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MBBS IV - Junior Clerkship WCS > JC72 (Surgery) - Hematuria, Kidney stones, PSA, BPH, Prostate Cancer > Flashcards

JC72 (Surgery) - Hematuria, Kidney stones, PSA, BPH, Prostate Cancer Flashcards

1
Q

Renal causes of haematuria

A
  1. Glomerular:
    Glomerulonephritis
2. Tubular and parenchymal:
Polycystic kidney
Pyelonephritis 
Renal infarction 
RCC
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2
Q

Classical triad of presentation for RCC

A

flank pain (rare), painless haematuria and palpable flank mass (rare)

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3
Q

Post-renal causes of haematuria

A

Stone: Urolithiasis

Infection: UTI (rare)

Tumor: CA bladder, prostate

Trauma: Blunt trauma, iatrogenic e.g. catherization, TURP…etc

BPH

Non-infectious cystitis: previous radiation, chemotherapy

Exercise-induced hematuria: transient

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4
Q

Non-renal causes of haematuria

A

Benign idiopathic hematuria (rare): a/w exercise, febrile illness or vaccination, familial

Bleeding tendencies (rare): hematological disorders, anti-coagulants…etc

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5
Q

Define gross vs microscopic hematuria

A

□ Gross: visibly bloody or brown urine (as little as 1mL of blood/L urine)

□ Microscopic: >3 RBC per high-power field in ≥2 of 3 freshly voided, clean catch samples

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6
Q

False mimics of gross and microscopic hematuria

A

Gross:
→ Food: beetroot (anthrocyanins) → red urine
→ Drugs: levodopa (dark), senna, rifampicin, pyridium (orange)
→ Diseases: porphyria, alkaptonuria, bilirubinuria

Microscopic:
→ Menstruation (F)
→ Dehydration (concentrates urinary RBCs)
→ Heme in urine (also have peroxidase activity)
- Myoglobinuria due to rhabdomyolysis
- Haemoglobinuria due to intravascular haemolysis

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7
Q

List false positives and false negatives of dipstick hematuria

A

False positive: menstrual blood, hemoglobinuria, myoglobinuria, dehydration

False negative: Urine with high solute gradient, High ascorbic acid level, Nitrites (UTI), pH <5.0, Proteinuria

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8
Q

Define significance of initial stream, terminal stream and whole stream hematuria/ Timing of hematuria

A

□ Initial stream → anterior urethra (distal to urogenital diaphragm)
□ Terminal stream → bladder neck or posterior urethra
□ Throughout → bladder and upper urinary tract

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9
Q

Differentiate extraglomerular and glomerular hematuria

  • Color
  • Clots
  • Proteinuria
  • Urine microscopy
A
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10
Q

Hallmarks of nephrological causes of microscopic hematuria

A
  1. RBC cast - RBC extravasated into tubular lumen and complex with Tamm-Horsfall protein matrix)
  2. Dysmorphic RBC - RBC passage through defective basement membrane with osmotic damage
  3. Proteinuria
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11
Q

List nephrological causes of microscopic hematuria

A 
Autoimmune diseases:
- Berger's disease/ IgA nephropathy 
- Henoch-Scholein purpura/ IgA Vasculitis (lower limb purpura, arthralgia, hypertension)
- Goodpasture syndrome/ Anti-GBM disease (autoimmune disease vs kidneys and lungs)


Acute interstitial nephritis (mostly from infection or allergic drug reactions)
Acute nephritic syndrome

Alport's syndrome (SN deafness, Lens dislocation, mutation in collagen type IV)
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12
Q

Define irritative and obstructive LUTS

A

Irritative symptoms: frequency, urgency/urge incontinence, nocturia
→ Indicates storage problem (bladder pathology)

Obstructive symptoms: hesitancy, weak stream ± straining, terminal dribbling, incomplete emptying
→ Indicates voiding problem (urethral obstruction)

Dysuria: indicates ongoing infection or inflammation → UTI

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13
Q

Ddx painful and painless hematuria

A

Painful:
→ Loin pain → pyelonephritis, renal infarct, rarer causes (RCC, renal stones, GN)
→ Ureteric colic → ureteric stone or bleeding with clot colic in upper tract
→ Suprapubic pain → cystitis
→ Perineal pain → prostatitis

Painless: classically, painless gross haematuria in >35y/o = malignancy
→ Malignancy (esp if in advanced age)
→ Renal parenchymal diseases, eg. glomerulonephritis

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14
Q

Risk factors for urological malignancies

A

□ Male, advanced age (>35y), smoker118

□ Occupational exposure to chemicals or dyes (esp jobs involving plastic, petroleum, organic solvents)

□ Drugs, eg. aristoochic acid in TCM, cyclophosphamide, analgesic abuse

□ Hx of prior urinary sympotoms: gross haematuria, urological disease, irritative urinary symptoms, chronic UTI

□ Previous surgical/ medical: chronic indwelling FB, Radiation

□ FHx of renal cell carcinoma (FHx of urothelial CA is NOT a/w ↑risk)

□ FHx of kidney diseases, eg. polycystic kidney disease, stone disease

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15
Q

Outline P/E for hematuria

What to look for?

