HEMATURIA AND URINARY BLADDER TUMORS
Hematuria
microscopic hematuria
macroscopic hematuria
presented as RED URINE
Other
Differentials
of Red Urine
Red Urine
Heme positive
Hemoglobinuria,
G6PD deficiency
myoglobinuria,
like cases of
Rhabdonyalysis
Hematuria
Heme negative
Dyes and
certain
foods
Drugs, like
Refampicin
Bilirubin
Urates
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HEMATURIA AND URINARY BLADDER TUMORS
Definition
Presence of RBC's in urine. We can detect hematuria by dipstick or microscopy. You should consider
hematuria as a sign of malignancy until proven otherwise.
Medical vs surgical hematuria
Hematuria has medical causes (like nephritic syndrome) and surgical (urological) causes. If you find
out one of the following, this indicates a medical cause rather than a surgical cause;

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Presence of casts.
Predominance of dysmorphic RBC’s in the urine.
Glycosuria.
Significant proteinuria.
Renal insufficiency.
Fixed specific gravity, the kidney can't dilute or concentrate the urine.
The presence of clots goes with urological causes.
Initial questions in a history of
hematuria;
 Is the hematuria gross or
microscopic?
 At what time during
urination does the
hematuria occur?
 Is the hematuria
associated with flank pain,
fever, and irritative
symptoms?
 Is it associated with clots?
Do the clots have a specific
shape?
Mode of
discovery; gross vs
microscopic
Symptomatic
vs
asymptomatic
Hematuria
Act of voiding;
initial, terminal
and total
Presence of clots;
with clots, without
clots
a) Microscopic vs macroscopic hematuria
Hematuria can be silent microscopic hematuria or gross hematuria. The AUA definition of
microscopic hematuria is “three or more red blood cells per high-power field on microscopic
evaluation of urinary sediment from two of three properly collected urinalysis specimens”, from
this definition you can note that presence of less than 3 RBC's per high power field (HPF) is normal.
Microscopic hematuria is more dangerous, because;
 Time elapse before diagnosis
 Malignancy is more likely to present as microscopic hematuria. Nevertheless, the chances of
identifying significant pathology (like tumors) increase with the degree of hematuria, and
the severity of the condition can be proportionate to the severity of hematuria.
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HEMATURIA AND URINARY BLADDER TUMORS
b) According to act of voiding
According to its relation to the stream, hematuria can be classified into;
 Initial, the least common, usually arises from the urethra secondary to inflammation or
urethritis.
 Terminal, occurs at the end of micturition and is usually secondary to inflammation in the
area of bladder neck and prostatic urethra (forceful squeezing at the end of voiding will lead
to forceful closure of bladder neck and prostatic urethra, and by this the veins might bleed,
it is painful)
 Total, the most common, arises from the bladder or upper urinary tract
Microscopic hematuria is always assumed to be total hematuria
c) Symptomatic vs asymptomatic
Hematuria itself is not painful unless associated with obstruction or inflammation. Pain in
association with hematuria usually results in the upper urinary tract because the ureter is easily
obstructed (its inner diameter is only 3mm). On the other hand, hematuria which arises from the
bladder usually gives irritative symptoms and burning micturition.
d) Clots
The presence of clots usually indicates a more significant degree of hematuria, and, accordingly, the
probability of identifying significant urologic pathology increases. The urine itself has
anticoagulation substances (as urokinase), the presence of clots indicates that the amount of blood
is high that can overwhelm the amount of anticoagulant and thus produces clots.
Investigations
In a patient who presents with gross hematuria,
cystoscopy (endoscopy of the urinary bladder through
the urethra) should be performed as soon as possible,
because frequently the source of bleeding can be
readily identified.
Cystoscopy will determine whether the hematuria is
coming from urethra, bladder or upper urinary tract.
Because of this, Cystoscopy can be considered as part
of the initial workup in a patient complaining of
hematuria.
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HEMATURIA AND URINARY BLADDER TUMORS
The cystoscope will go up to the bladder only, so how can we know if it’s coming from the upper
urinary tract, right or left side?
