Did we take physical therapy serious after lithotripsy: a meta-analysis of prospective studies

Background Stone-free rate (SFR) after lithotripsy was one of the most frequent concerned issue, especially in patients following extracorporeal shockwave lithotripsy (ESWL) and flexible ureteroscopy (retrograde intrarenal surgery, RIRS). Physical therapy including percussion, inversion, physical vibration and their combinations was administrated to improve the SFR, but there was no conclusive evidence to support this theory. To conclude the effectiveness and safety of physical therapy on the SFR in patients received ESWL/RIRS. Methods We systematically reviewed the literature focused on physical therapy in patients after ESWL/RIRS on PubMed, Scopus, Cochrane library and Embase from 2000 to 2019 April. We mainly focused on stone-free rate and complications rate.

role of furosemide and tamsulosin in physical therapy or surgery need to be testified by large-scale, high-quality studies.

Background
Urolithiasis was one of the most frequent noted diseases in urology. The incidence of urolithiasis varies from 1% to 13% in different area, and is still increasing 1,2 . Without medical intervention, the recurrence rate following the operation will 50% within 5 years and 80-90% within 10 years, brought great challenge to urologists 3 .
Percutaneous nephrolithotomy (PCNL) was well established procedure for the management of upper urinary tract stone larger than 2 cm, while extracorporeal shockwave lithotripsy (ESWL) and retrograde intrarenal surgery (RIRS) were regarded as the first line choice for moderate size stones ranged from 1cm to 2 cm 4-6 . Exactly, the PCNL had a higher stone free rate when compared to ESWL and RIRS for a large burden stone, but also associated with a higher complication rate, especially the percutaneous tract related hemorrhage following PCNL, destined that ESWL and RIRS had their certain position in the management of upper urinary tract stones 7,8 .
With the improved lithotripsy efficiency in ESWL and the dusting technique in RIRS, RIRS and ESWL were more and more popular in small burden stones while the fragments following ESWL and RIRS became much more concerned, especially the lower caliceal stones (LCS) 9 . It was reported that the SFR following ESWL was about 23.1%-91.5%, and ranged from 45.6% to 96.7% in patients with RIRS 10 . The residual fragments would influence the SFR undoubtedly, and was prone to bring stone recurrence. Residual fragments' related complications following ESWL and RIRS were also foreseeable, renal colic, urinary tract infection (UTI), and sometimes ureteral steinstrasse required additional surgical interventions. 11,12 Auxiliary procedures were introduced to facilitate stone fragments passage, we summarized two aspects and their combinations. Firstly, medical expulsive therapy (MET), such as diuretics, sometimes Chinese patent medicine, α receptor blockers (Tamsulosin), and so on 13 . Secondly, physical therapy like increasing physical activity, body inversion, percussion on renal region, sleeping on the healthy side, and so on [14][15][16] .
Tamsulosi was widely used in clinic to expel SF even its function efficacy is still under great suspicion.
Some multi-center RCTs showed there was no significance in the stone passage when compared to the placebo group [17][18][19] . Exactly, the stone fragments in lower pole were much more prone to stay since the gravity and the influence of lower calycael anatomy. Roller coaster and intercourse were reported to promote renal stone passage 20,21 . Thus, the physical treatment was theoretically effective to accelerate the stone fragments passage, when changing the body position and rolling the stone fragments into ureteral pelvic junction. More recently, new technique like external physical vibration lithecbole (EPVL) was designed to facilitate stone fragments Passage.
However, there was no conclusive evidences on physical therapy facilitating SF passage, nor clear guidelines in introducing standard physical therapy to facilitate stone fragment passage after lithotripsy. The present systematic review and meta-analysis was aimed to evaluate the overall therapeutic effect of physical therapy and its complications compared to patients without physical interventions. And provide a higher evidence to support the effectiveness and safety of physical therapy. Hopefully, urologists may take more physical therapy into consideration when patient receiving RIRS or ESWL.

Literature Search and article selection
A systematic literature review was performed in March 2019 utilizing PubMed, Scopus, Cochrane library and Embase. A comprehensive literature search was done separately with the following search terms: "physical or mechanical percussion", "inversion", "vibration", "External physical vibration lithecbole", "(EPVL), "extracorporeal shockwave lithotripsy", (ESWL) and "flexible ureteroscopy" (RIRS) "for urinary tract stone". Selection of relevant studies was in accordance with protocol items of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines (http://www.prisma-statement.org). All potentially eligible studies from cited references from the selected articles retrieved in the search were also assessed as significant papers.
All the process as showed in Figure 1 (Figure legends -Flow of studies selection for systematic review and meta-analysis.) was completed by two reviewers Peng and Wen, and disagreements were resolved by consensus after consulting W.Z.

