Update Surgical Management of Stones

Dean G. Assimos, MDDepartment of Urology

U.A.B. School of Medicine

Format

• Medical Expulsive Therapy• Increasing Utilization of Ureteroscopy• Ureteroscopic Stone Removal• Percutaneous Nephrolithotomy• New Technology

Medical Expulsive Therapy

• Patients with uncomplicated ureteral stones ≤ 10 mm should be offered observation and those with distal stones of similar size MET with α-blockers.

• Strong Recommendation• Evidence, Grade B

Distal Stone < 10 mmα-Blocker vs. Control

Distal StonesTamsulosin 0.4mg vs. Control

Distal Stones < 10mmNifedipine vs. Control

Proximal Ureteral Stonesα-Blocker vs. Control

Middle Ureteral Stonesα-Blocker vs. Control

Impact of Distal Ureteral Stone Size

• Recent trial of 316 patients < 10 mm distal stones, 0.4mg tamsulosin vs. placebo

% Passage< 5mm 5-10 mm

Tamsulosin 88 83Placebo 89.5 61

95% CI 3-1%-41.6% p=0.03

Furyk et al. Annals of Emergency Medicine, 67:86, 2016.

Panel’s Meta-analysis Size ImpactTamsulosin for Distal Stone

OR 95% CI

< 5 mm 1.23 0.61-2.47

5-10 mm 4.53 2.90-7.07

Limited numbers of subjects prompted decision to recommend MET for distal stones < 10 mm.

Inform patient of off label utilization.

Randomized TrialDistal Ureteral Stones

• Multi-center trial in China• 3450 randomized to 0.4 mg tamsulosin or

placebo for 28 days• Primary endpoint stone passage confirmed

with CT• Secondary Endpoints time to passage,

analgesic use, adverse eventsLi et al. European Urology, 73:385, 2018.

Secondary Outcomes

• Expulsion time shorter with tamsulosin, > 5mm stones

• Analgesic use less with tamsulosin for ≤ 5 mm and > 5 mm

• No difference in adverse events.

Meta-analysis Silodosin for MET

Ding et al. Renal Failure, 9:1311, 2016.

Ding et al. Renal Failure, 9:1311, 2016.

Lancet Study

• RCT 1167 patients with ureteral stones• 65 % distal, 25 % proximal, 10 % middle• 75% ≤ 5 mm, 25% 5-10 mm• Placebo, Tamsulosin 0.4 mg, Nifedipine 30 mg• Primary outcome lack of need for further

intervention 4 weeks after randomization.

Pickard et al. Lancet, 386:341,2015.

Reasons Not Incorporating Lancet Study

• Not comparable to other studies in which actual stone passage was primary outcome.

• High absence of need for intervention 80% in placebo group as compared to the 53% radiographic evidence of stone passage in the control arms of other α-Blocker studies.

NIH Trial

• Presented at 2017 AUA Meeting, Meltzer et al. • 0.4 mg tamsulosin versus placebo• Mean stone diameter 3.8 mm• Primary outcome stone passage within 28 days

of randomization• Not designed to assess for differences based on

stone location• Stone passage 52% tamsulosin versus 49%

placebo, p=0.447

Pipeline

• PDE5 inhibitors human trials (sildenafil, taldalafil)

• Peri-ureteral botulinum toxin type A injections (porcine model)

• Predicting success with ureteral wall thickness on CT

• Intercourse 3-4 times a weekCordona and Garcia-Perdomo. Investigative Clinical Urology, 58:82, 2017.Bayraktar and Albayrak. Int Urol Nephrol, 49:1941, 2017. Tuerxun et al. 98:436, 2017.

Trends and Inequalities in Ureteral Stone Management in the U.S.

• Medicare Data from 2001, 2004, 2007, and 2010.

• Men more likely to undergo stone removal• Ethnic minorities were less likely• Predominant approach ureteroscopy• Women more likely to ureteroscopy• Patients from south and ethnic minorities

more likely to undergo SWL

Seklehner et al. BJU Int. 113:476, 2014.

Trends in Surgical Management of Ureteral Stones

Medicare

Seklehner et al. BJU Int, 113:476, 2014

Lee and Bariol. BJU Int. 108:29, 2011 (Australia).

Canadian Trends

Ordon et al. Journal of Urology, 192:2014.