We introduce a small catheter, one in each ureter and collect samples, we also take a sample from
the bladder, and then we have to see which one has hematuria. This is called “differential
samples’’ (from both ureters & the bladder).
We do this (diff. samples) if we go in & find the bladder is normal, so we don’t stop here , we must
find the source of hematuria ,to achieve this we do differential samples;
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If the bladder sample was +ve for hematuria , & ureters was (-ve), this means that the cause
is in the bladder even if you couldn’t see anything by cystoscopy; because:
 There is a missing area in the bladder which we can’t see by the cystoscope which is
present in our country. There is what we call “flexible cystoscope ’’ by which we can
do “retroflex”& see this area.
 Misinterpreted lesions as carcinoma in situ which appears like a carpet of a velvety
lesion which needs experienced eyes to be seen.
If the lesion is inside the bladder, the sensitivity of cystoscopy is more than 90%.
Other tests in the initial workup in a patient complaining of hematuria;
- Urinalysis, for conformation.
- Urine culture is always in the list as some infections may cause hematuria.
- Urine cytology (flow cytometry), to look for abnormal cells in the urine.
- Upper tract imaging (CT, IVU, U/S, angio),
In IVU, we depend on the ability of the kidney to
and this is according to the scenario, we
handle
the contrast material. While in retrograde
don't do this to every patient.
pyelography we control this problem by
- Retrograde pyelography.
ballooning the collecting system and do imaging
so we can see any abnormality
Possible causes of hematuria
 All over above the age of 50, TCC "Transitional Cell Carcinoma" is the most common cause
of gross hematuria (in both sexes together).
 BPH "benign prostatic Hyperplasia" is the most common cause in aging men.
 UTI is the most common cause in females
Risk factors for significant disease in patients with microscopic hematuria
 Smoking history
 Occupational exposure to chemicals or dyes (Benzenes or aromatic amines)
 History of gross hematuria
 Age > 40 years
 History of urological disorders or disease or congenital anomalies.
 History of irritative voiding symptoms
 History of UTI
 Analgesic abuse
 History of pelvic irradiation
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HEMATURIA AND URINARY BLADDER TUMORS
Urinary bladder tumors in general are 2.5 more common in males than females. Bladder cancer has rarely
been found incidentally at autopsy, because it's symptomatic.
Histologic types of urinary bladder tumors;
 Transitional Cell Carcinoma (TCC) (95%), the most common type as the urinary tract is lined by
transitional epithelium. Transitional Cell Carcinoma is the most common malignancy diagnosed in
patients with hematuria.
Put in mind that transitional epithelium lines the urinary tract from the minor calyces to the end of
the prostatic urethra, which means that Transitional Cell Carcinoma, although mostly arises in the
bladder, could arise from other places in the urinary tract.
 Adenocarcinoma (4%)
 Squamous Cell Carcinoma, accounts for (1%) except in the Nile River region where Bilharzia
(schistosomiasis) is endemic; SCC may account for 60% - 70% of urinary bladder tumors in this
region.
Risk factors
1. Chemicals, like dyes, paint, aromatic amines and rubber industry. Most bladder carcinogens are
aromatic amines including aniline and benzene based dyes.
2. Smoking increases the risk by 4-5 times
3. Chronic irritation (chronic cystitis -like schistosomiasis-, and catheters), more with squamous and
adenocarcinoma.
4. Pelvic irradiation,
prostate cancer treatment there was a competition between surgeons and radiotherapists, then
after a while there was a report says : "people who had radiotherapy for prostate cancer 12 years
ago they have higher incidence of bladder cancer" , surgeons will work more !!
5. Patients treated with cyclophosphamide have up to nine folds increased risk of developing bladder
cancer. This drug is used in the treatment of cancers, autoimmune diseases and nephrotic
syndrome.
6. Genetic background, activation oncogenes (like P53) or inactivation of suppressor genes. P53 is the
most frequently altered gene in human cancers, it controls a checkpoint where the abnormal cells
are sent to G0, so when this gene is abnormal then abnormal cells are allowed to replicate.
Clinical presentation
Patient usually comes with painless hematuria (85%). The disease could present as irritative LUTS or distant
metastasis (5%)
Patient's profile (we look for risk factors):
1. Occupation: If the patint works in a gas station, paints cars... etc.
2. Age (old age): If a child comes to you with painless hematuria we don’t think of UBT; we think of nephritis.
If the pt is young you think of stones.
