New Tech & Imaging

Edmond Wong

Radiation

Radiation mSv (millisieverts) CXR equivalent

Annual Background (UK) 2

CXR 0.02

KUB 0.5 (0.2-0.7)

IVU 2.5 120

NCCT 5 250

CT abd/pelvis + contrast 10 500

CT chest 7 (6.5-8)

PET 6 (5-7)

PET-CT 24 (23-26)

MAG3 0.5 (0.4-0.7)

DTPA

DMSA 1

MCUG 1

Bone scan 4

10mSv increased risk of cancer by 1in 2000

What are the important issues of irradiation?

• The international unit of radiation dose is Gray

• One gray is the radiation dose that results in the energy deposition of 1J/kg

• The old unit was rad• One gray is equivalent to 100 rad• Fetuses are least vulnerable to radiation

between 0-4 week and most vulnerable during organogenesis (8-15 weeks)

ESWL

What are the four components of ESWL?

• Energy source

• Medium for transmission of energy (e.g water)

• A focusing device

• Imaging modality

What is Electrohydrolic ESWL?• Electrohydraulic • 1st generation Dornier HM3 spark-gap lithotripsy • A spark is produced between two electrodes, causing sudden expansion

and collapse of gas bubble and energy transmission• Focus device : Metal hemi-ellipsoid reflector to localize the energy• Adv

– Most effective in stone fragmentation (Dornier HM3)• Disadv

– Pain– Substantial pressure fluctuation b/w shocks (haematoma 0.6%)– Short electrode life

• Reference standard for comparison– USA Cooperative study group– Methodist Hospital of Indiana

• Nowadays, Dornier lithotripter S II• 2nd /3rd generation

– Tight focal zone– High ascoustic pressure

Electromagnetic

• Electromagnetic • Energy: Rely on Cylindrical electromagnetic source• Focus device : Acoustic lens. • E.g : Storz Modulith SLX-F2• Adv

– More controllable & reproducible SW– Less pain due to low energy density at skin– Small focal point– Long electrode life

• Disadv– ↑ subcapsular haematoma (3-12%) due to small focal

region of high energy

Piezoelectric

• Piezoelectric • Energy: Ceramic elements produce electrical

discharge under stress or tension (direct effect)• When electricity pass through element movement

of source shock wave (converse piezoelectic effect)

• E.g: EDAP LT02• Adv

– High focusing accuracy– Long service life– Least pain due to low energy density at skin, may be

anesthesia free• Disadv

– Less effective due to lower power

Acoustic shock wave

• 2 phase: • Short +ve phase:

– Erosion at entry and exit pt of stone– Compressive effect of wave also cause shattering

internally– Compression / tension-induced cracks (Spallation)

• Longer –ve pressure phase: – Formation of microbubbles– Collapse of these bubbles cause further erosion of

stone surface via formation of “microjet”

Campbell

• The newer lithotripter are less efficacious than the original Dornier device, & no data to suggest newer lithotripter produce fewer adverse events for equivalent degree of efficacy

Electroconductive (ECL)

• Electroconductive– Large focal diameter of SW (12.8-25mm)– Longer pulse duration– Relatively lower peak pressure (<9MPa)

• highly conductive solution channels the discharge between anode and cathode

• spark generation exactly at F1• Compare to EHL:

– Reduction in shockwave pressure variability– Improved energy transfer to the stone– Improved stone fragmentation

ECL

• Tolley– Patients treated with Sonolith between 2004

and 2006– plain KUB and USG at 1 and 3 months– stone-free rates

• 77% (<10mm), 69% (11-20mm), 50% (>20mm)

• 74% (lower), 70% (upper), 78.5 (middle), 74% (renal pelvis)

– Conclusion: Achieved a high success rate, comparable with that using the HM-3 machine but with lower analgesic requirement and very low re-treatment rates

ESWL

Mechanism of stone fragmentation1. Spall fracture

2. Squeezing-splitting or circumferential compression

3. Shear stress

4. Amplification of stress inside stone

5. Cavitation i.e. formation & subsequent dynamic behavior of bubbles

ESWL• Indications

– Renal pelvis stone <2cm– Lower pole stone <1cm– Upp ureteric stone <1cm– Sandwich therapy in conjunction with PCNL

• Contraindication– Absolute

1. Uncorrected coagulopathy2. Uncontrolled HT3. Active UTI4. Pregnancy5. Distal obstruction

– Relative1. Morbid obesity2. Hard stone (cystine or Ca oxalate monohydrate)3. AAA4. Abdominal pacemaker

How to consent pt for ESWL?• Common complications:

– Hematuria – Loin pain/ ureteric colic– UTI require Antibiotic

• Occasional complications: – Failed fragmentation of stone– Repeat ESWL required– Recurrence of stone

• Rare complications: – Preinephric hematoma– Steinstrasse– Severe systemic infection– Adjacent organ damage – HT – Arrhythmias

What is the mechanism of Lithoclast?

• Pneumatically generated energy• Compressed air delivered from external supply

fires the projectile in the handpiece into a probe which in contact with stone to fragment it

• Adv: bounce off ureter, less damage• Disadv:

– retrograde propelled stone in ureter– Use only in rigid instrument

• Swiss lithoCloast Master

Laser

What is Laser?

• Light Amplification by Stimulated Emission of Radiation.• Laser is formed by supplying energy to a lasing medium

(pumping), which release photons & undergo population inversion & light amplification, producing light that is coherent (parallel), monochromatic (same wavelength) & collimated (in phase)

• Laser chamber fully reflective apart from an aperture that allow light to escape when reach a certain intensity

• Population inversion: more light is release than absorbed • Photothermal effects

– ↑ temp heat production incision & ablation• Photomechanical effects

– Fluid evaporation-> small plasma cavitation bubble-> rapidly expand & collapse-> shockwave-> stone fragmentation

• Photochemical effects

What are the different types of Laser?

• Most common usage• Holmium: YAG

– Wavelength 2140nm, depth of penetration 0.4mm– Rapidly absorbed by water more of photothermal (weak

cavitation bubble only)– Higher pulse energy but lower peak power than pulsed dye laser– 200-um, 365um fiber

• KTP (potassium-titanyl-phosphate) / LBO (lithium triborate)– ND-YAG pass thru a KTP crystal , ½ the WL & double frequency– Wavelength 532mm, depth 2mm– Selectively absorbed by Hb

• ND-YAG– Wavelength 1064nm, depth 3-5mm – Poorly absorbed by water/ body pigmentation-> coagulation

What are the Lasers used for BPH: PVP?

• PVP (KTP 80W, LBO HPS 120W) Greenlight– Side firing single use fibre– Adv (most long term data from 80W)

1. Saline irrigation-> avoid TUR syndrome

2. Excellent haemostasis– ↓ bleeding & blood transfusion– Anticoagulants may not need to be stopped (largest series:

Ruszat)

3. Equally effective voiding improvement at 1 yr vs TURP

4. Effective & durable outcome in voiding parameters at 5 yrs

(Ruszat)

5. ↓ catheter time & ↓ hospital stay vs TURP (RCT by Bouchier-Hayes)

What are the disadv / Limitations of PVP?

1. Lack of tissue for histopathology

2. Cost

3. Impaired vision (esp 120W)• Injury to UO/ bladder perforation

4. Higher re-op rate vs TURP (7% vs 4% at 5 yrs, Ruszat)

5. Lack of long term data on 120W HPS

What is holmium: YAG laser: HOLEP?

• Most promising

– Morcellator, mimic open simple prostatectomy

• Adv

1. Saline irrigation-> avoid TUR synd

2. Good haemostasis properties

• ↓ blood transfusion vs TURP/ open prostatectomy (Kuntz)

3. Histology available (vs PVP)

4. Effective & durable outcome on voiding parameters at 6 yrs (RCT by Gilling)

5. Equal improvement in voiding parameters vs TURP at 3 yrs & open prostatectomy at 5 yrs (both Kuntz)

6. ↓ catheter time vs TURP (Kuntz)

7. Late Cx similar to TURP at 3 yrs (Kuntz)

8. Re-op rate similar to open prostatectomy (Kuntz)

• Disadv/ Limitations

1. Deep learning curve

2. Cost

3. Insufficient data on anticoagulation patients

What are the lasers used for stone?

• Holmium: Adv– All stone types can be fragmented

• excellent absorption by stone surfaces

– High safety profile• Small cavitation bubble, depth 0.4mm only

– Transmission through small optic fibre e.g. 200µm• Can be used in flexible URS

• Pulsed dye laser– Greenlight 504nm, cavitation bubble & shockwave– Selectively absorbed by stone but not ureter– Relatively ineffective against harder stone– Machine warm up time 20min– Dark eyewear required

Laser safety precautions in OT

1. OT door closed throughout2. Warning sign & light at OT door3. Non-reflective wall coating4. Staff number minimized5. Laser safety officer present6. Surgeons trained7. Eye protection goggles8. Laser “stanby” when not in use9. Laser pedal has guard10.Clear safety guidelines

Laser• Mechanism

– Photothermal/ photomechanical

• BPH:– KTP laser

• Selectively absorbed by haemoglobin• At high power, rapid photo-thermal vaporisation of intracellular tissue

water• PVP, photoselective vaporisation of prostate• Side-firing, single use fibre with deflecting device at the tip• Saline irrigation• Excellent haemostatic properties• Coagulation zone about 2mm deep• Speed of tissue removal is limited to 0.3 – 0.5g/ min• Tissue specimen for histological examination cannot be obtained

Laser: BPH

• One RCT comparing KTP laser vaporisation with TURP– Delivers equally good micturition outcome at 1 year

post-op (TURP 8.7 to 17.9 ml/s; PVP 8.5 to 20.6 ml/s)– No need for blood transfusion– Shorter catheter time (TURP mean 44.5 hrs; PVP

12.2 hrs) – Shorter hospital stay (TURP mean 3.4 days; PVP

1.08 days)

Bouchier-Hayes DM (2006)

Laser: BPH

• Ho:YAG Laser– Wavelength: 2,140 nm

• Close to the absorption peak of water: 1,910 nm• Rapidly absorbed by tissue water

– Penetration depth of 0.4 mm– Causes vaporisation without deep coagulative tissue

necrosis– Tissue ablation (vaporisation), incision, resection &

enucleation by a clean char-free cut.– Dissipating heat causes simultaneous coagulation of

small and medium-sized vessels to a depth of 2–3 mm.

