THE PREVALENCE OF UROLOGICAL CANCERS

AMONG PATIENTS WITH GROSS HAEMATURIA AT

THE LAGOS UNIVERSITY TEACHING HOSPITAL (LUTH)

SUBMITTED BY

DR. MOSES ADEBISI OGUNJIMI

TO THE

NATIONAL POSTGRADUATE MEDICAL COLLEGE OF NIGERIA

IN PART FULFILLMENT OF THE REQUIREMENTS FOR THE

AWARD OF THE FINAL FELLOWSHIP OF THE MEDICAL

COLLEGE IN SURGERY (FMCS)

AUGUST 2007

ii

DECLARATION

I, Dr M.A. Ogunjimi, declare that this work was carried out by me under the

stated supervisors and that it has neither been submitted in part or in full for

any other examination or for publication.

……………………………….

Dr M.A. Ogunjimi

iii

DEDICATION

To my late father and friend, Timothy Aderoju Ogunjimi, who through affirmation

and encouragement with much affection first stimulated my interest in the study of

medicine and surgery.

iv

ATTESTATION

We attest to the fact that the work titled: ‘The Prevalence of Urological Cancers

among Patients with Gross Haematuria at the Lagos University Teaching

Hospital (LUTH)’ was done by DR M.A. Ogunjimi and that this dissertation was

written by him under our close supervision.

Supervisors:

………………………………………….

1. Professor D. N. Osegbe M.B., FRCSE, FMCS (Nig), FWACS.

Consultant Urologist,

Formerly Professor & Head,

Department of Surgery, CMUL/

Lagos University Teaching Hospital.

…………………………………..

2. DR. F. O. Adetayo M.B.BS., FMCS (Nig), FWACS.

Senior Lecturer/Consultant Urologist,

Department of Surgery, CMUL/

Lagos University Teaching Hospital.

v

ACKNOWLEDGMENT

I am sincerely grateful to all those who contributed to the completion of this

work.

I am profoundly grateful to my teachers Professor D.N. Osegbe and Mr

F.O. Adetayo for their kind guidance and supervision

I also thank Mr K.H. Tijani for the immense help he rendered throughout the

course of this work and my training.

I am humbled and motivated by the positive attitude shown towards me by

Dr E.A. Jeje over the years since I passed my primary fellowship

examinations and especially for allowing me use his endoscopic facilities

for this work.

Dr M.O. Afolayan graciously consented to peruse this dissertation and

made useful suggestions; I thank him for this and for all his help during my

training.

I thank all the resident doctors and housemen who worked with me for their

cooperation and assistance during this work. I am grateful to Dr Chidi Ogo

for his invaluable companionship, encouragement and useful contribution to

this project

The supports and encouragements of my siblings and mother and the

sweet memories of my late father have been a continual source of

inspiration.

My daughter, Anuoluwapo many times kept me awake while ‘sleep-working’

on this dissertation; I thank her and I’m most thankful to God for the joy and

enthusiasm this gift of His has brought to me in the course of this work.

vi

Finally and most specially, I acknowledge the endurance and

understanding of my wife, Dr Mrs O.H. Ogunjimi, during the long and lonely

days of this work when I was seemingly completely married to it; all my

love.

The almighty God has kept me in good health and given me special grace

and favour through all the years of my studies, to Him be the glory.

vii

Approval of Research and Ethics Committee

viii

TABLE OF CONTENTS

Declaration………………………………………………………… ii

Dedication………………………………………………………….iii

Attestation………………………………………………………….iv

Acknowledgment……………………………………………………v

Approval of Research and Ethics Committee………………………vii

Table of Contents…………………………………………………..viii

List of Tables and Figures……………………………………….. …x

Summary…………………………………………………………….xi

Chapter One

Introduction…………………………………………………………..1

Chapter Two

Literature Review…………………………………………………….3

Chapter Three

Aim and Objectives………………………………………………….28

Chapter Four

Methodology…………………………………………………………29

Scope and Limitations………………………………………………..33

Chapter Five

Results………………………………………………………………..34

Chapter Six

Discussion……………………………………………………………54

ix

Chapter Seven

Conclusion…………………………………………………….60

Recommendations…………………………………………………...61

References…………………………………………………………...62

Appendix: Proforma………..………………………………………..69

x

LIST OF TABLES AND FIGURES

Table 1: Duration of gross haematuria in all patients studied……………………. 37

Table 2: Haemoglobin concentration of patients with haematuria……………….. 40

Table 3: Bacterial isolates from urine of patients with gross haematuria…….….. 40

Table 4: IVU features in various disease conditions..………………………….… 43

Table 5: Urethrocystoscopic findings in various pathological conditions……….. 43

Table 6: Causes of Haematuria in the study population………………………..… 47

Table 7: Age and gender profile of patients with Urological malignancies ……... 50

Table 8: Benign and malignant diseases in patients below and above 50 years

…………………………………………………………………………………......51

Table 9: Benign and malignant lesions in female and male patients with

haematuria………….…………………………………………………………….. 52

Table 10: Characteristics of haematuria in patients with benign and malignant

lesions…………………………………………………………………………….. 53

Figure 1: Age distribution of patients…………………………………………..….37

Figure 2: Pictorial representation of the common aetiologies of haematuria ……..48

Figure 3: Organ involvement in the aetiology of haematuria.........................……..50

Figure 4: Patients with Benign and malignant diseases below and above 50 years

…………………………………………………………………………………..…51

Figure 5: Distribution of various malignancies in different age groups…………...52

xi

SUMMARY

Seventy nine consecutive adult patients who presented at the Lagos University

Teaching Hospital between February 2006 and January 2007 with gross haematuria

were prospectively studied to determine the common causes of the haematuria and

the prevalence of urological cancers among them.

Sixty of the patients (75.9%) were males while 19 (24.1%) were females with a

male to female ratio of 3.2: 1. The age range of these patients was 17 to 90 years,

their mean age was 54.4 years and the peak age incidence was in the seventh

decade of life.

The leading causes of macroscopic haematuria in these patients were benign

prostatic hyperplasia (30.4%), bladder carcinoma (12.7 %) and carcinoma of the

prostate (10.1%). The prevalence of urological malignancies (29.1%) was high

among the patients with macroscopic haematuria. The incidence of malignancies

was strongly related to age and sex of the patients with higher prevalence in males

and patients older than 50 years.

Therefore, the investigation of macroscopic haematuria especially in older patients

must be given a top priority. Improved patient education, prompt referral by general

practitioners and increase in the capacity of urological/haematuria clinics will

improve rapid diagnosis and treatment outcomes

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Chapter One

INTRODUCTION

Haematuria is defined as the presence of blood in the urine. It may present itself in

a macroscopic (gross) or microscopic form. In either case, it is an indicator of

disease(s) in the urinary tract. Haematuria is a common symptom and sign that may

be encountered in almost all medical specialties. The passage of blood-stained urine

may be the first sign of a serious disease in the urinary tract, and a single episode of

gross haematuria warrants a thorough urologic investigation. The possibility that

haematuria may signal an underlying malignancy means that it must not be ignored.

Gross haematuria is usually alarming to the patients and they are usually frightened

by the sudden appearance of blood in the urine and frequently present early to their

family physician or to the emergency room for evaluation and care. Recent

studies1,2 are showing a change from infections and infestation to malignancies as

the most important causes of haematuria in our environment. Unfortunately, many

general practitioners in this environment still do not exhibit the proper

understanding of the significance of haematuria. They often do not promptly refer

these patients for proper investigation and treatment preferring to treat them

empirically with anti- schistosomal drugs1.

In the developed countries, clinicians consider gross haematuria a key symptom

suggesting the presence of a tumour of the urinary tract until proved otherwise3.

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Macroscopic haematuria, especially in older patients, is often associated with a

malignancy and its investigation should be given a top priority4.

In our environment, the diagnosis of most patients with urological tumours

presenting with haematuria is often made in the advanced or late stages of the

diseases when only palliative treatments are possible1,4. Early presentation and

prompt referral for diagnosis and treatment will likely improve prognosis in these

patients.

Osegbe and Amaku1 earlier reported a prevalence rate of 17.4% for urological

malignancy among their patients with gross haematuria in Lagos. In a more recent

study from Zaria, Dawam et al4 documented a much higher prevalence of 31%. In

the western world, figures of 24% and 25% were reported by Boman et al4 and

Alishahi et al5 respectively for the prevalence of urological malignancies in

Caucasian patients with macroscopic haematuria.

Is the incidence of Urological Cancers among Patients with gross haematuria truly

rising or is the increase due to improved diagnostic modalities? It seems highly

appropriate for a prospective study examining the current prevalence rate of

urological cancers among patients with gross haematuria in this locality to be

carried out. This will create further awareness and alert general medical

practitioners in our environment on the significance of haematuria as a symptom

requiring prompt and thorough investigation before treatment.

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Chapter Two

LITERATURE REVIEW

Definition and Classification

Haematuria, which was known at the time of Hippocrates, is defined as the

presence of an anomalous number of red blood cells in the urine. It has been

recognized as an important symptom and sign of pathology of the urinary tract

since the earlier centuries and ancient times6,7. Hippocrates7 stated, “If a patient

passes blood, pus, and scales, in the urine, and if it has a heavy smell, ulceration of

the bladder is indicated.”

It is helpful clinically to classify haematuria. Quantitatively, it is called microscopic

haematuria if demonstrable only under the microscope; and gross haematuria if it is

evident to the naked eye. The presence of blood in the urine may be obvious to the

unaided eyes as ‘red, dark brown or dark urine’ (macroscopic haematuria) when it

is present in significant quantity. Gross haematuria results when about 0.5ml of

blood mixes with 500mls of urine6 However, some other substances including

colourants, beetroot, haemoglobin, porphyrin and some drugs can also colour urine

red and this could be confused with haematuria8. Bright-red blood in the urine

causes instant alarm for the patient and usually generates an emergency

presentation or appointment.