A

Vitals: fever (pyelonephritis), HTN (nephritic syndrome)

General examination: pallor (anaemia), oedema (GN), rashes (vasculitis, CTD), bruises (bleeding tendency)

Abdominal examination:
□ Loin tenderness → renal pathology
□ Ballotable renal mass → RCC (rare), polycystic kidney, gross hydronephrosis (rare)
□ Renal bruit → renal artery stenosis (infarction)
□ Distended bladder → bladder outflow obstruction

DRE and external genitalia:
□ DRE for pelvic mass and prostatic enlargement
□ Varicocele may be due to large Lt RCC extending into renal vein
□ Urethra for urethral bleeding, clots

± other systems:
□ CVS: new murmurs (endocarditis)
□ Lungs: crackles, wheezes (Goodpasture’s syndrome)

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16
Q

First-Investigations for hematuria (excluding imaging)

A

Blood:
□ CBC: anaemia (uncommon in haematuria alone), leukocytosis (UTI)
□ RFT: renal impairment and electrolyte abnormalities

Urinalysis
1. Repeat dipstick to confirm haematuria and detect other pathologies
2. Biochemistry for protein and glucose
3. Microscopy: centrifuged
→ Confirm presence and delineate morphology of RBC
→ Detect WBC (pyuria = >5WBC/HPF) and organisms
4. Microbiology:
→ Culture and sensitivity → exclude UTI
→ EMU × AFB → exclude urinary tract TB
5. Cytology for malignant cells

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17
Q

2 mandatory investigations for gross hematuria

A

Cystoscopic exam of bladder

Upper tract imaging

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18
Q

List all imaging modalities for Ix of hematuria

A

Cystoscopy (standard)

Upper tract imaging (standard): Non-contrast CT, Ultrasound, CT urogram*, MR urogram, IV urogram

XR kidney, ureter and bladder (KUB)

Invasive:

  • Retrograde pyelogram
  • Ureteroscopy
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19
Q

Flexible cystoscopy

  • Indication
  • Function
  • Field of examination
A

Indication: ALL patients with gross non-glomerular haematuria

Direct visualization of pathology, biopsy for histopathology

Field: Anterior and posterior urethra, entire bladder

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20
Q

USG for Ix of hematuria

  • Indication
  • Advantage
  • Disadvantage
A

Indication:
Bedside screening for hydronephrosis, renal mass, renal stones

Advantage:

  • Detect renal and bladder lesions
  • Allow prostate size measurement

Disadvantage:

  • Cannot detect ureter lesions e.g. ureteral stones
  • Indirect evidence of obstruction
  • No functional information
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21
Q

IV urogram

  • Indication
  • Advantages
  • Disadvantages
A

Indication:
Upper tract imaging

Advantage:

  • Direct evidence of obstruction
  • Functional assessment

Disadvantage:

  • Contrast anaphylaxis, nephrotoxicity
  • Miss small parenchymal tumors
  • No coronal and sagittal imaging
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22
Q

MR urogram

  • Indications
  • Advantages
  • Disadvantages
A

Indications: pregnancy, contrast allergy, children, renal impairment

Advantage: No radiation

Disadvantage: image inferior to CT scan, poor images for stones, expensive

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23
Q

Invasive urogenital imaging

  • Examples
  • Indications
A

suspicious of serious pathology, eg. cancer, strictures

□ Eg. retrograde pyelogram: injection of contrast by catheterization of lower ureter via cystoscopy
□ Eg. ureteroscopy for brush cytology

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24
Q

Risk stratification system for microscopic haematuria

Investigations of low, intermediate and high risk patients

A

AUA microhematuria risk stratification system:

Low risk: repeat urinalysis in 6 months or Cystoscopy + USG kidneys

Intermediate risk: Cystoscopy + USG kidneys

High-risk: Cystoscopy + CT urogram

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25
Q

Urine cytology for malignant cells

  • Recommended or not? Why?
  • Specificity and sensitivity
A

Not recommended

  • Only positive in HIGH grade cancer
  • Negative in most low grader bladder cancer
  • Poor sensitivity (50%) for bladder cancer
  • Dependent on cytopathologist experience
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26
Q

List 2 iatrogenic causes of cystitis

Associated history/ diseases

A

Irradiation cystitis
Context:
→ Usually delayed for a few years after irradiation for pelvic malignancies
→ Seen in patient with cervical and colorectal cancer after irradiation

Haemorrhagic cystitis:
□ Context: pt with haematological malignancy with chemo
□ Cause: viral cystitis (immunocompromised), drug-related (cyclophosphamide, ifosfamide)

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27
Q

List primary renal neoplasms

A

Renal cell carcinoma (80-85%) from renal tubular cells

Urothelial carcinoma (~8%) from renal pelvis

Nephroblastoma (Wilms’ tumour, 5-6%) from embryonic nephrogenic tissues in children