– HoLAP, HoLRP, HoLEP

HoLAP• Holmium laser ablation of prostate

• First performed in 1994– Side-fire fibre with a deflecting device at the fibre tip with a 60W

machine• Randomized comparison between HoLAP and TURP (Mottet, 1999)

– Less bleeding– Shorter catheterisation– Shorter hospital stay– Similar efficacy after 1 year

• HoLAP was slow with the 60W machines, superseded by holmium laser resection and enucleation of prostate

• High powered 100 W machine is now available allowing faster tissue vaporisation– Large series and RCTs of HoLAP with 100W machines are yet not

available

HoLRP

• Holmium laser resection of prostate

• The adenomatous tissue is resected down to the capsule, and cut into pieces small enough to be evacuated through the resectoscopes sheath.

• At the end of the procedure all adenomatous tissue is removed, and the prostatic cavity is similar to that produced by conventional TURP.– About 50% of removed tissue is lost to vaporisation.

• Randomised clinical trials proved that HoLRP had– Significantly less perioperative morbidity (Gilling PJ 1999)– Equivalent efficacy in terms of peak flow, symptom scores,

potency and continence when compared with TURP after a minimum of 4 years of follow-up (Westenberg A 2004)

HoLEP

• Holmium laser enucleation of prostate

• With the use of soft tissue morcellator• The prostatic lobes can be enucleated in

their entirety, pushed into the bladder and then be mechanically fragmented and aspirated by the morcellator

• HoLEP mimics open prostatectomy via a transurethral route

HoLEP

• Enucleation:– Tip of laser fibre dissects the adenomatous tissue

away from the surgical capsule

• Haemostasis:– Small and medium-sized vessels coagulated

“automatically” and large arteries are immediately coagulated by “defocusing”

• A nearly bloodless procedure• Use of NS as irrigating fluid

– No risk of TUR syndrome

HoLEP• Prospective randomised trial (J Urol 2008)

100 consecutive patients with symptomatic obstructive BPH randomised at 2 centres

n=52 HoLEP n=48 TURP

Mean OT time 74 min 57 min p < 0.05Mean cath time 31 min 57 min p < 0.001Mean LOS 59 min 86 min p < 0.001

Freddy laser

FREDDY Laser

• FREquency Doubled Double-pulse Nd:YAG Laser (World of Medicine, Berlin, Germany)

• Approved by FDA in January 2001• Short pulsed, double frequency laser• By incorporating a KTP crystal into the

resonator of a Nd:YAG laser, the FREDDY laser produces two pulses (532 nm and 1,064 nm) simultaneously.

• Specially designed for stone fragmentation

http://www.world-of-medicine.com/investor_relations/annualreport2002/index-dateien/gb2002/gf600.htm

FREDDY Laser

• Photoacoustic effect: Laser light at 532 nm initiates plasma formation at the stone surface, while light at a wavelength of 1,064 nm heats the preformed plasma, causing expansion and contraction, using pulse durations of 0.3–1.5 microseconds -> produces mechanical shock wave

• Safety: No plasma formation on issue -> low risk of tissue injury

Evidence

• Experiments show the FREDDY laser is capable of lithotripsy while both animal and human model studies show little to no effect on normal tissues

• Hochberger J, Bayer J, Tex S, Maiss J, Tschepe J, Hahn EG (1997) Frequenzverdoppelter Doppelpuls ND:YAG Laser (FREDDY) fur die Gallensteinlithotripsie—Praklinische und erste klinische Ergebnisse. Biomedizinische Technik “Laseranwendungen III” 442:330

• Zorcher T, Hochberger J, Schrott KM et al (1999) In vitro study concerning the effciency of the Frequency-doubled Double-Pulse Neodymium:YAG Laser (FREDDY) for Lithotripsy of Calculi in the Urinary tract. Lasers Surg Med 25(1):38–42

• Delvecchio F, Zhu S, Weizer A, Silverstein A, Auge B, Pietrow P, Albala D, Zhong P, Preminger G (2001) In vitro fragmentation analysis of the FREDDY laser. Oral presentation at the WCE 2001, Bangkok

• Bazo A, Chow WM, Coombs L, Barnes DG (2001) Freddy will crack it for you: a new device for urinary calculi lithotripsy. In: BAUS conference proceedings, section of Endourology, SheYeld, UK

• Santa-Cruz RW, Leveillee RJ, Krongrad A (1998) Ex vivo comparison of four lithotripters commonly used in the ureter: what does it take to perforate? J Endourol 12(5):417–422

Evidence

• A study of 50 patients using FREDDY laser lithotripsy showed overall 95% immediate stone free rates in treatment of ureteral calculi with no complications

• Schafhauser W, Zorcher W et al (2000) Erste klinische Erfahrungen mit neuem frequenzverdoppeltem Doppelpuls Neodym:YAG Laser in der Therapie der Urolithiasis. Poster presentation at the DGU, Hamburg, Germany

• A study showed an 87% combined stone free rate for kidney, ureteric and bladder stones, with no complications.

• Stark L, Carl P, Zauner R (2001) A new technique for Laser-Lithotripsy: FREDDY, the partially frequency-doubled double-Pulse Nd:YAG Laser. Poster presentation at the 1st int. consultation on Stone Disease, Paris

Evidence

• A study of 21 patients showed 100% stone free rates in kidney and ureteric stones, but a 57% stone free rate for bladders stones using the laser

• Bazo A, Chow WM, Coombs L, Barnes DG (2001) Freddy will crack it for you: a new device for urinary calculi lithotripsy. In: BAUS conference proceedings, section of Endourology, SheYeld, UK

Evidence

• several studies have shown the FREDDY laser ineffective in the treatment of “hard” urinary calculi, such as calcium oxalate monohydrate, cystine, and brushite stones

• Dubosq F, Pasqui F, Girard F, Beley S, Lesaux N, Gattengno B, Thibault P, Traxer O (2006) Ednoscopic lithotripsy and the FREDDY laser: initial experience. J Endourol 20(5):296–299

• Stark L, Car P (2001) First clinical experiences of laser lithotripsy using the partially frequency-doubled double-pulse neodymium: YAG laser (“FREDDY”) (abstract). J Urol 165:362A

Laser spectrum

What is it?

• Tm:YAG

• Laser with wavelength: 1930 – 2040 nm (~2 micron)

• Continuous / pulsed mode

• Power: 5 – 120 W

• Proposed by Xia in 2005 for use in surgery of prostate

Comparison with other laserWavelength

(nm)characteristics Prostate

penetration depth

Clinical use

Holmium

Ho:YAG

2100 – 2150 rapidly absorbed by water and cell fluid

0.4 mm Enucleation of prostate

Ablation/ resection: abanodoned

Greenlight

KTP/ LBO

532 Strongly absorbed by Hb, not absorbed by water

1-3 mm vaporization

Diode laser 940

980

1470

compared with KTP:

conflicting result on tissue ablation, hemostais

coagulation zone:

4.5 mm

vaporization but limited clinical study

Thulium

Tm:YAG

1930 – 2040 rapidly absorbed by water, excellent hemostasis, vaporization and resection

< 1 mm vaporesection, vaporization, vapoenucleation, laser enucleation

Surgical techniques and outcomes

T. Bach et al. World J Urol (2010) 28:163–168

EHL

What is EHL?

• Underwater spark generation by applying current to two electrodes which 1mm apart and separated by insulation

• Sudden expansion and collapse of gas bubbles generates a hydraulic shock wave

• Placed not more than 1mm from the stone

• Avoided using EHL in ureter due to risk of perforation of ureter

What is USG lithotripsy?

• USG generator transmitted USG to hollow probe > vibration of probe tip

• Vibration in contact with the stone producing drilling or grinding action

• Avoided using USG in ureter due to thermal effect

What is USG machine?

• Sound wave by passage current through piezoelectric transducer and subsequently focused

• Lower frequency for deeper object• 7MHz for transrectal• 3.5MHz for transabdominal• USG pass into body via interface of soft rubber coating

and gel • Sound wave was deflected back to transducer forming

the image• Larger density (fluid and stone) produced greater echo

Robots

What is the classification of Robots?

1. Fixed path robots– Pre-programmed, completely automated– No interaction with surgeons– Prostate & renal access

2. Surgeon-driven robots– Copy surgeons movements in precise & tremor free

way– Endoscopic manipulators

• AESOP, Naviot

– Master-slave system• Zeus, Da Vinci system

What is Da Vinci robotic surgical system?

• It consists of powered control patient-side cart with 3 or 4 robotic manipulator arms which is linked to a surgeon console.

• The system provide 3D magnified vision through a binocular lens camera, &

• with specialized articulatory joins at the tip of robotic arms, the hand movements of surgeons at the console are translated into a more precise & tremor free manner

What are the advantages of Da Vinci?

1. Classical advantages of laparoscopy2. Superior visualization

1. 3D2. Magnified field 12x3. High resolution; these -> more accurate tissue handling & dissection

3. Superior dexterity, precision & control1. 7 degree of freedom (wristed instruments)2. Tremor reduction3. Motion scaling4. 4th arm-> ↓ assistance

4. Superior ergonomics1. Operate in seating position2. Natural hand-eye alignment at console3. Added mechanical strength; these -> ↓ surgeon fatigue & ↑ pt safety

5. Relative short learning curve for surgeons with open skills1. Due to direct translation of surgeon hand movements

What are the disadvantages of Da Vinci?