Selection criteria
Studies were included in the present analysis if met the following inclusion criteria: (1) Prospective studies published in English either randomized controlled trials (RCTs) or non-RCTs; (2) with more

Statistical analysis
Meta-analysis of comparable data was conducted using Review Manager Version 5.3 software and Stata Edition 14.2.
The level of evidence (LE) was assessed using GRADE system to assess the methodological quality of the studies, non-randomized controlled trials (N-RCTs) using the Newcastle-Ottawa Scale (NOS) and the Jadad scale were applied for RCTs.
Since the categorical variables of SFR and complications rate were our primary study subjects, statistical analysis was carried out using odds risk (OR) and 95% confidence intervals (CIs).
Heterogeneity was assessed using chi-squared test and the Higgins I 2 statistic. No matter the significant heterogeneity (P >0.1, I 2 >50%) exist or not, the random effect model was used for pooled analysis at first, and would be testified later. Additionally, the source of heterogeneity, analysis publish bias and subgroup pooled analysis was administrated.
To analysis the influence of physical therapy, stone location, medical interventions and drinking water. Stone fragments location was classficated into lower calyx stone (LCS), upper calyx stone (UCS), middle calyx stone (MCS), renal pelvic stone (RPS) and upper ureteral stone (UUS). Medical interventions contained tamsulosin and furosemide. All the useful results would be available for the subgroup analysis.

1.
Study characteristics All the physical therapy, we enrolled, was finally concluded into EPVL and PDI. As it demonstrated in the Table 2, 5

Stone-Free Rate
A total of 9 eligible studies reported the SFR referred to physical percussion, EPVL and PDI after ESWL, RIRS or not. A higher SFR was provided by physical therapy (OR= 2.72, 95% CI: 1.79-4.14, p = 0.000,

SFR changed with time
With time after treatment moved on, SFR was also changing. Specifically

Influence of stone location to SFR
In

Influence of medical interventions to SFR
According to the analysis result (

Influence of drinking water before therapy
When the studies were divided according to whether patients drink enough water before receiving physical therapy as it was showed in Figure 10

Discussion
Since our study were based on prospective studies, our study was a high level evidence to support what we found and concluded. But in sub-group analysis, we realized that in some area, large-scale RCTs were supposed to testified our findings as we described below. As mentioned i before, the role of tamsulosin in ureteral stone was uncertain even systematic reviews came to a conclusion that tamsulosin can facilitate the stone passage in distal ureter in our study, Liu et al focused on EPVL combined with tamsulosin to promote a higher SFR for an upper ureteral stone fragment. But this three-arm study found a significant difference in the first week between EPVL combined with tamsulosin and tamsulosin alone. The stone free rate was much higher in EPVL+ tamsulosin (91.1%, P < 0.05), but it hard to tell whether single EPVL (50%) or single tamsulosin (50%) was more helpful. Interestingly, the SFR (94.5%, 93.6% and 93.5%, p > 0.05) showed no significant difference in the second week. We supposed that may be all of the methods above were working and one can increase the efficacy of other. It still needs further research to prove their function.
From guideline, one of suggestions to prevent urolithiasis formation or recurrence is drinking water.
Whether drinking water and when to drink water will help stone fragments expulsion. We divided the studies into a water group and a blank group based on patients received enough water before therapy, we surprisingly found that enough water before the therapy is essential to improve the SFR for both of the treatment and control groups, and it was suggested to drink more than 1500ml water per day (OR: 3.31; 95% CI: 2.39-4.60; P = 0.0001).
Even though we analyzed the efficacy of PDI before, but when we considered the effect of diuresis alone, we found only 2 of 4 PDI studies had specified description on the use of furosemide, and the use of furosemide did not improve the SFR (OR: 5.21; 95% CI: 0.53-50.72; P = 0.156). But we had to admit the limitation of studies enrolled. The same situation happen in tamsulosin group, which confused us was the tamsulosin and EPVL seemed to enhance each other when they combined together. But when they used separately, they showed no difference in SFR.
When it comes to the complications of physical therapy, we did not found any significant difference in terms of hematuria, dizziness, lumbago and urinary infection. As EPVL and PDI are working through facilitating the stone passage, it did not increase the risk of renal colic or strainstrass formation.

Ethics approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Availability of data and mate
All data generated or analysed during this study are included in this published article and its supplementary information files.

Competing interests
The authors declare that they have no competing interests.

Funding
Not applicable.

Authors' contributions
L.P. owned the idea, designed the study and wrote the manuscript. J.W. performed the searching under the strategy and collected data. W.Z. and G.Z. revised methodology and manuscript and offered advice during the whole process. All authors mentioned above read and approved the final manuscript.   Figure 1 Flow of studies selection for systematic review and meta-analysis.

Figure 2
Results of bias assessment.

Figure 3
Meta-analysis of stone-free rate and subgroup analysis of different techniques.

Figure 4
Meta-analysis of stone-free rate in week 1, week 2, month 1 and month 3.

Figure 5
Funnel plot of publish bias.

Figure 6
Meta-analysis of stone expulsion in the first two days.

Figure 7
Meta-analysis of overall complication rate and subgroup analysis of specific complications.

Figure 8
Subgroup analysis of different stone locations in SFR.

Figure 9
Subgroup analysis of medical intervention in SFR.

Figure 10
Subgroup analysis of drinking water before physical therapy in SFR.

Supplementary Files
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