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Gross haematuria has been classified by some authors1,9,11 based on the degree of its

severity into mild (minor), moderate and severe. Hughes et al9, considered massive

haematuria as “a condition of blood loss in the urine at such a rate and to such an

extent that exsanguinations and death are possible”. This usually presents as a

serious emergency requiring urgent resuscitation including blood transfusion.

Moderate haematuria refers to considerable blood loss in the urine resulting in

reduction of the haemoglobin concentration of the patient but usually does not

require blood transfusion. Mild haematuria can be defined as minimal blood loss in

the urine without any systemic change in the patient. Puchner and Miller11

attempted to quantify haematuria by devising a grading system, which took into

account the frequency and severity of haematuria. They considered minor episode

as one that resolved within 24 hours, a moderate episode lasted for more than 24

hours but ceased without hospital admission, and a severe episode resulted in clot

retention and hospital admission

Microscopic haematuria is diagnosed from urinalysis using urine dipstick or from

urine microscopy. Although the significance of evaluating of macroscopic

haematuria is well established, some have questioned the potential benefits of

evaluating asymptomatic microscopic haematuria10. Microscopic haematuria is

more commonly nephrologic in origin, whereas gross haematuria is more

commonly of urologic origin. The presence of cell casts and protein with

microscopic haematuria strongly suggests intrinsic renal disease. Normocytic red

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cells suggest a post-glomerular origin and it is among these sets of patients with

microscopic haematuria that the possibility of an underlying malignancy exists12.

Several studies13,14,15,16 have tried to define a safe or significant level for

microscopic haematuria without a common conclusion as the number of red blood

cells (RBCs) per high power field which is deemed significant has been

controversial. Various levels have been suggested, such as ten13, five14 and (most

widely accepted) three15 RBCs per high power field. Other studies16, 17 have

however demonstrated that there is no level at which one can be completely certain

of not missing urological malignancy or other significant pathological condition

without further investigation of microscopic haematuria.

The likelihood of discovering significant pathology increases with the degree of

haematuria. Thus, it is uncommon for patients with gross haematuria not to have

identifiable underlying pathology, whereas it is quite common for patients with

minimal degrees of microscopic haematuria to have a negative urologic evaluation.

Haematuria can also be classified by the time of its appearance during voiding into

initial, terminal or total haematuria18,19. This classification frequently helps in

identifying the site of bleeding and is also useful in guiding the choice of

investigations especially where there are limited resources. Initial haematuria,

where blood appears only at the beginning of micturition suggests an anterior

urethral lesion. In terminal haematuria, the blood is more conspicuous at the end of

micturition and it usually arises from the posterior urethra or bladder neck. Total

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haematuria is characterised by the presence of blood in the urine throughout

micturition. It usually arises from the bladder or the upper urinary tracts.

Further clinically relevant distinctions can be made between painful and painless

haematuria. Gross painless haematuria is often the first manifestation of a urinary

tract tumour and must be regarded as a symptom of urological malignancy until

proved otherwise even in bilharzial endemic areas1,18. Painful haematuria may be

due to urinary tract infection, injury or calculi.

Epidemiology

Gross haematuria is quite common and has been reported worldwide and in all age

groups; but its incidence varies from place to place2,17,20. It is estimated to account

for 4% to 20% of all urological visits in Caucasian populations17. In the United

States, Carter and Rous20 reviewed 1050 consecutive urologic admissions and

reported an incidence of gross haematuria of 10.5% in 110 patients (56 males and

44 females). Dawam et al2 in Zaria, Nigeria in their study found out that

482(17.7%) of a total of 2726 urological patients seen over a period of 7 years had

haematuria with a male to female ratio of 4.1:1.

The reported incidence of urological malignancies in patients with gross haematuria

also varies from one centre/ region to the other1,2, 3, ,5,20, 21, 22. In Nigeria, Mbonu et

al21 (Enugu) reported urinary tract malignancies in 14% of their haematuric

patients. Osegbe and Amaku1 in Lagos earlier documented prevalence rate of

17.4% for malignancies in their series. Most recently, Dawam et al2 (Zaria) got a

- 7 -

much higher prevalence rate of 31%. Yeboah et al22 in Ghana studied 202 patients

with haematuria and observed that 27.2% of them had tumours of the genitourinary

tract. In the series by Carter and Rous20 in the United States, malignancies

accounted for the haematuria in 22.7% of their patients. The highest prevalence rate

of 37% for urological malignancies in patients with haematuria was reported by

Gillatt and O’Reilly23 in the United Kingdom.

Aetiology

The causes of gross haematuria vary with the age, geographical location and sex of

the patients. The common urologic causes of haematuria are infections, neoplasms,

urinary stones, BPH and trauma to the urinary tract1,2,3,4,5. Less common causes

include sickle cell disease or trait, tuberculosis, renal infarction, renal vein

thrombosis, coagulation and platelet deficiencies, exercise-related causes (e.g.,

jogging), hypercalciuria, and vasculitis18,19. Studies in West Africa have shown age

specificity in the aetiology of haematuria with mean age incidence as follows:

vesical schistosomiasis- 25 years, Trauma -30 years, UTI- 35 years, calculi- 45

years, Bladder cancer- 50 years, BPH- 65 years and prostate cancer 69 years24.

Most causes of haematuria in children represent medical conditions that often

require referral to paediatric nephrologists. Indications for referral to a urologist are

more limited and include stones that do not pass spontaneously or are more than 5

mm in diameter, renal injury from trauma and anatomic abnormalities25. The most

common cause of gross haematuria in the paediatric age group is urinary tract

- 8 -

infection. Congenital lesions, bleeding disorders and haemoglobinopathies are other

important causes in children while urologic malignancies are uncommon with

haematuria in this age group25,28.

Macroscopic haematuria is caused by genitourinary cancers in 17 to 27% of cases10.

In a review of 1,000 patients with gross haematuria, Mariani et al17 found tumours

in 21.5% of the patients; two-thirds of these were bladder tumours. Carter and

Rous20 reported that 41.8% of their 110 patients with gross haematuria had benign

and malignant neoplasms with malignancies accounting for more than half of these.

The gross haematuria in all patients aged 40 years and above in the study was due

to urological malignancies. A similar result was earlier obtained in another study by

Lee and Davies30 where 22% of their patients with haematuria had malignancies.

Studies from the West African sub-region1,2,21,22 have shown varying prevalence

rates for urological malignancies in patients with macroscopic haematuria from

centre to centre as previously discussed under epidemiology.

The malignant lesions causing haematuria are found throughout the whole urinary

tract1,20,21,22. Of the 22.7% of patients whose haematuria was due to malignancies in

the Carter and Rous20 series, bladder tumours accounted for 9%, renal tumours 6%,

prostatic carcinoma 6% and urethral tumours 1%. Chahal et al31 discovered fifty-

five tumours (19.2%) in their study of 285 patients with haematuria; of these

48(16.8%) were transitional cell carcinomas of the bladder, 3 renal cell carcinomas

and 3 carcinomas of the prostate. In the study by Khadra et al15 with a total of 1,930

patients, 12% had bladder cancer, kidney and upper tract tumours were noted in 14

- 9 -

patients (0.7%), including 4 who presented with microscopic haematuria and

prostate Ca in 8(0.4%) patients. Transitional cell carcinoma of the bladder was also

the most common malignancy diagnosed (8%) by Tan et al31 in their study. Osegbe

and Amaku1 found Carcinoma of the bladder in 6.8% of their haematuric patients.

Renal tumours accounted for 1.6% and 3% of the haematuria in the series by

Yeboah et al22 and Mbonu et al21 respectively.

Recurrent gross haematuria is a bothersome symptom often associated with benign

prostatic hyperplasia (BPH) in men older than 60 years of age. Haematuria

associated with BPH is related to increased vascularity in the prostate. Marshall and

Narayan32 postulated that angiogenesis is significant in BPH and that androgen

deprivation causes suppression of angiogenesis. Foley et al33, reported that the

microvessel density is higher in those patients predisposed to haematuria compared

with controls. Mebust et al29 reviewed the records of more than 3,000 men who

underwent transurethral prostatic resection and observed that haematuria was an

indication for surgery in 12%. In the study by Mbonu et al21, BPH was the

commonest cause of haematuria accounting for 27% of the cases. BPH was the

second commonest cause of haematuria in the series by Dawanm2 et al and was

found in 64 patients (15%). It accounted for the haematuria in 7.9% and 8% of the

patients in the series by Osegbe and Amaku1 and Carter and Rous20 respectively.

Carcinoma of the prostate rarely manifests in this manner as haematuria occurs in

fewer of these patients than in those with BPH.

- 10 -

Urinary tract infection (UTI) is also a very common cause of gross haematuria

especially in the young females1,20,23,24. It was the commonest cause of haematuria

in the studies by Osegbe and Amaku1 (accounting for 22.6% of cases) and Khadra

et al15 (13%). Eleven percent of patients with gross haematuria had UTI in the study

by Gillatt and O’Reilly23. Other studies from this sub-region also produced

comparable incidence of UTI in patients with gross haematuria. Yeboah et al22 in

Ghana reported UTI in 11% of their patients while Mbonu et al21 in Enugu, Nigeria

found UTI as the aetiological factor in 16% of 100 patients with haematuria.

Escherichia coli, accounted for most cases of the UTI in these studies1,15,23. Other

members of the Enterobacteriaceae family, including species of Klebsiella, Proteus,

Enterobacter, Pseudomonas, Serratia, and Citrobacter, were also cultured from the

urine. Of the gram-positive organisms, streptococcus faecalis and, less commonly,

Staphylococcus aureus and streptococcus pyogenes are important causes of UTI

giving rise to gross haematuria.

