Tubeless versus tubed percutaneous nephrolithotomy for treating kidney stones

Abstract

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:

To assess the effects and efficacy of tubeless mini percutaneous nephrolithotomy versus standard percutaneous nephrolithotomy for the treatment of renal stones in adults.

Background

Description of the condition

Nephrolithiasis (kidney stones) is a common disease with a 10% lifetime risk in men and 5% in women (Stamatelou 2003; Scales 2012). Incidence rates of renal calculi vary between 0.1% and 1.5% per year in North America and Europe (Hesse 2003; Liske 2006). Patients suffering from nephrolithiasis are at risk of developing renal colic, hydronephrosis and eventually progressive loss of renal function. Asymptomatic caliceal stones may be managed conservatively. Active treatment is recommended in cases of stone growth, de novo obstruction, associated infection, or acute or chronic pain (Türk 2015). In recent decades, tremendous advancements have been made both in technologies and surgical techniques of treatments for renal stones. Currently, treatment options include shock wave lithotripsy (SWL), percutaneous nephrolithotomy (PNL), retrograde intrarenal surgery (RIRS) and laparoscopic, robotic assisted or open ureterolithotomy.

Description of the intervention

Current European Association of Urology (EAU) guidelines recommend PNL as the treatment of choice for large (> 20 mm in longest diameter) or complex (e.g. staghorn stones involving the renal pelvis and ≥ two calices) renal stones (Türk 2015). American Urological Association (AUA) guidelines slightly differ in the indications but also recommend PNL for large stones > 20 mm (Assimos 2016). PNL may be performed with the patient in the prone or supine position. Most surgeons prefer to place a ureteric stent or ureteric occlusion catheter prior to the procedure. After positioning of the patient, contrast medium is injected directly into the collecting system (via the indwelling ureteric stent or occlusion catheter) to dilate the pelvicaliceal system. Percutaneous access is established using ultrasound and/or fluoroscopy guidance. The tract is then dilated to an appropriate size. Tract size (the size of the access sheath of a particular PNL system) depends on the size of the stone and preferences of the performing surgeon. After placement of an appropriate access sheath the nephroscope is inserted. Stone fragmentation is performed under direct vision using laser, ultrasonic, or ballistic (pneumatic) energy sources. After removal of stone fragments the procedure is terminated by insertion of a nephrostomy tube via the percutaneous tract ('standard PNL') or removal of all devices without nephrostomy placement (tubeless) (Kamphuis 2015). About 25% of endourologists use this tubeless approach (Sivalingam 2014). Some authors suggest tract sealing using haemostatic agents in case of tubeless PNL. In general, 'standard PNL' describes a system and surgical technique that involves both an outer tract diameter of ≥ 24 Fr (up to 34 Fr) and postoperative placement of a nephrostomy. PNL procedures using a system with an outer tract diameter of 23 Fr or less are described as 'mini PNL'. These smaller systems have been developed to reduce patients' morbidity from the procedure. However, data comparing standard and miniaturised PNL are scarce. Some publications indicate lower transfusion rates in miniaturised PNL (Kamphuis 2015).

In this review we will use the following terms.

• Standard PNL (≥ 24 Fr and placement of a nephrostomy tube)

• Standard mini PNL (≤ 23 Fr and placement of a nephrostomy tube)

• Tubeless PNL (≥ 24 Fr, no nephrostomy tube, but ureteral stenting)

• Tubeless mini PNL (≤ 23 Fr, no nephrostomy tube, but ureteral stenting)

• Totally tubeless PNL (≥ 24 Fr, no nephrostomy tube, no ureteral stenting)

• Totally tubeless mini PNL (≤ 23 Fr, no nephrostomy tube, no ureteral stenting)