Others (rare): oncotyoma, collecting duct tumours, renal sarcomas

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28
Q

Renal cell carcinoma

  • Risk factors
A

Smoking
HTN and obesity

Acquired PKD (chronic dialysis)
Toxin/ carcinogen exposure: e.g. asbestos, cadmium, aspirin, NSAID, chemotherapy, kidney irradiation

Medical diseases: Chronic Hep C, Sickle cell disease, Kidney stones

Genetic:

  • Von Hippel-Lindau disease (VHL)
  • Hereditary papillary RCC (HPRCC) with mutated MET protooncogene
  • Tuberous sclerosis complex
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29
Q

Renal cell carcinoma

Clinical presentation: local, regional and systemic manifestations

A

Asymptomatic in early stages
Local symptoms: classical triad of flank pain + painless haematuria + renal mass only in <9%

Regional venous involvement:
→ Scrotal varicoceles (*classically left-sided, kidney tumour obstructing gonadal vein)
→ IVC involvement: LL oedema, ascites, Budd-Chiari syndrome, pulmonary embolus, dilated veins on abdomen

Systemic:
→ Metastatic symptoms: commonly lungs, LNs, bone, liver, brain
→ Constitutional symptoms

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29
Q

Renal cell carcinoma

Clinical presentation: local, regional and systemic manifestations

A

Asymptomatic in early stages
Local symptoms: classical triad of flank pain + painless haematuria + renal mass only in <9%

Regional venous involvement:
→ Scrotal varicoceles (*classically left-sided, kidney tumour obstructing gonadal vein)
→ IVC involvement: LL oedema, ascites, Budd-Chiari syndrome, pulmonary embolus, dilated veins on abdomen

Systemic:
→ Metastatic symptoms: commonly lungs, LNs, bone, liver, brain
→ Constitutional symptoms
→ Paraneoplastic syndrome

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30
Q

Renal cell carcinoma

Histological subtypes

Paraneoplastic symptoms associated

A

Subtypes:
Clear cell (70%)
Papillary (15%)
Chromophobe (10%)

  • Anaemia (29-88% advanced ds): disproportionately severe, ACD pattern
  • Pyrexia of unknown origin (20%): intermittent, a/w night sweats, anorexia, weight loss, fatigue
  • Hypercalcaemia (15%) due to production of PTHrP or lytic bony mets
  • Polycythaemia (1-5%) due to production of EPO
  • Others: hepatic dysfunction (Stauffer syndrome), AA amyloidosis,
    thrombocytosis, polymyalgia rheumatica, hypertension (renin)
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31
Q

Renal cell carcinoma

First-line investigations and typical findings

A

Contrast CT abdomen (Renal protocol)***

  • Structure: complex cystic, thickened/irregular walls
  • Contrast: 20-70HU ± necrosis, calcification on plain film, hyperenhancing (>10-15HU) on post-contrast phase

Ultrasound: diff. renal mass and cysts
- Cystic cancer: irregular, thickened walls, complex structure with septa

(CT-guided core biopsy: traditionally NOT done due to risk of tumour seeding)

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32
Q

Ddx benign and malignant renal masses

A

Benign masses:
→ Angiomyolipoma: fat attenuation, a/w Tuberous sclerosis
→ Oncotyoma
→ Simple renal cyst
→ Infectious, eg. renal abscess, focal pyelonephritis

Malignant:
→ Renal metastasis
→ Lymphoma
→ Other primary renal neoplasm, eg. Wilm’s tumour, sarcoma, urothelial carcinoma

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33
Q

Renal cell carcinoma

Localized RCC treatment options

A
  1. Surgical resection: Partial or Total/ radical nephrectomy
  2. Ablative therapies: Radio-frequency ablation, Cryotherapy
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34
Q

Renal cell carcinoma

Metastatic RCC treatment options

A

Local: Cytoreductive nephrectomy, Metastasectomy

Systemic:Targeted therapy options

Immune checkpoint inhibitors: Eg: nivolumab (anti-PD-1), ipilimumab (anti-CTLA4)

Antiangiogenic therapy:

  • Small molecule TKIs, eg. sunitinib, pazopanib, cabozantinib, axitinib, sorafenib
  • Anti-VEGF mAb, eg. bevacizumab

mTOR inhibitor, eg. temsirolimus, everolimus

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35
Q

Urothelial carcinoma

Sites of involvement
S/S
Dx and Ix

A

Most commonly arise from bladder, other sites of urinary tract incl renal pelvis, ureter, urethra (less common)

S/S: haematuria (70-80%), obstructive flank pain (20-40%), LUTS, constitutional Sx (<10%)

Dx: urinary tract imaging, ureterorenoscopy + cystoscopy

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36
Q

Bladder cancer

Major histological subtypes

A

Urothelial (90%) arise from transitional cell epithelium of bladder

Non-urothelial (<5%):
→ Adenocarcinoma (1%) from remnant of urachus in bladder fundus/ metastasis
→ SCC (7-9%) from metaplasia due to chronic irritation by stones or infection