1. Absence of haptic feedback (i.e. tactile & force)– Compensated by superior visual quality & intra-op visual

cues

2. Cost of initial investment & maintenance

3. Large size– May restrict use in paedi pts & adults with small body frame– Large OT room

4. Set up time may be long esp initially e.g. docking

5. Expertise of surgeons & nurses, training required

What are the outcomes of Da Vinci?

• Lack of RCT1. Intra-op Cx

– ↓ Intra-op bleeding & blood transfusion (3% ORP-> 0.5% RoRP, Farnham, review by Ficarra)

– Overall Cx comparable with LRP2. Oncological outcomes

– +ve margin rate similar to ORP & LRP• 13% +ve margins, 7% biochem recurrence at 2 yr, Badani/ Menon)

– Longer FU required for long term biochem recurrence 3. Continence

– Continence (0 or 1 pad) at 1 yr similar to ORP & LRP (~90%)– May be earlier continence (40% ORP -> 70%, Ficarra)

4. Potency recovery– Similar to ORP & LRP

• ~70% at 1 yr after bilat NS (Menon)

Stent

What are the properties of a stent?

• Hollow tube and tapered end allows insertion

• Coils prevent migration

• Some are hydrophillic

• They are impregnated to make them radio-opaque

What are the stents?• Characteristics of ideal stents (Tolley)

1. Good memory, with configuration to prevent migration2. Excellent flow3. Radio opaque (bismuth/ barium coating)4. Biologically inert 5. Resist biofilm formation, encrustation & infection6. Flexible material with high tensile strength7. Easy to insert8. Easy to remove or exchange9. Reasonable price10. Minimal Cx

• Duration: – 6-12 mth due to encrustation, biofilm, infection & stone

• Configuration– Complete coils, J-tip, pigtail– 22-30cm long– 4.7-8 Fr

What are the materials of stents?

1. Polyurethane – Combined silicone & polyethylene– Disadv: Induce epithelial ulceration & erosion, cytotoxic

2. Silicone– Resistant to encrustation, but stiffer and more irritation > difficulty to

manipulate, thicker wall & smaller lumen, up to 1 year3. Metal

– Nitinol (nickel-titanium), in malignancy ureteric obstruction– Epithelized & ↓ encrustation

4. Polyethylene– Not used because prone to encrustation / UTI. – Adv: stiff

5. C-Flex TPE6. Percuflex7. Biodegradable

– Polymer of polylactic & polyglycolic acid– No need removal

What are the indications of stents?

1. Prophylactic– Adjunctive treatment for upper tract stone– Facilitate intra-op ureteric identification

2. Therapeutic– Drainage of infection or obstructed collecting

system– Urinary extravasations– Protect anastomosis

• Extranatomical stent: Paterson-Forrester stent

What are the complications of stent?

1. Irritative LUTS– Solutions: Avoid unnecessary stent– Avoid longer length– Softer & smaller stent– Patient explanation– Early removal

2. Migration

3. Encrustation

4. Infection

5. Blockage

Recent advances in ureteric stent

1. ↓ biofilm formation & UTI– Triclosan-eluting DJ (not that useful Denstedt)

2. ↓ irritative symptoms– Tapered & softer distal end

3. For malignancy obstruction– Stent w/o side holes– Dual-lumen stent– Coiled metal wire stent (e.g. Resonance)

4. Facilitate small stone removal– Self-expanding stent

5. Drug-eluting stent– Paclitaxel-eluting stent to ↓ blockage ? Therapeutic usage

6. Biodegradable stent

What is some important issues of ureteric stent?

• Ureteric stents in the absence of urteric obstruction will therefore cause partial ureteric obstruction

• When positioned for uretric obstruction, JJ stent allows urine drainage primarily around it and that is the reason for not functioning very well in malignant ureteric obstruction where the tumour will occupy that space between the stent and the ureteric wall.

• An alternative is to positon 2 stents that will allow drainage through the interspace between the stents.

• Pearle J Urol 1998– Randomized trial comparing JJ stent to nephrostomy as a treatment of

ureteric obstruction in the presence of infection– equally good at resolving the infection and ensuring urine drainage– Patients treated with nephrostomy were hospitalized for 1-2 days longer

but the JJ stent insertion was the more expensive mode of treatment• In theory JJ stent insertion have the risk of causing pyelovenous /lymphatic

reflux with irrigation pressure potentially resulting in worsening sepsis

Catheter

What are different types of catheter?

1. Latex 2. Silicone covered latex - silastic3. PTFE covered latex4. 100% silicone5. PVC (Polyvinyl chloride)6. Coated silver alloy• Different types of tip eg coude- or

whistle-tip

How is catheter size measured?

• According to the French system

• Remember the French size is the external diameter multiplied by 3 ( it is not the circumference )

• Similar value because circumference is diameter multiplied by 3.142/Pi)

What is prostate stent?• Temporary

– 1st generation: Urospiral, Prostakath, Intraurethral catheter– 2nd generation: Memokath, Prostacoil

• Permanent– Urolume wallstent (tubular mesh)

• Adv– Insertion 15min under regional anaesthesia– Bleeding minimal– Same day discharge

• Disadv– ↑ urination & incontinence– Mild discomfort– Dislodged-> obstruction/ total incontinence– Difficult to remove if infected– Fixed diameter-> limit subsequent endoscopy

Memokath

• Nickel-titanium alloy • Closed, tight spiral structure: prevent urothelial ingrowth• Adopt natural curves of urethra/ureter• Lack of outward pressure: ↓risk of secondary ischemic

damage• Titanium: resist corrosion in urinary tract• Shape memory

– warm to 50 C : expand to original shape

– Cold saline < 10C make it soft for removal

• Two types–Urethral stent–Ureteral stent

• 14 case series, 839 men• High surgical risk• Indications: LUTS or urinary retention• FU period: 3 month to 7 year• 4% unsuccessful initial insertion (due to incorrect stent

length)• Reduction in IPSS of 11-19 points• Comparable to that after TURP• Long term failure rate ~ 25%• Conclusions:

– Memokath appears to be safe and effective

– Inconsistent follow-up means that durability of Memokath cannot be drawn

• 74 stents, 55 patients• Mean FU 16 months• Indications: malignancy, recurrent benign disease• Normal drainage in all but 3 patients• Immediate complications

– Urinary extravasations (1)– Poor thermo-expansion (1)– Equipment failure (1)

• Late complications– Migration (13)– Encrustation (2)– Fungal infection (3)

• 14 patients need re-insertion due to migration, encrustation, stricture progression

• Conclusion: Memokath ureteric stents is a safe alternative to conventional JJ sent

Guidewires

What are different types of guidewires?

• Guidewires– Materials

1. Hydrophilic wire (Terumo)

2. PTFE (polytetrafluoroethylene) coated

– Configuration• Hydrophilic (Terumo) wires• Hydrophilic tip (Sensor)• Stiff (Amplatz super stiff)

– 0.035-0.038 Inch in diameter– 150cm long

Baskets

What are the various baskets?

• Nitinol

• Tipped or flat wire (segura)

• Tipless in flexible scope– Avoiding trauma to the collecting system– Easier access with flexible URS

• Open in different ways– Parachute or helical

Baskets

• Materials (2-3Fr)– Nitinol: flexible, versatile– Metal: strong

• Open in different ways

• Tipped • Tipless

– Avoid trauma to urinary tract– Easier access with flexible URS

Telescope

Describe how a modern telescope used in cystoscopy.

• Series of long glass rods in a metal cylinder separated by lenses of air spaces – rigid cystoscopy

• Optic-fibres are flexible glass (or plastic) fibres – flexible cystoscopy

• Advantages – durable, superior light and image passage

• Halogen light source, which emits yellowish light – need white balance. Neon light source does not need white balance, but expensive

Describe how a modern telescope used in cystoscopy.

• Cystoscopy – 30cm long– 17-25Fr

• Semi-rigid URS – 34cm long– With tip 7-10Fr– May have dual lumen

• Flexible URS– 70-80cm long– With tip <9Fr– May have dual lumen

• Resectoscopy – External sheath 26 or 28 Fr

Ureteric access sheath

What is ureteric access sheath?

• Indication: Intrarenal procedure with flex URS

• Adv:1. Better drainage-> ↓ intrarenal pressure

2. Better flow & vision

3. Easier to insert & remove scope

4. May ↓ OT time

• Disadv1. Costly

2. May be difficult to insert

3. May split ureter

Biofilm

What is Biofilm?• Def: Accumulation of microorganisms & their extracellular

products to form a structured community on a surface

• How to form?1. Proteinaceous molecules in body fluid are absorbed onto the

device forming a conditioning film2. Bacteria esp with fimbriae attach onto the film 3. Bacteria up-regulate genes & produce exopolysaccharide to

form a glycocalyx matrix & lead to irreversible attachment4. Further bacterial attachments, growth & multiplications form a

matrix-enclosed community i.e. biofilm

• Structures1. Linking film which attach to surface of biomaterial2. Base film of compact bacteria3. Surface film on outer side where free-floating bacteria can

spread

What is Biofilm?• Why resistant to Rx?

1. The glycocalyx matrix restrict access & diffusion of antibiotics

2. Bacteria in biofilm have many phenotypes, & antibiotics only targeted to free-floating bacteria, hence not effective & may lead to antibiotic-resistant strains due to selective pressure esp slow growing bacteria deep in biofilm

3. Bacteria can sense the external environment & communicate & transfer genetic information with each other

4. Bacteria in biofilm can survive despite 1000x usual concentration of antibiotics

What is Biofilm?

• Solutions1.To prevent instead of eradicate2.Avoid unnecessary devices e.g. catheter & early

removal3.Prophylactic peri-op antibiotics4.Surgical techniques5.Theater precautions6.New advances to ↓ biofilm

• New biomaterial• Surface coating e.g. silver, antibiotics (triclosan),

hydrogel (polyethylene glycol, heparin)

Intracorporeal Lithotriptors

What are the different types of intracorporeal Lithotriptors?