How the intervention might work

Placement of a nephrostomy tube at the end of a PNL procedure is considered the standard exit strategy. A nephrostomy tube will provide adequate drainage of the pelvicaliceal system (potentially less 'clotting') and low intrarenal pressure (potentially lower risk of bacteriaemia or sepsis). A nephrostomy tube may also seal potential bleeding from the access tract (Hüsch 2015). In addition, preservation of the percutaneous tract will facilitate a second‐look procedure if necessary. Some authors proposed the insertion of a ureteral stent instead of a nephrostomy tube to ensure drainage and to prevent urinary retention (tubeless PNL + ureteral stenting). Potential advantages of this modification of the procedure include less postoperative pain and analgesic requirements and a shorter duration of hospital stay (Bellman 1997; Garofalo 2013). However, tubeless PNL may cause stent‐related complications and require cystoscopic removal of the ureteral stent. The totally tubeless PNL avoids both a nephrostomy tube and an ureteral stent. The potential advantage is the absence of stent‐related complications.

Why it is important to do this review

Feasibility and safety of tubeless PNL and totally tubeless PNL have been reported in a number of publications and in one systematic review (e.g. Gonen 2009; Chang 2011; Amer 2012). All published trials were limited to standard PNL ≥ 24 Fr. Amer 2012 performed a systematic review but did not include studies with patients treated by miniaturised systems. A considerable number of trials on tubeless mini PNL (≤ 23 Fr) have been published, fuelling an ongoing debate on the subject. In mini PNL, tract bleeding rates are expected to be lower. Hence avoiding a nephrostomy might be even more successful than with larger PNL systems (> 23 Fr). The subject is of clinical relevance and therefore should be studied further. No Cochrane review has been performed on this subject before.

Objectives

To assess the effects and efficacy of tubeless mini percutaneous nephrolithotomy versus standard percutaneous nephrolithotomy for the treatment of renal stones in adults.

Methods

Criteria for considering studies for this review

Types of studies

We will include randomised or quasi‐randomised trials (randomisation based on alternation, date of birth, or case record number) regardless of their publication status or language of publication. We will consider the first phase of cross‐over studies if data of the first phase are reported separately. If these data are not available the study will be excluded to avoid biased results. Cluster‐randomised trials will be excluded.

Types of participants

Inclusion: Men and women 18 years of age or older receiving percutaneous nephrolithotomy (PNL) for nephrolithiasis. Only studies on unilateral PNL using a single‐tract access (or separate analysis for single‐tract access cases) will be included.

Exclusion: Patients with kidney transplantation, horseshoe kidney and other malformations or congenital abnormalities of the kidney.

Should we identify studies in which only a subset of participants are relevant to this review, we will include such studies if data are available separately for the relevant subset.

Types of interventions

We plan to investigate the following comparisons. Auxiliary procedures will have to be the same in the experimental and comparator groups to establish fair comparisons. Studies with combined percutaneous and retrograde intrarenal surgery (RIRS) will be excluded. We will include studies with interventions in all operating positions (prone and supine, semi‐supine, lateral).

Experimental interventions

• Tubeless PNL (≥ 24 Fr, no nephrostomy tube, but ureteral stenting)

• Tubeless mini PNL (≤ 23 Fr, no nephrostomy tube, but ureteral stenting)

• Totally tubeless PNL (≥ 24 Fr, no nephrostomy tube, no ureteral stenting)

• Totally tubeless mini PNL (≤ 23 Fr, no nephrostomy tube, no ureteral stenting)

• Totally tubeless mini PNL (≤ 23 Fr, no nephrostomy tube, no ureteral stenting)

Comparator interventions

• Standard PNL (≥ 24 Fr and placement of a nephrostomy tube, no ureteral stenting)

• Standard mini PNL (≤ 23 Fr and placement of a nephrostomy tube, no ureteral stenting)

Comparisons

• Standard PNL versus tubeless PNL

• Standard PNL versus totally tubeless PNL

• Standard mini PNL versus tubeless mini PNL

• Standard mini PNL versus totally tubeless mini PNL

We will not compare groups with PNL ≥ 24 Fr versus PNL ≤ 23 Fr. A discussion about advantages and disadvantages of 'big' versus 'mini' systems is not the focus of this review.