3. Sex (M>F)
Symptoms of UBT:
1. The pt usually comes with hematuria that is: gross, total, painless, intermittent, with or without clots.
2. The tumor could be associated with lower urinary tract symptoms (e.g. frequency, urgency)
3. Obstructive symptoms: if the tumor was in the bladder neck.
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HEMATURIA AND URINARY BLADDER TUMORS
4. Upper tract symptoms: the patient may come with obstruction to both ureters or hydronephrosis.
5. Nonspecific symptoms
Physical examination
Usually doesn’t reveal any findings unless it was an advanced tumor with metastasis or LNs
involvement then we may find signs in other systems. For example: If the tumor reached the lymph
nodes (Lymphadenopathy) the patient may come with bilateral lower limp swelling and sometimes
this is the first presentation.
Investigations
It is the same of the workup for Hematuria "as it is the most common presentation", it includes;
1. Cystoscopy, we take a biopsy with a flexible cystoscope then send it to the lab to see the
grade and the stage of the tumor. If it is possible to remove the whole tumor, then we
resect it, it is preferable to remove part of the muscle along with it to know where the
tumor has reached.
2. Urine cytology, in high grade tumors, we may find atypical or malignant cells in the urine.
3. Imaging studies;
 Ultrasound: we may find a lesion in the bladder.
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Intravenous Urogram (IVU): To make sure it didn’t reach the upper urinary tract
(About 4% of lower urinary tract tumors are accompanied with upper urinary tract
tumors and about 40% of upper tract tumors are accompanied with lower tract
tumors)
Enhanced Ct-scan: Not for diagnosis but for staging
MRI with contrast: Also for staging.
Grading and Staging
There's a strong correlation between the grade and stage of Urinary Bladder Tumors (UBT), that is,
the less differentiated tumor "higher grade", the more likelihood to spread.
Grades are from 1 to 3, only grade 3 is considered as high grade tumor and by itself is a poor
prognostic factor.
UBT follows the concept of field change effect, which means that the whole field is not stable. (i.e.
it has a high recurrence rate, and most of the recurrences don't come in the same place because it’s
a field change ; as if you plant seeds in the ground, not all of them will grow together)
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HEMATURIA AND URINARY BLADDER TUMORS
Staging: we usually use the (TNM) system:
a. T (Tumor): mostly corresponds the stages "see below"
- T0: There’s no tumor.
- Tx: Couldn’t stage.
- Tis: Carcinoma in situ (The epithelium is only affected)
- Ta: Superficial tumor affecting the mucosa.
- T1: Reached the lamina propria.
- T2: reached the muscle layer.
- T3: Reached the serosa layer.
- T4: Reached the surrounding parietal
organs in the pelvis (Seminal vesicles, prostate, Urethra.. etc)
Superficial tumors
Invasive tumors
** Tis, Ta and T1 are superficial tumors.
** T2, T3 and T4 are Invasive tumors, T3b and T4 = extravesical extensions.
b. N (Lymph nodes):
- N1: Regional LNs involvement
- N2: Extra-regional LNs involvement
c. M (Metastasis):
- M0: No mets.
- M1: Mets.
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HEMATURIA AND URINARY BLADDER TUMORS
Stage 0, cancer cells on the surface of the inner lining of the bladder.
Stage 1, tumor has grown through the inner lining of the bladder "papillary"
Stage 2, tumor has spread into the muscle of the bladder wall "invasive"
Stage 3, tumor has spread through the muscle wall to the fatty layer of tissue surrounding the
bladder
Stage 4, tumor has spread through the bladder wall into the walls of the abdomen or pelvis, mets.
UBT is characterized by independent prognostic factors, this means if one prognostic factor is bad,
this is enough to consider the whole disease as bad.
Treatment
1. Superficial tumors (Tis, Ta and T1):

We do transurethral resection (TURBT); we resect the tumor using the cystoscope and after
3 months we do a cystoscopy and if there was any recurrence we resect it.
