Haematuria and Urological Malignancies

Question 1

Causes of Haematuria

Answer 1

-Trauma: blunt, penetrating
-Infection: bacterial PN, TB, parasitic (schist)
-Inflammation: interstitial cystitis
-Infarction: renal infraction
-Neoplasm: RCC, UTUC, bladder cancer
-Metabolic: renal stones, bladder stones
-Autoimmune: IgA nephropathy, GN, HSP
-Psychogenic, prescription drugs: pen, cyclophos, anti-coag/ -plt
-Surgical: post TURP/TURBT

Question 2

Causes of transient or spurious non-visible haematuria

Answer 2

urinary tract infection
menstruation
vigorous exercise (this normally settles after around 3 days)
sexual intercourse

Question 3

Causes of persistent non-visible haematuria

Answer 3

cancer (bladder, renal, prostate)
stones
benign prostatic hyperplasia
prostatitis
urethritis e.g. Chlamydia
renal causes: IgA nephropathy, thin basement membrane disease

Question 4

Causes of loin pain

Answer 4

-Trauma: blunt, penetrating
-Infection: bacterial PN, pyonephrosis, renal abscess, lobar pneumonia
-Infraction: renal
-Neoplasm: RCC, UTUC (upper tract urothelial cancer)
-Metabolic: renal stones
-Surgery: post-renal surgery, Abd-AAA, acute pancreatitis/ cholecystitis, appendicitis, ectopic pregnancy, torsion/ rupture of ovarian cyst

Question 5

Causes of palpable loin mass

Answer 5

-Trauma: blunt, penetrating
-Infection: renal abscess/ peri-renal abscess
-Neoplasm: RCC, UTUC
-Metabolic: renal stones with associated perirenal abscess
-Surgical: post renal surgery

Question 6

Definition of haematuria

Answer 6

-The presence of red blood cells (RBC) in the urine.

-Visible (prev Macroscopic) / VH
=Rose urine, claret
=+/- clots
=MUST be investigated

-Non-Visible (prev Microscopic) / NVH
=Trace blood is NOT haematuria
=Must have ≥ 1+ on Urinalysis on 2 or more occasions
=Symptomatic NVH or Asymptomatic NVH (age >40) MUST be investigated

Question 7

Causes of haematuria

Answer 7

-Trauma:
=Blunt/penetrating injuries, instrumentation
-Infection:
=UTI, pyelonephritis, schistosomiasis
-Inflammation:
=Interstitial cystitis
-Neoplasia:
=BlCa, RCC, UTUC, PrCa
-BPH
-Metabolic:
=Stones / Urolithiasis – renal, Ur, bladder
-Autoimmune
=IgA nephropathy, GN, HSP
-Surgery:
=Post TURP / TURBT
-Drugs– pen., cyclophos, anti-coag/-plt
-Strenuous Exercise:
=March h’turia, Marathon-runners h’turia

Question 8

Investigation of visible haematuria

Answer 8

-Risk of Urological Malignancy >50y: 20-25%

-History & Exam
-MSU: UA, mc&s, (cytology)
-Routine bloods (FBC, U&E)
-Flexible Cystoscopy (2 weeks)
-CTU (CT Urogram)

Question 9

Investigation of non-visible haematuria

Answer 9

Risk of Urological Malignancy >50y: 5%

-Symptomatic NVH, or Asymptomatic NVH (in pts >40y)
=History & Exam
=MSU: UA, mc&s, (cytology)
=Routine bloods (FBC, U&E)
=Flexible Cystoscopy (4-6 weeks)
=Renal USS

Question 10

Referral for haematuria

Answer 10

Urgent referral (i.e. within 2 weeks)

Aged >= 45 years AND:
unexplained visible haematuria without urinary tract infection, or
visible haematuria that persists or recurs after successful treatment of urinary tract infection

Aged >= 60 years AND have unexplained nonvisible haematuria and either dysuria or a raised white cell count on a blood test

Non-urgent referral

Aged 60 >= 60 years with recurrent or persistent unexplained urinary tract infection

Since the investigation (or not) of non-visible haematuria is such as a common dilemma a number of guidelines have been published. They generally agree with NICE guidance, of note:
patients under the age of 40 years with normal renal function, no proteinuria and who are normotensive do not need to be referred and may be managed in primary care