Types of outcome measures

We will not use the measurement of the outcomes assessed in this review as an eligibility criterion.

Primary outcomes

• Severe adverse events: Clavien 3 to 5 (complications classified with the Clavien‐Dindo score will be used as provided in individual studies. If no Clavien‐Dindo score is reported, specific complications will be categorised according to the “Clavien‐Dindo score adopted for PNL” (de la Rosette 2012; Appendix 4). This categorisation will be done by two authors independently (KW and SH). Any discrepancies will be solved through consensus or recourse to a third review author (MS))

• Postoperative pain on day one after the intervention

Secondary outcomes

• Operating time

• Length of hospital stay

• Stone‐free rate (as indicated in publications, various definitions and modes of detection allowed)

• Adverse events: complications classified with the Clavien‐Dindo score will be used as provided in individual studies. If no Clavien‐Dindo score is reported, specific complications will be categorised according to the “Clavien‐Dindo score adopted for PNL” (de la Rosette 2012; Appendix 4). This categorisation will be done by two authors independently (KW and SH). Any discrepancies will be solved through consensus or recourse to a third review author (MS)

Asside from the aggregate complications as defined above, we will also report on the following specific complications of particular clinical interest.

• Blood transfusion

• Sepsis or fever > 38°C (as indicated in publications)

• Urinary leak (as indicated in publications)

• Readmission during the first 30 days after the intervention

Method and timing of outcome measurement

• Surgery‐related mortality. Severe adverse events Clavien 5 during the first 30 days after surgery

• Adverse events: complications reported according to the Clavien‐Dindo score and measured during the first 30 days following the intervention

• Postoperative pain: pain as measured by a visual analog scale (VAS) or numeric rating scale (NRS) during hospital stay

• Operating time: time from needle puncture to final tract suture or nephrostomy tube placement

• Length of hospital stay after the intervention (hours)

• Stone‐free rate: percentage of patients with complete stone clearance or residual fragments ≤ 4 mm

Main outcomes for 'Summary of findings' table

We will present a 'Summary of findings' table reporting the following outcomes listed according to priority.

1. Severe adverse events Clavien grade 3 to 5

2. Postoperative pain on day one after the intervention

3. Operating time

4. Length of hospital stay

5. Blood transfusion

6. Sepsis or fever

7. Readmission during the first 30 days after the intervention

Search methods for identification of studies

We will perform a comprehensive search for publications with no restrictions on date, language of publication or publication status. We plan to rerun searches within three months prior to anticipated publication of the review.

Electronic searches

We will search the following databases.

• Cochrane Library

  • Cochrane Database of Systematic Reviews (CDSR) (www.cochranelibrary.com/cochrane‐database‐of‐systematic‐reviews/index.html)

  • Cochrane Central Register of Controlled Trials (CENTRAL) (www.cochranelibrary.com/about/central‐landing‐page.html)

  • Database of Abstracts of Reviews of Effects (DARE) (community.cochrane.org/editorial‐and‐publishing‐policy‐resource/overview‐cochrane‐library‐and‐related‐content/databases‐included‐cochrane‐library/database‐abstracts‐reviews‐effects‐dare)

  • Health Technology Assessment Database (HTA) (www.inahta.org/hta‐tools‐resources/database/)

• MEDLINE (via Ovid)

• Embase (via Ovid)

• Web of Science (www.apps.webofknowledge.com)

We will also search the following.

• ClinicalTrials.gov (www.clinicaltrials.gov/)

• World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal (www.who.int/ictrp/)

If we detect additional relevant key words during any of the electronic or other searches, we will modify the electronic search strategies to incorporate these terms and document the changes.

