Haematuria and Urinary Tract Haematuria and Urinary Tract TumoursTumours

Mr C Dawson MS FRCSMr C Dawson MS FRCS

Consultant UrologistConsultant Urologist

Edith Cavell HospitalEdith Cavell Hospital

HaematuriaHaematuria

Macroscopic vs MicroscopicMacroscopic vs Microscopic Painful vs PainlessPainful vs Painless Initial, terminal, or mixed with urinary Initial, terminal, or mixed with urinary

streamstream

Microscopic HaematuriaMicroscopic Haematuria

““Excretion of abnormal quantities of Excretion of abnormal quantities of erythrocytes in the urine”erythrocytes in the urine”

Red blood cells identified by colour and Red blood cells identified by colour and shape (Yellow-red / biconcave)shape (Yellow-red / biconcave)

Dipstick testing for haematuriaDipstick testing for haematuria

Hb from red cells catalyses conversion Hb from red cells catalyses conversion of indicator by peroxideof indicator by peroxide

Test detects intact RBC’s, free Hb, and Test detects intact RBC’s, free Hb, and myoglobinmyoglobin

Oxidising agents - false positivesOxidising agents - false positives Reducing agents - false negativesReducing agents - false negatives

Dipstick testing for haematuriaDipstick testing for haematuria

Dipsticks not sensitive for screening Dipsticks not sensitive for screening (miss 10% of patients with microscopic (miss 10% of patients with microscopic haematuria)haematuria)

Best accomplished by microscopy of Best accomplished by microscopy of freshly voided, concentrated urine freshly voided, concentrated urine samplesample

> 3 RBC’s / hpf in a centrifuged > 3 RBC’s / hpf in a centrifuged specimen considered abnormalspecimen considered abnormal

Nephrologic vs Urologic Nephrologic vs Urologic haematuriahaematuria

Look for casts and proteinLook for casts and protein Haematuria associated with ++ or +++ Haematuria associated with ++ or +++

proteinuria should always be assumed to be proteinuria should always be assumed to be of glomerular or interstitial originof glomerular or interstitial origin

Most common glomerular causes of Most common glomerular causes of haematuria are haematuria are – IgA NephropathyIgA Nephropathy– Mesangioproliferative GNMesangioproliferative GN– Focal segmental proliferative GNFocal segmental proliferative GN

Investigation of HaematuriaInvestigation of Haematuria

MSU and Urinary CytologyMSU and Urinary Cytology IVU [KUB and Renal U/S)IVU [KUB and Renal U/S) Cystoscopy [Flexible Cystoscopy]Cystoscopy [Flexible Cystoscopy] Always do a DRE!Always do a DRE!

– 21% have a malignancy21% have a malignancy– 10% have bladder cancer (99% TCC) 10% have bladder cancer (99% TCC) – 10% have 10% have Ca ProstateCa Prostate

Urothelial tumours of the Urothelial tumours of the Urinary TractUrinary Tract

Predominantly TCC (>90%)Predominantly TCC (>90%) SCC shows great variability worldwideSCC shows great variability worldwide

– 75% of bladder cancers in Egypt75% of bladder cancers in Egypt– only 1% of bladder cancers in Englandonly 1% of bladder cancers in England

Adenocarcinoma - <2% of primary bladder Adenocarcinoma - <2% of primary bladder cancerscancers– Primary vesicalPrimary vesical– UrachalUrachal– MetastaticMetastatic

Epidemiology - IncidenceEpidemiology - Incidence

Bladder most common siteBladder most common site 47000 new cases in U.S. in 199047000 new cases in U.S. in 1990 M:F 2.7:1M:F 2.7:1 Men - 4th most common cancer (Prostate, Men - 4th most common cancer (Prostate,

lung, colorectal - 10% of all)lung, colorectal - 10% of all) Women - 8th most common cancer (4% of Women - 8th most common cancer (4% of

all)all) Median age of diagnosis 67-70 yrsMedian age of diagnosis 67-70 yrs

Epidemiology - MortalityEpidemiology - Mortality

10200 bladder cancer deaths in U.S. in 199010200 bladder cancer deaths in U.S. in 1990 Accounts for 5% of all cancer deaths in men, Accounts for 5% of all cancer deaths in men,

and 3% in womenand 3% in women Mortality rates in Whites similar to BlacksMortality rates in Whites similar to Blacks Younger patients have more favourable Younger patients have more favourable

prognosis (present with lower grade) but risk prognosis (present with lower grade) but risk of disease progression is the same grade-for-of disease progression is the same grade-for-gradegrade

