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
***DDx of elevated PSA
- BPH
- Prostate cancer
- Prostatitis / Prostate subjected to acute retention of urine (AROU)
- Prostate trauma / manipulation
- biopsy
- massage
- surgery - UTI (SpC Revision)
Elevated PSA
- “Normal” <4 ng/ml
- ***Arbitrary value
—> ↓ threshold of 4 ng/ml —> more prostate cancer diagnoses with more unnecessary biopsies
—> ↑ threshold of 4 ng/ml —> less unnecessary biopsies with less cancer diagnosed
NB: ***Avoiding biopsy in patients will inevitably missing cancer no matter how high accuracy is increased!!!
Ways to increase PSA accuracy
- ***Age-specific PSA (∵ ↑ age —> ↑ prostate volume)
- 40-49 (2.5)
- 50-59 (3.5)
- 60-69 (4.5)
- 70-79 (6.5) - ***PSA density
- ***Free / Total PSA
- ↓ % free PSA (more bound to serum protein) —> ↑ % of cancer - PSA doubling time
- PSA velocity
- ***Prostate health index (PHI)
History taking for elevated PSA
- Reason for PSA test in the beginning (health check?)
- Confounding factors for PSA result
- UTI
- Retention of urine
(- BPH
- Prostatitis) -
**Symptoms suggestive of prostate cancer?
- **Haematuria / Haematospermia (uncommon)
- **Bone pain (advanced)
- **Lower limb weakness (advanced)
- ***Weight loss (advanced)
P/E for elevated PSA
- Signs of uraemia (obstructive uropathy) / cachexia (widespread metastasis)
- ***Lower limb weakness (cord compression)
- Abdominal examination
- **ballottable kidneys
- **distended bladder - PR exam
- anal tone
- **size, consistency of prostate
- **induration, nodules, median groove
Investigations of elevated PSA
- ***Prostate biopsy
- in absence of confounding factors
- after shared decision making with patient - Spurious PSA
- confirmed / refuted by another PSA ***4 weeks from last one (allow complete washout of PSA from serum)
***Prostate cancer (+ SpC Revision)
- Diagnosis
- Suspicion: **Elevated PSA +/- **Abnormal DRE
- Symptoms is absent in early disease
- Diagnosis: Can only be made by ***Prostate biopsy
—> Transrectal vs Transperineal
—> Template vs Fusion-targeted (i.e. Multiparametric MRI) - Clinical staging
- Assess extent of disease ***before treatment (compared to pathologic staging) - ***Clinical staging (Nomograms)
- DRE + PSA + Gleason score - ***+/- Radiologic imaging
- Multiparametric MRI
- Bone scan
- PET scan (18F-PSMA / 68Ga-PSMA)
(3. Pelvic lymphadenectomy)
- ***Risk stratification of prostate cancer
- Treatment
- Prostate cancer screening
Prostate biopsy
- ***Only means of diagnosing prostate cancer intentionally
- TRUS-Bx: biopsy done transrectally using transrectal USG (TRUS) guidance
- ambulatory (day-case) procedure
- topical / local (periprostatic block) anaesthesia
- antimicrobial prophylaxis before biopsy (∵ contaminated procedure)
- ***systemic biopsy obtained under TRUS guidance using trucut needle + Biopsy gun
- ***cancers cannot be seen by TRUS / USG
Common indications:
1. Elevated serum PSA
2. Abnormal PR exam
***given that:
- understand risk of prostate biopsy (3-4% PBI)
- diagnosis of prostate cancer would affect clinical management (usually <75 yo)
Complications:
Common, Self-limiting:
1. Haemospermia
2. **Haematuria
3. **PR bleeding
4. Dysuria
5. Transient increase in LUT symptoms
Uncommon, Serious:
1. Vasovagal syncope
2. **Acute urinary retention
3. **Post-biopsy infection
2021 Prostate biopsy:
1. MR/USG fusion-targeted biopsy
2. ***Transperineal prostate biopsy
- close to zero sepsis risk
- equal / better cancer detection rate (esp. anterior cancer)
Post-biopsy infection (PBI)
- 4.3%
- 11% required ICU care
- fever +/- chills/rigors as a result of prostate biopsy
- mostly within 1 week of biopsy (usually <24 hours)
- most required ***hospitalisation (∵ commonly associated hypotension / septic shock)