• Pneumatic (lithoclast)– Compressed air is used to fire metallic projectile in hollow tube which

strike a solid probe like a jackhammer & transmit kinetic energy to fragment stone mechanically when in contact

– Adv• Less trauma to urothelium-> wide margin of error• Little heat production• No cavitation bubble• Cheap

– Disadv• Rigid scope only

• Ultrasonic– Ultrasound generator produce ultrasound waves down a hollow tube

leading to vibration of probe tip & a drilling action to fragment stone. Often with suction.

– Disadv• High temp at probe tip-> not used in ureters• Rigid scope only

What are the different types of intracorporeal Lithotriptors?

• Laser: Holmium, YAG, Freddy– NdYAG laser had wavelength of 1064 and

penetration of 10mm

• EHL– Electricity generate an underwater spark between 2

electrodes, which lead to vaporization , formation of a cavitation bubble, which rapidly expand & collapse , & generate shockwave to fragment stone

– Adv• Can be used in flexible scope

– Disadv• Traumatic to urothelium, usu only for bladder stone

Min. invasive Tx option for small RCC

Minimal invasive therapy for RCC• Cryotherapy, RFA, microwave ablation, HIFU• Adv (vs partial nephrectomy)

1. Minimally invasive, no need pedicel control, low Cx• Suitable for pts with limited LE & poor surgical risk

2. Rapid recovery, short hospitalization• Disadv

1. Higher local recurrence (2-3x for Cryo & RFA) (Meta-analysis, Landman)2. Lack of specimen for pathological staging3. Poor definition of treatment success 4. Unable to confirm complete tumour eradication5. Intentensive FU required6. Salvage nephron-sparing surgery can be difficulty

• Renal Bx prior or at time of MIS– Accuracy 90% to differentiate malignant from benign– Inconclusive in 10%– Cx

• Bleeding unusual• Tumour seedling <0.01%• Limitation in hybrid or cystic tumours

RCC – Cryo & RFA

• Mechanisms

• Suitable patients & tumour

• Advantages

• Disadvantages

• Long term results

• Comparison of thermal ablations with partial nephrectomy?

RCC – cryo mechanism• Mechanism

1. Based on Joule Thompson principle2. Cell destruction during rapid & repeated freeze-thaw cycles3. Rapid gas expansion of compressed argon leading to ultracold

condition (-19°c)4. Extracellular ice formation & extracellular fluid became hyperosmotic 5. Fluid shift causing intracellular dehydration 6. Further cooling leads to intracellular ice formation7. & disrupt cell organelles & cell membrane8. Delayed microcirculatory failure

• Percutaneous or lap• Inclusion

1. Small renal tumour (<3cm)2. Exophytic & non-hilar tumour3. Limited LE or poor surgical risk

RCC – cryo mechanism• Advantages:

– Low complication rate (bleeding 1%), rapid recovery– No need for hilar clamping– Real time monitoring of ice-ball under USG possible (vs RFA)– Longer FU data a/v than RFA – ? Less local recurrence (cryo 5%, RFA 13%) & re-ablation than

RFA• Disadv:

– NO RCT , pts highly selected• Cx: bleeding , vascular thrombosis, ureteric stricture, urinary

fistula• Ev: 8YCSS 90% , local and systemic recurrence 15% (Gill,

Clveland clinic)

RCC – cryo result

• Cleveland clinic experience in 66 patients:– 5 year FU after lap cryoablation– 5 year overall survival: 81%– 5 year cancer specific survival: 98%

RCC - RFA

• Mechanism1. High frequency (400-500kHz) alternating current flows

from needle electrode to target tissue

2. Cause ionic agitation & molecular friction

3. Generate heat (>50-100°c)

4. Denature of cellular protein & cell membrane

5. Cell death & coagulation necrosis

• Percutaneous or Lap• Goal: maintain target tissue at 50-100° C

– Adequacy of ablation is assessed by temperature or impedance from RF generators

RCC - RFA• Suitable cases:

– small renal tumor less than 3cm– non-hilar exophytic cases– Limited LE or poor surgical risk

• Advantages:– No need for hilar clamping– no renal warm ischaemia– low complication rate, rapid recovery

• Disadvantages:– The process of RFA itself cannot be actively monitored in real

time imaging– though impedance can be measured.– No RCT, pt highly selected– Lack of long term results– Higher local recurrence (13%) than Cryo (5%)

RCC - RFA

• Results– No long term results available– Technology still evolving– Medium term FU up to 20 months– favorable cancer specific survival ranging

from 80-100%– 4yr CSS 94%, local recurrence 5%

(McDougal)

• Cx: urinary fistula, ureteric stricture

Notes & LESS

What are Notes & LESS?• NOTES

– Natural orifice transluminal endoscopic surgery– Adv

• Cosmesis, no skin incision risk, less invasive, less physiological impact

– Disadv• Access navigation, peritonitis, fistula, intraop bleeeding

– For nephrectomy, bladder surgery

• LESS– LaparoEndoscopic Single-site Surgery– Instruments

• Access portals: Triport/ Quad port• Instruments: Standard straight lap, fixed bent, articulating, robotics• Scopes: End light source / Rt angle light cord; Articulating eye pieces

(Endoeye)– Adv: Cosmesis, ↓ skin incision risk

Any other alternatives for TURP?

BPH: min. invasive Tx options

• TUNA – TU RF needle ablation – Done under LA – Heat → localized necrosis of prostate – Modest improvement in SS and Qmax – Min. invasive option for LUTS – ? LT effectiveness

• TUMT – IU catheter with cooling system – Prostatic heating and coagulative necrosis – SS improvement in 75% patient – Long cath time, ↑ UTI and irritative voiding Sx – For those avoid surgery

BPH: min. invasive Tx options

• HIFU – Focused USG, ↑ temp to prostate. – TR probe. GA. – Investigational

• Prostatic stent – Temp: usu. after procedure – Permanent, metal coil Urolume – Memokath: Nickel-Titanium stent with thermal

shape-memory effect for treating prostatic obstruction and enlargement

BPH: stents

• Advantages – They can be placed in less than 15 minutes under regional

anesthesia. – Bleeding during and after surgery is minimal. – The patient can be discharged the same day.

• Disadvantages – They may cause increased urination and limited incontinence. – They may cause mild discomfort – They can become dislodged, leading to urinary obstruction or total

incontinence. – They can become infected and can be very difficult to remove. – Their fixed diameter limits subsequent endoscopic surgical

options.

TUNA and TUMT

What is TUNA ?TUNA• TU RF needle ablation• Done under LA• Low level RF energy Heat → localized necrosis of prostat• Modest improvement in SS and Qmax• Not for: Prostate >75cc or BNO• Adv:

– LA, Day case– Min. invasive option for LUTS

• Disadv: – Irritative symptoms lasting up to 4 weeks– 20% require additional txn– No long term result available

• Evidence: – Only one RCT : Symptomatic improvement: 50%, flow rate 40%

What is TUMT?

• Transurethral microwave therapy (Proststron)

• IU catheter with cooling system• Prostates heating and coagulative

necrosis• SS improvement in 75% patient• Long cath time, ↑ UTI and irritative voiding

Sx• For those avoid surgery

Bipolar TURP

BPH bipolar TUR

• Bipolar TURP (B-TURP) addresses a fundamental flaw of monopolar TURP (M-TURP) by allowing performance in normal saline, and the technique seems to be promising

• 16 RCT– Short term efficacy: no difference– >12 months: scarce reports– B-TURP is preferable due to a more favorable safety profile

(lower TUR syndrome and clot retention rates) and shorter irrigation and catheterization duration.

– Well-designed multicentric/international RCTs with long-term follow-up and cost analysis are still needed.

Eur Urol 5 6 ( 2 0 0 9 ) 7 9 8 – 8 0 9

What is bipolar TURP?• Plasmakinetics, TURis• Adv

1. ↑ Safety profile• ↓ TUR syndrome due to normal saline irrigation (0 case, NNT 50)• ↓ clot retention rate (NNT 20)• ↓ post op irrigation duration• ↓ catheterization duration

2. Equal short term efficacy (<1yr) in voiding parameters eg. Qmax, IPSS/QOL3. No difference in OT time, tranfusion rate, retention after TWOC, urethral Cx

• Disadv– ? ↑ Urethral stricture (Ho & S Yip, Singapore)

• Due to electric current return (leak) via resectoscope sheath• ↑ diameter• Higher ablative energy• ↑ OT time

– Scare data on >12 month study• Ev

– Meta-analysis by Mamoulakis 09: 1406 pt, 16 RCT.• Limitation: Limited FU (12 mth)

Botox in BPH/ LUTS

LUTS/BPH: Botox

• Botulinum neurotoxin type A (BoNT-A) intraprostatic injection seems to relieve patients with lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE). However, the level of evidence and grade of recommendation are relatively low. Therefore, there is a need for large placebo-controlled studies and long-term results.

Eur Urol 2008 54(4): 765-777

What is Botox in BPH/ LUTS?