Secondary, eg. colon, rectum, prostate, uterine cervix

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37
Q

Risk factors of bladder cancer

A

Smoking: most important risk factor

Occupational carcinogen exposure

Drugs/toxins:
→ Aristolochic acid in TCM
→ Cyclophosphamide
→ Chronic analgesic abuse

Prior urological conditions:
→ Chronic cystitis (SCC)
→ Chronic urinary catheter placement for >10y
→ HPV infection
→ Upper tract urothelial CA
→ Bladder augmentation: a/w ~1% risk of CA bladder
→ RT to pelvis

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38
Q

List occupational risks a/w Bladder cancer

A

Examples: paint components, polycyclic aromatic hydrocarbons, diesel exhausts, benzene, hair dye, aniline-containing dyes,…

Occupations affected: textile workers, dye workers, tyre rubber and cable workers, petrol workers, leather workers, shoe manufacturers and cleaners, painters, hairdressers, lorry drivers, drill press operators, chemical workers, rodent exterminators and sewage workers

39
Q

Bladder cancer

Clinical presentation

A

Painless gross haematuria (90%)
- Typically intermittent and present throughout micturition

LUTS: commonest in carcinoma in situ
→ Irritative (~1/3): frequency, urgency ± incontinence, nocturia
→ Obstructive (less common): strangury, intermittence, weak stream, incomplete voiding

Pain: usually indicates at least muscle-invasive disease
→ Flank pain
→ Suprapubic pain

Constitutional symptoms

40
Q

Bladder cancer

Invasion/ metastatic complications

A

Complications:
Local due to fistula formation by extension to other organs
- Vesicocolic fistula → pneumaturia
- Vesicovaginal fistula → incontinence

Systemic due to metastasis

41
Q

Bladder cancer

First-line investigations

A

Urinalysis for microscopy (confirm haematuria)
Urine cytology ×3: very insensitive (34%) but very specific (>98%)

Cystoscopy + Bx: gold-standard for diagnosis + staging
- flexible cystoscopy ± fluorescence

Urinary tract imaging: CTU, IVU, USG kidneys/bladder

Transurethral resection of bladder tumor (TURBT)***: for dx + staging ± Tx
- histopathology (final dx) + assess tumour invasion (T staging) [imaging may not be accurate] ± as primary therapy (in non-muscle invasive disease)

42
Q

Non- Muscle invasive bladder cancer

  • 2 subgroups with high recurrence and progression rate
  • Treatment options
A

High risk subgroups:

  • T1HG disease
  • Cis disease

Tx:

  • Intravesical BCG: instillation of BCG + NS into bladder via catheter
  • Intravesical chemotherapy: mitomycin C (MMC), gemcitabine
  • Radical cystectomy with pelvic LNectomy + urinary diversion
43
Q

Muscle invasive bladder cancer

  • Treatment options
A

Radical cystectomy (RC) with urinary diversion + pelvic LNectomy + Neoadjuvant chemotherapy: cisplatin-based

Multimodality treatment (MMT) = maximal TURBT + chemoirradiation

44
Q

Metastatic/ unresectable bladder cancer

  • Treatment option
A

Metastatic or unresectable bladder cancer (stage IV):
→ Cisplatin-based chemotherapy (1st line): PGC, GC or MVAC ± G-CSF

→ Immunotherapy (2nd line): pembrolizumab, atezolizumab

→ Other chemotherapy (2nd line): carboplatin-based, vinfluine

45
Q

Upper tract urothelial carcinoma

  • Risk factors
  • Standard Tx
A

RF:

  • Smoking
  • Aristolochia fangchi (Chinese herb nephropathy)
  • Arsitolochic acid (Balkin endemic nephropathy)
  • Arsenic poisoning (Blackfoot disease)
  • Hereditary: Lynch syndrome, HNPCC

Tx:

  • Nephroureterectomy
  • Partial ureterectomy with reconstruction
46
Q

Urolithiasis

Risk factors

A

Diet:

  • Low fluid
  • Excessive calcium supplement
  • Dietary oxalate: Tea, spinach, beets…etc

History of prior stones

Family history of stones

Recurrent UTI (struvite stone)

Medical:

  • Malabsorptive conditions
  • Urinary pH change - chronic diarrhea, T1RTA
  • DM, obesity, HTN
  • Gout
  • Crohn’s
  • Hyperparathyroidism
47
Q

5 compositions of kidney stones, respective morphology

A
  1. Calcium (70%) - Calcium oxalate, phosphate: Irregular mulberry stones with sharp projections
  2. Urate (5%) - hard, smooth, ligh brown
  3. Struvite (1%) - Smooth, dirty white, Staghorn
  4. Cystine (2%) - multiple, very hard
  5. Xanthine and pyruvate stones
48
Q