- some required intensive care + multi-organ support
- potentially fatal
Pathophysiology:
Local bacteria in rectum gained entry into systemic circulation / prostate during transrectal biopsy
—> Majority of susceptible bacteria eliminated by antimicrobial in circulation
—> Small number of remaining bacterial isolates trigger **sepsis + **SIRS in some patients
—> Possible additional insult from uropathogens esp. if there is concomitant ROU
Clinical staging (Nomograms)
Mathematical models combining pre-treatment parameters
—> ***Predict possibilities of ECE (extra-capsular extension), LND (LN disease), SVI (seminal vesicle invasion)
Example:
- MSKCC
Parameters commonly used:
1. **Serum PSA level
2. **Gleason score (primary / secondary)
3. ***Clinical T-stage (PR exam)
4. Positive + Negative biopsy core numbers
Risk stratification:
- Predicts **prognosis + **guide treatment decisions
***D’Amico stratification system:
1. Low risk
- PSA <= 10
- Gleason score <=6
- cT1 to T2a
- Intermediate risk
- PSA 10-20
- Gleason score 7
- cT2b - High risk
- PSA >20
- Gleason score 8-10
- >=cT2c
Radiologic imaging
2 aims:
1. Accurately stage disease to guide correct treatment (exclude metastatic disease)
- often necessary in intermediate - high risk disease
- ***Whole body bone scan
—> old standard
—> able to detect bone metastases only
—> 99m Tc labelled-methylene diphosphonate as radiopharmaceutical
-
**PSMA-PET scan
—> new standard
—> able to detect all sites of metastases
—> radiotracer-labelled **prostate specific membrane antigen (PSMA) antagonist is used
—> binds preferentially to PSMA (transmembrane receptor) which is overexpressed in prostate cancer cells (esp. aggressive ones)
- Treatment planning
- assessment of prostate for specific treatment e.g. radical prostatectomy
- ***Multiparametric MRI prostate
—> size of prostate
—> configuration of prostate
—> extraprostatic extension
—> seminal vesicle invasion
—> rectal wall involvement
—> LN enlargement
—> pelvic bone lesions / metastasis
Multiparametric MRI prostate
Done together with elevated PSA
- Detect suspicious lesions in prostate (compared to USG)
- Grade the suspicion as a result of MRI features during different sequence of MpMRI
—> **PiRADS (grade 1 (very low) to grade 5 (very high))
—> **grade 3 (20% risk) to 5 (>50% risk) need biopsy - Can provide target for targeted-biopsy in addition to standard template / systematic biopsy if MRI images can be “fused” into real-time TRUS images
—> ***MR/USG fusion-targeted biopsy
***Treatment of Prostate cancer (+ SpC Revision)
Stratified by Risk (D’Amico system):
1. Low risk
- AS
(WW can be option)
2. Intermediate risk
- Prostatectomy / RT
(AS / WW can be option)
3. High risk
- Prostatectomy / RT
(AS not an option, WW can be option)
Stratified by stages:
1. Organ confined disease
- Aim to cure
—> **Surgical extirpation (Radical prostatectomy)
—> **Radiotherapy
—> ***Active surveillance: Regular PSA + Regular DRE + Regular prostate biopsy (only suitable for low risk, low volume, low grade disease in suitable patients)
- Locally advanced disease
- Prostate cancer with **extraprostatic extension / **seminal vesicle invasion (SVI)
- Small volume regional **LN metastases
- Aim to cure
—> **Multimodal treatment necessary
—> Radical prostatectomy + Post-op RT / ADT
—> Neoadjuvant ADT + RT - Metastatic disease
- Aim NOT cure but palliate existing symptoms + prevent / delay complications
—> **Androgen deprivation therapy (ADT) (Surgical castration (Bilateral orchiectomy) / **Medical castration (Anti-androgen, LH antagonist))
—> ***Upfront additional therapy (Cytotoxic chemotherapy e.g. Docetaxel / AR-targeted agent e.g. Enzalutamide) - ***Castration resistant disease (CRPC)