• Experimental/ animal studies– Relaxation of prostate– Atrophy– Inhibit trophic effect of autonomic system-> ↓ size

• Clinical studies: 9 case controlled, only 1 RCT• Meta-analysis by Oeconomon (FU<19mth)

– ↑ Qmax– ↓ QOL/ IPSS, PVR, PSA, prostate vol– If AROU-> All can void post-op – Local or systemic S/E rare– Effect can last 12 mth

• Limited evidence-> still experimental

Narrow band imaging (NBI)

Narrow Band Imaging (NBI)• Traditional diagnosis is by white-light imaging

(WLI) cystoscopy• WLI fails to detect small papillary and subtle flat

CIS lesions• NBI improves the detection rate of above lesions• Other uses

– Barrett’s esophagus in OGD– Ca lung in bronchoscopy– Neoplastic polyp in colonoscopy

• Optical image enhancement technology from the Olympus Lucera sequential RGB endoscopy

• Narrow the bandwidth of light output• Wavelength: 415 nm and 540 nm• Strongly absorbed by haemoglobin

and penetrated only the surface of tissue

• Urothelial carcinomas are vascular

• ↑ visibility of surface capillaries and blood vessels in the submucosa

• Enhance the contrast between superficial tumors and normal mucosa

Olympus Lucera

EvidenceWLI NBI

No. of tumours

64 79

29 patients recruited15 more tumor lesions were found in 12 patients0.52 lesion / patient (P <0.001, Wilcoxon signed-rank test)

Richard T. Bryan, Lucinda J. Billingham and D. Michael A. Wallace. Narrow-band imaging flexible cystoscopy in the detectionof recurrent urothelial cancer of the bladder. BJU International 2008; 101, 702-706

NBI improves the detection of recurrent bladder tumours (esp CIS) in surveillance WLI cystoscopy

Increase tumour detection rate

WLI NBI

Sensitivity 87% 100% (p=0.05)

Specificity 85% 82% (NS)

PPV 66% 63% (NS)

NPV 96% 100% (NS)

Harry W. Herr and S. Machele Donat. A comparison of white-light cystoscopy and narrow-band imaging cystoscopy to detect bladder tumour recurrences. BJU Intenational 2008; 102,1111–1114

*nine showed CIS*

Check cystoscopy in NMIBC 427 patients

Evidence

• 26Fr resectoscope with Exera II Olympus• 47 patients NBI assisted TURBT after WLI TURBT and 6 cores Bx

(2nd look TURBT)• 40 more biopsies taken, 11/40 biopies were positive• 6 more patients was found to have Ta high grade tumor / CIS

Adding NBI biopsies at the end of an extensive second TUR protocol in patients with newly diagnosed high-grade NMIBC

Angelo Naselli, Carlo Introini, Franco Bertolotto, Bruno Spina and Paolo Puppo. Narrow band imaging for detecting residual/ recurrent cancerous tissue during second transurethral resection of newly diagnosed non-muscle-invasive high-grade bladder cancer. BJU International 2009; 05, 208–211

New Optical techniques for Diagnosis of Ca Bladder

2. Narrow band imaging– An optical image enhancement technique to enhance contrast

b/w mucosal surface & microvascular structure w/o use of dye during cystoscopy & aim to detect more CaB

– It is based on phenomenon that depth of light penetration into mucosa ↑ with ↑ wavelength, & the mucosal surface is illuminated with light of a narrow bandwidth, blue & green spectrum, which are strongly absorbed by haemoglobin, hence the vessels appear dark brown or green against a pink or white normal mucosal background

– No RCT– Results

• ↑ detection of tumour recurrence in NMICaB by 12% (Herr)• Sn ↑ from 90 -> 100%

New Optical techniques for Diagnosis of Ca Bladder

3. Raman spectroscopy– An optical imaging technique that measure the

molecular components of tissue based on the unique wavelength shift, of tissues molecules with different histopathology

– Adv• Real time, objective prediction of pathologic Dx• Capable of differentiating inflammatory from malignant

tissue– Disadv

• Experimental, no human in vivo studies• Limited field of view

New Optical techniques for Diagnosis of Ca Bladder

4. Optical coherence tomography– An optical imaging technique which produce high resolution cross-

sectional imaging of tissues using elastic light scattering as the contrast mechanism, which aims to improve prediction on histology

– Adv• High resolution image comparable with histopathology• Info about depth of tumour

– Disadv• Experimental

Metaanalysis by Cauberg, Mowatt

Sn Sp

White light cystoscopy

70% 70%

Cytology 50% 90%

PDD 90% 60%

NBI 100% 80%

Photodynamic Diagnosis

Fluorescence cystoscopy

PDD

– An optical image enhancement technique which – aims to improve visualization of bladder tumour by

using fluorescence as a contrast mechanism to detect pathology

– e.g. 5-aminolevulinic acid (5-ALA), which is starting point of haem biosynthesis pathway & is predominantly accumulated in tumour tissue, & its intermediate protoporphyrin appears red under blue-violet light, while normal tissues appears blue.

– 5-ALA administered 2 hrs before cystoscopy through catheter

– Special telescope & light source (D-light)-> switch from white to blue light

Photodynamic diagnosis (Fluorescence cystoscopy

– Adv1. ↑ detection of CaB, esp CIS 40% (sn 70 (white)->

90%)2. Improve tumor resection (↓ residual tumour in 2nd

TURBT)3. ↑ recurrence-free survival (Meta-analysis, 5 RCT,

Kausch)

– Disadv1. False +ve 30% (low specificity) e.g. inflammation,

scar, previous intravesical therapy2. Expensive 3. Time consuming (2hr administration)

Additional – PDD (photodynamic diagnosis)

• Meta-analysis• 20% (95% CI, 8–35) more tumour-positive patients were

detected with PDD in NMIBC• 39% (CI, 23–57) more in subgroup CIS only• Residual tumour was significantly less often found after PDD

(odds ratio: 0.28; 95% CI, 0.15–0.52; p < 0.0001)• Recurrence-free survival was higher at 12 and 24mo in the

PDD groups than in the WLI-only groups (p<0.0002)

Ingo Kausch et al, Photodynamic Diagnosis in Non–Muscle-Invasive Bladder Cancer: A Systematic Review and Cumulative Analysis of Prospective Studies. European Urology, 57(2010) 595–606

Imaging

Ca prostate staging

• Bone scan equivocal:– Any alternative?

Ca prostate staging

• SPECT

• PET

SPECT

• SPECT (Single Photon Emission CT)– CT + radionuclide tracer– Spine is a frequent site for degenerative joint disease,

• the diagnostic accuracy of planar BS is low, particularly for a single focus of abnormal increased tracer uptake.

– SPECT can minimise the shortcomings of planar BS in the assessment of the spine

• Optimised the use of planar BS, with improved Sn range of 87%-92% and Sp of about 91%, and a PPV of 82%, negative predictive value of 94%, and an accuracy of 90%.

Semin Nucl Med. 2009 Nov;39(6):396-407. Review.

What is SPECT?

• Single photon emission CT

• A radionuclide scan with multiplanar & 3D reconstructed CT images

• Used if bone scan equivocal

• ↑ bone met detection sn 90%, sp 90%

• Vs PET (exam question)– Measure radionuclide directly, cheaper, but ↓

resolution

Contrast issues

Contrast nephropathy/ allergy

• Patient on metformin

• Contrast nephropathy– Definition– Mechanism– Risk factors– Interventions to minimise risks

• Contrast allergy– Underlying cause– Preventive measures

What are the CI to IV contrast ?

1. Allergy to contrast media

2. Impaired RFT (Cr > 130 umol/L)

3. Metformin usage

4. Untreated hyperthyroidism and myelomatosis

Contrast nephropathy

• While patient is on metformin:– Guideline from European Society of Urogenital Radiology

– 1. if serum creatinine: normal• stop metformin (at the time of exam until 48 hours passed and serum Cr

remain normal)

– 2. if serum creatinine: impaired• stop metformin 48 hours before exam, resume metformin 48 hours later if

serum Cr remained at pre-exam level

– 3. if contrast given to patient taking metformin• metformin stopped immediately• hydration to ensure U/O 100ml/hr x 24 hours• monitor serum Cr, lactic acid and blood gas

Contrast nephropathy• Definition

– 25% increase in Serum Cr, or at least 44 umol/L– during 3 days following contrast administration

• Mechanism:– Direct toxic effect on tubular cells– Vasoconstriction– High osmolar content induce marked natriuresis and

diuresis– This would trigger tubulo-glomerular feedback response

with constriction of glomerular afferent arterioles

Lactic acidosis

• Symptoms:–Vomiting, anorexia, hyperpnea, lethargy,

diarrhoea, thirst

• Lab results–blood pH <7.25, lactic acid> 5mmol/L

Risk Factors for Contrast Nephropathy

• Age >70

• Renal impairment

• Diabetes

• Dehydration

• Congestive heart failure

• Concurrent treatment with nephrotoxic drugs

How to minimize the risk of Contrast Nephropathy?

• stop nephrotoxic drugs if any

• adequate hydration

• administration of N-acetylcysteine–600mg bd

Contrast ‘Allergy’

• Is it really allergy?

• What is the underlying cause?

Contrast medium Adverse reactions

• Anaphalactoid– Idiosyncratic reaction unpredictably and

independently of dosage and concentration of the contrast media• Related to ionic and high osmolar content of the

contrast• Leading to release of different mediators

• Chemotoxic– Severity related to dosage/concentration of

contrast media– Also related to characteristics of the agent

Prevention of Contrast Adverse reaction

• use low molecular non-ionic contrast medium

• Corticosteroid

USG

What is USG machine?

• Diagnostic• Sound wave by passage current through piezoelectric

transducer and subsequently focused• Lower frequency for deeper object• 7MHz for transrectal• 3.5MHz for transabdominal• Sound wave was deflected back to transducer forming

the image• Larger density produced greater echo (like stone)• Time taken for waves to come back to transducer can

determine the depth

What is USG machine?

• Therapeutic

• USG lithotriptsy

• HIFU

• Guidance for brachytherapy, cryotherapy and ESWL

USG for CaP• Power Doppler USG

– The magnitude of colour flow output is displayed rather than Doppler frequency signal

– Not display flow direction or diff velocities– Used to ↑ sensitivity to low flows & velocity– Adv

1. Sensitive to low flow2. ↑ CaP detection 50 (conventional TRUS) ->70%

– Disadv1. No directional info2. Poor temporal resolution3. Susceptible to noise

Elastogram

Rationale

• Ca prostate• Higher cell density• Altered tissue elasticity• Measured and

displayed by US elastography

• Aim detect ‘hard’ lesion

• For targeted biopsy

How it works?

• Visualize local displacement on compression

• Compare USG image pairs (compressed vs decompressed)

• System compute the tissue strain by degree of local displacement

• Stiffness displaced as different colours

Role in Mx of Ca prostate

• For ca prostate detection

Role in mx of Ca prostate

• For lesion guided biopsy

• May decrease the no. of cores needed to detect a cancer

Role in Mx of Ca prostate

• Potential to illustrate ECE and SVI (for staging information

• Interrupted ‘soft rim artifact’

• Increase stiffness of SV

limitation

• Inter-observer variability of ‘stiffness’: different degree of compression

• Not every hard nodule is cancer

What is 3D USG?