Searching other resources

We will search reference lists of potentially eligible trials or ancillary publications to identify unpublished studies. We will search the reference lists of retrieved included trials, reviews, meta‐analyses and health technology assessment reports. We will also contact study authors of included trials, and companies, to identify any further unpublished studies that we may have missed. We will search for grey literature by screening abstract proceedings of relevant meetings from 2013 to 2016:

• American Urological Association: www.auanet.org/;

• European Association of Urology: eaumunich2016.uroweb.org/;

• World Congress of Endourology: www.endourology.org/;

• Experts in stone disease: esdconference.com/; and

• EULIS Meeting: www.sciencedirect.com/science/journal/15699056.

Data collection and analysis

Selection of studies

We will use Covidence software (Covidence 2016) for reference management. Two review authors (KW, SH) will independently screen the abstract, title, or both, of retrieved records, to determine which studies should be assessed further. Two review authors (KW, SH) will investigate all potentially‐relevant records as full texts, map records to studies, review against the inclusion and exclusion criteria and classify studies as included studies, excluded studies, studies awaiting classification, or ongoing studies in accordance with the criteria for each provided in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a). We will resolve any discrepancies through consensus or recourse to a third review author (SS). If resolution of a disagreement is not possible, we will designate the study as 'awaiting classification' and we will contact study authors for clarification. We will document reasons for exclusion of studies that may have reasonably been expected to be included in the review in a 'Characteristics of excluded studies' table. We will present an adapted PRISMA flow diagram showing the process of study selection (Liberati 2009).

Data extraction and management

We will develop a dedicated data abstraction form that we will pilot test ahead of time.

For studies that fulfil inclusion criteria, two review authors (KW, SH) will independently abstract the following information, which we will provide in the 'Characteristics of included studies' table

• Study design

• Study dates (if dates are not available then this will be reported as such)

• Study settings and country

• Participant inclusion and exclusion criteria

• Participant demographic and clinical baseline characteristics: gender, age, stone laterality, size, history of prior PNL, American Society of Anesthesiologists (ASA 2014) score if provided

• The number of participants by study and by study arm

• Details of relevant experimental and comparator interventions, such as size of the outer tract diameter and the diameter of the nephrostomy or double‐J stent used

• Definitions of relevant outcomes, and method and timing of outcome measurement as well as any relevant subgroups

• Study funding sources

• Declarations of interest by study authors

We will extract outcomes data relevant to this Cochrane review as needed for calculation of summary statistics and measures of variance. For dichotomous outcomes, we will attempt to obtain numbers of events and totals for population of a 2 x 2 table, as well as summary statistics with corresponding measures of variance. For continuous outcomes, we will attempt to obtain means and standard deviations or data necessary to calculate this information.

We will resolve any disagreements by discussion, or, if required, by consultation with a third review author (SS).

We will provide information, including trial identifier, about potentially relevant ongoing studies in the table 'Characteristics of ongoing studies'.

We will attempt to contact authors of included studies to obtain key missing data as needed.

Dealing with duplicate and companion publications

In the event of duplicate publications, companion documents or multiple reports of a primary study, we will maximise yield of information by mapping all publications to unique studies and collating all available data. We will use the most complete data‐set aggregated across all known publications. In case of doubt, we will give priority to the publication reporting the longest follow‐up associated with our primary or secondary outcomes.

Assessment of risk of bias in included studies

Two review authors (KW, SH) will assess the risk of bias of each included study independently. We will resolve disagreements by consensus, or by consultation with a third review author (SS).

We will assess risk of bias using Cochrane's 'Risk of bias' assessment tool (Higgins 2011b). We will assess the following domains.

• Random sequence generation (selection bias)

• Allocation concealment (selection bias)

• Blinding of participants and personnel (performance bias)

• Blinding of outcome assessment (detection bias)

• Incomplete outcome data (attrition bias)

• Selective reporting (reporting bias)

• Other sources of bias

We will judge risk of bias domains as 'low risk', 'high risk' or 'unclear risk' and will evaluate individual bias items as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011b). We will present a 'Risk of bias' summary figure to illustrate these findings.