SWL URS PCNL

Ancillary Procedures

Reasons for Shift

• URS is a point of service procedure• Better technology• Video generation• Comparative effectiveness

SWL versus Ureteroscopy

• Meta-analytic study• Ureteral stones• Cochrane review• 7 RCTs (1205 patients)• Higher stone free rates with URS (RR 0.84)• Retreatment rate lower for URS (RR 6.18)• Higher complication rate with URS (RR 0.54),

majority minor

Aboumarzouk et al. Cochrane Review 2012.

Comparative Effectiveness

• US privately insured 2002-2010• 21,937 SWL and 25,914 URS• Additional procedure URS 18.7% and 23.6 %

for SWL• Adjustments for observed and unobserved

variables estimated probability of repeat intervention 11.0% for SWL and 0.3% for URS

Scales et al. JAMA, 149:648,2014.

Comparative Effectiveness

• Medicare 2009-2010• SWL and URS• SWL 1.73 times more likely to undergo at least

one repeat procedure• SWL 2 times more likely to undergo multiple

retreatments• For ureteral stones SWL 2.27 times more likely

to undergo repeat procedure

Matlaga et al. Journal of Endourology, 28:723,2014.

Symptomatic Patient with Total Non-Lower Pole Stone Burden < 20 mm:

SWL vs URSStrong RecommendationEvidence Level Grade B

• Stone-free rates acceptable with both

• Less morbidity than PCNL• URS lower risk of repeat procedure stone-free quicker than SWL

• SWL advantage: non-invasive, patient preference, lack of stent

• Requires shared decision-making process

Active Fragment Extraction for Renal Stones

EDGE Consortium• Prospective study, multicenter study• 159 patients with 5-20 mm renal stones• 84 fragment extraction (SA 63.3 mm2), 75 dusting (SA

96.1 mm2)• All received a 30 days of an alpha blocker and were

stented • S.F. for active extraction 74.3 % versus 58.2% % for

dusting (p=0.04 for univariate analysis, p=0.11 for multivariate analysis

• No difference in readmission, complications or ER visits• Follow-up 3 months

Humphreys et al. Journal of Urology in Press.

Chew et al. Journal of Urology, 195:982, 2016.

Chew et al. Journal of Urology, 195:982, 2016.

Stone Displacement

89100

77

29

0

20

40

60

80

100

120

< 1 cm > 1 cm

% Stone Free Displacement

Schuster et al. Journal of Urology, 168:43, 2002.

Access Sheath

• Recommend initial optical dilation with semi-rigid ureteroscope.

Traxe

Symptomatic Patient with Total Non-Lower Pole Stone Burden > 20 mm: PCNL

Strong RecommendationEvidence Level Grade C

• PCNL has higher stone free rate than SWL or URS– Less invasive than open or

laparoscopic/robotic surgery– Less affected by stone location,

composition or density• Increased invasiveness and risk of

complications

PCNL vs Staged Flexible URS> 2 cm renal pelvis stones

• Prospective, randomized trial

Karakoyunlu et al. Urolithiasis 2015

Impact of Number of Accesses on Renal Function

• 2011-2012 307 PCNL cases• 110 patients with pre and postoperative

Tc99m-MAG3 Lasix renal scans• 74 single access, 36 Multiple Accesses• Mean age, BMI and preoperative serum

creatinine not different between single and multiple access cases.

Gorbachinsky et al. Journal of Urology, 196:131,2016.

Risk of ESRDRenal Deterioration Index

Score 1 3 5Combined Cortical Widths (mm)

> 20 10-20 < 10

GFR ml/min. > 60 30-60 < 30Proteinuria 0 1+ > 1+Urine Culture Positive

Mishra et al. Journal of Endourology, 27:1405, 2013.

July 2016Recurrent UTIsUnchanged Stents 1.5 yrs.Creatinine 3.7 mg/100 mleGFR 13 ml/minute4+ proteinuria

January 2017Creatinine 5.1 mg/100 mleGFR 9 ml/minuteHemodialysis

PCNL: Tube vs TubelessConditional recommendation

Evidence Level Grade C

• UNCOMPLICATED PCNL presumed stone-free nephrostomy tube is optional– Nephrostomy – increased morbidity

• Pain – greater narcotics requirement• Increased LOS

• Contraindications:– Active hemorrhage– Second stage PCNL needed to remove

residual stones

PCNL: Tube vs TubelessConditional recommendation

Evidence Level Grade C

• Panel’s meta-analysis– 38 studies – 7 RCTs, 2073 pts– Similar overall SFR– Similar complication rate

Meta-analysisProne versus Supine PCNL

• 6 RCT, 7 retrospective studies• SFR higher for prone• Operative time and transfusion rate lower for

supine• Complications similar

Yuan et al. Journal of Endourology, 30:754, 2016.