• ↑ detection of CaP• Assessment of brachytherapy seed placement• Cryoablation guidance• Local staging in CaP / Ca bladder

Contrast USG

What is contrast USG?

• Based on microbubble-based contrast to detect region of ↑ vascularity

• targeted Bx for CaP 1. ↑ CaP detection ~ 80%2. Additional info on tumour size/ aggressiveness3. ↓ no of Bx needed to obtain same detection rate4. Tumour detected have ↑ Gleason score than random Bx

• Monitor minimal invasive/ medical treatment results e.g. HIFU/ cryoablation/ hormone

• CE-USG Bx for RCC– Better differentiation of malignancy & benign renal tumour

RenogramRenogram

Radiopharmaceuticals in renogram?• 1. Glomercular: Technetium-99m(99mTc) diethylenetriamine pentaacetic acid (DTPA):

peak renal activity 3-4 min after injection; 90% glomerular filtration in first 2 hr; Used to access renal blood flow, function and drainage; Measure GFR as only glomerular filtration with no tubular reabsorption / excretion

• 2. Tubular: 99mTc-mercaptoacetyltriglycine (MAG-3): 90% promximal tubular excretion and 10% glomerular filtration in animal study; Measure renal plasma flow, renal function and drainage; Especially for patients with decreased renal function and of infants

– Adequately hydrated, empty their bladder, frusemide is the diuretic of choice

– Vascular phase (0-60s), parenchymal phase (3-5 mins), excretory phase (>5 mins)

– Tc 99m has a half life of 6 hours

– IV frusemide in renography will increase the urine flow from 1ml/min to 20ml/min within 3 min and 40ml/min after 15 mins

• 3. Cortical:99mTc-dimercaptosuccinic acid: uptake in distal convoluted tubules; pelvicalyceal system not visualized; static image after 2-4hr, maximum activity 3rd-6th hr

Radionuclide scintigraphy

• DMSA for renal scarring/ static scan• MAG3/ DTPA scan for differential function and

assessment of obstruction/ dynamic scan

MAG3 DTPA

Glomerular filration < 5% > 95%

Tubular secretion 95% Minimum

Clearance Predominantly by tubular secretion;

small proportion by glomerular filtration

Min. tubular secretionor absorptionAlmost completely byglomerular filtration

Cost Higher Lower

Radionucline scintigraphy

• Patient prep:– Adequate hydration– Empty bladder before procedure

• Factors affecting the scan:– Renal function– Hydration status– Collecting system capacity– Bladder effect

How to describe renogram curves?

How to describe renogram curves?

• O’Reilly classify the renogram curves, during F+20 lasix renogram• Type 1

– Normal curve of a nonobstructed kidney. It is characterized by early uptake of the radioisotope pharmaceutical by the kidney and a prompt excretion of that. The excretion part of the curve is characterized by an upward concavity

• Type 2 – Consistent with ureteric obstruction

• Type 3a – Represent a dilated but non obstructed pelvicalyceal system

• type 3b – An equivocal curve that need further investigation with F-15 renogram. Type 3b curve could

be secondary to partial ureteric obstruction or impaired renal function. An F-15 renogram might be able to distinguish between the two by ensuring adequate diuresis

• Type 4 curve – Homsy’s sign – obstruction with delayed decompensation. It represents a delay upward

deflection of the excretory part of the curve. It could represent VUR or significant extravasation with recirculation of the radiopharmaceutical (more commonly seen in children)

– Confirmed by F-15

What are the causes of nonobstructive upper tract dilatation?

Whitaker test

What is Whitaker test?

• Indicated in equivocal ureteric obstruction• When a F+20 renogram shows a type 3b curve, an F-15

renogram should be carried out before Whittaker test which is invasive

• It involves establishing a percutaneous access to renal pelvis, this allows infusion of saline or contrast at 10ml/min

• The nephrostomy line and a catheter are connected to manometers and the pressure difference (PD) between the bladder and the pelvis is recorded.

• <15 non obstructed, 15-22 equivocal, >22 obstructed

What is Xray safety precaution?

• Pregnancy test of childbearing female

• Theatre doors were closed

• Warning signal and red warming light

• Lead apron and thyroid shield

• ALARA

• Xray as close as the operating table so as to keep distance from radiation source

Bone scan

Bone scan• Aim: A radionuclide scan used to detect bone abnormalities which has increased

osteoblastic activity• Technitium 99-medronate (methylenediphosphonate)• 60% eliminated via kidney• Rationale: high phosphate uptake by immature bone (Sv 95% in CaP)• Procedure

– 99Tc-medronate injected– Adequate hydration– Empty bladder b/w injection & imaging, & just before imaging to ↓ bladder

shadow to pelvis– Image collection at 3 hrs after injection (Ant, post)

• Radiation: 3.5mSV, T1/2: 6 hrs• ↑ uptake (& false +ve)

– Bone metastasis– Fractures– Degenerative bone disease– Paget’s disease– Metaphyseal-epiphyseal growth in children

• False –ve– Aggressive tumor that induce little osteoblastic attempt at repair

• reflects osteoblastic activity and skeletal vascularity at sites of active bone formation

• If IV bisphosphonate is use: – it is recommended that bone scan be deferred

for 4 weeks after completion of intravenous bisphosphonate therapy, because it reduce tracer uptake in the normal bone

Man with disseminated Ca prostate• What is this investigation? (0.5) Isotope used? (0.5)• What is this picture commonly called? (1)

• Bone scan (0.5)

• Technetium-99m labelled methylene diphosphate (MDP) (also known as medronate or medronic acid) (0.5, no mark for abbreviated name)

• Superscan (1)

SuperscanSuperscan

• Patients with disseminated CAP may demonstrate a “superscan”– A symmetrical increased uptake throughout

the skeleton– Minimal soft tissue activity– Absent or dim renal uptake

• Due to increase skeletal uptake very little tracer is distribute to the soft tissue or excreted in the kidneys

What is DEXA?• Dual energy Xray absortiometry• Measure bone mineral density, to detect osteoporosis• Mechanism

– 2 Xray beam with different energy levels aim at bone– Subtract soft tissue absorption– BMD calculated from absorption of each beam by bone

• Radiation: 1/10 of CXR• T score (vs young adults), Z score (vs age matched)• Osteoporosis (<-2.5 sd), osteopenia (-2.5 to -1 sd)• Adv

– Simple & non invasive– No anaesthesia– Extremely low radiation– Most accurate Dx of osteoporosis– Equipment readily a/v– No S/E

• Disadv– Still radiation– Pregnancy

On table IVU

On table IVU

– When, because of shock and need for immediate laparotomy, a patient is transferred immediately to the operating theatre without having had a CT scan, and a retroperitoneal haematoma is found, a single shot abdominal X-ray, taken 10 min after contrast administration (2ml/kg of contrast), can establish the presence/absence of a renal injury and the presence of a normally functioning contralateral kidney where the ipsilateral kidney injury is likely to necessitate a nephrectomy.

New technology

Ca bladder

Any better option for cystoscopy?

Ca bladder - Dx

• Photodynamic Dx for bladder tumour– Fluorochrome 5-aminolevulinic acid (5-ALA) and its ester

derivative hexaminolevulinate can be safely instilled in the bladder

• where they preferentially accumulate in neoplastic tissue. Malignant areas appear red, and normal tissue blue, when the bladder surface is illuminated with blue–violet light via a rigid cystoscope.

• PDD detects more bladder tumour–positive patients, especially more with CIS, than WLC. More patients have a complete resection and a longer RFS when diagnosed with PDD.

(Systemic Review: Eur Urol 2010)

How about urine markers for Ca bladder

Urine Markers for Ca bladder

1. Fluorescence in situ hybridization (FISH)2. ImmunoCyt3. Nuclear matrix protein (NMP22)4. BTA stat test (viva)5. Telomerase (viva)

• All higher sn but lower sp than cytology

• Highest sn: Immunocyt (85%), FISH (75%), NMP22 (70%), cytology (50%)

• Highest sp: Cytology (90%), FISH (85%), NMP22 (80%), ImmunoCyt (75%)

TissueLink

What is it

• Device used to seal off blood vessels, as pre-coagulation so enable ‘bloodless’ dissection

• Initial invented for hepatectomy

• Currently extend to kidney , pancreas , brain, colon, orthopedics surgery either open or laparoscopic

Mechanism

• Simultaneously deliver radio-frequency ( RF ) energy and saline as thermal energy to the tissue to seal off bleeding vessel

• The coupling of saline and RF allows the device temperature to stay at approximately 100°C, nearly 200°C less than conventional RF energy devices, resulting in a tissue effect without associated charring.

• It stops bleeding by transforming collagen, remodelling and resulting in a permanent seal.

benefits

• No need to clip or tie during parenchymal transection

• Bloodless transections, often no need for in-flow occlusion

• Produces a sealed remnant organ bed that will not crack and rebleed

• Single device for either pre-coagulation alone or simultaneous pre-coagulation and blunt dissection

• No char and a virtually bloodless field make the plane of dissection clear

• Simple set-up - all you need is a standard electrosurgery generator and a bag of saline

Urology application

• Solid organ dissection partial nephrectomy

• Potentially bloodless dissection w/o clamping pedicle

Energy source

What are the different types of energy source?

• Diathermy– High frequency alternating current– 400kHz to 10MHz, / 0.25 to 2 MHz– Up to 1000 degree– Nerve and muscle are not stimulated with high

frequency current as no time for cell membrane to become depolarised

– Large patient plate is required not for heat dissipation– Radiofrequency ablation is not a form of diathermy– Cutting mode – continuous sine wave, 125-250W, for

vaporisation and cutting, low charring– Coagulation mode – pulsed sine wave, 10-75W, for

fulguration, high charring

What are the potential complications of diathermy?