We follow up the patient : we do a cystoscopy every 3 months for 2 years then every 6
months for 3 years and then once every year for 10 years.

According to the grade, multiplicity and recurrence rate of the tumor we may give
intravesical therapy (Immunotherapy or chemotherapy)
 It affects the recurrence not the progression.
 Indications; large tumor size, rapid and frequent recurrences, multicentricity,
presence of Cis.
 Common agents used; BCG, metamycin C, Adriamycin, thiotepa, methotrexate.
 BCG is the most commonly used, cheapest and has best results regarding recurrence
rate (decreases the recurrence rate up to 30%). It activates the immune system to
attack the transitional epithelium.
We give the patient 6 cycles of chemotherapy or BCG; every week we give one
injection using Foley’s catheter. After 3 months we may need to give the patient
another 3 injections.
 Failure of intravesical chemotherapy denotes a bad prognosis
 Contraindicated in; immunosuppressed patient "life-attenuated bacteria", active UTI,
active TB, hematuria "blood stream is opened, access to blood)
2. Invasive tumors (T2, T3 and T4):
The best thing to do is radical cystoprostatectomy especially if it was localized (i.e no LNs involved
or mets), then we make urine diversion.
 In males : Resection of the bladder, prostate, seminal vesicle, and the urethra (in selected
cases)
 In females: Resection of the Bladder, Anterior vagina, uterus and cervix, fallopian tube,
ovaries and the urethra.
 In both this is followed by extended pelvic lymph node dissection.
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HEMATURIA AND URINARY BLADDER TUMORS
Urine diversion: It is any one of several surgical procedures to reroute urine flow from its normal
pathway. It includes the following types;
i.
Continent diversion: (three types)
a. Orthotropic or neobladder diversion using the urethral sphincter.
b. Ureterosigmoidostomy using the rectal sphincter to evacuate urine: The ureters are
diverted into the sigmoid colon. We should make sure that the rectal sphincter is
competent and won’t return the fluid by doing ano-rectal manometry.
c. Continent catheterizable diversion: we make a bladder from the intestines and we
make an opening for it in the skin (e.g. In the umbilicus) so the pt every 4-6 hrs
inserts a catheter to empty the bladder (this is called Mainz pouch I)
In order to make continent diversion the upper urinary tract should have a good
function (Serum creatinine < 2mg\dl)
ii.
Incontinent diversion:
a. Ileal conduit: we cut a segment from the ileum (About 10-15cm) then we anastomose
the remaining parts. The ureters are diverted into that segment that opens as a stoma on
the abdominal wall in the right iliac fossa. Urine is collected in an external collection bag.
b. Other type of incontinent diversion is ureterostomy were the ureter opens as a stoma
on the abdominal wall. This is done especially when the pt has one kidney.
c. Colon conduit were the segment is taken from the colon.
Complications of urine diversion:
 Because the urine is going to the GIT there will be a lot of mucus discharge.
 infection.
 Stone formation.
 Metabolic abnormalities (The most important): The lining of the bladder (transitional
epithelium) doesn’t absorb the urine but in the ileum, colon or the stomach the absorption
will be high so urea, creatinine, salts and other contents of urine will be reabsorbed and
cause electrolytes and acid-base imbalance (Hyperchloremic metabolic acidosis).
 Problems in stoma: Stenosis, prolapse, parastomal hernia, irritation, bleeding…etc.
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HEMATURIA AND URINARY BLADDER TUMORS
3. Advanced tumors (LNs involvement and mets):
In addition to surgery we use systemic combined chemotherapy (e.g. Methotrexate) as sandwich
therapy (i.e. Adjuvant + neo-adjuvant chemotherapy).
If the tumor was localized we may use radiotherapy (e.g. just certain LNs in the pelvis are involved)
The prognosis of advanced tumors is usually very bad (5 years survival is less than 20 %).
LAST WORDS;
Whatever we do TCC has high recurrence rate (after cystectomy): 50%, (80% of recurrences are
distant and 20% are local "in the pelvis"). Which means the presence of ditent metastasis form the
beginning in high proportion of cases.
Our only chance in winning this war is by diagnosing the disease in an early stage.
All starts with hematuria.
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