Struvite kidney stones

Risk factors
Presentation

A

Risk factors:
Upper urinary tract infection with urease-positive organism (eg. Proteus, Klebsiella): produces ammonium (from urea) → ↑pH→ ppt of NH4PO4

Prior oxalate stones: predisposes to infection → forming mixed stones

Presentation:

Rarely classical renal colic,
usually UTI, mild flank pain or haematuria with alkaline pH (>8)

49
Q

Calcium renal stones

Risk factors
Clinical presentation

A

Risk factors:

  • High Calcium: supplement, hyperPTH, chronic acidosis, idiopathic or familial
  • High Oxalate: dietary oxalate, bile acid malabsorption, idiopathic/primary
  • Low citrate: chronic metabolic acidosis, high animal protein diet, idiopathic/primary
  • High urine pH: e.g. urease- producing bacteria UTI

Presentation:
Early, symptomatic, sharp flank pain due to sharp shape of stones

50
Q

Urate renal stones

Risk factors
Radiological feature

A

↑urine uric acid: hyperuricaemia, uricosuric drugs
↓urine pH (5-5.5): DM/metabolic syndrome, IEM, distal RTA (↓pH → ↑ppt of uric acid)

Radiolucent stones, usually seen as filling defects on CT

51
Q

Pathogenesis of different types of renal stones

  • Calcium/ urate/ cysteine
  • Struvite
  • Drug-induced
A

Calcium/ urate/ cysteine:

  • Supersaturation of urine constituents&raquo_space; precipitate and form crystals
  • Calcium phosphate crystals form in renal medullary interstitium first and forms Randall’s plaque, more calcium compounds deposit on the nidus

Struvite: urinary tract infection with urease-positive organisms, produce ammonia

Drug-induced: precipitation of medication or their metabolites in urine

52
Q

Clinical presentation of renal stones

A

Obstructive symptoms: result in loin pain or ureteric colic
→ Occurs only when lodging at pelviureteric junction (PUJ), ureter and at bladder neck
→ Site of obstruction determines location of pain

Ulcerative symptoms → haematuria (gross or macroscopic haematuria)

Predisposition to infection: pyelonephritis, pyonephrosis, urosepsis

Passing of stones: painful

53
Q

Compare the presentation between renal, ureteric and bladder stones

A

Renal: usually asymptomatic if only in renal calyces (only painful when pass distally)
→ Renal pain occur if stone lodged in PUJ, hydronephrosis ± pyonephrosis

Ureteric stones: usually symptomatic
→ Ureteric colic: agonising pain a/w N/V
→ Radiates from loin downward around waist obliquely across abdomen just above inguinal ligament to genitals
→ Gross or microscopic haematuria (95%)
→ Bladder irritation (in distal ureter): dysuria, urgency, frequency

Bladder stones: usually asymptomatic
→ Irritative symptoms: frequency, urgency
→ Obstructive symptoms: sometimes BOO
→ Haematuria: esp occur at end of micturition

54
Q

Renal stone management

Stone factors
Patient factors
Surgeons factors

A

Stone: Size, number, composition, unilateral/ bilateral

Patient:
Anatomy, Fitness for anesthesia, bleeding tendency, susceptibility for radiation, renal function

Surgeon: technology, expertise

55
Q

First-line investigations for renal stones

A

General: CBC, CRP ± clotting if surgical procedure is planned
RFT: bilateral obstruction only
Calcium and urate

Imaging:
Non-contrast CT Abdomen + Pelvis***
X-ray KUB (screening)
USG kidney/bladder (preferred in pregnancy or children)
CT urogram: gross hematuria or renal mass

56
Q

First-line emergency treatment options for renal stones

A

Supportive Tx:
→ Pain control: NSAIDs (1st line), opioids (hydromorphine, pentazocine, tramadol)
→ α-blockers can help reduce recurrent colic
→ Abx if complicated by infection

Urgent decompression by JJ stent (under fluoroscopy) or percutaneous nephrostomy (PCN)
→ Indication: uncontrolled sepsis, progressively worsening renal function,

Conservative Tx and medical expulsion therapy (MET): wait for spontaneous passage with supportive treatment

57
Q

Definitive treatment options for renal stones

A

Extracorporeal shock wave lithotripsy (ESWL): US/XR-guided shock waves aimed at stones → crystalline stones disintegrate under impact of shock waves

Percutaneous nephrolithotomy (PCNL): flexible cystoscopy for ureteral cannulation → nephroscope passed into kidney by percutaneous technique → retrieval of stone in whole or in fragments after laser/USG/electrohydraulic lithotripsy

Ureterorenoscopy (URS): for lithotripsy (ureteric) or retrograde intrarenal surgery (RIRS) (renal): ureteroscope introduced transurethrally across the bladder into the ureter to remove stones directly or after laser lithotripsy

58
Q

Treatment options for different sizes of renal stones

10, 10-20, 20mm?