• Burn

• Explosion

• Obturator jerk

• End artery necrosis

• Pacemaker damage

Energy source• Bipolar electrocautery

– Adv• For haemostasis & also dissection• Minimize damage of adjacent tissue• Allow selection of depth of tissue damage by using diff sized forceps

– LigaSure• Bipolar radiofrequency generator & lap Maryland forceps• Combination of pressure & energy to create vessel fusion• For vessels ≤6mm (inadequate for renal pedicle)• Safe, cost effective, time-saving

• Monopolar electrocautery– Tissue-link

• Monopolar radio-frequency energy with low-vol saline irrigation for haemostasis & blunt dissection

• Disadv– May cause carbonisation & impair vision of operative field– Damage to significant margin of healthy tissue e.g. collecting system

What are the different types of energy source?

• Harmonic scalpel– High frequency ultrasound for

haemostasis(>55kHz) & dissection (25kHz)– Adv

• Less collateral damage• Avoid carbonisation of tissue• ↓ local thermal damage

– Disadv• For small vessels only (<4mm)

Tissue Sealants & Haemostatic agents

Haemostasis in laparoscopy• Proper case selection• Intra-op measures to ↓ bleeding

– Primary prevention• Proper tissue dissection• Identification of supplying blood vessels• ↓ pneumoperitoneum at the end to identify venous bleeding

– Haemostasis1. Energy sources

– Bipolar electrocautery» Ligasure, Plasmakinetic

– Monopolar electrocautery» Argon beam coagulator, Tissuelink

– Ultrasonic device» Harmonic scalpel

2. Clip system– Self-locking ligation clip: Hem-o-lock– Titanium clip: tend to slip– Vascular endo-stapler: Endo-GIA: Insufficient sealing for major vessels; costly

3. Haemostatic & sealing agents4. Surgical techniques

– Sutures, local compression

What are the tissue Sealants & Haemostatic agents?

• Usage: Haemostasis, tissue adhesion, urinary tract sealing• Renal trauma, partial nephrectomy, urinary tract fistula,

PCNL tract, RRP nerve sparing, promote wound healing• Types

1. Enzymatic agents• Fibrin: tisseal• Thrombin: floseal

2. Cross linking sealants• Coseal

3. Mechanical scaffold• Porcine (pig) gelatin: Gelfoam• Collagen• Oxidized cellulose: Surgicel

• Cx in general1. Thromboembolism due to intravascular use2. Coagulopathy after repeated use of bovine (cow) products3. Allergy to bovine antibrinolytic (tisseal)

What are the tissue Sealants & Haemostatic agents?

1. Tisseal– Fibrin sealant– Human fibrinogen & thrombin & antifibrinolytic aprotinin (bovine/ synthetic)– Contraindication: Intravascular use due to systemic thrombosis– Delivered using a dual-chamber delivery system-> rapid clot formation– Adv

1. Also for tissue adhesion & urinary tract sealing2. Also promote wound healing due to ↓ dead space & induce fibroblast

migration– Disadv

1. Required a dry (bloodless) surgical field2. Viral transmission (human)3. Not if bovine allergy

What are the tissue Sealants & Haemostatic agents?

2. Floseal– Matrix haemostat– Combine 2 component :

• Human thrombin component • bovine gelatin matrix granule cross-linked gelatin granules

– Both enzymatic & mechanical haemostasis– Gelatin matrix granule fill the wound & expand 20% within 10 min when in

contact with blood– Form clot & matrix provide mechanical tamponade– Matrix reabsorbed within 6-8 wk– Adv

• Localized effect, only when blood present (due to no fibrinogen)• Ease of application of flowable preparation• ↓ Bleeding in lap partial nephrectomy (12 -> 3%) even w/o need to

renal ischaemia (Gill)– Disadv

• Not tissue glue or urinary tract sealant, only pure haemostasis• Do not inject or compress Floseal Matrix into blood vessels. • Do not apply Floseal Matrix in the absence of active blood flow, eg.,

while the vessel is clamped or bypassed. • Extensive intravascular clotting and even death may result• May carry a risk of transmitting infectious agents, e.g., viruses, and

theoretically, the Creutzfeldt-Jakob disease (CJD) agent

What are the tissue Sealants & Haemostatic agents?

3. Gelform– Porcine gelatin sponge– Mechanical scaffold for platelet adhesion & clot formation– Absorbed within 4-6 wk

4. Surgicel– Oxidized cellulose– Acidic material to form a mechanical scaffold for clot formation– Antibacterial– ↓ urinary fistula & bleeding in LPN (Gill)

• e.g. surgical bolster– Disadv

• Confusing in post-op imaging after PN– ? Tumour recurrence / abscess

What are the tissue Sealants & Haemostatic agents?

5. NovoSeven– Recombinant activated factor 7 for haemophilia – IV administration

• Bind to exposed tissue factor or activated platelets & cause clotting at site of bleeding only

– Very limited evidence, only off label use in e.g. trauma

– Reported elective use in urology: RRP & renal transplantation

– ↓ bleeding in RRP (Friederich)– Safe (Cx esp thromboembolism 1%)

PCA3

What is PCA3?1. PCA3 (Prostate cancer gene 3 assay) (UPM3 test): PROGENSA

– A prostate specific non-coding mRNA that is over-expressed 100 times in 95% of CaP specimen than in benign prostate

– Aim1. To improve CaP detection2. To guide decision for TRUS Bx3. To differentiate clinically significant from indolent disease

– Suitable scenarios 1. ↑ tPSA & -ve Bx2. ↑ tPSA 2.5-103. ↑ tPSA & concomitant urinary condition e.g. BOO/ prostatitis4. Normal tPSA & FHx

– Measure PCA3 & PSA mRNA concentration in urine collected after DRE– PCA test-> PCA3 score = PCA3 mRNA/ PSA mRNA x 1000 (abnormal if

>35)– Adv

1. High sensitivity (70%) & specificity (90%) & similar in all PSA levels (Hessels)2. Not affected by prostate vol, age , previous bx, tPSA level3. Correlated with tumour vol4. May be a predictor of extracapsular extension5. Greater dx accuracy predicting outcome of repeat bx than tPSA and fPSA

Ca Prostate New Markers

1. Human Kallibrein 2 (hK2)– Product of KLK2 gene. Predictor of ECE & SV

invasion2. Prostate specific membrane antigen

(PSMA)3. Prostate specific antibodies4. Urokinase-type plasminogen activator

receptor (uPAR)5. Early Prostate cancer antigen (EPCA)6. GSTP-1 Hypermethylation

TMPRSS2-ERG fusion gene

What is TMPRSS2-ERG fusion gene?

• TMPRSS2 gene - androgenregulated gene

• Increased urine TMPRSS2-ERG fusion transcript in Ca prostate

• Measured by Polymerase chain reaction (qPCR)

• Noninvasive detection of prostate cancer

Ca Prostate• Androgen responsive tumor

• Gene mutation

– TMPRSS2

• Prostatic specific androgen related transmembrane protease serine 2

• Function of this gene unknown– ERG

• ETS (Erythroblastosis virus 26) Related Gene

• Family member of ETS transcript factors• Act as positive or negative regulators of the

expression many genes and that are implicated in cellular proliferation, differentiation, hematopoiesis, apoptosis, tissue remodeling, angiogenesis, transformation

– Both located in chromosome 21

– Gene fusion by

• Deletion

• Insertion

Gene fusion• TMPRSS2-ERG gene fusion

– TMPRSS2:ERG fusion in 50% of prostate cancer– Absent in BPH

• Mechanism of action– Fusion of untranslated sequences of TMPRSS2:

ETS– Other molecular changes include loss of PTEN

(phosphatase and tensin homolog ), a tumor suppressor.

– Increased expression of an ETS transcription factor in response to activated androgen receptor then occurs.

– The ETS transcription factor would then induce transcription of genes that block checkpoints triggered indirectly by inactivation of PTEN.

– This allows for down regulation of receptor tyrosine kinases (RTKs)—allowing for unchecked activity of AKT/PKB (protein kinase B), which promotes cell proliferation and survival.

Clinical Implications

• Cancer Detection and Diagnosis

• Risk stratification

• Treatment

Detection and Diagnosis

• Urine based assay – TMPRSS2-ERG fusion transcript in urine– Sensitivity: 30-50%– Specificity: >90%– Detect 15-20% of men with Ca prostate but

have normal DRE and PSA <4

• Assist in tissue diagnosis– Ongoing research on its association with

PIN/PINATYP

Risk stratification

• Untreated TMPRSS2-ERG prostate cancer has more aggressive clinical course than fusion-negative cancer

• Conflicting result about prognosis of fusion-positive vs fusion-negative cancer post prostatectomy

• No reports of association btw gene fusion and RT/ADT/monitoring of recurrence

Treatment• Potential therapeutic targeting of

ETS gene fusions:– Androgen or estrogen signaling

– Short interfering RNA (siRNA) target on chimeric ETS gene transcripts

– Interaction of encoded ETS proteins and cofactors that regulate transcription of target genes

– Binding of ETS genes to specific DNA sequences present in the regulatory region of downstream targets

– Some downstream target proteins that are required for the phenotypic effects caused by ETS gene fusions may also be targeted.

References

Prostate Core Mitomic Test

Mitomics Inc.

• Mitomics is a biotech company found in 2001, headquartered in Ontario, Canada

• Works on mitochondrial DNA based on large-scale deletions in mitochondrial DNA (mtDNA) can indicate cellular changes that are associated with the development of cancer

• Several test kits:– Prostate Mitomic Test : CA prostate– Breast Mitomic Test : CA breast– Endometrial Mitomic Test : endometriosis

Prostate Core Mitomic Test™- The First Choice for Avoiding Second Biopsies

• Indicated when initial prostate biopsy negative but – persistently elevated PSA or a rising PSA, or

abnormal DRE– Atypical small acinar proliferation (ASAP)– High-grade prostatic intraepithelial neoplasia

(HGPIN)

• Based on first biopsy specimen– Sensitivity 80 - 84 %; Specificity 71 – 79 %

Artificial neural network

What is artificial neural network?