UTI may occur in isolation or may co exist with other pathologies such as tumours

or urinary calculi which can cause gross haematuria on their own1,34. Therefore,

patients with gross haematuria and a positive urine culture should still have a full

urological evaluation to exclude other possible aetiological factors.

Even though vesical schistosomiasis is no longer the commonest cause of

haematuria in the tropics as previously reported, it is still a significant cause of

haematuria in this subregion1. It accounted for the haematuria in 14.2% of patients

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in the study by Osegbe and Amaku1. Dawam et al2 reported schistosomiasis in

64(12%) of their patients. Yeboah et al22 obtained a similar result in Ghana with

16.2% of their patients diagnosed with schistosomiasis. Mbonu et al21 found

schistosomiasis in only 2% of their patients.

Gross haematuria is also a common feature in urolithiasis1,2,20,22. In some instances,

gross haematuria may be the only presenting complaint in patients with urinary

stones or more commonly may present along with colics or dysuria. Urine

examination in most patients with urolithiasis reveals the presence of microscopic

or gross haematuria. Press and Smith35 however, reported that 15% of their series of

140 patients with urinary calculi had no haematuria. Urinary stones may cause

haematuria by either infection or direct irritation of the mucosa.

Carter and Rous20 in the USA reported that urinary stones were responsible for the

haematuria in 13.6% of their patients. Studies from the developing countries1,22

showed that urolithiasis is less common as an aetiological agent for gross

haematuria when compared to the western world. This may be explained by the

differences in our diets and environmental temperatures.

Haemoglobinopathies have been identified as important causes of haematuria

among the black race24,29,36. Haematuria has been observed to be commoner in

individuals with the sickle cell trait (genotype AS) than in those with sickle cell

anaemia36,37. It usually results from papillary necrosis following vascular occlusion

when there is hypoxia, increased osmolality or low PH within the renal papilla. The

- 12 -

presence of the abnormal haemoglobin genotypes should however, not preclude the

exhaustive search for other causes of haematuria36. The diagnosis of the cause of

haematuria in individuals with genotype AS should not be reached by exclusion but

by the demonstration of papillary necrosis1.

In the study by Osegbe and Amaku1, four patients (2%) had papillary necrosis due

to haemoglobinopathy responsible for their haematuria. The patients had genotypes

SS, SC and CC. In all their patients with genotype AS (37%) except one, they

found definite causes for the haematuria. Yeboah et al22 also found haematuria due

to haemoglobinopathy in 2% of their patients.

Trauma is also an important cause of gross haematuria especially in the active age

groups23,38,39,73. Blood in the urine is common following blunt abdominal trauma38.

In a series39, more than 95% of the patients had microscopic or gross haematuria

and it was most often the first indicator of renal injury. However, it is a nonspecific

finding and does not correlate with the severity of the renal damage. Haematuria is

also a hallmark finding with bladder injuries40. Carroll and McAninch40 observed

gross haematuria in more than 95% of their patients with bladder injuries and

microscopic haematuria in the remaining patients. Urogenital trauma was the cause

of gross haematuria in 21% of patients in Enugu21, 13.7% in Lagos1 and 8% in

Ghana22. However, Carter and Rous20 in the USA found trauma as the cause of the

haematuria in only 1.8% of their patients, probably because safety awareness and

campaign are more common in the western world.

- 13 -

Other known but less common causes of gross haematuria include tuberculosis24,

exercise-induced haematuria42, arteriovenous malformations43, blood dyscrasias24,

renal cysts and hydroneprosis23, radiation cystitis20, urethritis22 and drugs15,41.

However, patients on anticoagulants in the normal therapeutic range and who have

haematuria must be fully investigated to exclude other possible causes41.

Unexplained Haematuria

The failed diagnosis rate of the cause of haematuria of 5-10% is frequently

quoted20,30,44. Some series1 have lower rates while others15 have reported much

higher figures. The discrepancies may be a reflection of the degree of

exhaustiveness of their investigations. Some cases of haematuria previously

considered to be of unknown origins or idiopathic are now being diagnosed with

adequate investigations45,46. In a five year follow up study of patients with

unexplained haematuria, Rasmussen et al47 found urological tumours in 18% of

those with recurrent haematuria and in 3% of patients without any further episode

of haematuria after the initial evaluation. O’Reilly45 also followed up some patients

with undiagnosed haematuria and subsequently found some causes including renal

tumours for the haematuria in some of the patients. It has been suggested that

patients who remain undiagnosed after a complete evaluation should be followed

with periodic urinalysis and cytology to allow early detection of malignancy48.

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Clinical Features

History and physical examination provide important information in the evaluation

of patients with haematuria. Although it is tempting to become dependent on

laboratory and radiological investigations, history and physical examination remain

key components of the diagnostic evaluation for haematuria. They will frequently

elucidate the probable diagnosis and simplify the process thus allowing the

urologist to select the most appropriate diagnostic studies48.

The age, sex, occupation, geographical location and the race of the patient among

other demographic data are associated with the aetiology of haematuria19,48.

Infection and other benign causes account for most cases in children and young

adults while urological tumours are common in the older age groups25,26,29.

Haematuria resulting from sickle cell disease is found mainly in the negroid race36.

Schistosomiasis is endemic in some areas in the tropics and may account for the

haematuria in patients from such areas24. These should therefore be asked for while

taking clinical history from these patients.

It is important to inquire about the onset, duration, timing and severity of

haematuria and its association with other urinary symptoms. A short history

suggests acute infections or neoplasm while a long history is indicative of chronic

diseases like tuberculosis, schistosomiasis, polycystic kidneys or calculi. The

timing of haematuria during micturition frequently indicates the site of origin. Total

haematuria suggests that the bleeding is most likely coming from the bladder or the

- 15 -

upper urinary tracts. Terminal haematuria occurs with lesions in the bladder neck or

prostatic urethra. Initial haematuria usually arises from the anterior urethra24.

Haematuria, although frightening, is often not painful unless it is associated with

inflammation, obstruction or injury to the urinary tract. Gross painless haematuria

may be the first manifestation of a urinary tract neoplasm. Pain in association

with haematuria often results from obstruction of the upper tracts by calculi, clots

or tumours. Passage of calculi or clots along the renal pelvis and ureters is often

associated with severe colicky flank or loin pain, and this helps to identify the

source of the haematuria.

Associated irritative symptoms like dysuria, urgency, frequency, and nocturia

suggest an inflammatory process. Ulcerated bladder tumours complicated by

infection and bleeding may also present with symptoms of cystitis. Straining,

hesitancy, intermittency, feeling of incomplete bladder emptying, and dribbling

urination suggest an obstructive process like prostatic enlargement. Bladder

calculus causes haematuria but infection is often present and there may be

symptoms of bladder outlet obstruction. Flank pain may also indicate pelvi-ureteric

junction obstruction, pyelonephritis or symptomatic vesicoureteral reflux. A history

of recent athletic endeavours may suggest exercise-induced haematuria.

Constitutional symptoms, such as progressive weight loss, anorexia, chronic cough

and bone pains will indicate a metastatic malignant lesion18,19.

- 16 -

History of trauma in a patient with gross haematuria will suggest genito-urinary

injury as its cause. However, haematuria following trauma, especially minor ones

may also indicate the presence of pre existing diseases of the urinary tract like

hydronephrosis or polycystic kidneys.

The family history is significant for genetic conditions like the

haemoglobinopathies and other blood dyscrasias as well as for diseases with known

familial associations like stone disease, prostate cancer. A family history of renal

disease, renal cysts, nephrolithiasis, and sickle cell disease may suggest the cause in

a child.

Physical examination should be systematic and thorough. It must include a general

examination for anaemia, jaundice, cachexia, lymphadenopathy and secondary

deposits. The cardiovascular system should also be assessed.

Abdominal examination may reveal hepatomegaly due to metastases in cases due to

malignancy. The kidneys may be palpably enlarged in patients with renal tumours,

hydronephrosis, cyst or polycystic disease of the kidneys. The suprapubic region

may reveal urinary retention, bladder or pelvic tumours. Digital rectal examination

should be done to evaluate for prostatic carcinoma, benign prostatic hyperplasia and

prostatitis. The bladder base and the adnexae in the female can also be examined

rectally.

The external genitalia should be examined for blood, urethral discharge and for

induration along the urethra from strictures

- 17 -

Investigations

The aims of investigations in the patient with haematuria include confirmation of

the haematuria, diagnosis of its cause and to prepare for any necessary surgical

intervention. The aetiology of haematuria may be suspected after the initial history

and physical examination, and should be confirmed with appropriate investigations.

Standard investigations such as urinalysis, urine microcopy and culture, intravenous

urography, and cystoscopy will reveal the source of haematuria in many cases

while further studies may be required in the remaining patients44,48,52.

Standard Investigations

1. Examination of urine

Red urine does not always denote haematuria. Some drugs and food additives also

colour the urine red. After clinical evaluation, the urine should be examined for red

and white blood cells using dipstick urinalysis and urine microscopy. The presence

of any crystals, casts, ova or parasites should also be noted and the culture of a mid-

stream specimen carried out. When schistosomiasis or tuberculosis is suspected, a

first void urine sample is usually requested. Haematuria associated with red blood

cell casts and heavy proteinuria is usually due to renal parenchymal lesions,

particularly of glomerular origin.

