USG prostate mean weight
Pre_op Post_op
BAR DIAGRAM - 13
The mean postoperative USG residual prostate weight in group A
and B were 18.3 and 19.9 grams respectively. The mean reduction in
prostatic weight after TURP in group A & B were 27.2gms and 26.1 gms
respectively. The p value was calculated to be 0.054.Though group A had
more reduction in prostate weight than group B, this difference had no
statistical significance.
61
Preoperative Comparison Of Qmax
TABLE -20
Uroflowmetry Q max (ml/sec) Range
Q max (ml/sec) Mean
Standard deviation
Group A 8 TO 12 10.65
1.019
Group B 7.5 TO 12
10.53
1.085
Total study group Qmax
7.5 TO 12 10.59 1.067
Preoperative Comparison Of Qmax
BAR DIAGRAM - 14
10.46
10.48
10.5
10.52
10.54
10.56
10.58
10.6
10.62
10.64
10.66
GROUP A GROUP B for total group
10.65
10.53
10.59
urin
e flo
w
time in seconds
Q MAX(ml/sec)
62
The above depicted table and bar diagram show that preoperative
uroflometry Qmax (maximum urine flow) for group A patients ranged
from a minimum of 8 ml/sec up to maximum of 12 ml/sec. Qmax range for
group B was 7.5ml/second to 12 ml/second. The mean Qmax for group A
and B were 10.65 &10.5 ml/second respectively. The standard deviations
are mentioned above and students T test shows p value of 0.987. Hence the
two groups were comparable.
Comparison between Pre and Post Operative Qmax
TABLE – 21
Uroflowmetry
Q max (ml/sec)
MEAN –
PREOP
Q max (ml/sec)
MEAN- POST
OP
STANDARD
DEVIATION
GROUP A 10.65 14.24 1.019
GROUP B 10.56 13.1 1.085
TOTAL STUDY
GROUP
Q MAX
10.59 14.7 1.067
63
10.6
14.2
10.5
13.1
0
5
10
15
20
25
30
35
Qmax pre op ml/sec post opQmax (ml/sec)
Qmax raise after TURP
group B
group A
This table shows the comparison between pre and post operative
mean maximum urinary flow rate Qmax (ml/second). In group A after
TURP the maximum urinary flow rate had improved from 10.65 ml/second
to 14.24 ml/second. Similarly Qmax value for Group B also improved
from the baseline preoperative value of 10.56 ml/second to postoperative
value of 13.1 ml/second. So the mean raise of Qmax after relieving the
obstruction was 4.8ml/second in group A and 3.6 ml/second in group B.
This data shows significant improvement of Qmax in both the groups after
TURP. Also in group A Qmax improvement was significantly higher than
in group B and chi square test p value is 0.017, hence found to be
statistically significant.
64
Comparison of Post Op Clot Retention between the two groups A
TABLE – 22
CLOT RETENTION
PRESENT ABSENT
GROUP A(N) 3 47
GROUP B(N) 6 44
BAR DIAGRAM – 15
6%
94%
12%
88%
0%
20%
40%
60%
80%
100%
Yes NO
%
Clot retention by group
Group-A Group-B
65
Chi-Square Tests
TABLE – 23
Value df
Asymp.
Sig. (2-
sided)
Exact
Sig. (2-
sided)
Exact
Sig. (1-
sided)
Pearson Chi-Square .706a 2 0.401
Continuity
Correctionb 0.314 1 0.575
Likelihood Ratio 0.71 1 0.399
Fisher's Exact Test
0 0
Linear-by-Linear
Association 0.699 1 0.403
N of Valid Casesb 100
The table and bar diagram above shows that there were 3 patients in
group A who had post operative clot retention. Clot evacuation and
bladder wash was given bedside for the 3 patients. There was no further
clot formation, and all of them improved. In group B there were 6 patients
who developed clot retention in the first post operative day. Out of 6, 4
patients underwent bed side clot evacuation and bladder irrigation.
Remaining 2 patients had associated hematuria, hence they were shifted to
the operating theatre, where clot evacuation and control of bleeding with
66
group A, 175 mlgroup B - 220
ml
electro-fulguration was done under anaesthesia. All patients improved well
and the post operative period was otherwise uneventful. It was statistically
significant
Calculated Intraoperative Blood Loss
TABLE- 24
BLOOD LOSS
(ml) RANGE MEAN
STANDARD
DEVIATION
GROUP A 95 to 270 175 95.25
GROUP B 150 to 320 220 125.45
67
Student T- Test
TABLE - 25
Group N Mean
Std.
Deviation P-value
Calculated Group A 50 175 95.264 0
Blood loss Group B 50 220.08 125.452
The estimation of intraoperative blood loss was calculated from the
irrigation fluid used for TURP. The method of estimation has been
explained in the materials and methods. The calculated blood loss for the
patients in group A ranged between 95 to 270 ml and for patients in group
B between 150 to 320 ml. The mean blood loss in group A & B were 175
ml and 220 ml respectively. Tables (24,25) and pie chart shows that
patients in group A had less intra-operative calculated blood loss than
patients in group B. This was statistically significant, and indicates that
preoperative short course finasteride therapy in BPH patients is likely to
significantly reduce intra-operative blood loss
68
Postoperative blood transfusion
TABLE -26
Blood Transfusion Present Absent
Group A(number) 2 48
Group B(number) 6 44
BAR DIAGRAM – 16
2
48
6
44
0 10 20 30 40 50 60
Present
Absent
Present Absent
Group B(N) 6 44Group A(N) 2 48
Blood Transfusion
69
Chi-Square Test
TABLE - 27
Value df Asymp. Sig.
(2-sided)
Exact Sig.
(2-sided)
Exact Sig.
(1-sided)
Pearson
Chi-Square 1.778a 1 .182
Continuity
Correctionb 1.000 1 .317
Likelihood Ratio 1.823 1 .177
Fisher's Exact
Test .318 .159
Linear-by-Linear
Association 1.760 1 .185
N of Valid Casesb 100
Two patients (4%) in Group A and six patients (12%) in group B
required post operative blood transfusion. For all the 8 patients one unit of
packed cell was transfused. Though more number of patients in group B
required blood transfusion when compared to group A, this was found to
be statistically insignificant.
70
Return to Operation Theatre for Bleeding Control
TABLE - 28
RETURN TO OPERATION
THEATRE
Present
Absent
GROUP A(N) 1 49
GROUP B(N)
3
47
BAR DIAGRAM – 17
0%
20%
40%
60%
80%
100%
PRESENT ABSENTGROUP A 2% 98%
GROUP B 6% 94%
2%
98%
6%
94%
Return to OT for bleeding control
71
TABLE - 29
CHI-SQUARE
TEST Value df
Asymp. Sig.
(2-sided)
Exact Sig.
(2-sided)
Exact Sig.
(1-sided)
Pearson Chi-
Square 1.042a 1 0.307
Continuity
Correctionb 0.26 1 0.61
Likelihood
Ratio 1.088 1 0.297
Fisher's Exact
Test 0.617 0.309
Linear
Association 1.031 1 0.31
N of Valid
Casesb 100
One patient (2%) in group A and three (6%) patients in group B had
persistent post operative hematuria. One patient in group A and 2 patients
in group B were shifted to the operation theatre within 2 hours of surgery.
Under regional anaesthesia Cystoscopy was done. Two patients (one in
each group) had active bleeders in the prostatic fossa. The active bleeding
points were coagulated with the TUR loop through monopolar current.
72
Complete hemostasis was achieved. One patient in group B had persistent
diffuse ooze even after electro-coagulation, and endoscopic vision was
lost. So we proceeded with open transvesical exploration and prostatic
fossa packing. The patient was monitored in the intensive care unit. Pack
was removed after 24 hours, and bleeding was controlled. Following this
the postoperative period was uneventful. Though more patients in group B
had post TURP surgical intervention, this was not statistically significant.
