Urology JC072: Common Presentation For Common Urology Disease: Blood In Urine And Raised PSA In Blood Test Flashcards
Haematuria
- Bloody urine
- Presence of ***abnormal amount of RBC in urine
- ~20% adult urology consultations
2 types:
1. Gross (visible) (VH)
- alarming symptom (patients usually will not delay in seeing doctor)
- **Painless haematuria is **cancer until proven otherwise
- always demand complete investigation (need to workup even not suspect cancer)
- Microscopic (non-visible) (NVH)
- ***>=3 RBC per high power field on microscopic examination
- 2.4 - 31.1% amongst healthy volunteers (i.e. can be normal finding)
Risk of malignancy in patients with VH / NVH from 1-3.1% —> majority ***Bladder cancer
***DDx of Haematuria
- Menstrual blood contamination
- Concentrated urine due to dehydration
- ***Bilirubinuria (tea colour urine in obstructive jaundice)
- ***Myoglobinuria (rhabdomyolysis)
- ***Haemoglobinuria (haemolysis)
- Pigments in urine
- Betanin (Beeturia)
- Azo (Phenazopyridine / Pyridium)
- ***Rifampicin
Dipstick haematuria
- Microhaematuria discovered just on dipstick alone
- Relies on perioxidase activity of Hb on a chromogen on dipstick
- Dipstick +ve: 20-74% have **normal urinalysis on microscopic examination
—> ALL dipstick haematuria **must have microscopic examination to confirm / refute microscopic haematuria
False +ve:
- menstrual blood
- **haemoglobinuria
- **myoglobinuria
- dehydration
False -ve:
- **urine with high SG (specific gravity)
- **high level of ascorbic acid
- ***nitrites
- pH <5
- proteinuria
***Causes of Haematuria
Classified based on pathology, anatomical location, surgical vs medical etc.
- ***Neoplastic
- RCC
- Urothelial carcinoma
- Prostate cancer
- Angiomyolipoma - ***Infective
- UTI
- GUTB (Genitourinary tuberculosis)
- Schistosomiasis - ***Calculus
- Renal stones
- Ureteral stones
- Bladder stones - ***Trauma
- Blunt
- Penetrating - Others
- ADPKD (**AD polycystic kidney disease)
- **BPH
- Irradiation cystitis
- ***Bleeding tendencies
- Anticoagulation
Timing of haematuria
Whole stream / Start stream / Terminal stream / Haematuria independent of micturition (i.e. Urethral bleeding)
- each signifies a ***different location of origin of bleeding
- except for urethral bleeding, most of timing difficult to be relied upon in practice
Start stream: Distal to UG diaphragmatic (落d)
Terminal stream: Bladder neck / Prostatic urethra (上d)
Throughout: Bladder / Upper urinary tract (再上, ∵血一早係尿裡面)
Nephrological causes of microscopic haematuria
Most nephrological causes —> Microscopic haematuria only
Hallmark of nephrological causes:
1. ***RBC casts
- RBC extravasated into tubular lumen + trapped within solidified Tamm-Horsfall protein matrix (commonest protein noted)
- ***Dysmorphic
- RBC with irregular shape + contour (∵ result of passage through defective basement membrane of glomerulus + subsequent osmotic injury during passage through tubular lumen) - Proteinuria
Causes:
1. **IgA nephropathy
2. **Alport’s syndrome
3. Henoch-Scholein purpura (IgA vasculitis)
4. Goodpasture syndrome
5. Acute interstitial nephritis
6. Acute nephritic syndrome
***History taking of Haematuria
- Gross / Microscopic
- ***Painless / Painful
- Timing of haematuria (difficult to be relied upon)
- Onset, Duration, Precipitating / Exacerbating factors of haematuria
- Associated symptoms
- **Loin pain
- **Fever (infection)
- ***LUTS
- Stone passage - Social history
- Smoking
- **Occupational exposure to carcinogens (e.g. **aromatic amines) - Family history
- ***ADPKD
- Urolithiasis - Drug
- ***Anticoagulants
(9. Trauma
- Social history
- Foreign travel (Schistosomiasis))
***P/E of Haematuria
Often unremarkable
1. General examination
- Abdominal examination
- **Ballottable kidneys?