The value of urine cytology in evaluating patients with haematuria remains

controversial. Its inclusion in an investigative protocol is recommended routinely

- 18 -

by the American Urological Association best practice policy on asymptomatic

microscopic haematuria only in patients with risk factors for transitional cell

carcinoma (TCC) 49. Chanal et al50 investigated 258 patients with haematuria and

found that cytology did not diagnose any additional tumours and proffered that

urine cytology’s role is at best supportive in the investigation of patients with

haematuria and should not be done routinely. Hofland and Mariani51 in their study

found that urine cytology had a sensitivity of 55% and a specificity of 99.3% and

suggested that urine cytology can have an important role in the evaluation of

haematuria when risk factors for urological malignancies are used to select patients

for the test. It is recognized that cytology is useful in detecting high-grade TCC and

carcinoma in situ (CIS) with high sensitivity49. Furthermore, with positive cytology

in the presence of a low-grade superficial bladder tumour, concurrent higher grade

disease should be sought in the upper tracts. Urine cytology has a higher yield in

patients with high-grade bladder tumours. Negative urine cytology does not exclude

the presence of a tumour, while a positive urinary cytology in the presence of a

normal radiographic evaluation should alert the physician to the presence of a

tumour somewhere along the urinary tract which may be related to the upper tracts

or foci of CIS of the bladder 52.

2. Biochemistry/ haematological investigations

All patients should have haemoglobin estimation/ haematocrit and a full blood

count with an erythrocyte sedimentation rate done to identify any associated blood

- 19 -

dyscrasia, anaemia or leucocytosis. Serum urea, creatinine and electrolytes should

be measured to assess the patient’s renal function. Prostate specific antigen is

usually elevated in prostatic carcinoma.

3. Imaging Studies

Intravenous urography

The intravenous urogram (IVU) has long been considered important for the

evaluation of the urinary tract providing both anatomic and functional information.

It still remains one of the examinations of choice for visualising the upper urinary

tracts in patients with macroscopic haematuria by demarcating lesions in the renal

parenchyma, the pelvicalyceal system, ureters, and bladder that may cause

haematuria16,48. It is useful in the diagnosis of urinary calculi and tumours of the

urinary tract15. It is also valuable in evaluating haematuria arising from significant

genitourinary tract injury38. Speelman et al53 found out that the sensitivity and

specificity with regard to the diagnosis of upper urinary tract pathology in patients

with haematuria were 67% and 91% for IVU. Sharfi and Hassan44 found

intravenous urography useful in the detection of the cause of the haematuria in 56%

of their patients while Nwofor34 reported a much higher diagnostic rate of 75%

among 92 patients. Alishahi et al5 reported that IVU was more sensitive than an

ultrasound scan in detecting upper tract calculi and upper tract transitional cell

carcinoma in their patients with haematuria, whereas ultrasound scan was more

sensitive than IVU in detecting renal parenchymal lesions. A combination of IVU

- 20 -

and ultrasound scan has been reported to have much higher sensitivity for detecting

upper urinary tract malignancies in patients with haematuria53. However, Goessl et

al54 from their study of 314 newly diagnosed patients with bladder tumour

concluded that routine excretory urography at initial diagnosis of bladder cancer in

screening the upper urinary tract for concomitant tumours is unnecessary because

of a low 0.3% chance of discovering such tumour.

Although there is said to be a 0.03% risk of anaphylactic shock with the use of

contrast medium and a considerable radiation exposure, IVU is still regarded by

many authors as a standard investigation for patients with haematuria16,34,48.

Ultrasound scan

Ultrasonography is a non-invasive test that is readily available and affordable with

no radiation hazard and requires minimal preparation. It can be used in patients

with significant renal impairment or allergy. Ultrasound scan differentiates

accurately between cystic and solid lesions causing haematuria. IVU has been the

investigation of choice for the upper urinary tract, but ultrasonography is now being

used with increasing frequency16. However, ultrasound scanning may be limited by

its operator dependence. It has been suggested that ultrasound is as sensitive as IVU

and yet more cost effective for imaging of patients presenting with microscopic

haematuria55. Aslaken et al55 proposed that IVU could be safely omitted from the

investigation algorithm for microscopic haematuria since it would mean significant

savings and elimination of morbidity related to the contrast-induced renal failure

- 21 -

with only a small sacrifice in accuracy. Yip et al56 comparing the efficacy of

ultrasonography and urography in evaluating patients presenting with painless gross

haematuria for urinary malignancies reported that ultrasonography was significantly

more sensitive (83/85; 98%) in the detection of bladder tumours, compared to

urography (42/78; 54%); in the upper tract, they found no significant difference in

the sensitivity of lesion detection. Datta et al57 investigated 1007 patients with

haematuria using a protocol based on ultrasonography as the upper tract imaging

modality of choice and reported that an ultrasonography-based protocol missed

fewer upper tract transitional cell carcinomas than a standard IVU-based service

would miss renal cell cancer. They also found that the sensitivity of ultrasound with

respect to bladder cancer was 63% and the specificity 99%. It has been suggested

that a combination of plain abdominopelvic radiography and ultrasound of the

urinary tract could replace IVU in the diagnostic approach to haematuria55,57.

4. Urethrocystoscopy

Urethrocystoscopy allows the urologist to directly visualize lower urinary tract

anatomy and identify macroscopic lesions which may be responsible for

haematuria34. It also provides access to the upper urinary tract for diagnosis of the

source of bleeding in the upper tract. In addition, material for both cytologic and

histopathological examination can be obtained cystoscopically.

Most clinicians1,4,5,15,34,41,44,48, agree that that cystoscopy should be an essential part

in the aetiological evaluation of haematuria. They all believe it is the only accurate

- 22 -

way to exclude a bladder tumour. Cystourethroscopy can be performed with either

rigid or flexible endoscopes.With the advent of flexible cystoscopes, it has become

a simple clinic/outpatient procedure performed under local anaesthesia. Bladder

biopsies are easily performed via the flexible cystoscope58. Biopsies of abnormal

mucosa should also be taken. Random biopsies are needed if the cytological result

is positive even if the bladder mucosa looks normal. Flexible cystoscopy has also

reduced the need for inpatient beds for the follow-up of patients previously treated

for bladder cancer52. Beyond its diagnostic use, cystoscopy also has therapeutic

uses in patients with haematuria. Herr59 treated 185 patients with superficial bladder

tumour with fulguration using flexible cystoscope on out-patient basis and reported

good outcomes. Wedderburn et al60 also reported flexible cystodiathermy as well

tolerated and efficacious in the treatment of recurrent superficial bladder tumours

If flexible cystoscopy done under local anaesthesia reveals a bladder lesion, the

patient may require further examination under general anaesthesia with rigid

cystoscopy and transurethral biopsy for definitive diagnosis. If a resectable bladder

tumour is discovered then definitive treatment can be performed at the same time.

Sharfi and Hassan44 reported that cystoscopy was diagnostic in 29% of their

patients with haematuria while Nwofor34 got a higher diagnostic rate of 75%.

Khadra et al15 through cystoscopy discovered bladder cancer in 7 of their

haematuric patients younger than 40 years and suggested that cystoscopy cannot be

safely avoided even in younger patients with microscopic haematuria. Hattori et al61

reported bladder cancer to be the most common malignancy among the lesions

- 23 -

found in their evaluation of patients with microhaematuria and concluded that

cystoscopy should be an essential part in the aetiological evaluation of even

microscopic haematuria. Tan et al62 noted that a significant 22.2% of the bladder

cancers diagnosed in their series were found on cystoscopy and missed on the

cystogram phase of the intravenous urogram; noting that some urological lesions

would have been missed if cystoscopies were not performed. They emphasised the

importance of cystoscopy as one of the standard investigations for patients with

haematuria.

Other investigations

A thorough history, physical examination, and the use of standard tests including

urine microscopy and culture, intravenous urography, ultrasound scan and

cystoscopy will reveal the source of haematuria in many cases. The use of more

sophisticated and invasive diagnostic tests should be chosen on the basis of the

assembled clues. The physician must be careful in selecting further studies in the

remaining patients; since the procedures may be expensive and potentially harmful,

and the probability of finding a treatable condition may be low63.

Computerised tomography (CT) may be more effective in detecting smaller renal

tumours than IVU or ultrasound. Computerised tomography scan assesses the renal

cortex; retroperitoneum and pelvis more accurately than ultrasound scan and may

give a definitive diagnosis without the need for biopsy64. Contrast-enhanced

- 24 -

computed tomography (CT) provides better anatomic details which facilitates very

accurate grading of renal injuries than excretory urography65.

Magnetic Resonance Imaging (MRI) with gadolinium enhancement is very

similar to CT with iodinated contrast. However, since CT is less expensive and

readily available, it is still the preferred technique for evaluating parenchymal

abnormalities of the kidney. MRI is replaced by CT in patients with severe

iodinated contrast allergy or renal dysfunction. MRI can also be done in patients

whose lesions are still indeterminate after other imaging studies have been done.

MR urography provides a noninvasive method of investigating the ureters for

causes of haematuria. MRI has been found useful for staging bladder cancer

invasion of the bladder wall66,67.

Retrograde uretero-pyelography can be used to visualise the upper tract when

renal function is not adequate to allow administration of intravenous contrast. The

ureter and pelvicalyceal system can be outlined by the retrograde injection of

contrast media via a cystoscope. It is also often employed after an excretory

urogram that inadequately visualized the anatomy of the upper tract and it is

occasionally performed in patients in whom IV contrast material is

contraindicated66.

Ureterorenoscopy: When radiographic studies have failed to identify an obvious

cause for haematuria, an endourologic approach has become the final and definitive

step in the diagnostic regimen68. In suspected ureteric lesions presenting with

- 25 -

lateralizing haematuria, further information can be gained by either retrograde

pyelography or direct inspection via the ureteroscope. Flexible ureterorenoscopy69

allows the inspection of all the calyces of the kidney, the renal pelvis and the entire

length of the ureter to detect early transitional cell carcinomas or other lesions of

the upper tracts which may be missed on IVU.