Failure to Void
TABLE - 30
Group Failure to void
Total Yes NO
Group-A Count 2 48 50
% within group 4.0% 96.0% 100.0%
Group-B
Count 5 45 50
% within group 10.0% 90.0% 100.0%
Total Count 7 93 100
% within group 7.0% 93.0% 100.0%
73
BAR DIAGRAM – 18
From table no –30, it is inferred that 2 (4%) out of 50 patients in group A,
5 (10%) out 50 patients in group B had failure to void after post operative
catheter removal. The catheter was then reinserted and retained for a week
and then removed, at the end of which all of voided well. The number of
patients in group B who had failed to void following removal of catheter
was 10%, which was clinically significant.
group A group B total group
2 5 7
48 45
93
Failure to voidpresent absent
74
Microvessel density
TABLE -31
MICROVESSEL
DENSITY mm2
SUBURETHRA
L REGION
INTRAPROSTA
TIC REGION
Standard
deviation
GROUP A 16.52 18.43 4.88
GROUP B 21.45 24.34 5.46
Micro vessel density of the sub urethral part of the prostate gland
was assessed by histo-pathological examination. The mean micro vessel
density in group A was 16.5 in suburethral region and 18.4 in intraprostatic
region. Similarly micro vessel density of suburethral & intraprostatic
regions in group B was 21.4 & 24.3 respectively. While analyzing these
parameters the microvessel density in Group A was found to be
significantly lower than in group B (p value =0.03).
75
BAR DIAGRAM – 19
POST TURP (LUTS) URINARY TRACT INFECTION
TABLE - 32
UTI POST TURP
LUTS (N)
URINE CULTERE GROWTH POSITIVE
CULTURE NEGATIVE
GROUP A
10
3
7
GROUP B
15
6
9
N= NUMBER OF PATIENTS
suburethral region intraprostatic MVD
16.5 18.4
21.45 24.3
Tissue Micro Vessel Densitygroup A group b
76
BAR DIAGRAM – 20
From table no 32 the incidence of post operative urinary tract
infection was analysed. In group A, 1O patients presented with irritative
LUTS at one month follow up. Out of 10, 3 (6%) patients had post
operative significant bacteriuria. In group B 15 patients had irritative
LUTS. Out of 15, 6(12%) patients had significant bacteriuria. E coli was
the most common organism isolated from both the groups. When
comparing with group A, group B had clinically significant post-operative
LUTS & bacteriuria.
0 5 10 15
H/O LUTS
URINE CULTURE POSITIVE
CULTURE NEGATIVE
10
3
7
15
6
9
H/O LUTS URINE CULTURE POSITIVE CULTURE NEGATIVE
GROUP B 15 6 9GROUP A 10 3 7
POST TURP LUTS
77
Pre op Comparison of IPSS symptom score
TABLE-33
IPSS SCORE MILD
(0-7)
MODERATE
(8-19)
SEVERE
(20-35)
GROUP A 0 19 31
GROUP B 0 21 29
0
19
31
0
21
29
0
5
10
15
20
25
30
35
pre operative IPSS score
GROUP A
GROUP B
No
of P
atie
nts
78
Post Turp IPSS Score Comparison
TABLE -34
IPSS SCORE MILD (0-7)
MODERATE (8-19)
SEVERE (20-35)
GROUP A 47 3 0
GROUP B 44 6 0
The IPSS score for the patients in this study mostly fell into the
moderate to severe symptoms category. Pre operatively these parameters
were comparable with p value of 0.75. After TURP IPSS score was again
assessed at one month post-op. There was significant improvement in
symptoms score among both the groups. About 92% of group A patients
and 86% of group B patients had very good symptom score reduction.
Only 8% in group A and 14 % in group A had persistence of moderate
IPSS score, while none of them had severe symptoms.
46
4 0
43
700
102030405060708090
100
MILD (0-7) MODERATE(8-19) SEVERE(20-35)
GROUP B
GROUP A
Post TURP IPSS SCORE
No
of P
atie
nts
79
OVERVIEW OF RESULTS
Comparison of patient demographics
TABLE - 35
Parameters Group A Group B
Age 65.7 yrs 65.0 yrs
DRE grade Grade ii Grade ii
USG prostate
weight(mean)
45.5 gms
46.05gms
Mean
HB/PCV(PREOP) 11.7g/31.5% 12g/31.5%
Mean Q max(pre op) 10.5 ml/sec 10.6 ml/sec
IPSS score-pre op Grade iii(60%) Grade iii(60%
80
Comparison of Post op parameters and complications
TABLE -46
Parameters Group A Group B P value
Post op HB loss (11.7-10=
1.7 g)
(12.2-9.4=
2.8g) 0.000
Resection Time 46. minutes 52.8 mintes 0.002
Resected tissue
weight 27.7 g 24.1 P=0.024
Intra op blood loss 175 ml 220 ml P=0.000
Post op IPSS Mild(0-7) -
94%
Mild (0-7)-
88% P= 0.034
MVD 18.04 24.3 P= 0.03
Persistent hematuria 2% 6%
Blood transfusion 4% 12% Significant
Clot retention 6% 12% Significant
Usg – weight loss 45.6 – 18.3 =
27.3g
45.6 -
19.9=25.7g P=0.054
UTI with culture
positive 6% 12% -
Failure to void 6% 10% Significant
DISCUSSION
81
DISCUSSION
Benign prostatic hyperplasia (BPH)54 is one of the common
urological diseases after fifty years of age. The symptoms can start at any
age and may present even in early age group. At 50 years of age, up to
50% of men have symptoms or histological evidence of BPH. The
incidence of symptomatic BPH is known to increase with age54.
When prostate get enlarged, the prostatic urethra gets compressed
between the prostatic lobes. This outflow obstruction produces impedance
to urinary flow from the bladder and it may cause storage and voiding
symptoms like frequency, urgency, hesitancy, nocturia and decreased
stream. These symptoms are collectively known as lower urinary tract
symptoms (LUTS). As the disease progresses, the associated
complications like recurrent UTI, bladder calculi, diverticulum formation,
refractory hematuria and obstructive uropathy also increase5. Therefore
treatment for symptomatic BPH is the corner stone for avoiding these
complications in older age group.
Intraprostatic Dihydrotestosterone (DHT) is the main mediator for
BPH progression.
82
5 α reductase is the main nuclear enzyme which converts
testosterone to DHT. Hence 5 α reductase inhibitors have been the main
drugs used in the medical management of BPH.
Finasteride and dutasteride are the two common 5 α reductase
inhibitors (ARI) used in the current medical management of BPH.
Dutasteride inhibits both5 α reductase Type 1 & 2, but finasteride inhibits
only 5 α reductase type 1. Due to this dual action dutasteride reduces
serum DHT up to 90%, whereas finasteride reduces DHT levels by only 70
to 80%.Within the prostate 5 α reductase type 2 is the predominant
enzyme, and reduces intraprostatic DHT up to 90%55-56. These drugs
mainly induce apoptosis of stromal and glandular components of the
prostate. Up to 30% glandular volume reduction is noticed after six months
of finasteride therapy55-56.
α blockers are also used in the medical management of BPH. They
act by relaxing the smooth muscles in the prostate and bladder neck region
by inhibition of α1A receptors that open the bladder neck and prostatic
urethra. The onset of action of α blockers is 3 to 5 days, where as ARI’s
take four to six months to achieve symptomatic relief in BPH.
When medical management fails or there is a history of recurrent
urinary retention, surgery is the treatment of choice. TURP is the gold
83
standard modality for the surgical management of BPH. Peri-operative
bleeding is a common complication in TURP. Apart from glandular
volume reduction, these 5 α reductase inhibitors also have anti-angiogenic
properties. This has been analyzed in recent randomized trials. One meta-
analysis reported that finasteride effectively controls peri-operative blood
loss following TURP55, 57. However their data lacks sufficient details
regarding their analysis of the anti-angiogenic properties of finasteride.
Another meta-analysis evaluated the effect of Dutasteride on post
TURP blood loss and concluded that Dutasteride has no effect on bleeding
control following TURP58. As far as bleeding is concerned, American
Urological Association (AUA) guidelines14 mentioned that the data is
insufficient to recommend 5α reductase inhibitors peri-operatively.
We therefore undertook a prospective randomized controlled trial
comparing finasteride with placebo to evaluate its efficacy in reducing
peri-operative blood loss following TURP. The patient population was
well matched in both the groups and there was no significant difference in
Age, DRE grade, preoperative Hb, PCV, USG prostate weight, Qmax and
IPSS symptoms score in both the groups.