Question 11

Prevalence of haematuria and malignancy

Answer 11

-Bladder cancer
=VH 20%
=NVH 5%

-Renal cell cancer
=VH 1%
=NVH 0.3%

-Upper tract urothelial carcinoma
=VH 0.1%
=NVH 0.1%

Question 12

Investigation of haematuria

Answer 12

-Bloods: FBC, U&E
-MSU → Urinalysis
-MSU → mc&s
-MSU → urine cytology

-LUT (Lower Urinary Tract)
=Flexible Cystoscopy

-UUT (Upper Urinary Tract)
=VH: CTU
=NVH: Renal USS

Question 13

Haematuria criteria for admission

Answer 13

-VH with sig chronic bleeding: Symptomatic Anaemia
-VH with sig acute bleed: Hypovolaemic Shock
-VH with voiding difficulties: Clot retention (may be pending)

Question 14

Emergency management of haematuria

Answer 14

-A, B, C
-IVF +/- Blood Tx
-3-way Catheterisation

-Bladder washout: 50ml catheter-tipped syringe with N saline
-Bladder washout: remove FDPs
-Bladder washout in Theatre: if clots significant

Question 15

Epidemiology of bladder cancer

Answer 15

-Urothelial Ca…..
=Squamous Cell C 1-7%: Schistosomiasis / Bilharzia
=Adeno Ca 2%: dome- ?patent urachus
=Urothelial transitional cell carcinoma >90%. 70% will have papillary growth pattern

=Benign: inverted urothelial papilloma and nephrogenic adenoma uncommon

-Incidence
=5th most common Ca: Lifetime risk 1-3%
=Age Standardised (AS) Incidence (UK) 18 : 100,000
-Bladder cancer is the second most common urological cancer. It most commonly affects males aged between 50 and 80 years of age. Those who are current, or previous (within 20 years), smokers have a 2-5 fold increased risk of the disease. Exposure to hydrocarbons such as 2-Naphthylamine increases the risk

-Age
=Disease of elderly, generally… but can present in 20s & 30s
=Rise gradually from 50s…. and peak in 90s

-Sex/Gender
=M:F = 3:1

-Geography:
=Western World: UC- smoking, industrial
=Africa: SCC- Schistosomiasis / Bilharzia

Question 16

Aetiology of bladder cancer

Answer 16

-Cigarette Smoking: active/passive
-Chemical Exposure: (Rubber, Dye, Textile Industries) Aromatic Amines, (Petroleum industry) Polycyclic aromatic hydrocarbons(PAHs), Benzenes; (Chemo Rx) Cyclophosphamide
-History of pelvic EBRT
-Previous Chemo Rx: Cyclophosphamide
-Chronic Irritation (SCC): UTIs, Schistosomiasis, Urolithiasis

Question 17

Presentation of bladder cancer

Answer 17

-Painless VH (macroscopic)
-NVH (Asymptomatic or Symptomatic)
-Incidentally on CT imaging during unrelated investigations

Question 18

Staging investigation and diagnosis of bladder cancer

Answer 18

-Dx: Flexible Cystoscopy
-Dx: TURBT & EUA, bladder Bx
-Staging CTU & CT C/A/P… MRI pelvis (pre-TURBT). PET CT for nodes of uncertain significance

Question 19

Treatment of bladder cancer

Answer 19

-NMIBC (non muscle invasive): TURBT, regular check cystoscopies; BCG & MMC
-MIBC: Radical Cystectomy + Ileal Conduit / Neobladder; EBRT

Question 20

Bladder cancer: TRUBT & Radical Cystectomy

Answer 20

-TURBT: Trans Urethral resection of Bladder Tumour
=For Dx & Mx of bladder Ca
=Treats NMIBC (non-muscle invasive BlCa)
=Dx MIBC (muscle-invasive BlCa)

-Radical Cystectomy & Ileal Conduit Urinary Diversion
=For MIBC

-Success rates: variable (40-90%), recurrent disease, depends on grade & stage

Question 21

Describe Non Muscle-Invasive bladder cancer

Answer 21

-NMIBC (Non Muscle-Invasive Bl Ca) / Superficial: pTa, pT1
=Urothelial & suburothelial (=mucosa, submucosa) … not muscle
=TURBT both diagnostic & therapeutic (potentially curative)
=Can recur: dep on Grade (G1-3)

Question 22

Installation Rx of non muscle invasive bladder cancer

Answer 22

-MMC (mitomycin C): reduces recurrence rate…. but not likelihood of progression to invasive disease (MIBC)
-BCG: for HG UC- G3, CIS; provokes pro-inflamm IL-response that reduces rate of progression to MIBC; sig SEs
-On-going BlCa surveillance: regular check flexi cystoscopies

Question 23

Describe muscle invasive bladder cancer

Answer 23

-As invaded muscularis +/- beyond to adjacent tissues
-TURBT both diagnostic only: samples muscle
-Extent is det by TURBT pathology, EUA & staging CT (C/A/P) / MRI