Modern imaging modalities, largely have supplanted the need to obtain a

confirmatory tissue diagnosis in renal masses, however, when the urologist seeks a

more definitive diagnosis, an ultrasound scan or CT-guided aspiration or needle

biopsy of the lesion may be indicated70.

Angiography, which has been the gold standard for visualization of vascular

tissues, is being rapidly supplemented by computed tomographic angiography

(CTA), magnetic resonance angiography (MRA), and color Doppler ultrasound71.

Renal angiography or arteriography combined with renal phlebography is

indicated if the initial standard assessments are negative in the presence of recurrent

or massive haematuria. It is mainly aimed at detecting a vascular malformation6,43.

Also in patients with unexplained haematuria after undergoing the standard

investigations and seen to be bleeding from a ureter during cystoscopy,

arteriovenous malformation is a strong differential diagnosis. The other imaging

modalities will not reliably clinch the diagnosis while angiography may be useful

both in making the diagnosis and for therapeutic intervention72. Angiography is also

the gold standard for diagnosing vascular injuries in renal trauma though CT is the

best overall screening tool72,73.

- 26 -

Treatment

The treatment of patients with haematuria depends on its aetiology. The

management plan at the initial presentation should be aimed at resuscitating when

indicated, ensuring free drainage of urine with or without catheterization and

arranging for necessary investigations promptly.

The majority of patients presenting with mild to moderate macroscopic haematuria

can be managed on an outpatient basis, with short follow-up arranged for detailed

investigations and subsequent treatment. Such patients should be advised to take lot

of fluids to increase their urinary output and thus prevent clot formation and

retention.

However, patients with severe haematuria require hospitalization for resuscitation

and emergency treatments to achieve haemostasis. Intravenous fluids and blood are

administered for volume replacement. Urethral catheterization is done to evacuate

blood clots or to relieve retention and for continuous bladder irrigation with saline

or glycine to prevent further clot formation/retention.

Emergency measures to secure haemostasis would largely depend on the site of

haemorrhage. In patients with non-traumatic bladder lesions causing life-

threatening haematuria, cystoscopic cauterization59,60 of the source of bleeding or

bladder irrigation with alum or formalin solutions74,75may be considered. Cases of

severe exsanguinating haematuria that are refractory to conservative measures may

benefit from embolization or surgical ligation of the internal iliac arteries76.

- 27 -

Recurrent haematuria of prostatic origin is initially treated conservatively with

limitation of physical activity, tamponade with a urethral catheter, fulguration of

the bleeding points, or the use of anti-fibrinolytic agents such as tranexamic acid.

Recently finasteride has been suggested as an option for treating haematuria

associated with BPH with promising results in uncontrolled retrospective and

randomized prospective studies11,33. Severe haematuria of Prostatic origin not

responding to the conservative measures will require emergency prostatectomy by

open method or TURP29.

Most patients with mild haematuria resulting from renal injuries are managed

successfully by conservative means, which consist of bed rest; fluid therapy and

blood transfusion73 Massive haematuria can occur from a kidney tumour, renal

trauma, or vascular malformations. Severe haematuria of renal origin refractory to

conservative measures may require nephrectomy to achieve haemostasis73.

Nephron-sparing surgery or selective angio-embolization may be indicated in

patients with solitary kidney or non-functioning contralateral kidney77,78

- 28 -

Chapter Three

AIM AND OBJECTIVES

Aim

The main objective of the study is to assess the diagnostic value of macroscopic

haematuria in the diagnosis of urological cancer among patients with gross

haematuria at the urologic unit of the Lagos University Teaching Hospital, Idi-

araba Lagos.

Objectives

The specific objectives of this work include the:

To identify the causes of macroscopic (gross) haematuria in patients where it is

the main presenting symptom.

To determine the prevalence of urological cancers among patients with

macroscopic haematuria.

To asses the influence of age, sex, and the nature of gross haematuria on the

diagnosis of urological malignancies in these patients

- 29 -

Chapter Four

METHODOLOGY

Materials and Methods

Approval for the study was obtained from the Ethical Committee of the Lagos

University Teaching Hospital. The consent of the consultant Urologists was also

sought for the use of the patients registered under them and for their expert

supervision of the project.

The study was conducted prospectively over one year period (February 2006 to

January 2007). Consecutive patients aged sixteen years and above, presenting at the

surgical outpatient clinic and the accident and emergency room of the Lagos

University Teaching Hospital with gross haematuria during the period formed the

population for the study. Formal consent was also obtained from the patients.

All the patients were seen and assessed by me at presentation for detailed clinical

evaluation. Their subsequent investigations and the definitive management of their

conditions followed the unit’s protocol and were monitored and coordinated by me

under the direct supervision of the consultants.

Demographic data including age, sex, occupation, tribe and residential address were

obtained.

The investigation of the patients began with detailed history with emphasis on the

duration; number of episodes, timing and degree of haemturia was taken from each

patient. Other relevant urological symptoms including abdominal pains, irritative

- 30 -

and obstructive voiding symptoms and history of trauma were also sought for.

Patient’s past medical history with emphasis on previous haematuria, bleeding

tendencies and drug ingestion was documented. Enquiries were also made about

family history of haematuria or any bleeding disorder.

A thorough systematic physical examination with particular attention to

genitourinary system was carried out on each patient. A general assessment was

made to establish or exclude weight loss, pallor, jaundice and peripheral

lymphadenopathy. Particular attention was paid to the abdomen with further

emphasis on the lumbar and suprapubic regions. Digital rectal examination was

done on each patient to evaluate the status of the prostate gland and the bladder

base in males and the adnexae and the bladder base in the females. Their

haemodynamic status was assessed by evaluating the cardiovascular system

including measurement of their blood pressure. The genitalia were carefully

examined for evidence of trauma, urethral bleeding and other lesions. The other

systems were also assessed in all the patients.

Laboratory and imaging investigations were ordered for in stages as directed by the

patients’ clinical state at the initial presentation. During the first visit, urine samples

were taken for urinalysis, urine microscopy and culture and urine cytology. Blood

samples were also obtained from the patients for their haemoglobin/haematocrit

estimation, full blood count, erythrocyte sedimentation rate and the haemoglobin

genotype. Clotting profile was requested for in those whose history was suggestive

- 31 -

of a bleeding disorder. Serum prostate specific antigen was requested in males with

prostate enlargement.

Clinically stable patients were then scheduled to do ultrasound scan of the abdomen

and pelvis, intravenous urography and urethrocystoscopy on an out-patient basis

where there were no contraindication to any of these tests in them. Patients with

significant evidence of renal impairment from their serum electrolytes urea and

creatinine were exempted from doing IVU. Patients who sustained genitourinary

trauma were excluded from doing urethrocystoscopy at presentation. Four multiply

injured patients who required emergency surgical intervention for haemodynamic

instability could not do ultrasound scan.

Some patients had various surgical intervention including exploratory laparatomy

for renal and bladder injuries, bladder exploration for massive clot retention and

suprapubic cystostomy for urethral injuries and failure of urethral catheterization in

those with urinary retention. These surgical procedures were both diagnostic and

therapeutic for most of them. A significant limitation in the investigation of these

patients was with urethrocystoscopy which had to be done outside the study centre

because the hospital cystoscope set was faulty during the study period.

Urethrocystoscopy was done on the patients at two private hospitals with the

requisite facilities manned by consultant urologists with the author in attendance.

Other investigations that were relevant to individual patients such as biopsy for

tissue diagnosis, computerised tomography scan, and blood clotting profile were

also done when indicated. All these investigations were conducted in stages as

- 32 -

directed by the patients’ clinical state and provisional diagnosis from the standard

investigations in order to minimise costs to the patients.

The data obtained from each patient were entered into a proforma designed for the

study ( appendix 1 ) These were sorted out manually and analyzed using a computer

software; Statistical Package for Social Studies (SPSS Inc. Chicago Illinois). The

SPSS is a comprehensive integrated system for statistical data analysis. Pearson

chi-square test was used to determine the statistical significance at P< 0.05.

- 33 -

Scope and Limitations

Scope

The study was conducted prospectively over a year period. All patients presenting

with gross haematuria at the accident and emergency centre and the urology clinic

of the hospital constituted the population for the study.

The study population was limited to the patients in whom I personally participated

in their management during the period of the study.

Patients who had been previously investigated for haematuria, but with no on-going

haematuria at the time of the study were excluded from the study. Paediatric

patients younger than 16 years were also excluded from the study.

Limitations

1. Some patients were not able to afford the cost of some of the investigations

and these prevented the establishment of a definitive diagnosis in such

patients and were therefore, excluded from the study.

2. LUTH’s cystoscope set was faulty during the study period necessitating

Urethroscopy being done on the patients in two private hospitals manned by

consultant urologists with the requisite facilities with me in attendance.

Some patients opted out because of this.

3. Patients used for the study had to use the same imaging and laboratory

facilities along with the other hospital patients for their investigations and

were sometimes given long appointments which delayed prompt diagnosis.

- 34 -

Chapter Five

RESULTS

From February 2006 to January 2007 when this study was carried out, 90 adult

patients presented with gross haematuria. Eight of these patients defaulted from

follow up while 3 patients died before being adequately investigated. These eleven

patients were therefore, excluded from the study.

DEMOGRAPHY

The data of the remaining seventy-nine patients that were sufficiently investigated

were analyzed. Majority of the patients, Sixty (75.9%) were males while 19

(24.1%) were females; giving a male to female ratio of 3.2: 1. The age range of

these patients was 17 to 90 years with a mean age of 54.4 years (standard deviation:

17.4, standard error of mean: 1.9). The age distribution of the study population is as

shown in figure 1, with most of them belonging to the seventh decade of life

CLINICAL FEATURES

Fifty four patients (68.4%) had total haematuria, while the haematuria was terminal

and initial in 19 (24%) and 6 (7.6%) cases respectively. There was no associated

pain with the haematuria in 50 of the patients (63.3%) while 29 patients (36.7%)

had painful haematuria. The duration of the symptom before presentation ranged

from minutes to many years. Table1 shows that more than half of the patients had

their symptoms for more than 1 month before presentation at the hospital. Only 11

- 35 -

patients (13.9%) who were mostly victims of trauma presented within 24 hours of

the onset of their haematuria.