84
Post TURP bleeding
In our study blood loss was estimated by comparison of pre and post
operative hemoglobin and packed cell volume changes and calculation of
intraoperative blood loss from the irrigation fluid. The mean hemoglobin
loss in group A & B was 1.7g/dl (1.7±0.4g) and 2.8 g/dl (2.8±1.0g). Mean
PCV loss in group A and B was 1.9 and 3.5%. Donohue et al11 did a
similar study with two weeks of preoperative finasteride and they reported
a mean Hb loss of 0.9 g/dl in the finasteride group and 1.6g/dl in the
placebo group.
TABLE - 37
Haemoglobin
loss(g/dl) Finasteride group Placebo group
Liu et al 200360 1.86±1.4 3.17±1.11
Ozdal et al 200559 1.88±0.93 3.19±1.8
Donohue et al11 0.9±0.7 1.6±1.0
Our study 1.7 ±0.3 2.8±1.0
The above table shows that our results are comparable with results
reported from the literature. We conclude from analyzing this hemoglobin
loss that the preoperative short course finasteride therapy significantly
85
reduces the peri-operative blood loss following TURP. Various studies
have reported similar results, with the duration of preoperative therapy
varying from 2 weeks to 3 months59,60.
Intraoperative calculated blood loss
The mean intraoperative operative blood loss for our group A and B
patients were 175ml (175±95 ml) and 220 ml (220±125) respectively.
Sandfeult et al61 estimated the intraoperative blood loss from the irrigating
fluid and their reported mean loss in the finasteride group was 320 ml and
in placebo group 368 ml9.
TABLE - 38
Operative Blood
loss-ml
Finasteride group
(ml)
Placebo group
(ml)
Liu et al 200360 135±90 245±160
Ozdal et al 200559 173±60 239±76
Sandfelt et al61 320±236 368±257
Our study 175±95 220±125
Another study by Ozdal et al59 reported similar results study with 2
weeks of preoperative finasteride therapy. The mean intraoperative blood
86
loss in their study was 173 ml in the finasteride group and 239 ml in the
placebo group. Hence our results have been comparable to the other
reported results.
Operative time
The total resection time in group A was 47minutes (47±7.5 min) and
in group B 53minutes (53±8.6 min). The mean difference between the two
groups was 6 minutes with a p value of 0.004. Similarly Robert G hohn62
reported mean TURP operating time of 55minutes (±15min) in the
finasteride group and 65 minutes (±15) in the placebo group. This
indicates that patients on finasteride therapy had decreased operative time
which would have been due to less bleeding with secondary better field of
vision allowing the procedure to be easier.
Resected prostatic Tissue weight
The mean resected prostatic tissue weight in our group A and B
patients was 27gms (±7g) & 24gms (±8g) respectively. There was a
difference of weight of 3 grams, with weight being greater in group A. The
p value was 0.024, which is significant. Similarly Donohue11 reported
23grams (±8g) resected in finasteride group and 18 grams (±7g) in placebo
group. Sandfelt61 also reported greater resected weight with finasteride, i.e
20 grams in the finasteride group and 17.5 grams in the placebo group. Our
results are comparable with these above published results. Hence our
87
conclusion that patients on preoperative finasteride therapy have more
resected tissue weight during surgery.
Microvessel Density
Microvessel Density (MVD) is the key factor which indicates the
vascular status of the organ. In our study MVD of the intra-prostatic
resected tissue in group A & B was 18.4(±4.5) and 24.3(±5.4) %
respectively. Sub-urethral portion MVD for group A & B was 16.5 and
23.4%. In group A there is significant reduction of vascular density in the
sub-urethral and intra-prostatic region. This is statistically significant when
compared with the placebo group. David A Hochberg et al63 reported that
MVD in Finasteride and placebo group was 14±5.3 Vs 20±2.8, which was
similar to our study.
TABLE - 39
Micro vascular
density finasteride group placebo group
Liu et al 200360 21±9.7 33±11.27
Donohue et al11 60±2.5 71±3.5
Memis et al64 14.5±2.36 19.8±2.57
Our study 18±4.5 ml (24±125)
88
When analyzing our results with other studies(table – 39), our
results are almost similar to those given in literature. Hence MVD is an
important marker for vascularity and also indirectly indicates the chances
of bleeding following TURP. So finasteride has anti-angiogenic properties
that indirectly reduce vascularity. Few studies have also reported that
finasteride inhibits the VEGF -the vascular endothelial growth factor.
Persistent post operative Hematuria and need for blood transfusion
Post operative persistent hematuria is an alarming sign of bleeding
in TURP. In our study population only one patient (2%) in the finasteride
group and 3(6%) in placebo group underwent repeat endoscopic procedure
for bleeding control. In group B out 3 patients with bleeding one had to
undergo exploration for prostate fossa packing. No mortality was reported.
Similarly Mark Lynch29 from U.K reported 19 cases of post TURP
bleeding for which endoscopic bleeding control was performed. Out of 19
cases one patient required open prostatic fossa packing. Finally he
concluded that even though endoscopic related bleeding rates have
decreased, they can still be life threatening, so unnecessary delay for open
procedure should be avoided if endoscopic techniques fail to control
bleeding.
89
Because of persistent hematuria, two patients in finasteride group
and 6(12%) patients in placebo group had postoperative blood transfusion.
In group B transfusion rate was higher (18%). Most of the patients in our
study had preoperative low hemoglobin. This was one of the confounding
factors which could have indirectly increased the blood transfusion rate.
But when comparing with group A, a significantly greater number of
patients required blood transfusion in group B. Other studies reported
blood transfusion rate that varied from 0 to 7%.
Clot retention
Clot retention rate in our study and control group was 6% and 12%.
This clearly indicates that the patients in finasteride group had less
incidence of clot retention when comparing with the placebo group and it
was found clinically significant. Similarly shanmugasundaram et al53
reported 6 to 11% incidence of clot retention in their dutasteride group.
Clot retention rate reported by the recent studies are 0 to 5% (kuntz
2004)24. So this is one of the outcomes which is significantly and
favourably influenced by administration of preop finasteride.
90
Failure to void
In our study, failure to void in group A was only 4%, whereas in
group B the failure rate was 10% and this is clinically significant. Recent
literature65 reports the incidence of post TURP voiding failure rate to be 3
to 7%. But patients with clot retention or associated pre operative UTI or
significant preoperative PVR are also potential candidates for voiding
failure. Here, patients in the finasteride group experienced lesser voiding
difficulty than those in placebo group. It suggests that finasteride may
decrease the incidence of post TURP voiding failure in BPH patients.
Qmax improvement
In our study the mean qmax improvement after TURP in group A &
B was 4.8 ml/sec and 3.6 ml/sec respectively. It suggests that in the
finasteride group, there was better qmax improvement than among patients
in the placebo group with 1.2 ml/sec greater qmax seen in group A.
Reports from literature suggest that following TURP there is 3 to 5 ml/sec
improvement in qmax66. Our results were comparable with other studies
and indicate that preoperative finasteride shows better qmax improvement
after TURP.
91
Post TURP Urinary Tract Infection
Usually the infection rate is low and the reported incidence is 3 to
5%. But one study reported 21% incidence of post TURP urinary tract
infections. In our study the post operative urine culture was sent for those
patients with LUTS. 6% in group A and 12 % in group B patients had
culture proven UTI. Patients in the finasteride group had less postoperative
infection than those in the placebo group. This could be due to the fact that
finasteride group patients had lesser incidence of hematuria and clot
retention, which contributed to the lesser incidence of culture positivity.
IPSS symptoms Score changes
Prior to surgery, the mean IPSS score in our group A & B was 25 &
26 respectively. At one month following TURP, 94% of patients in group
A and 88% of the group B patients showed better symptomatic
improvement and most of them had only grade I score (0-7) (Mean IPPS
score POST OP- 6). Only 6% of the patients in group A and 12% in group
B had grade II IPSS score (8-19), while none of them reported grade III
score (20-35). Most of the patients in grade II category had associated peri-
operative complications like bleeding, clot retention and post operative
UTI. Hence after surgery, patients in the finasteride arm demonstrated
better symptomatic improvement than those in placebo arm.
92
Our study showed that short course preoperative finasteride therapy
( 5mg od for two weeks) significantly reduced the intra and post operative
blood loss, operative time and resulted in greater resection of tissue and
lessened the complications like post operative clot retention, voiding
failure, requirement of blood transfusion.