- **Pelvic mass? - External genitalia
- PR exam
***Investigations of Haematuria
Baseline, Non-invasive:
1. CBC (Hb, WCC)
2. **RFT (Ur, Cr)
3. **Urinalysis
4. ***Urine culture
(5. EMU (for AFB, low yield, ∵ less prevalence of GUTB now)
6. Urine cytology
- poor sensitivity
- avoid morning urine (∵ cell lysis after prolonged period)
- whole stream urine to increase yield)
Gross haematuria:
1. **Lower tract imaging: **Cystoscopic examination of urinary bladder (mandatory)
- Flexible / Rigid
-
**Upper tract imaging (mandatory)
- USG
- IV urogram
- **CT urography (now used)
- MR urography
(- Antegrade / Retrograde pyelography)
Flexible cystoscopy
- ***Mainstay of diagnostic cystoscopy now
- Done in office / endoscopy suites
- Topical analgesia
- Cannot be replaced by other investigations now (e.g. USG)
Assess:
1. Anterior urethra
2. Posterior urethra
3. Bladder
USG
Advantages:
- easily accessible, can be done at bedside
- can detect **hydronephrosis readily
- can see **renal stones’ presence
- “secondary” information about function (e.g. obstruction) —> indirect evidence of obstruction (in Hydronephrosis)
Disadvantages:
- does NOT give information about ureteral stones
IV urogram / Excretory urogram
- Time-honored investigation
—> Scout, Nephrogram, 5 min, 10 min, PM
—> Compression, Prone views
Advantages:
- Gives information about **Function (∵ kidneys with no function —> cannot excrete contrast)
- **Direct evidence of obstruction
Disadvantages:
- Involves contrast with risk of **anaphylaxis + nephrotoxicity
- Can miss small tumours in **parenchyma
Contrast CT urogram/ CTU
***Standard investigation in workup of gross haematuria / renal mass
Delayed / Urogram phase added —> CTU to outline ureters
Advantages:
- Good quality images
- Can do **reconstruction to outline **vascular system (useful for pending donor nephrectomy)
MR urography
Advantages:
- ***No radiation —> may be considered in selected patients e.g. pregnancy, iodinated contrast allergy
Disadvantages:
- Image quality **inferior to CT for **moving organs e.g. kidneys (move with respiration)
- Poor images for ***stones (appears as signal void)
Retrograde pyelogram
Advantages:
- Mandatory in selective situation where excretion of contrast cannot be used to outline urologic tract (i.e. IV urogram cannot be used)
- Can **intervene at the same time e.g. insertion of **ureteral stents to relieve obstruction
Disadvantages:
- Require use of **cystoscopy —> **invasive
***Investigations for Microscopic haematuria
AUA risk stratification system:
1. Low risk group
- Repeat urinalysis in 6 months
or
- Cystoscopy + ***USG kidneys
- Intermediate risk group (older, smokers, higher RBC)
- Cystoscopy + ***USG kidneys - High risk group
- Cystoscopy + ***CT urogram
Urine cytology
- Detects abnormal cells in ***freshly voided urine
- Only positive in **High grade cancer + **CIS of bladder
- Negative in most Low grade bladder cancer
- should NOT be used as 1st line investigation for haematuria
Urine cytology for detection of bladder cancer:
- Low sensitivity (~50%)
- ***High specificity (96%) —> only applies to suspicious / cancerous result
Depends on experience of cytopathologist:
5 types of results:
1. Unsatisfactory for examination (low specificity)
2. Negative for malignant cells (low specificity)
3. Atypical cells (low specificity)
4. **Suspicious for malignancy
5. **Carcinoma cells present
—> ONLY 4,5 have high specificity for cancer
***Pathologies with haematuria
- RCC
- Bladder cancer
- Upper tract urothelial carcinoma (UTUC)
- cancer of urothelium (renal pelvis, ureter, bladder, urethra) - Renal stone