- Cytotoxic chemotherapy (Docetaxel)
- AR-targeted agents (Enzalutamide, Abiraterone)
- Radium-223 (for predominantly bone metastasis)
- Personalised cancer immunotherapy (Sipuleucel-T)
Radical prostatectomy
Curative treatment for localised disease
- pathology excised
- results more reassuring for patients
- minimally invasive using robots
Follow up with PSA a reliable way
Complex major operation requiring expertise for good results
Morbidity:
- **Erectile dysfunction
- **Urinary incontinence
Complications:
- Low mortality (<0.3%)
- Erectile dysfunction 30% even with good nerve sparing
- Urinary incontinence
—> 1st year (30-40%)
—> after 1st year (10%)
- ***Bladder neck stricture
- Bleeding
- Rectal injury
- Problems related to GA
Radiotherapy
Advantages:
- No need operation
- No continence problem
Disadvantages:
- ***No histology
- Follow-up may create anxiety in patient
- Still have erectile dysfunction (up to 30%)
Complications:
- ***Cystitis
- Proctitis (up to 10%)
**Role in metastatic disease:
1. Urgent treatment for **spinal cord compression by tumour
2. **Pathological fracture in combination with Fixation surgery
3. **Pain relieving (irradiation for local control of symptoms)
Surgery vs RT
- Roughly ***equivalent cure / survival rates
- Different spectrum of complications
- Different follow-up methods
Method of treatment for local recurrence:
1. Post-surgery BCR (biochemical recurrence): **Salvage RT
2. Post-RT recurrence: **Salvage surgery (high risk)
Androgen deprivation therapy (ADT) in Prostate cancer
- Testosterone stimulates growth in >90% of prostate tumour cells
- Suppressing secretion of testosterone / inhibiting its effects at androgen receptor can control growth
- Used for years in advanced prostate cancer for delaying progression + relieve symptoms
- Proven to reduce ***morbidity from metastatic prostate cancer
—> Pathological fracture
—> Cord compression
—> Obstructive uropathy etc. - Response to castration ~1-2 years
Types:
1. **Surgical castration (Bilateral orchiectomy)
2. **Medical castration (Anti-androgen, GnRH antagonist, GnRH agonist)
SE:
1. **Hot flush
2. **Decreased libido
3. ***Erectile dysfunction
4. Anaemia
5. Decreased cognitive function
6. Fatigue
7. Gynaecomastia
8. Abnormal LFT
Prostate cancer screening
- Screening of prostate cancer by PSA testing NOT yet satisfy all of Wilson and Jungner criteria
—> **lack of accuracy in the PSA test
—> **no level 1 evidence that screening leads to ↓ in prostate cancer specific mortality - Conflicting results regarding survival benefit
—> ERSPC vs PLCO vs CAP studies
Consensus:
- PSA testing should be a shared decision between patient and doctor
- Shortcomings + Benefits of PSA tests to diagnose prostate cancer in asymptomatic patients must be explained clearly before testing
SpC Interactive tutorial: Urolithiasis
Epidemiology and Risk factors for Urolithiasis
Epidemiology:
- Life time prevalence of urolithiasis: 1-15%
- Affected by multiple factors
- Prevalence of urolithiasis in the US: 10-15%
- High recurrence rate: 50-70% (SpC Revision)
- 5% of ESRF is caused by Urolithiasis
Risk factors:
1. Gender: M>F = 2:1
2. Race: Caucasians > other ethnicities
3. Age: Uncommon<20, peaks 4th-6th decade
4. Geography / Climate (sweat a lot)
5. Occupation (less fluid intake / sweating a lot)
6. BMI / body weight / obesity (problem with alkalinising urine)
7. Water consumption
(Daily urine output >2L —> Less chance of stone)
Classification of stones
Based on stone chemistry:
1. Ca containing stones
- Calcium oxalate (60%)
- Hydroxyapatite (20%)
- Brushite (2%)
- Non-Ca containing stones
- Urate (7%)
- Struvite (7%)
- Cystine (1-3%) (hard stone)
- Others (1-3%)