CONCLUSIONS
93
CONCLUSION
From our study we conclude that preoperative short course of
finasteride therapy (Tab.finasteride 5 mg OD) definitely reduces the peri-
operative complications like intra and postoperative blood loss, persistent
hematuria, need for blood transfusions, clot retention and postoperative
voiding failure. It also decreases operative time, tissue microvessel density
and post operative UTI. It aids removal of more prostatic tissue and also
improves the urinary flow rate (Q max). Hence based on our study we
recommend the use of preoperative short course (2 weeks) finasteride
therapy prior to TURP in the treatment of BPH, due to its role in effective
control of perioperative Blood loss and associated complications.
BIBLIOGRAPHY
BIBLIOGRAPHY
1) Meigs JB, and Barry MJ: Natural history of benign prostatic
hyperplasia, in Kirby R, McConnell JD, Fitzpatrick JM, et al(Eds),
Textbook of Benign Prostatic Hyperplasia. Oxford, UK, Isis
Medical Media Ltd, 1996, pp 139–148.
2) Lee, C., Kozlowski, J.M. and Gray hack, J.T. (1997). Intrinsic and
extrinsic factors controlling benign prostatic growth. Prostate 31:
131–138.
3) Berry SJ, Coffey DS, Walsh PC, et al: The development of human
benign prostatic hyperplasia with age. J Urol 132:474–479, 1984.
4) Russell DW, Wilson JD. Steroid 5alpha-reductase: two genes/two
enzymes.Annu Rev Biochem 1994;63:25
5) McConnell JD, Bruskewitz R, Walsh P, Andriole G, Lieber M,
Holtgrewe HL, et al. The effect of finasteride on the risk of acute
urinary retention and the need for surgical treatment among men
with benign prostatic hyperplasia: Finasteride Long-Term Efficacy
and Safety Study Group. N Engl J Med.1998;338:557–63
6) De la Rosette J, Alivizatos G, Madersbacher S, et al. Guidelines on
Benign Prostatic Hyperplasia.European Association of Urology.
2006.
7) Mebust WK, Holtgrewe HL, Cockett AT, et al. Transurethral
prostatectomy: immediate and postoperative complications. A
cooperative study of 13 participating institutions evaluating 3,885
patients. J Urol.1989;141:243–7
8) Alankar Shrivastava and Vipin B. Gupta1Various treatment options
for benign prostatic hyperplasia: A current update- J Midlife Health.
2012 Jan-Jun; 3(1): 10–19
9) Reich O, Gratzke C, Stief CG. Techniques and long-term results of
surgical procedures for BPH. Eur Urol. 2006;49:970–978
10) Dutasteride tablets [package insert]. GlaxoSmithKline, Research
Triangle Park, NC, 2002
11) Donohue, J. F., Hayne, D., Karnik, U., Thomas, D. R. & Foster,
M. C.Randomized, placebo-controlled trial showing that finasteride
reduces prostatic vascularity rapidly within 2 weeks. BJU Int. 96,
1319–1322 (2005)
12) Comparison of dutasteride and finasteride for treating benign
prostatic hyperplasia: the Enlarged Prostate International
Comparator Study (EPICS).BJU
13) Nickel JC, Méndez-Probst CE, Whelan TF, et al. the Canadian
Prostate Health Council and the CUA Guidelines Committee 2010
Update: Guidelines for the management of benign prostatic
hyperplasia. Can Urol Assoc J. 2010;4:310–6
14) Roehrborn CG, McConnell JD, Barry MJ, et al. AUA Guideline on
the management of benign prostatic hyperplasia.
http://www.auanet.org/content/guidelines-and-quality-care/clinical-
guidelines.cfm.
15) De la Rosette J, Alivizatos G, Madersbacher S, et al. Guidelines on
Benign Prostatic Hyperplasia.European Association of
Urology. 2006.
16) Assaad El-Hakim, MD, FRCSC TURP in the new century: an
analytical reappraisal in light of lasers; Can Urol Assoc J
2010;4(5):347-349.
17) Mebust WK, Holtgrewe HL, Cockett AT, et al. Transurethral
prostatectomy: immediate and postoperative complications. A
cooperative study of 13 participating institutions evaluating 3,885
patients. J Urol.1989;141:243–7
18) Wasson JH, Reda DJ, Bruskewitz RC, et al. A comparison of
transurethral surgery with watchful waiting for moderate symptoms
of benign prostatic hyperplasia. The Veterans Affairs Cooperative
Study Group on Transurethral Resection of the Prostate. N Engl J
Med. 1995;332:75–9.
19) Monopolar vs. bipolar TURP: assessing their clinical advantages-
Pierre-Alain Hueber, PhD; Ahmed Al-Asker, MD; Kevin C. Zorn,
MD, MDCM, FRCSC, FACS University of Montreal Hospital
Centre (CHUM), Montreal, QC
20) Complications of Transurethral Resection of the Prostate (TURP)—
Incidence, Management, and Prevention Jens Rassweiler a,*, Dogu
Teber a, Rainer Kuntz b, Rainer Hofmann c.
21) Doll HA, Black NA, McPherson K, Flood AB, Williams GB,Smith
JC. Mortality, morbidity and complications following transurethral
resection of the prostate for benignprostatic hypertrophy. J Urol
1992;147:1566–73.
22) Haupt G, Pannek J, Benkert S, Heinrich C, Schulze H,Senge T.
Transurethral resection of the prostate with microprocessor
controlled electrosurgical unit. J Urol1997;158:497..
23) Borboroglu PG, Kane CJ, Ward JF, Roberts JL, Sands JP.
Immediate and postoperative complications of transurethral
prostatectomy in the 1990s. J Urol 1999;162:1307–10.
24) Kuntz RM, Ahyai S, Lehrich K, Fayad A. Transurethralholmium
laser enucleation of the prostate versus transurethralelectrocautery
resection of the prostate: A randomizedprospective trial in 200
patients. J Urol 2004;
25) Zwergel U. Benignes Prostatahyperplasie-(BPH)-
Syndrom.Operative und interventionelle Therapieoptionen.
UrologeA 2001;40:319–29
26) Horninger W, Unterlechner H, Strasser H, Bartsch G.Transurethral
prostatectomy: mortality and morbitidy.Prostate 1996;28:195–
27) Berger AP, Wirtenberger W, Bektic J, Steiner H, Spranger
R,Bartsch G. Safer transurethral resection of the
prostate:coagulating intermittent cutting reduces
hemostaticcomplications. J Urol 2004;171:289–91.
28) Muzzonigro G, Milanese G, Minardi D, Yehia M, Galosi
AB,Dellabella M. Safety and efficacy of transurethral resectionof
prostate glands up to 150 ml: aprospective comparativestudy with 1
year of followup. J Urol 2004;172:611–5.
29) Postoperative haemorrhage following transurethral resection of the prostate (TURP) and photoselective vaporisation of the prostate (PVP) - MarkLynch,1 Seshadri,1 Kesavapillai,Subramonian,2 and Peter Thompson1Ann R Coll Surg Engl. 2010 Oct; 92(7): 555–558.
30) Blood loss during and after transurethral resection of prostate: a prospective study. Shrestha BM1, Prasopshanti K, Matanhelia SS, Peeling WB. Kathmandu Univ Med J (KUMJ). 2008 Jul-Sep;6(23):329-34
31) Management of Large (60 g) Prostate Gland: PlasmaKinetic Superpulse (Bipolar) versus Conventional (Monopolar) Transurethral Resection of the ProstateManish Bhansali Suresh Patankar, M.S., M.Ch., Sayten Dobhada, M.S., and Suparn Khaladkarjournal of endourology Volume 23, Number 1, January 2009.
32) Blood loss comparison during transurethral resection of prostate and high power GreenLight(™) laser therapy using isotopic measure of red blood cells volume. Bruyère F1, Huglo D, ChallacombeB, Haillot O, Valat C, Brichart N.