Fifty two patients (65.8%) had intermittent haematuria while in 27 cases (34.2%),

the haematuria was continuous. Among the patients with intermittent haematuria,

22(42.3%) had more than five episodes before presentation while only 13 patients

(25%) presented after one or two episodes.

Twenty six (32.9%) of the patients had no other symptom apart from haematuria.

The presence of at least one irritative lower urinary tract symptom in association

with haematuria was reported by 48(62%) of the patients. Other significant

associated findings from history were obstructive lower urinary tract symptoms in

33 patients( 41%), weight loss in 23 patients(29%), abdominal pains in 21

patients(26.5%), trauma in 9 patients(11.4%), fever in 10 patients(12.7%) and

spontaneous passage of urinary calculi in 2 patients. Seventeen patients (21.5%)

presented in acute or chronic urinary retention.

Forty patients (50.6%) were clinically pale on examination at presentation. 23

patients (29.1%) had tachycardia while 11(13.9%) had significant elevation of their

blood pressure. Other signs that were elicited on general examination included

pedal oedema in 4 patients (5.1%), significant peripheral lymphadenopathy in 7

patients (8.9%), paraplegia in 2 patients (2.6%) and jaundice in 1 patient (1.3%)

Abdominal examination revealed suprapubic or loin tenderness in 31 patients

(39.2%). Twenty four (30.4%) and 3(3.8%) patients had palpable suprapubic and

loin masses respectively at presentation. The prostate gland was found to be

- 36 -

enlarged in 39 of the male patients (65%). One patient had a locally advanced

anorectal tumour which was infiltrating into prostate gland. Vaginal examination

revealed tumour of the cervix that was infiltrating into the bladder in a woman.

Two patients who sustained urethral injuries had clotted blood at the external

meatus with one of them bleeding actively from the urethra at presentation.

- 37 -

Figure 1: Age distribution of patients

Age groupings(years)

90 to 99

80 to 89

70 to 79

60 to 69

50 to 59

40 to 49

30 to 39

20 to 29

<20

Frequency

30

25

20

15

10

5

0

Table 1: Duration of gross haematuria in all patients studied

Duration No of patients percentage

< 24 hours 11 13.9

1 to 7 days 14 17.7

1 to 4 weeks 6 7.6

1 to 6 months 24 30.4

6 to 12 months 14 17.7

> 1 year 10 12.7

Total 79 100

- 38 -

RESULTS OF INVESTIGATIONS

Haematological/ biochemical investigations

The haemoglobin concentration of the patients is shown in table 2. None of the

patients had deranged clotting profile. Fourteen patients (17.7%) had haemoglobin

genotype AS while the rest had genotype AA. The only patient who was eventually

diagnosed to have extensive papillary necrosis from histopathology of her kidney

following nephrectomy for exsanguinating haematuria had genotype AA. The

possible causative factor of the necrosis in this patient was an herbal preparation of

unknown composition which she ingested few days before the onset and which

surprisingly affected only one kidney.

Six patients (7.6%) had significantly elevated urea and creatinine with associated

hyperkalaemia necessitating haemodialysis in 4 of them. The serum electrolytes,

urea and creatinine were within normal limits in the remaining patients. 42 males

had serum prostate specific antigen (PSA) estimated; of these, 15 had PSA of <

4ng/ml, 11 had PSA of 4 to 10ng/ml while 16 had values >10ng/ml.

Urine examinations

Sixty four patients (81%) had macroscopically “red” urine at presentation and all

the patients were found to have microscopic haematuria from urinalysis. Bacteria

were isolated from the culture of urine in 24 patients (30.4%), majority of whom

had other identified non-infective causes of their haematuria. Escherichia coli was

the commonest bacteria and was isolated in 8 patients (10.1%). Others are shown in

- 39 -

table 3. Urine cytology could not be done in 27 patients; however, among the

patients who had it done, malignant cells were seen in only one patient who had an

advanced bladder tumour.

- 40 -

Table 2: Haemoglobin concentration of patients with haematuria

Haemoglobin concentration No of patients Percentage

> 10gm/dl 25 31.6

7- 10gm/dl 41 51.9

< 7gm/dl 11 13.9

Table 3: Bacterial isolates from urine of patients with gross haematuria

Bacteria No of patients Percentage

Escherichia coli 8 33.3

Klebsiella aerogenes 4 16.7

Proteus mirabilis 3 12.5

Staphylococcus aureus 2 8.3

Miscellaneous/ Mixed growth 7 29.2

Total 24 100

- 41 -

Imaging studies

Intravenous urography was done in most of the patients except those who had

significant renal impairment or emergency surgery which precluded them. Various

radiological features and signs suggestive or diagnostic of different clinical

conditions causing haematuria were seen as highlighted in table 4. Some patients

had multiple radiological features while some of the IVU features were not

conclusively diagnostic of some clinical conditions necessitating further evaluation

using other investigative tools. In all, IVU was diagnostic or suggestive of the cause

of haematuria in 47 (69%) of the 68 patients that had it done.

Retrograde urethrocystogram and micturating cystourethrogram were done in 13

patients with suspected urethral stricture and it demonstrated strictures in 7 of them.

However, other investigative tools showed that the haematuria in these patients

were from sources other than the urethral stricture. The urethrograms also showed

elongated posterior urethra suggestive of prostatic enlargement in 5 patients.

Abdomino-pelvic ultrasound scan was done in 75 of the patients. It revealed the

likely source of haematuria in 55(73.3%) patients. The sonological findings in these

patients included lesions of the prostate, bladder and kidneys as well

hydronephrosis and hydroureters from obstruction to the upper urinary tracts.

Abdomino-pelvic computerized tomography scan was done in 3 patients. One of

the patients in whom a kidney was seen to be non- functional on IVU but cystic and

hydronephrotic by ultrasound scan, had evidence of renal malignancy on CT scan.

- 42 -

The second patient with suspected expanding renal haematoma on serial abdominal

ultrasound scans following blunt abdominal injury had a minor renal injury from

the scan thus preventing a negative laparatomy. The third patient had advanced

bladder tumour with co-existing impassable urethral stricture which prevented

cystoscopy and the tumour was demonstrated on CT scan to be infiltrating

contiguous structures.

Endoscopy

The urethrocystoscpic findings in the patients are summarized in table 5. The

important lesions and sites of haemorrhage that were seen included bladder masses

and ulceration and enlarged prostate. Bleeding from the ureteric orifice(s)

localizing the source to the upper tracts was observed in 3 patients. Nineteen

patients had evidence of inflammation with cystitis solely responsible for the

bleeding in only 5 patients. Urethroscopy revealed bleeding multiple urethral warts

in a patient. Three patients had urethral stricture demonstrated on urethroscopy but

this was not the cause of their haematuria. The five patients in whom the origin of

their haematuria was not detected all had normal findings on cystoscopy.

A patient with locally advanced rectal tumour that was infiltrating into the bladder

had proctosigmoidoscopy and rectal biopsy done.

- 43 -

Table 4: Number of patients with different IVU features in various disease conditions

Calcific

densities

Along

the tract

Non

functional

kidney

Destruction/

Distortion

of calyces

Hydronephrosis/

Hydroureter(s)

Bladder

base

elevation

Bladder

filling

defect

Normal

study

Bladder

tumour

1 4 3 5 3

BPH 5 17 7 2

CaP 3 6 2 2

Urolithiasis 9 4

Renal cell Ca 1 1 3

Truama 1 8

Infection 1 7

Unknown 5

Table 5: Number of patients with various Urethrocystoscopic findings in various

pathological conditions

Prostate

enlargement

Inflamed

bladder

urothelium

Bladder

stone

Bladder

mass/

ulcer

Bleeding

from

ureteric

orifice

Urethral

stricture

Bladder

haematoma

Normal

BPH 16 4 1 - - - 7 -

CaP 5 2 2 -

Urolithiasis 2 1 1 1 -

Renal cell

carcinoma

1 1

Bladder

tumour

4 5 1 9 4 -

Papillary

necrosis

1 1 -

Cystistis 1 6 -

Unknown 5

- 44 -

Biopsy

Sixteen patients with prostatic enlargement that was associated with either elevated

PSA or abnormal findings on digital rectal examination had transperineal, digital

guided prostate biopsy done. The histopathology in 8 of these patients revealed

adenocarcinoma of the prostate while the rest had fibromuscular and glandular

hyperplasia. Histopathology of specimen obtained during cystoscopy in patients

with bladder tumours showed transitional cell carcinoma in 9 cases.

Diagnostic/therapeutic surgical interventions

Two patients who sustained bladder injuries from blunt abdominal trauma had

exploratory laparatomy and closure done. A multiply injured patient with a grade V

renal injury discovered at laparatomy had nephrectomy. Eight patients with BPH

and 2 others with Carcinoma of the prostate had emergency bladder exploration

done for clot retention during which the source of bleeding was localized to the

prostate gland. Two patients with urethral injuries also had surapubic cystostomy

done during which bleeding from the posterior urethral was observed; urethrograms

subsequently confirmed the diagnosis in retrospect.

Causes and sites of haematuria in the study population

From the clinical evaluation and the complimentary use of the various investigative

tools and surgical interventions, the cause of haematuria was determined in 74

patients (93.7%) while haematuria was of undetermined origin in 5 patients (6.3%).