Based on location:
1. Renal stone
2. Ureteral stone
3. Bladder stone
4. Urethral stone
***Urolithiasis mechanisms
Process:
1. Chemical nucleation
- Homogenous vs Heterogeneous nucleation
2. Crystal aggregation (from cellular debris)
3. Crystal growth
4. Crystal-cell interaction (∵ sharp edge cause injury + inflammation —> foreign body —> phagocytosis anchor stone to urothelium —> time for stone to aggregate)
5. Stone formation
Mechanism:
1. **Hypercalciuria
2. **Hyperoxaluria
3. **Hyperuricosuria
4. **Hypocitraturia
5. Low urine pH
6. Cystinuria
7. ***Infection stones (Triple phosphate stone)
Others factors in play beside solute concentration:
1. Inhibitors of urolithiasis
- ***Nucleation inhibitors (Citrate)
- Aggregation inhibitors (Mg, citrate, nephrocalcin, Tamm-Horsfall protein, bikunin, uropontin)
2. Urine pH
3. Urinary stasis
- Homogenous vs Heterogeneous nucleation
- Hypercalciuria
- Absorptive
- ***Renal abnormality
- ***Resorptive
- Primary hyperparathyroidism
- Sarcoidosis
- Malignancy-associated hypercalcemia
- Steroids
- Hyperoxaluria
- Primary
- Primary Hyperoxaluria Type I (PH)
- Primary Hyperoxaluria Type II - ***Enteric
- Fat malabsorption states (∵ fatty acids precipitate Ca from bowel —> less Ca to bind to oxalate in blood —> increase free oxalate)
—> Small bowel / Ileal resection
—> IBD
—> Jejunoileal bypass
—> Bypass surgery for bariatric purpose - Dietary
- High oxalate food (e.g. tea, spinach, chocolate) - Idiopathic
PH:
- AR
- ESRF by age 15 in 50% of patients
- Treatment : combined liver and renal transplants
- Hyperuricosuria
Urate:
- Enzyme degrading urate (uricase) absent in humans
- No known urinary inhibitors exist
- Solubility greatly depends on urine pH (other 2 factors urine vol and [urate])
- At pH 6.5, >90% urate remains soluble
- At pH 5.5, 50% crystallises
Causes:
1. **Excess dietary purine intake (animal protein)
2. **Gout (hyperuricemia)
3. ***Lymphoproliferative / Myeloproliferative diseases (∵ ↑ cell turnover —> ↑ uric acid production)
4. Hereditary deficiency of HGPRT (Lesch-Nyhan syndrome)
Effects of hyperuricosuria:
- Urate acid crystallisation (pH<5.5) —> Gouty diathesis
- Calcium oxalate formation through heterologous nucleation (pH>5.5) —> Hyperuricosuric calcium nephrolithasis (HUCN)
- Increased binding of GAGs that inhibit calcium oxalate aggregation
- Hypocitraturia
Caused by primarily metabolic ***acidotic states (Enhanced renal tubular absorption / Decreased synthesis in peritubular cells)
—> Acidosis reduces urinary citrates
—> Citrate a nucleation inhibitor
—> Predispose to stone nucleation
Causes:
1. Distal renal tubular acidosis (type I RTA) (Inherited / Acquired)
2. Chronic diarrheal states with alkali loss
3. Thiazide-induced
4. Idiopathic hypocitraturia
5. Excessive animal protein diet
- Low urine pH
- Predisposes to ***uric acid stone formation
- Now believed to be due to impaired ***ammonium excretion into urine in patients
- The underlying cause is now believed to be insulin-resistance tendency in some individuals
- Associated with increased body weight and obesity
- Cystinuria
- AR
- Defect in intestinal and renal tubular reabsorption of dibasic amino acids, one of which is cystine (others lysine, ornithine and arginine)
- Cystine very ***insoluble and found in very high concentration in urine
- Hard stone
- Infection stones
- Composed primarily of magnesium ammonium phosphate
- In addition may contain hydroxyapatite or carbonate apatite
- Formed in ***alkali conditions (pH >7.2)
- In the presence of ***urease
- Majority of ***staghorn stones are composed of struvite stones
Urease producing bacteria:
- Proteus
- Pseudomonas
- Providencia
- Klebsiella
- Staphylococcus spp.
- Mycoplasma, ureaplasma spp.