33) Factors influencing blood loss in transurethral resection of the prostate (TURP): auditing TURP.Kirollos MM1, Campbell N. Br J Urol. 1997 Jul;80(1):111-5
34) Does catheter traction reduce post-transurethral resection of the prostate blood loss? Walker EM1, Bera S, Faiz M. Br J Urol. 1995 May;75(5):614-7
35) Lee C, Kozlowski J M, Grayhack J T. Aetiology of benign prostatic hyperplasia. Urol Clin N Am1995; 22: 237–246
36) Walsh P C, Madden J D, Harrod M J et al. Familial incomplete male pseudohermaphroditism, type 2: decreased dihydrotestosterone formation in pseudovaginal perineoscrotal hypospadias. N Engl J Med 1974; 291: 944–949
37) Imperato-McGinley J, Guerrero L, Gautier T, Peterson R E. Steroid 5a-reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science 1974; 186: 1213–1215
38) Herr, H. W. The enlarged prostate: a brief history of its surgical treatment. BJU Int. 98, 947-952 (2006).Mercier, L. Recherches sur le traitement des maladies des organs urinaires. (Kessinger publishing, Paris, 185
39) McConnell JD, Roehrborn CG, Bautista OM, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003;349(25):2387–98.
40) Feneley M R, Span P N, Schalken J A et al. Aprospective randomized trial evaluating tissueeffects of finasteride therapy in benign prostatichyperplasia. Prostate Cancer Prostatic Dis 1999; 2
41) Marberger MJ, Andersen JT, Nickel JC, et al. Prostate volume and serum prostate-specific antigen as predictors of acute urinary retention: combined experience from three large multinational placebo-controlled trials. Eur Urol. 2000;38:563–568.
42) The effect of finasteride in men with benign prostatic hyperplasia. The Finasteride Study Group.Gormley GJ1, Stoner E, Bruskewitz RC, Imperato-McGinley J, Walsh PC, McConnell JD, Andriole GL, Geller J, Bracken BR, Tenover JS, et al.N Engl J Med. 1992 Oct 22;327(17):1185-91.
43) Clark RV, Hermann DJ, Cunningham GR, et al. Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5α-reductase inhibitor. J Clin Endocrinol Metab. 2004;89:2179–2184
44) Comparison of dutasteride and finasteride for treating benign prostatic hyperplasia: the Enlarged Prostate International Comparator Study (EPICS).BJU Nickel JC1, Gilling P, Tammela TL, Morrill B, Wilson TH, Rittmaster RS
45) A comparative study of fixed dose of Tamsulosin with finasteride vs Tamsulosin with dutasteride in the management of benign prostatic hyperplasiaNK Mohanty, Uday Pratap Singh, Nitin K Sharma, RP Arora, Vindu Amitabh-indian journal of urology- Year : 2006 | Volume : 22 | Issue : 2 | Page : 130-134
46) The Effect of Finasteride on Microvessel Density and Expression of Vascular Endothelial Growth Factor and 5α-Reductase in Prostatic Hyperplasia Jae-Ho Hyun, Kun-Hyun Cho, Dong-Seok Han, Jin-Bum Kim and Young-seop Chang
47) S. J. Foley, L. Z. Soloman, A. W. Wedderburn et al., “Aprospective study of the natural history of hematuria associated with benign prostatic hyperplasia and the effect of finasteride,”Journal of Urology, vol. 163, no. 2, pp. 496–498, 2000.
48) O. L. ¨ Ozdal, C. ¨ Ozden, K. Benli, S. G¨okkaya, S. Bulut, and A.Memis¸, “Effect of short-term finasteride therapy on peroperative bleeding in patients who were candidates for transurethral resection of the prostate (TUR-P): arandomized controlled study,” Prostate Cancer and Prostatic Diseases, vol.8,no.3,pp.215– 218, 2005
49) J. F. Donohue, H. Sharma, R. Abraham, S. Natalwala, D. R.Thomas, and M. C. Foster, “Transurethral prostate resection and bleeding: a randomized, placebo controlled trial of the role of finasteride for decreasing operative blood loss,” Journal of Urology, vol. 168, no. 5, pp. 2024–2026, 2002.
50) L. Sandfeldt, D. M. Bailey, and R. G. Hahn, “Blood loss during transurethral resection of the prostate after 3 months of treatment with finasteride,” Urology, vol. 58, no. 6, pp. 972–976,2001.
51) R. G. Hahn, T. Fagerstr¨om, T. L. J. Tammela et al., “Blood loss and postoperative complications associated with transurethral resection of the prostate after pre-treatment with dutasteride BJU International, vol. 99, no. 3, pp. 587–594, 2007
52) [Effect of dutasteride on reduction of intraoperative bleeding related to transurethral resection of the prostate].Boccon-Gibod L1, Valton M, Ibrahim H, Boccon-Gibod L, Comenducci A-Prog Urol. 2005 Dec;15(6):1085-9
53) R.Shanmugasundaram, J. Chandra Singh, Nitin S. Kekre- Does dutasteride reduce perioperative blood loss and postoperative complications after transurethral resection of the prostate? Indian J Urol. 2007 Jul-Sep; 23(3): 334–335.
54) Roehbon CG ,Benign prostatic hyperplasia-an over view-Review of urology 2005.7(9).
55) S. Haggstrom, N. Torring, K. Moller et al., “Effects of finasteride on vascular endothelial growth factor-a placebo-controlled randomized study in BPH patients,” Scandinavian Journal of Urology and Nephrology, vol. 36, no. 3, pp. 182–187, 2002.
56) J. D. McConnell, J. D. Wilson, F. W. George, J. Geller, F. Pappas,
and E. Stoner, “Finasteride, an inhibitor of 5ߙ-reductase, suppresses prostatic dihydrotestosterone in men with benign prostatic hyperplasia,” Journal of Clinical Endocrinology and Metabolism, vol. 74, no. 3, pp. 505–508, 1992
57) Pareek, M. Shevchuk, N. A. Armenakas et al., “The effect of finasteride on the expression of vascular endothelial growth factor and microvessel density: a possible mechanism for decreased prostatic bleeding in treated patients,” Journal of Urology, vol. 169, no. 1, pp. 20–23, 2003
58) Huan-Tao Zong1, Xiao-Xia Peng2, Chen-Chen Yang1 and Yong Zhang A systematic review of the effects and mechanisms of preoperative 5a- reductase inhibitors on intraoperative haemorrhage during surgery for benign prostatic hyperplasia; Asian J Androl. 2011 Nov; 13(6); 812–818.
59) O. L. Özdal, C. Özden, K. Benli, S. Gökkaya, S. Bulut, and A. Memiş, “Effect of short-term finasteride therapy on peroperative bleeding in patients who were candidates for transurethral resection of the prostate (TUR-P): a randomized controlled study,” Prostate Cancer and Prostatic Diseases, vol. 8, no. 3, pp.215- 218- 2005
60) Liu XD, Yang YR, Lu YP, Zhang XH, Li FY et al. Preoperative finasteride of decreasing operative bleeding during transurethral resection of prostate. Chin J.Urol 2003; 24:694–6.
61) Sandfeldt L, Bailey DM, Hahn RG. Blood loss during transurethral resection of the prostate after 3 months of treatment with finasteride. Urology 2001; 58; 972–6
62) Hahn RG. Influence of variations in blood haemoglobin concentration on the calculation of blood loss and volumetric irrigating fluid balance during transurethral resection of the prostate. Br J Anaesth 1987; 59: 1223–9.
63) David A. Hochberg Jay B. Basillote,Noel A. Armenakas,Liliana, Vasovic, Maria Shevchuk,Gyan Pareek;Decreased Suburethral Prostatic Microvessel Density In Finasteride Treated Prostates: A Possible Mechanism For Reduced Bleeding In Benign Prostatic Hyperplasia –April 2002.167, Issue 4, Pages 1731–173; The journal of urology.
64) Memis A, Ozden C, Ozdal OL, Guzel O, Han O et al. Effect of finasteride treatment on suburethral prostatic microvessel density in patients with hematuria related to benign prostate hyperplasia. Urol Int 2008; 80: 177–80
65) Madersbacher S, Marberger M. Is transurethral resection of the prostate still justified? BJU Int 1999;83:227–37.
66) Siavash Falahatkar, Gholamreza Mokhtari, Keivan Gholamjani MoghaddamBipolar transurethral vaporization: a superior procedure in Benign prostatic hyperplasia: a prospective randomized comparison with Bipolar TURP - Vol. 40 (3): 346-355, May - June, 2014 – international Brazilian Journal of urology.
67) Elmalik EM, Ibrahim AL, Gahli AM, et al. Risk factors in prostectomy bleeding. Eur Urol. 2000; 37: 199-204.