- Ureteral stone
(6. Prostate cancer)
Urological cancer (SpC Revision)
Upper tract:
1. Kidney
2. Ureter
Lower tract:
1. Bladder
2. Prostate
3. Urethra
4. Penis
5. Testes
- Renal cell carcinoma (RCC)
- Rising incidence
- Now radiologist’s tumour
- Not an aggressive cancer
- M:F = 2:1
- Peak at 65 yo
Risk factors:
1. Smoking
2. Dialysis (acquired renal cystic disease) (30x risk)
3. Hereditary cancer syndromes
- ***Von Hippel-Lindau disease (VHL)
4. ?Obesity, asbestos, cadmium exposure
Commonest pathology:
- ***Clear cell type
Clinical triad (now very very rare, <10%):
1. Renal mass
2. **Loin pain
3. **Haematuria
Other features:
1. Possible venous thrombus formation (up to IVC, RA)
- ***Varicocele (left renal vein thrombosis)
- IVC thrombus
-
**Paraneoplastic syndrome (up to 30%)
- **Stauffer syndrome (Isolated ALP elevation) (Diagnosis of exclusion, other DDx: Liver / Bone metastasis —> Heat labile test)
- Hypercalcaemia
- Hypertension
- Polycythaemia
- Anaemia
- Fever - Hereditary cancer syndromes
- ***Von Hippel-Lindau disease (VHL)
—> VHL gene on chromosome 3p25
—> predispose to young onset bilateral RCC
Investigations:
1. **Triple phase CT renal protocol + **Staging
- Renal parenchymal mass with **thickened irregular walls + **enhancement after contrast injection (∵ tumour is vascular) —> suggest malignancy (Andre Tan)
- **Contrast enhancing mass in kidney **without fat content ~80% chance RCC (SpC Revision)
- Small renal mass <4 cm: Malignant rate 80-85%
- CXR
- Rule out lung metastasis - PET
- 18F-FDG +/- C11-acetate
- Not routine, in suspected metastatic disease only - Biopsy
- Differentiate Malignant vs Benign
Treatment of RCC
Localised RCC:
1. ***Surgical extirpation
- Partial nephrectomy (aka Nephron-sparing surgery (NSS)) (for small renal mass <3-4cm, esp. exophytic)
- Total / Radical nephrectomy
- Ablative therapies (for patients unfit for GA, background of advanced malignancy, done by LA)
- ***RFA
- Cryotherapy
(Percutaneous vs Open / Lap) - Active surveillance
- Poor risk patients with small tumours
Locally advanced RCC;
- RCC with renal vein / IVC / RA thrombus (a peculiar features of RCC)
- Levels of thrombus (Novick vs Zincke classification)
1. ***Radical nephrectomy + Caval thrombectomy
- In absence of distant metastasis, aggressive surgery is a curative option
Metastatic RCC:
Targeted therapy (∵ RCC is **chemo-resistant + **RT-resistant)
1. ***Immune check point inhibitors
- Pembrolizumab, Nivolumab, Ipilimumab
- ***Tyrosine-kinase inhibitors
- Pazopanib, Sunitinib, Sorafenib, Axitinib - ***Anti-VEGF (SpC Revision)
- Bevacizumab - Combination of above (gives best results)
Partial nephrectomy (Nephron-sparing surgery (NSS))
Nephron sparing more technically challenging with higher complication rate than Radical nephrectomy
Absolute indications:
- Localised malignancy in patients with only one kidney (need to preserve kidney tissue)
- Bilateral synchronous renal lesions (need to preserve kidney tissue)
Relative indication:
- Renal tumours in patients whose contralateral kidney is threatened by local, systemic, genetic risk factors (e.g. hypertensive / DM nephropathy)
Elective indication:
- T1 tumours
- Bladder cancer
Risk factors:
1. **Smoking
2. Men
3. Age
4. White
5. Drugs (e.g. **cyclophosphamide)
6. ***Occupational / Carcinogen exposure (e.g. aromatic amines)
- Rubber
- Dye (newspaper factory)
- Hairdressers
- Plumbers
- Painters
- Petrol station
2 types:
1. **Non-muscle invasive (NMI) (Ta, T1, CIS)
- BAUS risk stratification —> Low / Intermediate / High
2. **Muscle invasive (MI) (>=T2)
CIS in bladder cancer:
- High grade tumour
- BAD!