Fifteen different specific diagnoses were made as the causes of haematuria in this

study. The three commonest causes of haematuria were BPH (30.4%), bladder

- 45 -

carcinoma (12.7 %) and carcinoma of the prostate (10.1%). Table 6 shows the other

causes of haematuria in this study. The causes of haematuria with common or

similar aetiopathogenesis were grouped together and the results (figure 2) show that

BPH (30.4%) and urological malignancies (29.1%) were the commonest diseases

responsible for haematuria in the study population. Trauma and urinary calculi

(urolithiasis) were each responsible for 11.4% of the cases.

The pattern of organ involvement as the source of haematuria is depicted in figure

3. The prostate gland (40.5%) and the bladder (26.6%) were the most frequently

affected organs. The kidneys and ureters constituting the upper urinary tract were

the origin of haematuria in 21.5% of cases.

Age and gender of patients with malignancies

The profile of patients whose haematuria were due to urological malignancies is

shown in table 7. Majority of these patients (34.7%) were in the seventh decade of

life. Seventeen (73.9%) patients with malignancies were males while 6 were

females giving a male to female ratio of 2.8: 1. The prevalence of benign and

malignant diseases was compared below and above age of 50 years which is very

close to the mean age (54.4 years) of the study population (Table 8). 82.6% of the

patients with malignancies were aged 50years and above while only 17.4% were

below 50 years of age. This is statistically significant (P= 0.045). However, similar

figures for patients with benign diseases 58.8% and 41.2% were not significantly

different. The prevalence of malignant diseases between male and female patients,

(Table 9) was also significantly different (P< 0.05). Figure 5 shows the distribution

- 46 -

of the urological malignancies in different age groups with carcinoma of the

prostate having the highest peak age incidence compared with the others.

- 47 -

Table 6: Causes of Haematuria in the study population

Clinical diagnosis Frequency Percentage

Bladder cancer 10 12.7

Bladder injury 2 2.5

Benign prostatic hyperplasia 24 30.4

Bladder stone 2 2.5

Carcinoma of the prostate 8 10.1

Cystitis 5 6.3

Vesico uterine fistula 1 1.3

Papillary necrosis 1 1.3

Renal cell carcinoma 4 5.1

Renal injury 5 6.3

Renal stone 4 5.1

Ureteric calculi 3 3.8

Urethral carcinoma 1 1.3

Urethral injury 2 2.5

Unknown 5 6.3

Urethral wart 1 1.3

Schistosomiasis 1 1.3

Total 79 100

- 48 -

29.1%

6.3%

11.4%

11.4%

3.8%

7.6%

30.4%

Malignancy

Unknow n

Urolithiasis

Trauma

Miscellaneous

Infection

BPH

Figure 2: Pictorial representation of the common aetiologies of haematuria

- 49 -

4%

6%

5%

41% 18%

27%

ureter

unknown

urethra

prostate kidney

bladder

Figure 3: Organ involvement in the aetiology of

haematuria

- 50 -

Table 7: Age and gender profile of patients with Urological malignancies

Gender

Age

(years)

Total

0

to

19

20

to

29

30

to

39

40

to

49

50

to

59

60

to

69

70

to

79

80

to

89

90

to

99

Female Bladder

Carcinoma

1 1 2

Renal Cell

Carcinoma

2 1 1 4

Male Bladder

Carcinoma

2 4 2 8

Carcinoma

of the

prostate

3 4 1 8

Urethral

Carcinoma

1 1

Total 4 3 8 7 1 23

- 51 -

Table 8: The prevalence of benign and malignant diseases in patients with

haematuria aged below and above 50 years

AGE

Total

Aged 50 years and above Aged below 50 years

Benign

diseases

Frequency 30 21 51

Percentage 58.8% 41.2% 100.0%

Malignant

diseases

Frequency 19 4 23

Percentage 82.6% 17.4% 100.0%

Total Frequency 49 25 74

Percentage 66.2% 33.8% 100.0%

P= 0.045

Figure 4:Patients with Benign and Malignant

Diseases below and above 50 years of age

Malignant diseasesBenign diseases

Fre

qu

en

cy

40

35

30

25

20

15

10

5

0

AGE

50 years and above

< 50 years

- 52 -

Table 9: Prevalence of benign and malignant lesions in female and male patients with

haematuria

GENDER

Total

Female Male

Benign

diseases

Frequency 10 41 51

Percentage 19.6% 80.4% 100.0%

Malignant

diseases

Frequency 6 17 23

Percentage 26.1% 73.9% 100.0%

Total Frequency 16 58 74

Percentage 100.0%

P < 0.05

Figure 5: Distribution of different malignancies

in various age groups of patients

Urethral C

arcinoma

Renal C

ell Carcinom

a

Prostate Carcinom

a

Bladder Carcinom

a

Fre

qu

en

cy

5.0

4.0

3.0

2.0

1.0

0.0

Age (years)

40 to 49

50 to 59

60 to 69

70 to 79

80 to 89

90 to 99

- 53 -

Nature of haematuria in patients with malignancies

Painful haematuria was more common in patients with benign conditions (45.1%)

compared with those whose haematuria was due to urological malignancies

(21.7%). 73.9% (17 out of 23) of the patients with malignant diseases and 58.8%

(30 out of 51) of those with benign diseases had intermittent haematuria. (table10).

The mean duration of haematuria before presentation in the patients with

malignancy (8 months, 2 weeks) and those with benign conditions (5 months) was

not significantly different.

Table 10: Comparison of the characteristics of haematuria in patients with benign

and malignant lesions

Nature of haematuria Benign conditions

Frequency (%) Malignant diseases

Frequency (%)

Intermittent 30(58.8%) 17(73.9%)

Continuous 21(41.2%) 6(26.1)

Painful 23(45.1%) 5(21.7%)

Painless 28(54.9%) 18(78.3%)

- 54 -

Chapter Six

DISCUSSION

Seventy nine consecutive adult patients who presented with gross haematuria to the

urology unit of the Lagos University Teaching Hospital (LUTH) between February

2006 and January 2007 were studied prospectively.

The age of patients ranged from 17 to 90 years (mean: 54.4 years ± 17.4 SD). This

mean age contrasts sharply with the findings of a similar study by Osegbe and

Amaku1 in this same centre over two decades ago. The mean age of the earlier

study which included paediatric patients from one year old was 37.8 years (SD

18.2). The current study was restricted to adults from 16 years and above and this

may largely account for the dissimilarity. Expectedly by the same token, some other

findings of the two studies from the same hospital would be at variance. However,

this finding is comparable with those of Khadra et al16 (mean 58.3 years) Mbonu

et al21 (44.9 years) and Dawam et al2 (44.8 years) who studied similar older

populations from the United kingdom, South-East and Northern Nigeria

respectively. The peak age group of the study population was in the seventh decade

of life. This is also in keeping with the findings of the other authors2, 16, 20, 21 who

studied adult patients.

The male to female ratio of 3.2: 1 obtained from this study is very similar to reports

of gender ratios of between 2.5: 1 and 4.6:1 by other workers1, 2, 10, 21.

The leading individual causes of haematuria in this study were BPH (30.4%),

bladder carcinoma (12.7 %) and carcinoma of the prostate (10.1%). This finding is

- 55 -

at variance with that of the study by Osegbe and Amaku1 who reported infection as

the commonest cause of haematuria among their patients. This disparity is

attributable to the difference in the age distribution of the two groups of patients

that were studied as earlier observed. This finding is however, similar to that of

Mbonu et al21 who reported BPH as the leading cause of haematuria in 27% of their

patients. BPH has also been reported by several other workers2,11 as a frequent

cause of haematuria in older men who were well represented in this study.

It is however, noteworthy that urological malignancies as a group constituted the

second principal cause of haematuria in both studies from our centre. Whereas in

this study urological malignancies accounted for the haematuria in 29.1% of

patients, the earlier study by Osegbe and Amaku1 revealed a much lower

prevalence of 17.4% for urological malignancies probably because their study

population included paediatric patients. Other authors4,5,17,20,30 have also reported

incidence of above 20% for urological malignancies in their studies. Bladder

carcinoma seen in 12.7% of the patients, constituted the leading malignant lesion

responsible for haematuria in this study. Dawam et al2, Khadra et al16 and Sharfi

and Hassan44 also reported bladder carcinoma as the commonest malignant cause of

haematuria in 31% and 11.9% and 10% of the patients in their series respectively.

Buntinx and Wauters10 evaluated the diagnostic value of macroscopic haematuria

for the diagnosis of urological cancers in primary care and referred patients. They

reported that in referred patients, the pooled sensitivity of macroscopic haematuria

for bladder cancer was 0.83 while it was 0.66 for ureteral cancer, and 0.48 for renal

- 56 -

cancer. The pooled Positive Predictive Value of haematuria for urological cancer in

their study was 0.22 (0.17-0.27). This could not be calculated from this study

because not all the patients with proven urological cancers were evaluated.

It is disheartening to note that the gloomy picture in treatment outcome arising from

late clinical presentation earlier observed by Osegbe and Amaku1 among patients

with bladder cancer in this environment over two decades ago is still the norm.

Majority of the patients with bladder tumours in this study presented in advanced

stages of the disease where only palliative treatments could be given to them. This

may not be unconnected with the empirical treatment of haematuria with anti-

infective agents by quacks and some general medical practitioner1,2. It is known

from earlier literatures79 that despite gross haematuria, up to three months often

pass on the average before the patients will visit a urologist. The urologist therefore

often diagnoses advanced urogenital tumours which can no longer be successfully

treated79. Public health enlightenment and continuing medical education for general

medical practitioners on the significance of haematuria as a potential harbinger of

cancer will go a long way in reversing the trend in our environment.