Other miscellaneous stones
- Xanthine stones
- Ammonium acid urate stones
- Medication-related stones
—> Indinavir
—> Triamterine
—> Silicate
—> Thiazides
—> Carbonic anhydrase inhibitors
—> Topiramate
Indinavir stone (for treating HIV):
- look like soft tissue on CT scan —> misled to think urinary tract tumour
Clinical features of Stones
- Asymptomatic
- ***Loin pain / renal / ureteral colic +/- N+V (Extreme pain)
- Haematuria (Gross / Microscopic)
- Upper tract infection, fever
- ***Sepsis +/- Septic shock (Pyonephrosis)
- Require urgent drainage of obstructed system to prevent mortality
—> Emergency Double-J stent insertion to relieve obstruction + drainage
—> Urgent percutaneous nephrostomy - Loss of kidney function
P/E:
1. Usually minimal physical signs
2. Fever / septic state
3. Loin tenderness
4. Ballottable kidneys
(- long standing ***partial obstruction + compliant renal tissue —> hydronephrosis
- complete obstruction —> pressure too big causing no glomerular filtration at all —> stop ballooning)
Investigation
- Baseline blood test
- WCC
- Ur, Cr
- Plt, INR
- CaPO4
- Urate - Urine microscopy
- Urine culture
- Urine pH
- Imaging
- KUB
- USG
- CT (***Plain, non-contrast (95-98% of stone visible already) / Contrast / CT urogram)
- Excretory urography (IVU)
- Retrograde pyelogram (RP)
- Radioisotope scintigraphy
Plain X-ray
- Easily accessible, quick
- Misses at least 30% of stones
—> Radiolucent stones (urate, xanthine, indinavir)
—> Mildly Radioopaque stones (cystine, struvite) - No information about the functional aspect
- No information about ?obstruction
(Andre Tan:
- Ureter exit from renal pelvis (L1 on left, L1/L2 junction on the right)
- Runs along tips of the transverse process
- Crosses in-front of the sacroiliac joint
- Runs laterally on the pelvic wall towards the ischial spine
- Curves anterior-medially to enter the bladder through the back at the VUJ
Points of constriction:
1. Pelvic-ureteric junction (PUJ)
2. Pelvic brim (near bifurcation of the common iliac arteries)
3. Vesico-ureteric junction (VUJ) – entry to the bladder)
CT (Non-contrast vs Contrast)
Non-contrast:
- Quick, identifies >95% of stones
- Also gives **extraurologic information
- Higher radiation dose
—> 10x KUB dose
—> KUB: 5-10x CXR
- Not as easily accessible in some centers
- Nowadays regarded as the investigation of choice for acute loin pain
- **Halo sign: edematous ureter around ureter stone
Contrast:
- **NOT used in acute loin pain evaluation
- But standard investigation in the workup of **gross hematuria / renal mass
- May add delayed / urogram phase = computer tomography urography (CTU) to outline ureters
Radioisotope scintigraphy
- Little role in acute loin pain evaluation
- But useful in assessing differential function of the two kidneys
- Used in planning surgery
- Isotopes used : DTPA, MAG3
***Management of Urolithiasis
***Options:
Medical:
1. Urine dissolution therapy (SpC Revision)
- Potassium citrate, Sodium bicarbonate
- Urate stones become soluble in alkaline urine
2. Medical expulsive therapy
Surgery:
1. ESWL (Extracorporeal Shockwave Lithotripsy)
2. RIRS (Retrograde Intrarenal Surgery) / Flexible URSL (Ureteroscopic Lithotripsy)
3. PCNL (Percutaneous Nephrolithotomy)
4. Open stone surgery
Summary:
1. Renal stones:
- <10mm: ESWL
- 10-20mm:
—> ESWL for non-lower pole
—> PCNL for lower pole (Other unfavourable factors: hard stones (high Hounsfield unit >1000), large SSD (skin-to-stone distance) etc.)