For performance bias (blinding of participants and personnel) and detection bias (blinding of outcome assessment), we will evaluate the risk of bias separately for each outcome, and we will group outcomes according to whether measured subjectively or objectively when reporting our findings in the 'Risk of bias' tables.

We define the following endpoints as subjective outcomes.

• Postoperative pain

• Stone‐free rate

• Adverse events other than Clavien 5

• Blood transfusions

• Fever

• Urinary leak

We define the following endpoints as objective outcomes.

• Surgery‐related mortality

• Severe adverse events Clavien 5

• Operating time

• Length of hospital stay

• Readmission during the first 30 days after the intervention

We will also assess the attrition bias (incomplete outcome data) on an outcome‐specific basis, and will present the judgement for each outcome separately when reporting our findings in the 'Risk of bias' tables.

We will further summarise the risk of bias across domains for each outcome in each included study, as well as across studies and domains for each outcome, in accordance with the approach for summary assessments of the risk of bias presented in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011b).

Measures of treatment effect

RevMan will be used to analyse results and treatment effects. We will express dichotomous data as risk ratios (RRs) with 95% confidence intervals (CIs). We will express continuous data as mean differences (MDs) with 95% CIs unless different studies use different measures to assess the same outcome, in which case we will express data as standardised mean differences with 95% CIs.

Unit of analysis issues

The unit of analysis will be the individual participant. Cross‐over trials and cluster‐randomised trials will be treated as explained in Types of studies. Trials with more than two intervention groups for inclusion in the review will be managed in accordance with guidance provided in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011c).

Dealing with missing data

We will obtain missing data from study authors, if feasible, and will perform intention‐to‐treat (ITT) analyses if data are available.

We will investigate attrition rates, e.g. drop‐outs, losses to follow‐up and withdrawals, and will critically appraise issues of missing data. We will not impute missing data.

Assessment of heterogeneity

In the event of excessive heterogeneity, we will not report outcome results as the pooled effect estimate in a meta‐analysis but will provide a narrative description of the results of each study.

We will identify heterogeneity (inconsistency) through visual inspection of the forest plots to assess the amount of overlap of CIs, and the I² statistic, which quantifies inconsistency across studies to assess the impact of heterogeneity on the meta‐analysis (Higgins 2002; Higgins 2003); we will interpret the I² statistic as follows (Deeks 2011):

• 0% to 40%: may not be important;

• 30% to 60%: may indicate moderate heterogeneity;

• 50% to 90%: may indicate substantial heterogeneity; and

• 75% to 100%: considerable heterogeneity.

When we find heterogeneity, we will attempt to determine possible reasons for it by examining individual study and subgroup characteristics.

Assessment of reporting biases

We will attempt to obtain study protocols to assess for selective outcome reporting.

If we include 10 studies or more investigating a particular outcome, we will use funnel plots to assess small study effects. Several explanations can be offered for the asymmetry of a funnel plot, including true heterogeneity of effect with respect to trial size, poor methodological design (and hence bias of small trials) and publication bias. We will therefore interpret results carefully.

Data synthesis

Unless there is good evidence for homogeneous effects across studies, we will summarise data using a random‐effects model. We will interpret random‐effects meta‐analyses with due consideration of the whole distribution of effects. In addition, we will perform statistical analyses according to the statistical guidelines contained in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a). For dichotomous outcomes, we will use the Mantel‐Haenszel method; for continuous outcomes, we will use the inverse variance method. We will use RevMan software to perform analyses.

Subgroup analysis and investigation of heterogeneity

• Stones size (diameter > 2 cm versus < 2 cm)

• Stone location (lower calyx versus other localisation

Sensitivity analysis

We plan to perform sensitivity analyses in order to explore the influence of the following factors (when applicable) on effect sizes:

• restricting the analysis by taking into account risk of bias, by excluding studies at 'high risk' or 'unclear risk'.