Majority of the patients with gross haematuria arising from urological malignancies

in this study were males (73.9%) and 50 years (82.6%) or older in age. These

differences were statistically significant (P< 0.05). Khadra et al16 also reported a

similar finding in their study where the peak age incidence for malignancy in

patients with gross haematuria was in the seventh decade of life. However, unlike

in their series where 7 patients were younger than 40 years; the youngest patient

- 57 -

with a cancer in this study was 42 years. Mariani et al17 found that the incidence of

life-threatening lesions in patients with haematuria increased with age, with a sharp

increase after age 50 years and the lesions were also more common in men (13. 6

per cent) than in women (4.9 per cent). Boman et al4 also reported that the

incidence of malignancies was strongly related to the age and sex of their patients.

Bruyninckx et al80 reported that in men older than 60 years of age, macroscopic

haematuria have a high positive predictive value for urological cancer and

recommended a thorough investigation in them whereas in patients under 40 years

of age of either sex, referral or watchful waiting can be justified.

The foregoing not withstanding, while it is generally known that the sensitivity of

gross haematuria for malignancy is high in the elderly10, no patient can be safely

excluded from thorough investigation of macroscopic haematuria on the basis of

age or sex16.

The organs that were responsible for the haematuria in most of the patients from

this study were the prostate (41%) and the bladder (27%). Mbonu et al 21 reported a

similar finding of prostatic involvement in 35% (27% BPH, 8% CaP) of their

patients. This finding is however, at variance with that of Osegbe and Amaku1 who

reported the bladder (40%) as the commonest anatomic origin of haematuria in their

study. Most of the patients in this study were elderly males who would expectedly

have higher incidence of prostatic diseases; hence the dissimilarities. Pathologies in

the lower urinary tract and the prostate accounted for the haematuria in 73% of the

patients. Osegbe and Amaku1 reported a comparable figure of 66%. A lot of such

- 58 -

diagnoses cannot be made without lower tract endoscopy. Tan31 discovered that

22.2% bladder cancers in their series were found on cystoscopy but missed on the

cystogram phase of the intravenous urogram and that ten urological lesions would

have been missed if cystoscopies were not performed. This underscores the

necessity of adequately equipping teaching hospitals and referral medical centres

with the necessary facilities by the government.

Schistosomiasis was the cause of haematuria in only one patient of the study

population. This finding supports earlier reports1,3 discouraging the empirical

treatment of patients presenting with gross haematuria with anti-schistosomal drugs

based on over assumption about the endemicity of schistosomiasis in this

subregion .

Infection was responsible for patients’ haematuria in 7.6% of the cases. However,

bacteria were isolated from urine samples of 24 patients (30.3%) most of whom had

other identified causes for their haematuria. As also noted by Osegbe and Amaku1,

the significance of this finding is that secondary bacterial infections often co-exist

with more sinister lesions in these patients. Therefore, they should not be treated

with only antibiotics without further investigations to exclude such serious

coincident diagnoses, which would lead to a delay in treatment.

The finding of malignancy was not associated with either the type or duration of

haematuria in this study. The haematuria in the patients with malignancy was often

painless (78.3%) and intermittent (73.9%) when compared with those who had

benign diseases (54.9% and 58.8% respectively). The mean duration of haematuria

- 59 -

before presentation in the patients with malignancy (8 months, 2 weeks) was also

longer than in those with benign conditions (5 months). However, these differences

were not statistically significant. Review of literatures corroborates this finding;

despite gross haematuria, on the average three months often pass before

presentation to the urologist79

No correlation between the presence or absence of associated symptoms and the

finding of malignancy was observed. Therefore, haematuria caused by urological

malignancy could not be specified by the type or duration of haematuria or its

association with other symptoms81. Other workers4,5 have made similar observation

and suggested that patients, especially the elderly ones, with painless,

asymptomatic and intermittent gross haematuria have a high-risk of harbouring

malignancy. This may be used as a guide during clinical evaluation and their

investigation must be given a high priority.

The cause of haematuria could not be found in 5 patients (6.3%). The failed

diagnosis rate is comparable with those of others21,45. Rasmussen et al47 reported

that 18% of such patients in their series had missed urological tumour on further

investigation. Sells and Cox46, however, found only one missed tumour during the

follow-up of 146 patients with undiagnosed gross haematuria and concluded that

repeat investigation is only warranted in patients who have recurrent bleeding after

initial investigation.

- 60 -

Chapter Six

CONCLUSION

The leading causes of macroscopic haematuria in adults in LUTH were

benign prostatic hyperplasia (30.4%), bladder carcinoma (12.7 %) and

carcinoma of the prostate (10.1%)

The prevalence of urological malignancies (29.1%) was high among the

patients with macroscopic haematuria.

The incidence of malignancies was strongly related to age and sex of

patients with higher prevalence in males and patients older than 50 years.

Macroscopic haematuria, especially in older patients, is often associated

with a malignancy and the investigation must be given high priority.

Improved patient education, prompt referral by general practitioners and

increase in the capacity of haematuria clinics will improve rapid diagnosis

and treatment outcomes

- 61 -

RECOMMENDATIONS

Regular health education for the general public and continuing medical

education for general medical practitioner on the significance of haematuria

as a harbinger of cancer is advocated to improve early diagnosis and

treatment.

Empirical treatment of haematuria with anti-infective agents without

thorough urological evaluation should be discouraged.

Government should adequately equip teaching and other referral hospitals

where patients with haematuria are referred with modern diagnostic tools,

especially facilities for endo-urology.

Urological units in teaching hospitals should be encouraged to organize

regular and integrated haematuria clinics encompassing clinical

consultations and investigations of patients presenting with haematuria in a

single centre. Such rapid diagnostic services will result in better patient

compliance for investigations and earlier detection and treatment of

urological lesions presenting as haematuria

- 62 -

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APPENDIX

STUDY PROFORMA

Demographic data

Name: ……………………………………………………… Hosp No: …………

Age ……………… Sex: ………………….

Residential address: ………………………………………………….

Occupation: ……………………… Tribe: ……………………….

History

Haematuria Duration…………………………………..

Timing: Initial, terminal or total…………………

Type: Intermittent or continuous………………..

Number of episodes since onset in intermittent haematuria……………….

Painful or painless………………………………

Associated urological symptoms

Irritatitive symptoms: Dysuria, Urinary frequency, Urgency, Nocturia

Obstructive symptoms:

Urinary retention: acute/chronic

Pain: loin, suprapubic,

Urethral discharge/ STI

Systemic symptoms Fever

Weakness/dizziness

Weight loss

Bleeding from other sites

Trauma

Blunt/penetrating abdominal injuries

Pelvic fractures

Falling astride

External genitalia injuries

Drugs

Anticoagulants

Antibiotics

Analgesics

Others

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Past medical/family history: Haematuria,

Schistosomiasis, hypertension

………………………………………………………………………………………

………………………………………………………………………………………

……………………………………………………………………………………...

Social history: Occupation. Smoking, Alcohol …………………………………..…

………………………………………………………………………………………

Review of other systems Respiratory: Haemoptysis, recent upper respiratory tract infection

GIT: melaena, rectal bleeding, altered bowel habit

CVS: Dizziness, fainting spells, palpitations

Others

Physical examination

General

Pallor

Jaundice

Fever

Weight loss

Pulse rate………… Blood pressure…………

Abdomen

Ascites

Tenderness……………………..

Organomegaly: Liver, spleen, kidneys, bladder…………………..

……………………………………………………………………..

Other masses………………………………………………………..

Digital rectal examination findings: prostate: size, consistency,

surface, other lesions ……………………………….………………

………….……………………………………………………………

……………………………………………………………………….

External genitalia: Urethral bleeding, discharge, stricture etc

………………………………………………………………………………………

………………………………………………………………………………………

………………………………………………………………………………..…….

Vaginal examination: Vaginal bleeding, discharge, cervical lesions etc

………………………………………………………………………………………

………………………………………………………………………………………

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Chest findings:

………………………………………………………………………………………

……………………………………………………………………………………..

Musculoskeletal system: Pelvic fractures, sensory loss, paraparesis, paraplegia

…….…………………………………………………………………………………

………………………………………………………………………………………

………………………………………………………………………………………

Provisional diagnosis ………………………………………………………………

Investigations

Haematology

Haemoglobin/ packed cell volume…………………………

White cell

count…………………………………………………………………………

Platelet

count…………………………………………………………………………….

ESR………………………………………………………………………………

Hb genotype …………………………………………………………………..

Clotting profile: PT, PTT ……………………………………………………………

Blood chemistry

Na……………. K………… Cl……………… HCO3…………. Ca ……………

Serum uric acid…………, Phosphate………….Urea……………..

Creatinine ……………….

PSA…………

Microbiology

Urinalysis: PH………. Sugar……….. Blood ………….. Protein…………..

Urine microscopy…………………………………………………..

Urine culture………………………………………………………..

Imaging studies

Chest x-ray………………………………………………………………………

Intravenous urogram............................................................................................

………………………………………………………………………………………

RUCG/MCUG ………………………………………………………………………

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Ultrasonography: Abdominal/ Pelvic ………………………………………………

………………………………………………………………………………………

………………………………………………………………………………………

Cystoscopy

………………………………………………………………………………………

………………………………………………………………………………...

Biopsy

…………………………………………………………………………………..……

……………………………………………………………………………………..

Urine

cytology………………………………………………………………………….

Others………………………………………………………………………………

………………………………………………………………………………………

………..………………………………………………………………………………

Definitive diagnosis …………………………………………………………………….

Treatment

………………………………………………………………………………

………………………………………………………………………………………

………………………………………………………………………………………

………………………………………………………………………………………

Outcome

…………………………………………………………………………………

………………………………………………………………………………………

……………………………………………………………………………………