AetiologyAetiology

Occupational Exposure to chemicalsOccupational Exposure to chemicals Cigarette smokingCigarette smoking AnalgesicsAnalgesics Artificial sweetenersArtificial sweeteners Bacterial / Parasitic infectionsBacterial / Parasitic infections Bladder calculiBladder calculi Pelvic irradiationPelvic irradiation Cytotoxic chemotherapyCytotoxic chemotherapy

Theory of CarcinogenesisTheory of Carcinogenesis

OncogenesOncogenes Deletion or inactivation of Supressor Deletion or inactivation of Supressor

genesgenes Amplification of expression of gene Amplification of expression of gene

productsproducts

Clinical presentationClinical presentation

Painless haematuria (85% of patients)Painless haematuria (85% of patients) ““bladder irritation” (frequency, urgency, bladder irritation” (frequency, urgency,

dysuria) - often associated with diffuse dysuria) - often associated with diffuse Cis or invasive cancerCis or invasive cancer

Flank pain (ureteric obstruction)Flank pain (ureteric obstruction) Pelvic massPelvic mass

InvestigationInvestigation

CytologyCytology IVUIVU CystoscopyCystoscopy

Cystoscopic appearance of Cystoscopic appearance of TCCTCC

Carcinoma in situCarcinoma in situ Papillary (70%)Papillary (70%) Nodular (10%)Nodular (10%) Mixed (20%)Mixed (20%)

TNM StagingTNM Staging

Bladder CancerBladder Cancer

The GoodThe Good The BadThe Bad The UglyThe Ugly

The GoodThe Good

T0/T1 superficial / exophytic papillary T0/T1 superficial / exophytic papillary TCCTCC

70% 5 year survival70% 5 year survival 15% Transformation each 10 years15% Transformation each 10 years Surveillance cystoscopy - more about Surveillance cystoscopy - more about

spotting change than treatmentspotting change than treatment

The Good...The Good...

Initial, low-grade, small tumours low risk Initial, low-grade, small tumours low risk of progression - TUR followed by of progression - TUR followed by surveillancesurveillance

T1, multiple, large, recurrent tumours, or T1, multiple, large, recurrent tumours, or Cis in random biopsy - consider Cis in random biopsy - consider intravesical chemotherapyintravesical chemotherapy

T1 G3 - high rate of progression - T1 G3 - high rate of progression - consider cystectomyconsider cystectomy

The BadThe Bad

Any Invasive TCCAny Invasive TCC 25-30% 3 year survival25-30% 3 year survival No real advance in 50 yearsNo real advance in 50 years T2 / T3 - partial or radical cystectomy, T2 / T3 - partial or radical cystectomy,

radiotherapy, or combination of bothradiotherapy, or combination of both T4 - Chemotherapy, followed by T4 - Chemotherapy, followed by

radiation or surgeryradiation or surgery

The UglyThe Ugly

Diffuse Cis, overtly MalignantDiffuse Cis, overtly Malignant 78% risk of invasion78% risk of invasion Intravesical chemotherapy preferred Intravesical chemotherapy preferred

primary treatment for Cis - treatment primary treatment for Cis - treatment effective in 30%. Intravesical BCG effective in 30%. Intravesical BCG produces complete regression in 50-65% of produces complete regression in 50-65% of patientspatients

Radiotherapy and chemotherapy ineffectiveRadiotherapy and chemotherapy ineffective

Tumours of the renal pelvis Tumours of the renal pelvis and ureterand ureter

2-4% of patients with bladder cancer2-4% of patients with bladder cancer [30-75% patients with upper tract [30-75% patients with upper tract

tumours will develop bladder TCC]tumours will develop bladder TCC] Pelvic tumoursPelvic tumours