'Summary of findings' table

We will present the overall quality of the evidence for each outcome according to the GRADE approach. This grading system includes five criteria related to both internal validity (risk of bias, inconsistency, imprecision, publication bias) and external validity (e.g., directness of results) (Guyatt 2008). Two review authors (KW, SH) will independently rate the quality of evidence for each outcome parameter as 'high', 'moderate', 'low', or 'very low' using GRADEpro GDT. We will resolve any discrepancies by consensus, or, if needed, by arbitration by a third review author (SS). We will present a summary of the evidence for the main outcome parameters in a 'Summary of findings' table, which will provide key information on the best estimate of the magnitude of effect in both relative terms and absolute numbers for each outcome parameter, numbers of participants and studies addressing each important outcome, and a rating of the overall confidence in effect estimates for each outcome (Guyatt 2011; Schünemann 2011). If meta‐analysis is not possible, we will present results in a narrative 'Summary of findings' table.

Appendices

Appendix 1. MEDLINE search strategy

1. Randomized Controlled Trials as Topic/

2. randomized controlled trial/

3. Random Allocation/

4. Double Blind Method/

5. Single Blind Method/

6. clinical trial/

7. clinical trial, phase i.pt.

8. clinical trial, phase ii.pt.

9. clinical trial, phase iii.pt.

10. clinical trial, phase iv.pt.

11. controlled clinical trial.pt.

12. randomised controlled trial.pt.

13. multicenter study.pt.

14. clinical trial.pt.

15. exp Clinical Trials as topic/

16. or/1‐15

17. (clinical adj trial$).tw.

18. ((singl$ or doubl$ or treb$ or tripl$) adj (blind$3 or mask$3)).tw.

19. PLACEBOS/

20. placebo$.tw.

21. randomly allocated.tw.

22. (allocated adj2 random$).tw.

23. or/17‐22

24. 16 or 23

25. case report.tw.

26. letter/

27. historical article/

28. or/25‐27

29. 24 not 28

30. exp kidney calculi/

31. exp Ureteral Calculi/

32. exp Urinary Calculi/

33. exp nephrolithiasis/

34. Nephrolithiasis.tw.

35. ((kidney or renal or urin* or ureth*) adj3 (calculi* or stone*)).tw.

36. ((nephro* or uro* or ureter*) adj3 lithi*).tw.

37. or/30‐36

38. exp Nephrostomy, Percutaneous/

39. nephrostom*.tw.

40. (Percutan* or pcnl or pnl).tw.

41. or/38‐40

42. 37 and 41

43. 42 and 29

44. exp animals/ not humans.sh.

45. 43 not 44

Appendix 2. Embase search strategy

Embase (Ovid)

1. Clinical trial/

2. Randomized controlled trial/

3. Randomization/

4. Single blind procedure/

5. Double blind procedure/

6. Crossover procedure/

7. Placebo/

8. Randomi?ed controlled trial$.tw.

9. Rct.tw.

10. Random allocation.tw.

11. Randomly allocated.tw.

12. Allocated randomly.tw.

13. (allocated adj2 random).tw.

14. Single blind$.tw.

15. Double blind$.tw.

16. ((treble or triple) adj blind$).tw.

17. Placebo$.tw.

18. Prospective study/

19. or/1‐18

20. Case study/

21. Case report.tw.

22. Abstract report/ or letter/

23. or/20‐22

24. 19 not 23

25. nephrolithiasis/

26. ureter stone/

27. urolithiasis/

28. urolithiasis.tw.

29. Nephrolithiasis.tw.

30. ((kidney or renal or urin* or ureth*) adj3 (calculi* or stone*)).tw.

31. ((nephro* or uro* or ureter*) adj3 lithi*).tw.