A

<10mm: ESWL

10-20mm: ESWL for non-lower pole or PCNL for lower pole

> 20mm: PCNL

59
Q

Medical expulsive therapy for renal stones

A

Supportive: ask pt to strain urine, adequate hydration (IV not necessary), observation

Oral chemolysis, eg. alkalinization of urine (uric acid stone) or acidification (struvite stones)

MET: best for distal ureteric + >5mm stones (presence of large numbers of α1-receptors in distal ureter)
→ Regimen: α-blocker tamsulosin

60
Q

Ureteric stones

Choice of therapy for upper and lower ureteric stones depending on size?

A

Upper:
<5mm = watchful waiting (WW)
5-10mm = URSL/ ESWL
>10mm = URSL

Distal:
<5mm = WW
5-10mm = URSL
>10mm = URSL

61
Q

PSA

  • physiological function
  • Production process
A

Production: produced as proenzyme (proPSA) by prostatic acini → active PSA produced by removing propeptide → soon inactivated into inactive PSA by proteolysis

Physiological function: a protease that dissolves the coagulum (fibronectin, semenogelin) that traps sperm → release sperm in vagina after ejaculation

62
Q

Serum PSA

  • Half-life
  • Process of release into serum
  • Different forms of PSA in serum
A

Release into serum: half-life = 3 days (takes 7 cycles to clear → check PSA ≥3-4w after acute episode)

Active PSA diffuse directly into circulation → become rapidly bound by protease inhibitor (complexed PSA)
Inactive PSA diffuse into circulation → form free portion of PSA in blood

63
Q

Elevated serum PSA in cancer

Pathophysiology

A

In prostate cancer, there is disruption of basement membrane
PSA release due to disruption of cellular architecture within prostate

Destroyed basal cells → ↑release of PSA into blood together with its precursors (proPSA)

Less proteolysis → ↑release of active PSA into blood → Lower %free PSA

64
Q

Causes of elevated PSA

A

□ CA prostate: cancer tissue produces serum PSA 10× that of benign tissue

□ Benign prostatic conditions:
→ BPH: due to ↑prostate vol and ↑PSA/unit vol
→ Prostatitis ± infection

□ Trauma or mechanical stimulation:
→ Procedure-related: biopsy, TURP, prostate massage, PR exam, cystoscopy
→ AROU: important to defer PSA for 2-6w after acute AROU
→ Other mechanical stimulation: after ejaculation, perineal trauma, vigorous cycling

65
Q

Natural, non-modifiable determinants of basal PSA level

A

Age: Increase 0.04ng/mL per year

Race: Black ethnicity has higher, White ethnicity has lower

Prostate volume

66
Q

Traditional/ arbitrary cut-offs for serum PSA levels and risk of prostate cancer

Which level indicates prostate biopsy?

A

<4ng/mL → considered normal (high false-negative rate)

4-10ng/mL → 15-20% risk of CA prostate → consider biopsy

> 10ng/mL → >50% risk of CA prostate → biopsy definitely indicated

67
Q

Additional PSA test metrics with higher diagnostic accuracy

A
  1. Age-specific PSA
  2. %free PSA = free PSA / total PSA
  3. PSA velocity = rise in PSA level / year
  4. PSA density = PSA / estimated volume of prostate (on TRUS)
  5. Prostate health index (PHI)

Other indices:
→ PSA doubling time (PSADT)
→ PSA transitional zone density
→ Supersensitive PSA

68
Q

Define cut-off values for Age-specific PSA

A
69
Q

% free PSA

Principle function of this metric

A

%free PSA = free PSA / total PSA
→ Principle: CA prostate gives ↑bound PSA than free
→ Finding: no agreed cutoff, usually used for stratification of ‘gray zone (4-10ng/mL)

70
Q

Non-PSA tests for diagnosis of prostate cancer

A

PCA3 test: gene-based urine test for PCA3/PSA mRNA ratio
→ Principle: PCA3 highly over-expressed (66×) in almost ALL CA prostate, but not in benign diseases

Fusion gene (TMPRSS2-ERG) detection in urine sample of pt w/ CA prostate

Circulating tumour cells in metastatic disease

Genomic tests with scoring for aggressiveness of tumour

71
Q

Risks of over-diagnosis and over-treatment of high serum PSA levels

A

From excess medication, protoscopy, biopsy, surgery…

erectile dysfunction, incontinence, bowel dysfunction, sepsis

72
Q

Prostate cancer

Risk factors

A 
Non-modifiable:
Ethnicity: Blacks > Caucasians > Asians
Old age 
Family history 
Hereditary mutations: eg. BRCA1/2, ATM, CHEK2, Lynch syndrome (HNPCC)

Hormonal: growth stimulated by androgens

Obesity

73
Q

Outline history taking and P/E for elevated PSA

A
  1. Intention of PSA testing
  2. True elevation or not: r/o confounding factors - prostatitis from STD, iatrogenic damage, history of BPH and Prostate CA, Perineal injury…etc
  3. Symptoms suggestive of prostate cancer: Hematuria, Bone pain, Lower limb weakness, Weight loss