ANNEXURE
PROFORMA
“EFFECT OF PREOPERATIVE FINASTERIDE THERAPY ON PERIOPERATIVE BLOOD LOSS IN TRANSURETHRAL RESECTION OF PROSTATE FOR BENIGN PROSTATIC
HYPERPLASIA” – A PROSPECTIVE RANDOMIZED PLACEBO CONTROLLED STUDY
SL No: Date:
Patient Name: Age/ Sex:
IP No:
Address:
Group: Group –A / Group-B :
Chief Complaint:
Presenting Illness:
Past Medical / Surgical History:
Personal History:
Family History:
General Examination:
Pulse: BP:
P/A: E/G:
DRE:
INVESTIGATIONS HB:
TC: IPSS Score-Preop / Postop :
DC: Blood transfusion -Yes / No:
ESR: Clot retention Yes / No:
RBS: MVD :
Blood Urea:
Serum Creatinine:
Serum Electrolytes:
Blood Grouping & Typing:
USG KUB:
Prostate Volume:
X-Ray KUB:
Urine R/E:
Urine C & S:
Operative Time:
Resected tissue weight:
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PATIENT CONSENT FORM
Title of the Project
“EFFECT OF PREOPERATIVE FINASTERIDE THERAPY ON PERIOPERATIVE BLOOD LOSS IN TRANSURETHRAL RESECTION OF PROSTATE FOR BENIGN PROSTATIC
HYPERPLASIA” – A PROSPECTIVE RANDOMIZED PLACEBO CONTROLLED STUDY
Institution : Department of Urology,
Kilpauk Medical College, Chennai-600 010.
Name: Date :
Age : IP No :
Sex : Project Patient No :
The details of the study have been provided to me in writ ing and explained to me in my own language.
I confirm that I have understood the above study and had the opportunity to ask questions.
I understood that my partic ipation in the study is voluntary and that I am free to withdraw at any time, without giving any reason, without the medical care that will normally be provided by the hospital being affected.
I agree not to restrict the use of any data or results that arise from this study provided such a use is only for scientific purpose(s).
I have been given an information sheet giving details of the study.
I fully consent to partic ipate in the above study regarding Finasteride drug intake 2 weeks before surgery. Transurethra l resect ion of the prostate surgery (TURP) and to give the prostatic specimen for the investigation.
Name of the Subject Signature Date
Name of the Invest igator
Signature Date
INFORMATION SHEET Title of the Project
“EFFECT OF PREOPERATIVE FINASTERIDE THERAPY ON PERIOPERATIVE BLOOD LOSS IN TRANSURETHRAL RESECTION
OF PROSTATE FOR BENIGN PROSTATIC HYPERPLASIA” – A PROSPECTIVE RANDOMIZED PLACEBO CONTROLLED STUDY
❖ We are conducting a study on the above mentioned title
among patients attending Government Kilpauk Medica l College & Hospital, Chennai and for that your co-operation may be valuable to study.
❖ The privacy of the patients in the research will be maintained throughout the study. In the event of any publication or presentation resulting from the research, no personally identifiable information will be shared.
❖ Taking part in this study is voluntary. You are free to decide whether to participate in this study or to withdraw at any time; your decision will not result in any loss of benefits to which you are otherwise entitled.
❖ The results of the special study may be intimated to you at the end of the study period or during the study if anything is found abnormal which may aid in the management or treatment.
❖ You have prostate enlargement due to aging that cause urinary tract obstruction. During the Transurethral resection of prostate surgery (TURP) complication like bleeding can occur. To find out the role for Tab. Finesteride in reducing the TURP complications, I agree to take the Finasteride tablets before surgery and to send the prostatic resected specimen for the investigation.
Signature of Investigator Signature of Participant Date : Date :
S.NO
NAME AGE
GR
OU
P
DR
E G
RA
DE
USG
PR
OST
ATE
WEI
GH
T
pre
op
OPE
RA
TIN
G T
IME
(MIN
)
RES
ECTE
D T
ISSU
E W
EIG
HT
(G
MS)
USG
PR
OST
ATE
WT
POST
OP
PREO
P H
B
POST
OP
HB
PREO
P-PC
V
POST
OP-
PCV
PREO
P-Q
MA
X
POST
OP
QM
AX
INTR
AO
P C
ALC
ULA
TED
B
LOO
D L
OSS
CLO
T R
ETEN
TIO
N (
YES
=1,
NO
=2)
BLO
OD
TR
AN
SFU
SIO
N
(Y
ES=1
, NO
=2)
EXPL
OR
ATI
ON
/
RET
UR
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G T
O O
T (
YES
=1,
NO
=2)
MV
D (S
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UR
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RA
L)
MV
D (I
NTR
A P
RO
STA
TIC
)
FAIL
UR
E TO
VO
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, N
O=2
)
UTI
(CU
LTU
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TIV
E -1
,
NEG
ATI
VE
- 2)
PR
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- IPS
S SC
OR
E (G
RA
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I (0
-7),
II
- (8
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, III
-
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35)
POST
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- IPS
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RA
DE
I (0
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II -
(8-1
9), I
II -
(20-
35)
1 HABEEB REHMAN 65 A 2 55.9 45 20 30 11.0 10.5 32 31 10 14 175 2 2 2 18.41 20.22 2 2 II I
2 PONNUSAMY 78 A 2 41 40 25 18 10.8 10.5 31 30 11 14.2 132 2 2 2 20.62 13.4 2 2 III I