32. or/25‐31

33. Nephrostomy, Percutaneous/

34. nephrostom*.tw.

35. (Percutan* or pcnl or pnl).tw.

36. or/33‐35

37. 32 and 36

38. 24 and 37

39. animal/

40. human/

41. 40 not (39 and 40)

42. 40 not 39

43. 38 and 42

Appendix 3. Cochrane Library search strategy

#1 MeSH descriptor: [Kidney Calculi] explode all trees

#2 MeSH descriptor: [Ureteral Calculi] explode all trees

#3 MeSH descriptor: [Urinary Calculi] explode all trees

#4 MeSH descriptor: [Urolithiasis] explode all trees

#5 MeSH descriptor: [Nephrolithiasis] explode all trees

#6 ((kidney or renal or urin* or ureth*) near/3 (calculi* or stone*)):ti,ab,kw

#7 ((nephro* or uro* or ureter*) near/3 lithi*):ti,ab,kw

#8 #1 or #2 or #3 or #4 or #5 or #6 or #7

#9 MeSH descriptor: [Nephrostomy, Percutaneous] explode all trees

#10 nephrostom*:ti,ab,kw

#11 (Percutan* or pcnl or pnl):ti,ab,kw

#12 #9 or #10 or #11

#13 #8 and #12

Appendix 4. Clavien‐Dindo score adopted for PNL (de la Rosette 2012)

None

Normal postoperative trajectory without any unexpected deviation Blocked nephrostomy managed by removal of nephrostomy (without consequences) Nephrostomy tube discomfort that requires removal of nephrostomy Postoperative pain managed by nonopioid analgesics

Clavien 1

Postoperative pain managed by opioid with or without adjunct analgesic regimen Postoperative fever (> 38.0 8C) managed by observation without antibiotics Deranged renal function that requires IV fluid management only Bleeding managed using IV fluid without need for blood transfusion Bleeding that requires a single episode of nephrostomy clamping Bleeding that requires skin compression/pressure dressing Renal pelvic perforation managed by watchful waiting Urine leakage managed by watchful waiting Ureteric clot managed by watchful waiting Bladder retention without blood clot that requires bladder catheterisation Pneumothorax managed by watchful waiting Hydrothorax managed by watchful waiting Displaced nephrostomy managed by watchful waiting Intestinal obstruction managed without nasogastric decompression

Clavien 2

Bleeding requiring blood transfusion Nephrostomy site cellulitis managed by antibiotics Symptomatic urinary tract infection (UTI) managed using antibiotics Postoperative fever (> 38.0 8C) managed with antibiotics in the ward Colon perforation managed conservatively using IV fluid and antibiotics without controlled colocutaneous fistula Postoperative ileus managed by nasogastric decompression Postoperative pneumonia managed by antibiotics Heart failure (NYHA I and II) requiring management by medications in the ward Hyposaturation managed by oxygen in the ward Pulmonary oedema managed by diuretics Supraventricular arrhythmias requiring antiarrhythmic medications Minor atelectasis requiring medical management

Clavien 3A

Febrile UTI or suspected sepsis without organ failure requiring supportive therapy and enhanced monitoring Bleeding requiring multiple bladder washouts/irrigations Bleeding managed with haemostatic agents placed endoscopically Bleeding that requires multiple episodes of nephrostomy clamping (> 4 hours apart) Bleeding managed by postoperative ureteric stenting without general anaesthesia Bleeding managed by postoperative placement of new larger‐bore nephrostomy tamponade Colon perforation managed conservatively using controlled colocutaneous fistula Hemothorax managed by intercostal draining under local anaesthesia Hydrothorax managed by intercostal draining under local anaesthesia Pneumothorax managed by intercostal draining under local anaesthesia Renal pelvic perforation managed by prolonged nephrostomy tube or postoperative placement of nephrostomy Renal pelvic perforation managed by ureteric stenting without general anaesthesia Ureteric clot obstruction managed by ureteric stenting without general anaesthesia Urine leakage managed by postoperative placement of a new nephrostomy tube Urine leakage managed by ureteric stenting without general anaesthesia Blocked nephrostomy managed by ureteric stenting without general anaesthesia Misplaced double‐J stent managed by repositioning Displaced nephrostomy requiring ureteric stenting without general anaesthesia Perirenal abscess managed by percutaneous drainage