- Extensive involvement within bladder wall without a fungating mass —> cannot be seen on cystoscopy
Histological types of Bladder cancer
Carcinoma:
1. Urothelial carcinoma (aka Transitional cell carcinoma)
- Adenocarcainoma
- Primary (Remnant of urachus in ***dome of bladder —> Glandular cells)
- Secondary (from other regions) - SCC
- Chronic irritation due to long-term catheter / stone
- Schistosomiasis
Sarcoma (rare, previous RT)
Treatment of Bladder cancer
-
**Staging TURBT (transurethral resection of bladder tumour) + **Mitomycin C instillation
- **All bladder cancers need to have to determine accurately the stage
- **Diagnostic + **Potentially therapeutic (depend on stage of tumour)
- If Primary-look TURBT fail to show muscle invasion
—> **Second-look TURBT indicated in selected cases to avoid understaging
- ***Immediate instillation of single dose MMC (Mitomycin C) after TURBT (significantly ↓ bladder recurrence but NOT progression)
NMI Ca bladder:
1. **Regular surveillance cystoscopy
- High recurrence rate (20-90% at 1 year) —> Need regular surveillance cystoscopy
- Subgroup with high recurrence + high progression rate (progress to MI: metastasis):
—> **T1HG disease
—> ***CIS disease
T1HG / CIS disease (High risk NMI Ca bladder):
2. **BCG (immunotherapy) induction + maintenance
- ↓ Recurrence + progression
- Live attenuated Mycobacterium bovine
- Uncertain mechanism
- Need to hold urine for 2 hours + change posture (for BCG to coat bladder)
- SE: **BCG sepsis (reactivation of TB)
3. **Early total cystectomy
4. If failed BCG —> **Radical cystectomy + Urinary diversion
MI Ca bladder:
1. **Radical cystectomy + **Urinary diversion
- Urinary diversion
—> Continent (Neobladder / Catheterisable pouch)
—> Incontinent (Ileal / Colonic conduit / Ureterostomy (obsolete))
- Without treatment: 85% 2 year mortality
- Radiotherapy (Trimodality treatment)
- Chemo + RT + Maximum TURBT (at least clear intraluminal pedunculated part)
- **Inferior treatment alternative
- **Palliative role in unresectable disease - Chemotherapy
- ***Pembrolizumab
- Neoadjuvant in locally advanced disease before surgery
- Metastatic disease
Staging TURBT + EUA
- All bladder cancers need to have to determine accurately the stage
- **Diagnostic + **Potentially therapeutic (depend on stage of tumour)
- ***Second-look TURBT indicated in selected cases to avoid understaging (if Primary-look TURBT fail to show muscle invasion)
Procedure:
- Irrigation fluid: Glycine
- Beware of obturator kick (obturator nerve stimulated during diathermy —> perforate bladder wall)
- **Deep muscle resection (to biopsy of muscle layer)
- **Cold-cup biopsy
- **Bimanual examination under anaesthesia (EUA)
- Post-op **Mitomycin C instillation
—> ↓ Recurrence risk by 30% but NOT progression
—> Kill off free floating cancer cell to prevent seedling
Complication:
1. ***Bladder perforation
2. Bleeding
3. Infection
4. Recurrence
5. Incomplete resection
Consent:
- Further adjuvant treatment
- +/- Catheterisation
- Upper tract urothelial carcinoma (UTUC)
- Disease of elderly (70-80s)
- Future bladder cancer up to 75% (∵ downstream seedling, field change effect, greater number of urothelial cells in bladder)
- But bladder cancer —> only 5% UTUC (∵ cancer cells cannot go upstream)
Risk factors:
- Similar to Ca bladder
1. **Smoking etc.