3 VISWANATHAN 56 A 2 39.1 40 25 20 11.5 10.0 31 29 10.5 14 132 2 2 2 21.24 14.98 2 2 II I
4 KANNIAPPAN 78 A 2 40.4 45 25 18 11.22 10.8 33 30 9 13.2 120 2 2 2 17.3 15.22 2 2 III I
5 GUNASEKARAN 53 A 2 41 40 20 15 12.5 10.0 32 29 8 15 214 2 2 2 14.42 16.4 2 2 II I
6 PREBAL 52 A 2 55.4 50 30 20 10.7 10.0 32 29 10 14.3 167 2 2 2 19.56 16.11 2 2 III I
7 RAMACHANDRAN 76 A 2 43.0 45 20 18 11.2 8.4 32 28 11.5 14.5 155 2 1 1 15.62 13.22 2 2 II I
8 LOGANATHAN 75 A 2 38.64 40 18 15 10.6 9.6 31 29 10.5 13.5 213 2 2 2 16.25 13.46 2 2 III I
9 SELVAM 67 A 2 41.5 47 19 20 12.4 9.6 30 29 11 14.5 198 2 2 2 14.56 20.62 2 2 II I
10 MANI 68 A 1 38.6 35 35 15 11.8 9.6 30 29 12 15.1 145 2 2 2 15.67 13.22 2 2 II I
11 RENGANATHAN 80 A 3 54.9 50 25 20 11.9 10.6 32 30 10.5 13 100 2 2 2 15.89 17.45 2 2 III I
12 GOVINDARAJAN 64 A 2 46.9 45 28 18 12.4 10.2 32 31 11.7 16 110 2 2 2 18.45 13.08 2 2 II I
13 PONNUSAMY 65 A 2 56.8 50 25 18 11.7 9 31 28 12 17 160 2 1 2 20.22 14.42 2 2 III I
14 SIVARAMAN 70 A 2 43.7 43 30 15 10.3 9.6 30 29 11 13.1 229 2 2 2 13.4 15.6 2 1 III II
15 CHANDRASEKAR 55 A 2 44.5 50 24 18 11.4 9.8 31 29 10.3 13 175 2 2 2 14.98 18.41 2 2 III I
16 DASS 69 A 2 45.0 43 28 27 12 10.5 32 30 8.5 14.5 270 2 2 2 15.22 20.62 2 2 II I
17 KANNIAPPAN 62 A 2 41.54 42 22 19 12 9.6 30 29 9.7 15 100 2 2 2 16.4 13.22 2 2 III I
18 RAJAMANIKAM 75 A 1 37.5 35 35 17 12.5 10.0 32 29 11 13.3 190 2 2 2 16.11 15.87 2 1 III I
19 RAJAGOPAL 75 A 2 40.3 40 20 15 12 10.4 31 30 10.5 14 223 2 2 2 13.22 14.98 2 2 II I
20 BAKTHAVACHALAM 81 A 2 42.2 45 36 18 12.4 10.0 31 30 9 13.7 142 2 2 2 13.46 15.22 2 2 II I
21 FRANCIS 80 A 2 30.5 40 30 15 12.4 10.2 32 30 8 13 190 2 2 2 13.08 16.4 2 2 III I
22 KANNIAPPAN 50 A 1 35.0 40 30 15 11.0 10.0 33 30 10 14 169 2 2 2 16.25 18.41 2 1 II I
23 PARASURAMAN 61 A 3 66.6 65 40 20 12.4 10 31 29 11.5 14.5 235 2 2 2 14.56 20.62 2 2 II I
24 JONPRAKASH 68 A 2 37.9 40 30 15 11.0 10 32 29 10.5 13.5 175 2 2 2 15.67 17.98 2 2 II I
25 NARAYANAN 70 A 2 43.9 42 20 19 11.8 10 32 28 11 13.5 118 2 2 2 18.41 13.81 2 2 III I
26 RAMESH 45 A 2 44.8 46 22 18 12 8.6 30 27 11.7 16 175 1 2 2 20.62 16.56 2 2 III II
27 PONNAN 67 A 2 65.0 55 30 30 11.1 9.6 31 30 12 14 156 2 2 2 21.24 14.67 2 2 II I
28 PERUMAL 60 A 2 55.0 49 30 28 12.0 10 32 30 11 14.3 208 2 2 2 17.3 15.67 2 2 III I
29 BALASUBRAMANIYAN 68 A 2 43.0 50 20 15 11.5 11.0 33 32 10.3 13.6 189 2 2 2 14.42 24.4 2 2 II I
30 CHOTTILA 71 A 2 75.0 60 45 25 12.0 10.5 32 31 11 14 155 1 2 2 15.6 22.23 2 2 II I
31 PANCHACHALAM 63 A 1 40.0 45 15 16 11.5 10.5 32 31 12 13.4 157 2 2 2 18.41 19.06 2 2 III I
32 ARUMUGAM 55 A 2 65.0 60 35 20 11.7 10.5 31 30 10.5 15 143 2 2 2 20.62 19.56 1 2 III I
33 ANNAMALAI 55 A 1 37.0 47 20 15 12.5 10.0 31 30 11.7 14.1 158 2 2 2 13.22 24.01 2 2 III I
34 VEERAMANI 75 A 2 43.0 60 30 20 11.22 10.8 32 31 12 13.1 187 2 2 2 15.87 24.67 2 2 III I
35 VEERAMANI 75 A 2 54.5 50 25 20 12 10.0 31 29 9 15 220 2 2 2 13.08 16.87 2 2 III I
36 ANANDHAN 68 A 2 55.6 50 24 18 12.2 10.0 32 29 8 13 202 1 2 2 15.6 27.87 2 2 III I
37 TEYABAL 65 A 2 37.0 42 35 15 11.2 9.6 33 30 10 14.1 168 2 2 2 15.34 21.6 1 2 III I
S.NO
NAME AGE
GR
OU
P
DR
E G
RA
DE
USG
PR
OST
ATE
WEI
GH
T
pre
op
OPE
RA
TIN
G T
IME
(MIN
)
RES
ECTE
D T
ISSU
E W
EIG
HT
(G
MS)
USG
PR
OST
ATE
WT
POST
OP
PREO
P H
B
POST
OP
HB
PREO
P-PC
V
POST
OP-
PCV
PREO
P-Q
MA
X
POST
OP
QM
AX
INTR
AO
P C
ALC
ULA
TED
B
LOO
D L
OSS
CLO
T R
ETEN
TIO
N (
YES
=1,
NO
=2)
BLO
OD
TR
AN
SFU
SIO
N
(Y
ES=1
, NO
=2)
EXPL
OR
ATI
ON
/
RET
UR
NIN
G T
O O
T (
YES
=1,
NO
=2)
MV
D (S
UB
UR
ETH
RA
L)
MV
D (I
NTR
A P
RO
STA
TIC
)
FAIL
UR
E TO
VO
ID (Y
ES=1
, N
O=2
)
UTI
(CU
LTU
RE
POSI
TIV
E -1
,
NEG
ATI
VE
- 2)
PR
EOP
- IPS
S SC
OR
E (G
RA
DE
I (0
-7),
II
- (8
-19)
, III
-
(20-
35)
POST
OP
- IPS
S SC
OR
E (G
RA
DE
I (0
-7),
II -
(8-1
9), I
II -
(20-
35)
38 KASINATHAN 55 A 2 54.5 60 35 20 10.6 9.6 31 29 11.5 14.5 190 2 2 2 17.98 21.12 2 2 III I
39 SUBRAMANI 78 A 1 43.0 46 19 17 12.2 9.6 31 29 10.5 13.5 180 2 2 2 13.81 18.97 2 2 III II
40 ZITARAM 50 A 2 31.3 40 19 15 11.5 9.6 30 28 11 14.5 170 2 2 2 13.56 25.89 2 2 II I
41 MARIMUTHU 70 A 2 43.2 55 40 15 12.5 10.0 32 30 11.5 14.5 230 2 2 2 14.67 22.87 2 2 III I
42 CHINNASAMY 72 A 1 35.5 40 25 15 12.3 9.8 32 29 10.5 13.5 154 2 2 2 15.67 23.98 2 2 III I
43 MARIAPPAN 63 A 1 45.0 45 30 15 12.5 10.0 31 29 11 14.5 226 2 2 2 14.76 23.45 2 2 III I
44 SITARAMAN 67 A 1 40.0 35 35 15 10 9.7 32 28 11.7 15.2 210 2 2 2 15.96 21.54 2 2 III I
45 VENKATESAN 50 A 2 48.0 65 38 15 12.0 10.0 32 31 12 14.1 120 2 2 2 18.98 20.76 2 2 II I
46 JEYARAMAN 65 A 1 37.5 45 35 18 11.6 9.5 32 31 11 16 198 2 2 2 16.87 24.56 2 2 III I
47 PALANI 60 A 2 41.6 40 21 18 12.5 9.8 31 30 10.3 13.6 236 2 2 2 17.98 21.63 2 2 III I
48 NACHIAPPAN 66 A 1 39.3 40 25 14 12.2 10.5 31 30 11 14.5 145 2 2 2 19.98 26 2 2 II I
49 KALIMUTHU 72 A 2 43.4 50 28 26 11.8 10.5 32 31 12 14.6 189 2 2 2 21.12 19.56 2 2 III I
50 GOPALAN 59 A 3 56.5 60 42 13 11.4 9.7 31 29 10.5 15 150 2 2 2 14.22 26.87 2 2 III I
51 GUNALAN 58 B 1 33.5 45 18 17 12 9.5 30 29 11.7 12.5 213 2 2 2 24.4 23.56 2 2 II I