- >20mm: PCNL
(Others:
- RIRS
- Open stone surgery)
- Upper ureteric stone:
- <5mm: WW
- 5-10mm: URSL / ESWL
- >10mm: URSL / ESWL - Distal ureteric stone:
- <5mm: WW
- 5-10mm: URSL
- >10mm: URSL
***General principles:
1. Stone factor
- Size
- Number
- Composition
- Unilateral / Bilateral
- Patient factor
- Function of renal unit
- Anatomy of renal unit
—> Caliceal anatomy (e.g. calyceal diverticulum)
—> Obstruction
—> Renal anomalies (e.g. duplex / horseshoe kidney)
- Fitness for anesthesia
- Body habitus (e.g. obese —> large skin-to-stone distance —> ESWL difficulty focus shockwave)
- Bleeding tendency
- Susceptibility for radiation (e.g. pregnancy —> cannot do ESWL, PCNL, at most URSL) - Surgeon factor
- Specific technology available or not
Prevention of stone recurrence (SpC Revision):
1. Fluid intake
- To produce 2L of urine daily
- Clear water (not tea / soft drinks)
- Dietary advice
- Low-calcium diet actually increases urinary oxalate excretion
- Minimise animal protein (promote acidic urine —> promote urate formation), dietary oxalate, purines
- Na restriction - Medications
- Allopurinol (for hyperuricosuria)
- Potassium citrate (for hypocitraturia, low urine pH)
- ESWL (Extracorporeal Shockwave Lithotripsy)
- Overall SFR (stone free rate) at 3 months: 70%, depend on:
1. Size
2. Composition
3. Location
4. ESWL machine
Pros:
- Minimally invasive
- ***NOT need anaesthesia
- Can be performed multiple times
Cons:
- Indirect (c.f. intracorporeal lithotripters)
- **Subject to stone skin distance
- **May not work for hard stones (e.g. cystine / brushite)
- Limitations by renal anatomy (e.g. diverticulum / lower pole)
Absolute CI:
- **Bleeding tendency
- **Active urosepsis
- Pregnancy
Complications:
1. Stone fragment-related
- regrowth
- renal colic
2. Infection
3. Tissue effect
- renal haematoma
- CVS events
- GI perforation, liver / spleen haematoma
- RIRS (Retrograde Intrarenal Surgery) / Flexible URSL (Ureteroscopic Lithotripsy)
Direct fragmentation of stone with flexible uretero-renoscope and intracorporeal lithotripter
Pros:
- Minimally invasive
- **Direct fragmentation of stone
- Body habitus-independent
- **Can be used in patients with bleeding diatheses (vs PCNL)
Cons:
- ***Requires anaesthesia + radiation
- Technology driven
Complications:
1. Intra-op
- Ureteral perforation
- Mucosal injury
- Ureteral avulsion
- Early
- Fever
- Persistent haematuria
- Renal colic - Late
- Ureteric stricture
- Persistent vesicoureteral reflux
- PCNL (Percutaneous Nephrolithotomy)
Pros:
- Stone free rates least limited by caliceal anatomy
- ***Direct stone fragmentation: stone composition not a concern
Cons:
- **Requires anaesthesia (in most centers) + radiation
- **Bleeding tendency contraindicated
- Body habitus may be a hindrance (e.g. obese)
Complications:
- Overall complications rate ~15%
- Mortality (<0.5%)
1. Access
- Bleeding requiring transfusion (7%)
- Require embolization (1%)
- Require nephrectomy (rare)
- Perforation of adj viscus (bowel <1%)
- Hydrothorax in supracostal puncture (15%)
- Otherwise thoracic complications 1.5%
- Access failure (5%)
- Stone removal-related
- Infection (fever 10%, sepsis 1%) (∵ pyelovenous reflux since require saline infusion in inflate calyce —> sepsis)
- TUR syndrome (rare)
- Extravasation of irrigant (30%)
- Renal pelvis injury
- Urinoma (<1%)
- Residual stone (10%)
Steps:
1. Placement of ureteric catheter with/without occlusion balloon + retrograde pyelogram
2. Needle puncture to gain entry into pelvicaliceal system under pyelogram (patient in prone position to avoid puncture of bowel)
3. Dilatation of needle tract
4. Entry of nephroscope to fragment + Remove stones
(5. Placement of a nephrostomy tube for post-op drainage)
Ideal puncture:
- Minimal bleeding and complications
- Allows access to stone and renal pelvis
- Shortest distance from skin to stone
Puncture:
- **Lower pole (avoids supracostal puncture)
- **Posterior calyx (takes advantage of the “bloodless” plane)
- Transpapillary directed towards the renal pelvis (avoids infundibular puncture)