Clavien 3B

Bleeding managed by angioembolisation Bleeding managed by nephrectomy Colon perforation managed by colostomy Ureteric stricture managed by balloon dilation Avulsion of the ureteropelvic junction managed by surgical repair Retained nephrostomy requiring removal under anaesthesia Intestinal obstruction managed by gastrostomy Perirenal abscess managed by open drainage

Clavien 4A

Bleeding (hypovolaemic shock) requiring intensive care unit (ICU) management Adult respiratory distress syndrome requiring ICU management Hyposaturation requiring ICU management Pulmonary oedema requiring ICU management Heart failure requiring ICU management Hypothermia requiring ICU management Acute renal failure requiring ICU management Arrhythmias with haemodynamic instability requiring ICU management Severe atelectasis requiring intubation and requiring ICU management

Clavien 4B

Urosepsis with multiple organ failure requiring ICU management

Clavien 5

Any complication leading to death

Appendix 5. Web of Science

from 1900 to current

#1 TS= (kidney calculi)

#2 TS= (ureteral Calculi)

#3 TS= (nephrolithiasis)

#4 TS= ((kidney or renal or urin* or ureth*) NEAR/3 (calculi* or stone*))

#5 TS= ((nephro* or uro* or ureter*) NEAR/3 lithi*)

#6 TS= (Percutaneous Nephrostomy)

#7 TS= (Percutan* or nephrostom* or pcnl or pnl)

#8 TS= #1 or #2 or #3 or #4 or #5

#9 TS= #6 or #7

#10 TS= #8 and #9

Appendix 6. ClinicalTrials.gov (www.clinicaltrials.gov/)

kidney calculi, ureteral Calculi, nephrolithiasis, nephro* or uro* or ureter*, Percutaneous Nephrostomy, Percutan* or nephrostom* or pcnl or pnl

Contributions of authors

Konrad Wilhelm (KW): wrote the protocol.

Simon Hein (SH): wrote the protocol.

Frank Kunath (FK): critical review of the protocol.

Martin Schönthaler (MS): wrote the protocol.

Stefanie Schmidt (SS): wrote the protocol.

Sources of support

Internal sources

• German Society of Urology, Germany.

  Salary, S. Schmidt

External sources

• No sources of support supplied

Declarations of interest

KW: none known.

SH: none known.

FK: none known.

MS:

‐ Schoelly GmbH, Denzlingen, Germany: Consultant (not related to tubeless PNL) ‐ LUT GmbH, Denzlingen, Germany: Performing workshops for 'Ultra‐mini PNL' (not related to tubeless PNL) ‐ Neotract Inc., Pleasanton, CA, USA: Performing workshops (for 'Urolift' for the treatment of lower urinary tract symptoms)

‐ Two pending patents: (a) Gel‐forming system for removing urinary calculi and fragments thereof (b) Kit for producing a cross‐linked gel to surround urinary calculi and/or fragments thereof

The patents have been submitted and will be owned by the collaborating institutions (University Medical Center Freiburg and Fraunhofer Institute Munich) on 22 Aug 2013. MS is participating as an inventor. The patents are pending (patents have been accepted by the European Patent Office, but a period for objection is still in progress). The patents are not related to a competing intervention; they do not relate to whether tubes are used or not.

SS: none known.

Notes

We have based parts of the Methods section of this protocol on a standard template developed by Cochrane Metabolic and Endocrine Disorders, which has been modified and adapted for use by Cochrane Urology.

New