- Unique to UTUC:
2. **Aristolochia fangchi (Chinese herb nephropathy, 廣防己)
3. **Aristolochic acid (Balkan endemic nephropathy)
4. Arsenic poisoning (Blackfoot disease, 烏腳病)
5. **Lynch syndrome / HNPCC
Investigations:
- Retrograde ureterogram
—> ***Goblet sign (酒杯形: distal + proximal ureteric dilatation due to slow growth)
Treatment:
1. ***Nephroureterectomy (with removal of a bladder cuff)
- high rates of bladder recurrence (50%) —> need regular surveillance cystoscopy
- ***Partial ureterectomy + reconstruction
- need surveillance ureteroscopy
- Stone (Renal / Ureteral)
***Options:
1. ESWL (Extracorporeal Shockwave Lithotripsy)
2. RIRS (Retrograde Intrarenal Surgery) / Flexible URSL (Ureteroscopic Lithotripsy)
3. PCNL (Percutaneous Nephrolithotomy)
4. Open stone surgery (Pyelolithotomy / Anatrophic nephrolithotomy / Ureterolithotomy)
Management principles:
1. Stone factors
- size
- number
- composition
- uni / bilateral
- Patient factors
- anatomy
- fitness for anaesthesia
- bleeding tendency
- susceptibility for radiation
- renal unit function - Surgeon factors
- expertise
- availability of specific technology
Renal stones:
- <10mm: ESWL
- 10-20mm: ESWL for non-lower pole / PCNL for lower pole (Other unfavourable factors: hard stones, large SSD (skin-to-stone distance) etc.)
- >20mm: PCNL
(Others:
- RIRS
- Open stone surgery)
Ureteral stones treatment:
1. Watchful waiting (WW) for them to pass naturally
2. Medical expulsive therapy
3. **Ureteroscopic lithotripsy (URSL: Ureteroscopy and laser stone fragmentation)
4. **Ureterolithotomy (Open stone surgery)
5. ***PCNL
Upper ureteric stone:
- <5mm: WW
- 5-10mm: URSL / ESWL
- >10mm: URSL / ESWL
Distal ureteric stone:
- <5mm: WW
- 5-10mm: URSL
- >10mm: URSL
***Prostate-specific antigen (PSA)
- aka Human kallikrein peptidase 3 (hK3)
- a serine protease coded by hKLK3 gene (one of 15 genes in kallikrein gene family)
- ***exclusive in prostate epithelial cells
- expression highly ***androgen-dependent
- t1/2: 2-3 days
Main physiological function:
- **Liquefy semenogelin + fibronectin within **semen (causes gel formation) after ejaculation
Normally PSA only released into seminal fluid, ***small amount released into circulation
—> differ in amount in 10^6
PSA elevation arises from:
1. Disruption of cellular architecture within prostate from diseases (eg. BPH, cancer)
2. ***Prostate manipulation (e.g. trauma, biopsy)
Both benign / cancerous prostate cells produce PSA (Similar amount) but **disruption of basement membrane etc. is more marked in cancer
—> releasing **more PSA into circulation than BPH
Factors affecting PSA level other than cancer:
1. **Age (0.04 ng/ml per year)
2. Race (black)
3. **Prostate volume (∵ more prostate cells)
PSA:
- an **organ-specific marker at best
- **NOT cancer-specific
- large overlap between benign + malignant causes underlying elevated PSA
PSA test in HK:
- one of most commonly ordered test in “health screening” amongst asymptomatic male patients
- promote stress + anxiety