-Rx
=Curative: Radical Cystectomy + Ileal Conduit / Neobladder; EBRT
=Neoadjuvant Chemo Rx: 5% survival advantage… but not everyone responds… Gem Cis, MVAC
=Adjuvant Chemo R: not evaluated in RCT

Question 24

Prognosis of bladder cancer

Answer 24

Stage 1: 90% 5 years
-2: 50%
-3: 15-30%
-4: 10%

Question 25

Epidemiology and aetiology of renal cell cancer

Answer 25

-RCC (clear cell 80%, papillary 15%, chromophobe 5%), Adenocarcinoma, Hypernephroma

-Incidence:
=7th most common malignancy: 13,000 new cases p.a. UK
=Most lethal of all urological cancers

-Age:
=Peak incidence 50-60y

-Sex/Gender:
=M:F is 3:1

-Aetiology:
=Largely unknown
=RFs: Smoking, obesity, Employment leather industry, FH vHL, middle aged men, tuberous sclerosis, PKD

Question 26

Presentation and types of renal cell cancer

Answer 26

-Usually asymptomatic – most commonly diagnosed incidentally on USS or CT inputs undergoing investigations for other conditions
-40-50% advanced/met at presentation
-Haematuria, flank pain, palpable mass, paraneoplastic synd polycythaemia from erythropoietin, hypercalcaemia fom PTH, ACTH), pyrexia of unknown origin
-Varicocele, Stauffer syndrome (cholestasis, hepatosplenomegaly)

-Micro:
=Majority Clear Cell Ca from PCT
=Other- Papillary, Chromophobe, Collecting Duct, Medullary

-Macro:
=Typically enhancing solid tumour on CT

“Cannonball metastases” in the lungs are a classic feature of metastatic renal cell carcinoma. These appear as clearly-defined circular opacities scattered throughout the lung fields on a chest x-ray.

Question 27

Diagnosis and staging of renal cell cancer

Answer 27

-Diagnosis: CT scan - Enhancing solid / heterogenous tumour (triple phase contrast)

-Staging
=Triple phase contrast CT
=& CT Chest
=Consider Bone Scan

Question 28

Treatment of renal cell cancer

Answer 28

-Depends on stage, tumour locus, pt fitness (Performance Status)
-T1-T2: LRN (lap radical nephrectomy), PN (partial nephrectomy if T1 tumour <7cm (open, robotic, lap), cryo- for small tumours, AS- in small tumoursand comorbid patients
-T3: LRN, ORN (open radical nephrectomy)
-Met: TKIs: Sunitinib, Pazopanib; cytoreductive nephrectomy

alpha-interferon and interleukin-2 have been used to reduce tumour size and also treat patients with metatases
receptor tyrosine kinase inhibitors (e.g. sorafenib, sunitinib) have been shown to have superior efficacy compared to interferon-alpha

Question 29

Indications for Partial Nephrectomy

Answer 29

-Absolute: Solitary kidney / Solitary functioning kidney
-Relative: Multifocal or bilateral renal tumours (esp with VHL) –aiming to avoid renal replacement therapy; advanced CKD
-Elective: Small (T1) peripheral tumour with normal contralat kidney

Question 30

Renal cell cancer prognosis 5 years

Answer 30

-T1: 70-95%
-T2: 50-75%
-T3: 22-70% (25% in T3c IVC wall invasion)
-T4: 5-40%

Question 31

Epidemiology of upper tract urothelial Ca/TCC

Answer 31

-UTUC (Upper Tract Urothelial Ca)/ UT-TCC of the renal pelvis or ureters

-Incidence: Rare - ~5% of all TCC, Less common than RCC
-Aetiol: As per bladder Ca- smoking, azo dyes etc; Also- HNPCC, Balkan nephropathy (aristocholic acid)
-Age: Peak incidence 70y+
-Sex/Gender: M:F is 3:1

Question 32

Presentation of upper tract urothelial Ca/TCC

Answer 32

Painless visible haematuria +/- clots, Loin pain / clot colic, incidental

Question 33

Investigation of UTUC

Answer 33

Flexi Cysto + CT Urogram (filling defect)

Question 34

Management and Rx of UTUC

Answer 34

-Confirm Dx: Ureteroscopy + Bx
-Stage the disease: CT Urogram + CT Chest

-Rx:
=Localised-Laparoscopic Nephroureterectomy (LNU)
=Advanced- palliative chemo/EBRT for bleeding
=Prognosis: dep on stage, 90% - 20%