– 5-10% all renal tumours5-10% all renal tumours– 5% all urothelial tumours5% all urothelial tumours

Tumours of the renal pelvis Tumours of the renal pelvis and ureterand ureter

Ureteric tumours 1-2% all urothelial Ureteric tumours 1-2% all urothelial tumourstumours

Rare before 40 yrs, peak incidence 60-70Rare before 40 yrs, peak incidence 60-70 Bilateral involvement 2-5%Bilateral involvement 2-5% Association with Balkan nephropathyAssociation with Balkan nephropathy Other aetiological factors similar to Other aetiological factors similar to

Bladder TCCBladder TCC

Diagnosis of Upper tract Diagnosis of Upper tract tumourstumours

Usually seen as a filling defect on IVU Usually seen as a filling defect on IVU or retrogradeor retrograde

Cystoscopy mandatory to rule out Cystoscopy mandatory to rule out coexisting bladder tumourcoexisting bladder tumour

Cytology less helpful as may be normal Cytology less helpful as may be normal in low grade tumoursin low grade tumours

Treatment of upper tract Treatment of upper tract tumourstumours

Renal pelvis - Nephroureterectomy with Renal pelvis - Nephroureterectomy with excision of cuff of bladderexcision of cuff of bladder

Upper/mid ureterUpper/mid ureter– Segmental resection if solitary or low gradeSegmental resection if solitary or low grade– Nephroureterectomy if multifocal or high Nephroureterectomy if multifocal or high

gradegrade Lower ureter - distal ureterectomy and Lower ureter - distal ureterectomy and

reimplantationreimplantation

Renal tumoursRenal tumours

Benign Renal tumoursBenign Renal tumours

Cysts account for 70% asymptomatic Cysts account for 70% asymptomatic renal massesrenal masses

Cortical adenomaCortical adenoma OncocytomaOncocytoma Angiomyolipoma (80% assoc with Angiomyolipoma (80% assoc with

tuberous sclerosis)tuberous sclerosis)

Renal cell carcinomaRenal cell carcinoma

3% adult cancers3% adult cancers M:F 2:1M:F 2:1 High incidence of carcinoma in patients High incidence of carcinoma in patients

with von Hippel Lindau diseasewith von Hippel Lindau disease No specific causative agent detectedNo specific causative agent detected

PresentationPresentation

Classic triad of pain, haematuria, and Classic triad of pain, haematuria, and flank mass (rare)flank mass (rare)

More commonly just pain and More commonly just pain and haematuriahaematuria

Symptoms of metastatic diseaseSymptoms of metastatic disease Paraneoplastic syndromesParaneoplastic syndromes

InvestigationInvestigation

Ultrasound - distinguish solid from Ultrasound - distinguish solid from cystic masscystic mass

CT - Staging, prior to surgeryCT - Staging, prior to surgery MRI - less sensitive than CT for lesions MRI - less sensitive than CT for lesions

less than 3cmless than 3cm Angiography - tumour in solitary kidney Angiography - tumour in solitary kidney

if partial nephrectomy consideredif partial nephrectomy considered

TreatmentTreatment

Radical nephrectomy remains only effective Radical nephrectomy remains only effective method of treating primary renal carcinomamethod of treating primary renal carcinoma

5 year survival5 year survival– 60-82% Stage I60-82% Stage I– 47-80% Stage II47-80% Stage II– 35-51% Stage III35-51% Stage III

Survival increased by pre-op radiotherapy in Survival increased by pre-op radiotherapy in some studiessome studies

Tumour in solitary kidney / Tumour in solitary kidney / bilateral tumoursbilateral tumours

Partial nephrectomy gives excellent Partial nephrectomy gives excellent short term results (72% tumour free short term results (72% tumour free survival at 3 yrs)survival at 3 yrs)

Survival independent of whether tumour Survival independent of whether tumour present in other kidneypresent in other kidney

Survival dependent on stage of local Survival dependent on stage of local tumourtumour

Treatment of metastatic Treatment of metastatic diseasedisease

ChemotherapyChemotherapy Hormonal therapyHormonal therapy ImmunotherapyImmunotherapy ““adjunctive” nephrectomyadjunctive” nephrectomy