52 SWAMIINATHAN 65 B 3 72.0 65 43 20 12.6 9.6 31 28 11.5 12.4 240 2 2 2 22.23 21.87 2 2 III I
53 TIKKARAM 74 B 1 31.0 45 20 15 12.5 10 31 30 10.5 15.5 330 2 2 2 19.06 24.76 2 2 II I
54 RAJENDRAN 63 B 2 57.0 55 40 15 12 9.4 32 28 11 13.6 265 2 2 2 19.56 26.76 2 2 III I
55 RAMACHANDRAN 75 B 1 31.0 50 15 18 12.2 9.6 32 29 12 14.5 220 2 2 2 24.01 20.43 2 2 II I
56 NANDHA KUMAR 75 B 2 50.0 60 35 30 12.4 9.5 32 30 10.5 12.4 321 2 2 2 18.95 19.76 2 1 III I
57 THANGARAJ 65 B 1 32.0 45 16 15 12.1 9.8 31 30 11.7 14.5 280 2 2 2 16.87 22.01 2 2 III II
58 PENICILLIAIYA 70 B 2 69.0 65 40 25 11.2 9.6 32 29 12 14 223 2 2 2 17.98 25.9 1 2 II I
59 NARAYANAN 64 B 2 53.0 65 30 23 12 9.6 31 29 11 13 156 2 2 2 21.6 22.45 2 1 III I
60 THIRUKUMAR 70 B 2 50.0 55 35 15 11.2 8.6 32 27 10.3 14 270 1 1 1 21.12 22.56 2 2 II I
61 RAMASAMY 74 B 2 54.0 58 34 20 10.8 9.8 31 28 8.5 12 230 2 2 2 18.97 26.98 2 2 II I
62 PARI 75 B 1 45.3 58 30 14 12.3 8.6 31 27 9.7 13.4 260 1 1 2 21.67 24.65 2 2 II II
63 KUPPUSAMY 76 B 2 55.0 60 35 20 10.6 9.4 31 26 11 13.5 257 2 2 2 18.98 24.65 2 2 III I
64 KRISHNAN 72 B 2 44.5 50 30 15 12.7 9.6 30 27 10.5 14.5 180 2 2 2 22.87 25.78 2 2 II I
65 SADAYAN 55 B 2 43.0 45 20 22 11.2 8.6 32 27 12 11.7 240 2 1 2 23.98 25.78 2 2 III I
66 CHAKRAVARTHI 63 B 1 33.6 40 20 13 12.3 9.4 31 27 11 14.2 280 2 2 2 23.45 24.78 2 1 III I
S.NO
NAME AGE
GR
OU
P
DR
E G
RA
DE
USG
PR
OST
ATE
WEI
GH
T
pre
op
OPE
RA
TIN
G T
IME
(MIN
)
RES
ECTE
D T
ISSU
E W
EIG
HT
(G
MS)
USG
PR
OST
ATE
WT
POST
OP
PREO
P H
B
POST
OP
HB
PREO
P-PC
V
POST
OP-
PCV
PREO
P-Q
MA
X
POST
OP
QM
AX
INTR
AO
P C
ALC
ULA
TED
B
LOO
D L
OSS
CLO
T R
ETEN
TIO
N (
YES
=1,
NO
=2)
BLO
OD
TR
AN
SFU
SIO
N
(Y
ES=1
, NO
=2)
EXPL
OR
ATI
ON
/
RET
UR
NIN
G T
O O
T (
YES
=1,
NO
=2)
MV
D (S
UB
UR
ETH
RA
L)
MV
D (I
NTR
A P
RO
STA
TIC
)
FAIL
UR
E TO
VO
ID (Y
ES=1
, N
O=2
)
UTI
(CU
LTU
RE
POSI
TIV
E -1
,
NEG
ATI
VE
- 2)
PR
EOP
- IPS
S SC
OR
E (G
RA
DE
I (0
-7),
II
- (8
-19)
, III
-
(20-
35)
POST
OP
- IPS
S SC
OR
E (G
RA
DE
I (0
-7),
II -
(8-1
9), I
II -
(20-
35)
67 KUMAR 55 B 2 60.0 65 25 18 12.5 9.6 31 29 11 13.6 180 2 2 2 21.54 28.41 1 2 II I
68 PACHAIAPPAN 67 B 2 60.0 65 30 20 12.4 9.6 31 28 11 14.5 270 2 2 2 20.76 26.78 2 2 III I
69 VELAVAN 70 B 2 49.4 60 20 20 11.8 8.5 31 28 12 14 289 2 2 2 24.56 27.89 2 2 III I
70 KANNAIYAN 58 B 2 55.0 60 26 30 12.3 8 31 27 10.5 13 223 1 1 1 21.63 22.78 2 2 III I
71 HARIKRISHNAN 65 B 3 70.0 70 50 18 11 8.7 33 28 11.7 13.8 157 2 2 2 20.67 23.56 2 2 II II
72 DASTHAGIRI 66 B 2 48.1 50 24 30 12.2 9.5 31 27 11.5 14.3 220 2 2 2 19.56 25.89 2 2 III I
73 MURUGESAN 53 B 1 35.3 46 20 20 11.9 9.6 31 27 10.5 16 210 2 2 2 26.87 22.56 2 2 II I
74 SWAPANMANDAL 53 B 1 38.5 48 18 17 11.8 8.4 31 28 11 11.6 225 2 2 2 22.56 24.98 2 1 II I
75 AROKIYAM 64 B 1 40 50 20 25 11.2 9.4 33 26 12 14.5 240 2 2 2 21.87 25.44 1 2 III II
76 BASKARAN 64 B 2 49 55 20 25 11.3 9.6 33 28 10.5 10.3 221 1 2 2 24.76 28.56 2 2 III I
77 SELVARAJ 67 B 2 32.5 45 18 20 11.6 9 31 27 11.2 12.2 133 2 2 2 17.76 22.56 2 2 II I
78 ALAPPAN 73 B 2 39.9 50 25 20 12.6 8.4 31 27 11 14 289 2 2 2 20.43 27.98 2 2 II I
79 EZHUMALAI 63 B 2 40.55 55 20 35 12.5 8.6 33 28 12 11.5 298 2 2 2 19.76 21.54 2 2 III I
80 SELVARAJ 62 B 2 46.4 50 25 19 12.7 8.2 31 29 10.5 12.5 100 2 2 2 22.01 23.75 2 2 II I
81 SUBRAMANI 82 B 2 30.8 40 17 20 12.5 9.6 33 28 11.7 15 312 2 2 2 18.9 24.56 2 2 II I
82 VASU 78 B 2 44.7 45 23 17 12.2 9.7 31 29 11 9.7 134 2 2 2 22.45 26.76 2 2 III I
83 RANGANATHAN 62 B 2 45.9 58 25 20 12.5 9.6 33 28 9 14.5 267 2 2 2 19.56 19.56 2 2 III II
84 DURAISAMY 80 B 2 45.9 52 20 14 10.1 9.5 30 28 8.7 10.4 189 2 2 2 26.87 26.87 2 1 II I
85 SAMINAHAN 55 B 2 42.1 45 22 16 11.5 8 33 27 7.5 12.5 168 1 1 1 22.56 22.56 2 2 II I
86 BALASUBRAMANIYAN 60 B 2 43.2 53 15 15 12.4 9.8 31 29 8.5 9.4 110 1 2 2 21.87 24.22 1 2 III I
87 baskaran 64 B 2 32.67 40 16 17 11.9 10.2 33 30 9 12.2 130 2 2 2 21.54 25.78 2 2 III I
88 ARUNACHALAM 62 B 2 50.6 65 26 20 12.5 9 30 28 8 15.3 345 1 2 2 20.76 22.76 2 2 II I
89 SUNDARAM 72 B 2 43.5 45 20 25 12.6 9.4 30 27 8.9 15 130 2 2 2 24.56 25.76 2 2 III I
90 BAKTHAN 61 B 2 46.7 55 20 18 12.6 9 30 27 8.3 13.6 234 2 2 2 21.87 23.98 2 2 III I
91 NATESAN 78 B 2 48.8 60 20 18 12.0 9.8 34 28 9.4 11.5 125 2 2 2 24.76 24.87 2 2 III I
92 VELMURUGAN 55 B 2 33.6 42 15 16 12.4 8.2 31 27 10.7 11.2 213 1 1 2 17.76 22.56 2 2 III I
93 ARUMUGAM 75 B 2 48.9 50 20 19 12 8.6 33 27 8.5 10.8 190 1 2 2 20.43 25.78 2 2 II I
94 VARADHAN 60 B 2 30.0 40 15 15 12.6 9.8 31 29 10.1 14 178 2 2 2 19.76 21.12 2 2 III I
95 SUBRAMANI 65 B 2 36.7 48 18 20 12.5 8.6 31 29 11 15 234 2 2 2 23.45 24.1 2 2 III II
96 JAYAPAUL 50 B 2 46.5 49 23 20 12.5 9.4 34 27 11.7 11.4 317 2 2 2 21.54 24.4 2 1 III I
97 GANESH 48 B 2 33.0 40 18 20 12.4 9.6 31 28 11 14.5 145 2 2 2 20.43 22.23 1 2 II I
98 SADAYAPPAN 46 B 1 40.0 50 22 25 11.2 8.6 32 27 10.5 12.4 156 2 2 2 20.76 24.67 2 2 III I
99 PONMUTHAN 66 B 2 58.0 65 20 24 12.5 9.8 32 29 11 12.1 190 2 2 2 20.78 25.56 2 2 III I
100 PERUMAL 61 B 3 60.0 70 30 20 12.6 9.6 31 28 12 13.4 220 2 2 2 21.67 24.01 2 2 III I