Storz –Miniperc set

12 F

Meta-analysisMini-PCNL versus Ureteroscopy

• 3 RCT, 10 retrospective Studies• SFR higher with Mini-PCNL• Greater decreased in hemoglobin with Mini-

PCNL• Operative time similar and no significant

difference in complications

Jiang et al. Biomedical Research International, 2017.

Laser Fiber

4.85 Fr Sheath

Telescope

Micro-PCNL4.85 Fr All seeing needle assembled for stone

fragmentation

Micro-PCNL versus URS

• Lower pole stones ≤ 15 mm• RRC 30 patients in each group• Stone free based on CT done at 3 months• Stone free micro-PCNL 83.3%, URS

86.7%• Complication rates low for both, 1

transfusion in micro-PCNL groupKandemir et al. World Journal of Urology, 35:1771, 2017.

Lumenis® Pulse™ P120H holmium laser system

Moses Fibers

• Moses Mode, separate the fluid and deliver the energy

• Special Fibers (Moses D/F/L fibers)• Less retropulsion, more efficient

fragmentation in in-vitro models

Elhilali et al. Journal of Endourology, 31:598, 2017

LithoVue™

• 40 cases (37 renal)• Visibility 65% very good, 30% good• Maneuverability 77.5% very good, 17.5%

good• Cost?

Doizi et al. World Journal of Urology, 35:809, 2017.

Update � Surgical Management of StonesFormat�Slide Number 3Medical Expulsive TherapyDistal Stone < 10 mm�α-Blocker vs. ControlDistal Stones�Tamsulosin 0.4mg vs. ControlDistal Stones < 10mm�Nifedipine vs. ControlProximal Ureteral Stones�α-Blocker vs. Control�Middle Ureteral Stones�α-Blocker vs. ControlImpact of Distal Ureteral Stone SizePanel’s Meta-analysis Size Impact�Tamsulosin for Distal StoneRandomized Trial�Distal Ureteral StonesSlide Number 13Secondary OutcomesSlide Number 15Slide Number 16Lancet StudySlide Number 18Reasons Not Incorporating Lancet StudyNIH TrialPipelineSlide Number 22Trends and Inequalities in Ureteral Stone Management in the U.S. Trends in Surgical Management of Ureteral Stones�MedicareSlide Number 25Slide Number 26Slide Number 27Slide Number 28Slide Number 29Slide Number 30Slide Number 31Slide Number 32Reasons for Shift SWL versus UreteroscopyComparative EffectivenessComparative EffectivenessSymptomatic Patient with Total Non-Lower Pole Stone Burden < 20 mm: SWL vs URS�Strong Recommendation�Evidence Level Grade BActive Fragment Extraction for Renal Stones�EDGE ConsortiumSlide Number 39Slide Number 40Stone DisplacementSlide Number 42Access SheathSlide Number 44Symptomatic Patient with Total Non-Lower Pole Stone Burden > 20 mm: PCNL�Strong Recommendation�Evidence Level Grade CPCNL vs Staged Flexible URS�> 2 cm renal pelvis stonesSlide Number 47Slide Number 48Slide Number 49Slide Number 50Slide Number 51Slide Number 52Impact of Number of Accesses on Renal FunctionSlide Number 54Risk of ESRD�Renal Deterioration IndexSlide Number 56Slide Number 57Slide Number 58PCNL: Tube vs Tubeless�Conditional recommendation�Evidence Level Grade CPCNL: Tube vs Tubeless�Conditional recommendation�Evidence Level Grade CSlide Number 61Meta-analysis�Prone versus Supine PCNLSlide Number 63Slide Number 64Meta-analysis�Mini-PCNL versus UreteroscopySlide Number 66Slide Number 67Micro-PCNL versus URSSlide Number 69Moses FibersSlide Number 71LithoVue™