• Group of smaller elements called neurons which each element has a set of inputs and a single output

• Each input is multiplied by a weight and the value of these weights is the one that determines the output of the neuron

• The result of the operation of the inputs and the weights is added together providing an output

Artificial Neural NetworkBiological Neural Network

Artificial Neural NetworkA mathematical model or

computer model that is inspired by the structure and/or functional aspects of biological neural networks

Consists of an interconnected group of artificial neurons

They are usually used to model complex / non-linear relationships between inputs and outputs

Application

Tumor Field of application

Reference

kidney Diagnostic aid Maclin PS et al. Using neural networks to diagnose cancer. J med Syst 1991; 15: 11-9

Bladder Diagnostic aid Qureshi KN et al. Neural Network analysis of clinicopathological and molecular markers in bladder cancer. J Urol 2000; 163: 630-3

Determination of prognosis

Fujikawa K et al. Predicting disease outcome of non-invasive TCC of urinary bladder using an artificial neural network model; results of patient following up for 15 years or longer. Int J Urol 2003; 10: 149-52

Testicle Staging aid Moul JW, Proper staging techniques in testicular cancer patients. Tech Urol 1995; 1: 126-32

Applications of ANNs in oncological urology

Application• CA prostate

• Screening and early diagnosis• Staging

• Disease progression

Randall’s plaques

What are Randall’s plaques?

• Are apatite deposits in the tip of renal papilla which provide ideal site for overgrowth of Calcium oxalate to form stone

• Microscopically the deposits are hydroxyapatite, & in the medullary interstitial space & originated in the basement membrane of thin loop of Henle

• Present in 20% pts (Randall)

HIFU

What is HIFU for Ca prostate?

• For CaP (Not recommended as 1st line)

• Use focused ultrasound waves emitted from rectal transducer to cause coagulative necrosis through both mechanical & thermal effects

• Require GA/SA, can be time consuming

Sterilisation, disinfection, cleaning and autoclaving

How do you classify surgical equipment in terms of cleaning?

• Critical-high risk of infection, direct contact with blood eg surgical instruments

• Semi-critical-intermediate risk of infection, contact with intact mucous membranes eg endoscopes

• Non-critical-contact with skin eg BP cuff

• How are rigid scopes cleaned ?– Autoclave

• How are flexible scopes cleaned ?– Have fragile optics and are heat sensitive, therefore

require liquid chemical sterilisation• Glutaraldehyde, ethylene oxide (toxic) or Gamma

radiation• Alcohol damage epoxy cement of scopes

• 2 parts : scope dismantled and working channel cleaned, scope then immersed chlorine dioxide for 30 mins

What are sterilization, disinfection and cleaning?

• Sterilization – complete destruction of living organisms, e.g. critical instrument like surgical instrument used in sterile tissue

• Disinfection – remove most viable organisms, not necessarily inactivate viruses and bacterial spores, e.g. semi-critical instrument used in mucosa– Flexible cystoscopy was cleaned with brushes and

detergent and disinfected with chlorine dioxide• Cleaning – physically remove contamination, but not

necessarily destroy microorganisms, intact skin e.g. non-critical instrument like blood pressure cuff

What is autoclaving?

• Combination of heat and pressure to sterilize instruments

• Temperature of liquids like water may be raised above boiling points

Anti-coagulant

How does aspirin work and what are you going to advise before OT?

• Binds irreversibly to platelets and prevents the production of thromboxane

• Takes 7 days after aspirin is stopped for platelet function to return to normal

• Stop 7 days prior to surgery

How does clopidogrel work and what are you going to advise before OT?

• Anti-platelet effect by binding irreversibly to ADP receptors on platelets

• Stop 7 days prior to surgery

• Discussion with cardiologist is required particularly if recent acute coronary syndrome, awaiting coronary stenting or recently undergone coronary stenting

how does warfarin work and what are you going to advise before OT?

• Interferes with VIT K metabolism and therefore results in hepatic synthesis of non-functioning factor I, IX, VII, II and protein C and S

• Stop 5 days prior to surgery• Ensure INR less than 1.5 prior to operation• In high risk cases of thromboembolism admit pre-

operatively for IV unfractionated heparin with appropriate APTT measurements (1.5-2.5). Stop 6 hours pre-op and restart 12 hours post-op– All anti-coagulant / antiplatelet drugs the risk of stopping

medications should be balanced against the risk of a thromboembolic event – discussion with haematologists and cardiologists is helpful

Blood product

What blood products are you aware of?

• Whole blood – source of all blood products therefore its use is restricted by most centres

• Centrifuged whole blood produces packed red cells and platelet-rich plasma

• Packed red cells stored at 4oC up to 35 days, volume approx 350ml, oxygen affinity falls with storage due to a decrease in 2,3-DPG

• Centrifuged platelet-rich plasma produces platelets and plasma Platelets, Stored at room temp. for 4-6 days, 1 adult dose increases platelets by 30-60, have to have rhesus compatibility and should have ABO compatibility

What blood products are you aware of?

• FFP - Frozen at -30 oC for up to 12 months, contains all clotting factors, volume approx 200mls, ABO compatibility testing required

• Freezing and rapidly thawing plasma produces cryoprecipitate - rich in factor VIII and fibrinogen, no ABO compatibility required

What blood conservation techniques are you aware of ?

• Preoperative autologous donation – patients donate a unit of blood in the month prior to the operation

• Preoperative erythropoietin

Cystistat

What is cystistat and how it work?

• Sodium hyaluronate

• Structural backbone of the extracellular protective layer

• Glycosaminoglycans protects the epithelium against toxic agents and bacteria

What are the indications?

• Interstitial cystitis– Improve the symptoms and QOLs

• Radiation-induced cystitis– Decrease radiation-induced toxicity and risk of

infection

• Bacterial cystitis– Decreases in the average number of

recurrences per year

What is the recommended regimen?

• 40mg sodium hyaluronate• Intravesical instillation after self voiding• Retained in the bladder for as long as

possible (a minimum of 30 minutes)• 4-12 Weekly dose regimen and then

monthly until symptoms resolve• Well tolerated except mild irritative LUTS

secondary to catheterisation• Not FDA approved drugs

Evidence

Evidence

• Ried et al– Uncontrolled study– 126 patients– Mean FU 6.5months– Questionnaire – 85 % symptoms improvement– 84% QOL improvement– Mean VAS 8.5 to 3.5

• However, no significant advantage over placebo in controlled studies

GVAX

GVAX®

• GVAX® (Cell Genesys, Inc., South San Francisco, CA) vaccines are cancer treatment vaccines comprised of genetically modified tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF).

• GM-CSF is an ideal vaccine adjuvant because it is a potent cytokine activator of dendritic-cell antigen presentation, and it participates in the initiation of danger signals needed to activate the immune system, break tolerance, and develop an antitumor immune response.

GVAX®

• A phase III trial comparing GVAX immunotherapy (CG1940/CG8711) to docetaxel plus prednisone was initiated in 2004. The study was designed to enroll 600 patients (pts) with a primary endpoint of superiority in overall survival

• Methods: Castration-resistant, chemotherapy-naïve men without cancer-related pain requiring opioid analgesics were eligible.

GVAX®

• GVAX CG1940/CG8711 (500 million cells prime/300 million cells boost doses q2 wks x 13 doses) was administered in the experimental arm (G) followed by maintenance GVAX immunotherapy (q4 wks).

• Docetaxel (75mg/m2 q3 wks x 9 cycles) plus prednisone (10 mg daily) was given in the control arm (D+P)

• Results and conclusions: Toxicity profile of GVAX is favorable compared to D+P. While survival was not significantly improved overall compared to chemotherapy

ERBEJET

ERBEJET®

ERBEJET®

• The ERBEJET® unique dissector, is an innovation in tissue preservation

• The extremely thin laminar jet, rotated in a helical fashion, forces softer, more water-soluble tissue to separate, while fibrin-rich structures are spared.

• This optimizes the preservation of vessels, ducts, and nerves

ERBEJET®

• The preservation of structures is important where cutting of vessels is common, such as hepatic (liver) resection. The potential for blood loss is minimized due to the unique vessel-sparing capability

• Also offers a benefit in applications where nerves are particularly at risk, such as during nerve-sparing radical retropubic prostatectomy.

ERBEJET®

Image guided Radiotherapy(IGRT)

CF Kan

Why image-guided despite pre-op planning?

• Change of position in each session– Organ movement– Setup errors– Change in tumor size and shape during RT

• Decrease margin to protect healthy tissues• More radiation to target organ to enhance

tumor control• As a supplement to conformal RT / IMRGT

– IMRT associated with a steep decline in dose outside target (Mackie TR, 2003)

Strategies

• Imaging by ultrasound and integrated linear accelerator CT-scanner system

• Online approach – acquires and assesses information from imaging before treatment and makes corrections if deviation exceed a predefined threshold

• Offline approach – Frequent acquisition of images without immediate intervention– Systemic component (mean offset)– Random component (standard deviation)

Benefit and limitation• Potential Benefit

– Measurement of tumour changes (e.g. bladder cancer) and better planning

– Reduce the planning target volume (Millender, prostate position error: right-left direction 11.4mm and superior-inferior direction 7.2mm)

– Dosimetric benefit (Ghilezan, increase target dose to prostate from 96.8% to 98.9%)

– Biochemical- relapse free survival 95% to 63% if RT planning for Ca prostate, 78 Gy, with full rectum (de Courvoisier, 2005)

• Clinical Benefit– Reduce in toxicity

• Limitation– Cost of new technology and man-power– Extra radiation for image guidance with risk of second

malignancy– No RCT on improvement in survival yet

Miscellanies

GeneticsGenetics

• C-erb is oncogene coding for EGF receptor

• Bcl2 gene prevents programmed cell death

AnatomyAnatomy

• Extravasation from bulbar urethra will not go to buttocks

• Genitofemoral nerve supplies both cremasteric and dartos muscles