- Puncture from lateral side (kidneys are supplied by end artery with no anastomosis —> if puncture from medial side —> large segment of kidney tissues will be dead)
- Supracostal puncture (above 12th rib): enables access to upper pole, can gain access to most of calices (complications req. chest drains e.g. ***hydro/haemo/pneumothorax (c.f. 0.5% from subcostal puncture)
Pre-op preparation:
1. Patient assessment
- Routine bloods (CBP, L/RFT, INR)
- T&S
- MSU
—> Preferably sterile (no growth)
—> Any positive culture must be treated before OT
- Stone assessment
- KUB
- IVU / CTU / Retrograde pyelogram (for detailed caliceal anatomy)
- Nuclear renal scan (for differential function of affected kidney)
- Serum calcium, phosphate, urate
- Urine pH (for underlying metabolic abnormality and stone type)
Antibiotics on induction:
- Must be given in PCNL (stone usually is infectious)
- Choice influenced by preoperative urine culture
- Cover **urease producing organism
- Antibiotics should be able to deal with **Pseudomonas
—> Aminoglycosides (eg. gentamicin, amikacin)
—> Pipericillin / tazocin / ticarcillin / timentin
—> 3rd generation cephalosporins (eg. sulperazone)
Dilation system:
1. Alken’s system
2. Balloon dilator
Nephroscopy:
- Rigid nephroscope
- Flexible cystoscope
Intracorporeal lithotripters:
- Ultrasonic
- Ballistic (Lithoclast)
- Laser (Holmium:YAG)
- Electro-hydraulic (EHL)
Nephrostomy tube:
- allow drainage from pelvi-caliceal system that has been expanded / injured during PCNL as the normal route (PUJ / ureter) will likely be inflamed and obstructed
- to have a tamponade effect on tract
- to leave access for 2nd look PCNL
- Open stone surgery
Procedures:
1. Pyelolithotomy
2. Anatrophic nephrolithotomy
- Seldom used nowadays to remove renal stones
- Much morbidity and blood loss
- Significant damage to renal function c.f. endourological techniques
Staghorn stones
- Defined as stone occupying renal ***pelvis
- extending to ***>=1 of the major calices
- Partial vs complete staghorn
- Most are composed of ***struvite stone
- Untreated staghorn stone destroy the affected kidney and leads to raised mortality in patient
Untreated staghorn stones:
- 10 yr mortality 28%
Treated staghorn stones:
- 10 yr mortality 7.2%
Management of Ureteral stones
Options:
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
Site of impaction:
- PUJ
- Pelvic brim
- Iliac bifurcation
- VUJ
Chance of passage:
- Stone <5mm likely to pass spontaneously
- Medical expulsive therapy
For stone <=5mm (esp. in distal ureter)
- Calcium channel blockers (Nifedipine) + Steroids
- ?Alpha-Adrenergic blockers (Tamsulosin)
- presence of large numbers of alpha 1 adrenoceptors in the distal ureter
- inhibit basal ureteral tone and peristaltic frequency
- decrease the intensity of ureteral contractions
Indications for urgent drainage in Ureteral stone
- Sepsis
- Intractable pain
- Deterioration of renal function
- Anuria
- Single functioning kidney
- Bilateral ureteral stones
SpC Interactive tutorial: Urological cancer
Angiomyolipoma
- Strongly associated with ***Tuberous sclerosis
- Benign renal tumour
***Lenk’s triad:
1. Loin mass
2. Acute loin pain
3. Hypovolaemic shock
Wunderlich syndrome:
- **Spontaneous non-traumatic renal haemorrhage occurs into the **subcapsular + ***perirenal space
CT scan:
- Fat within tumour (**-ve hounsfield unit (less dense than H2O))
- Vessels within tumour (have **contrast enhancement if given contrast ~RCC)
Treatment (SpC Clinic):
1. Embolisation
2. Partial Nephrectomy
(Tuberous sclerosis (From ERS27):
- TSC1/2 mutation —> too much mTOR activation —> abnormal cell growth/proliferation
- Rare multisystem AD genetic condition
- non-cancerous tumours in brain / other vital organ
Clinical features:
ASHLEAF
1. Ashleaf spots
2. Shagreen patches
3. Heart rhabdomyosarcoma
4. Lung hamartoma
5. Epilepsy due to cortical tubers
6. Angiomyolipoma in kidney
7. Facial angiofibroma (acne-like)
Treatment:
Rapamycin (Sirolimus) / Everolimus (2nd gen rapamycin derivative)
—> suppress mTOR pathway)