P/E:

  1. General: signs of uremia (lower urinary tract obstruction causing obstructive nephropathy)
  2. Metastatic symptoms, incl. lower limb weakness, weight loss, spinal pain (Batson plexus)…
  3. Abdominal: ballotable kidneys, bladder distension (lower urinary tract obstruction)
  4. DRE:
    - Anal tone (nerve invasion)
    - Size, consistency of prostate
    - Surface, induration of prostate/ median groove present or not
74
Q

Follow-up investigations after elevated serum PSA

A
  1. Prostate biopsy after r/o confounding factors

2. Spurious high PSA should follow-up with PSA test 4 weeks later

75
Q

Prostate cancer

Major histological subtype
Pre-malignant lesions subtypes

A

Adenocarcinoma (95%): 70-80% arise from peripheral zone
Other variants:
eg. ductal adenocarcinoma, mucinous adenocarcinoma, signet cell CA, small cell CA

Premalignant lesions: often identified in TURP for BPH or Bx
→ Prostatic intraepithelial neoplasia (PIN): architecturally benign prostatic acini and ducts lined by atypical cells
→ Others: atypical adenomatous hyperplasia, intraductal carcinoma of prostate

76
Q

Prostate cancer

Clinical presentation

A

Asymptomatic (80%): elevated PSA or abnormal DRE or on TURP specimens

Urinary symptoms:
→ LUTS
→ Haematuria or haemospermia (<1%)
→ Obstructive uropathy / renal failure due to ureteric/trigone invasion
→ Malignant priapism

Metastatic symptoms:
→ Vertebral metastasis (commonest): bone pain, pathological fractures, cord compression, hyperCa (via Batson’s plexus)
→ Other metastasis:
- Direct: stromal invasion through prostatic capsule, urethra, bladder base, seminal vesicles
- Lymphatics: sacral, iliac, para-aortic nodes
- Haematogenous: lungs, liver, bones

77
Q

DRE for prostate cancer

  • Features elicited
A

DRE: insensitive (cannot detect small cancers and cancer in other areas) and non-specific (30% PPV only)
→ Asymmetric induration
→ Frank hard irregular nodule fixed to pelvic wall
→ Obliteration of median groove
→ Theoretically can obtain T staging via DRE

78
Q

Prostate biopsy

  • Indications
  • Approaches (3)
  • Process of biopsy
A

Indication:
→ Abnormal DRE suggestive of CA prostate
→ Elevated PSA if would affect Tx decision (>10y life expectancy)
→ Clinically metastatic disease if diagnosis doubtful

Approach:

  • Transrectal (TR): traditional, worse infection rate and access
  • Transperineal (TP) **: newer approach, allows access to all areas + better cancer detection rate
  • MR/USG Fusion-Targeted Biopsy **

Process:

  • Antimicrobial prophylaxis, topical/ local periprostatic anesthesia
  • Imaging guidance: majority TRUS-guided
  • 12-core or 26 core systemic biopsy with labelling from different areas of prostate
  • Targeted biopsy only done after imaging localisation
79
Q

Prostate biopsy

Complications

A

Fever (1/4): common despite prophylactic Abx
Bleeding (1%): PR bleed, haematochezia, haematospermia, haematuria
Urosepsis (1%)
Transient LUTS

Rare, serious complications:
Vasovagal syncope
Acute urinary retention
Post-biopsy infection

80
Q

Post-prostate biopsy infection

Definition
Pathophysiology
Infection rate and ICU care rate

A

Fever +/- chills and rigor as a result of prostate biopsy
Within 24hours to 1 week of biopsy
Associated with septic shock and multi-organ failure

Pathophysiology:

  • Local bacteria in rectum enters systemic circulation during transrectal biopsy&raquo_space; resistant bacteria triggers sepsis and SIRS
  • Biopsy complicated by AROU&raquo_space; uropathogens cause sepsis

Post-biopsy infection rate = 4.3%, of which 11% needed ICU care

81
Q

Multiparametric prostate scan

  • Mechanism
  • Benefit
A
  • Targeted biopsy using multi-sequences of MRI and real-time TRUS imaging
  • Higher cancer detection rate, lower sepsis rate
82
Q

Prostate biopsy

  • 2 approaches associated with higher cancer detection rate and lower sepsis rate
A

Multiparametric MRI prostate

Transperineal Ultrasound guided biopsy (TPUS)

83
Q

Define metrics for Clinical staging of prostate cancer (c.f. pathological staging)

Function of clinical staging

A

Clinical staging:

  1. Nomograms: pre-treatment parameters to predict possibility of ECE, LND, SVI
    - Serum PSA
    - Gleason scores
    - Clinical T stage by DRE
    - Positive and negative biopsy core numbers
  2. Additional Radiological imaging (optional)
  3. Pelvic lymphadenectomy (optional)

Function:

  • Risk stratification of prostate cancer - predict prognosis and guide Tx
  • Extent of disease before treatment
84
Q

Outline the clinical risk stratification system for prostate cancer

A

D’Amico stratification system

Low risk:
- cT1 to T2a and PSA =< 10ng/mL and Gleason score < 6

Intermediate risk:
- cT2b and/or PSA 10-20ng/mL and/or Gleason score 7

High risk:
- cT2c or PSA >20ng/mL or Gleason 8-10

85
Q

Gleason score

  • Function
  • System for scoring
A

Function: quantify prostate cancer’s clinical behavior and mortality rates

Scoring: based on architectural features of CA cells from histological samples

primary (most prevalent histological pattern) + secondary (2nd most prevalent pattern)
Example: composite GS = 3 + 4 (or 7) = primary pattern 3, secondary pattern 4

86
Q

Additional radiological imaging for clinical staging of prostate cancer

  • 2 aims
  • 3 modalities
A

Aims:

  • Accurately stage disease, r/o metastasis
  • Treatment planning

Modalities:
- R/o metastasis: Whole body bone scan (Tc-99m methylene disphosphonate); PSMA-PET scan (antigen against prostate-sepcifc-membrane-antigen PSMA)

  • Treatment planning: Multiparametric MRI scan
87
Q

MRI prostate

  • Features attainable from scan?
A

Size of prostate

Prostate configuration

Invasion:

  • Extra-prostatic invasion
  • Seminal vesicle invasion
  • Rectal wall
  • Lymph node
  • Pelvic bone
88
Q

Prostate cancer

Treatment options
Indication for each option
Treatment for recurrence

A

Localized/ locally advanced

  1. Radical prostatectomy
  2. External Beam Radiotherapy

Advanced, systemic, metastatic:

  1. Combination therapy (Androgen-Deprivation therapy (ADT) + docetaxel or abiraterone + prednisolone)
  2. ADT monotherapy/ Surgical or medical castration
  3. Cytotoxic chemotherapy: Docetaxel, Abiraterone
  4. Androgen-targeted agent

Recurrence:

  • Post RARP BCR: Salvage RT
  • Post-RT recurrence: Salvage RARP
89
Q

Radical proctectomy

  • Extent of excision
  • Technique
  • Complications
A

Involves:

  • Resection of prostate, prostatic urethra, seminal vesicles, part of ureter
  • ± ePLND: obturator fossa, external iliac up to aortic bifurcation

Technique: nerve-sparing technique to prevent ED

Complications:

  • General: GA risk, mortality
  • Erectile dysfunction
  • Urinary incontinence , bladder neck (anastomotic) strictures
  • Others: bleeding, rectal injury, infection
90
Q

Radiotherapy for prostate cancer

  • Indications for local and metastatic PC
  • 2 forms
  • Complications
A

Indications for local:
- Localized or locally advanced

Indications for metastasis:

  • Urgent treatment for spinal cord compression by tumor
  • Pathological fracture with fixation surgery
  • Local symptom control, pain relief

Forms: EBRT/IMRT (common) or interstitial brachytherapy (rare)

Complications:

  • Erectile dysfunction: up to 30%
  • Cystitis, proctitis: up to 10%
91
Q

Treatment options for locally advanced prostate cancer

A

Radical proctectomy + Post-operation radiotherapy/ Androgen-deprivation therapy (ADT)

Neoadjuvant androgen-deprivation therapy + radiotherapy

92
Q

Androgen deprivation therapy for prostate cancer

  • Rationale/ mechanism
  • Modalities
  • Treatment for castration-refractory PC
A

Rationale: >90% of prostate tumour has testosterone-dependent growth
→ Suppression of testosterone secretion or inhibiting its effect at androgen receptor → ↓growth of prostatic tumour

Options:

  1. Surgical castration by bilateral orchiectomy
  2. Medical castration by hormonal therapy:
    - GnRH agonist, eg. Zoladex (goserelin), Lupron (leuprolide)
    - GnRH antagonist, eg. degarelix

Refractory:

  1. Cytotoxic chemotherapy
  2. AR-targeted agents (enzulutamide, abiraterone)
  3. Radium-223
  4. Sipuleucel-T
93
Q

S/E of androgen-deprivation therapy

A

Sexual dysfunction in majority: loss of libido in first few months, followed by ED

Osteoporosis and bone fractures: should measure baseline BMD
- Tx: lifestyle modification, osteoclast inhibition (bisphosphonate, denosumab)

Vasomotor symptoms, eg. hot flashes, nausea, sweating

↓lean body mass, ↑body fat, ↓muscle strength

↑risk of cardiovascular disease and ↑insulin resistance

94
Q

Population-wide PSA screening

Consensus?
Provisions of PSA screening?

A

No consensus

Screen if:

  • Shared decision between patient and doctor
  • Benefits and shortcomings of PSA testing in asymptomatic patient explained clearly before testing

MBBS IV - Junior Clerkship WCS (131 decks)

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