Is There a Relationship Between Smoking and Stricture Recurrence After the Urethroplasty? a Systematic Review and Meta-Analysis

doi:10.21203/rs.2.23580/v1

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Is There a Relationship Between Smoking and Stricture Recurrence After the Urethroplasty? a Systematic Review and Meta-Analysis

https://doi.org/10.21203/rs.2.23580/v1

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Background

Some retrospective studies have noted that smoking is a possible risk factor for recurrence of restenosis after urethroplasty, but not all of them are consistent. Therefore a meta-analysis is needed.

Method

Pubmed, Web of Science, Embase, Cochrane databases were searched with key words: “urethroplasty”, “buccal mucosa graft urethroplasty”, “oral mucosa graft urethroplasty”, “excision and primary anastomosis urethroplasty”, “urethral stricture recurrence” until Jan 30, 2020. The quality of included studies was assessed by Newcastle-Ottawa Scale (NOS) system. Hazard ratio (HR), odds ratio (OR), relative risk (RR) with 95% confidence interval (CI) were extracted or re-calculated from included studies. Meta-analysis was performed with Stata 15.0 based on univariate and multivariate data separately. Sensitivity analysis was performed to test stability of meta-analysis. I 2 was calculated to evaluate heterogeneity. Publication biases were assessed by egger’s and begg’s tests. Funnel plots of univariate analysis and multivariate analysis were also offered.

Results

12 studies with 3443 patients were involved into this meta-analysis. The analysis results of two stages were consistent. In the univariate meta-analysis stage, 9 studies with 2279 patients were pooled and the result indicated that smoking might promote stricture recurrence (RR=1.46, 95%CI: 1.11-1.93, P=0.008). In the multivariate meta-analysis stage, based on adjusted estimate, 7 studies with 2074 patients were pooled and the result indicated that smoking might promote stricture recurrence (RR=1.39, 95%CI: 1.04-1.85, P=0.026). There was no significant heterogeneity in both univariate and multivariate stage.

Conclusion

This meta-analysis of current evidence indicates that smoking may prompt stricture recurrence after the urethroplasty. Quitting smoking may be a good option for patients undergoing urethroplasty surgery.

Urology & Nephrology

Urethral stricture

urethroplasty

risk factor

smoking

meta-analysis

When urologists deal with the urethral stricture patients by urethroplasty, one of the most worrying situations is the stricture recurrence. In order to find out the possible causes of postoperative stricture recurrence, many retrospective studies have been conducted, and many risk factors such as length of stricture[1–3], previous urethroplasty history[2, 4–6], direct visual internal urethrotomy (DVIU) history have been reported[2, 3, 7, 8]. However, in addition to these risk factors that have a strong role in promoting stricture recurrence, there are still some risk factors that are relatively mild or need a long time for stricture promotion, which can only be described by a large sample size of clinical research. In 2010, a study pointed out that tobacco consumption may lead to stricture recurrence after urethroplasty[9]. However, in many subsequent retrospective studies, whether in univariate analysis or multivariate analysis, the role of smoking in the stricture recurrence after the urethroplasty has not been uniformly described.

In this study, a meta-analysis based on the univariate and multivariate results was conducted to obtain a stable assessment of the relationship between smoking and stricture recurrence after the urethroplasty.

1.1 Literature search and inclusion criteria

This meta-analysis was carried out according to the principle of preferred reporting items for systematic reviews and meta-analysis (PRISMA). We searched Pubmed, Embase, Web of Science and Cochrane Library to identify relevant studies. The latest search date was February 1, 2020. The searching key words included urethroplasty, smoking, smoker, tobacco consumption and stricture recurrence. Furthermore, reference part of every candidate literature was manually screened to find possible data source.

Detailed inclusion criteria were as follows: Patients were treated with onlay with buccal mucosa or penile fasciocutaneous flap or oral mucosa or any other type of substitution urethroplasty, anastomotic urethroplasty or any combined urethroplasty techniques for anterior or posterior urethral strictures. Odds ratio (OR), hazard ratio (HR) with 95% confidence interval (CI) of risk factors should be offered. Exclusion criteria were complied as follow: Reviews, meta-analysis, letters, comments, case serials and conference abstract were excluded. Studies didn’t contain regression information or enough data which could be used for secondary analysis were excluded.

1.2 Research Quality Evaluation

All included studies were evaluated by Newcastle-Ottawa Scale (NOS) system and the evaluation procedure was performed by two independent reviewers. According to the NOS, 7–9 score studies were thought as high-level quality, 5–6 score studies were thought as moderate-level and < 5 score studies were low-level quality. Low-level quality studies shouldn’t be involved in the meta-analysis.

1.3 Meta-analysis

In this study, based on univariate and multivariate analysis results, the relationship between smoking and stricture recurrence was pooled in meta-analysis. All analysis was powered by Stata 15.0 software (Stata corporation, College Station TX, USA). Statistical significance was defined as P < 0.05 in this study. Pooled estimate larger than 1 indicated that smoking would make patients more vulnerable to stricture recurrence. Heterogeneity was evaluated by I². When I² was larger than 50%, heterogeneity could be significant. If significant heterogeneity was detected, random effect model should be applied. To identity the potential factors which contributed to heterogeneity, meta-regression analysis was performed. Subgroup analysis based on meta-regression was also performed to get detailed information. Furthermore, sensitivity analysis was performed to test stability of meta-analysis results and publication-bias was tested by Egger’s and Begg’s tests. Funnel plots were used for publication-bias visual identification.

2.1 Study selection

1159 studies were identified from databases in total. After duplicates removement, abstract screening and full text reading, 12 studies were finally involved into this meta-analysis. Detailed screening procedure is displayed in the Fig. 1.There were 9 studies (total 2279 patients) contained smoking-stricture recurrence univariate analysis information[3, 8–15], 7 studies (total 2074 patients) contained multivariable analysis information[6, 7, 11–13, 16, 17]. Out of 12 involved studies, 11 studies are retrospective cohort studies and only 1 study was prospectively designed. Detailed baseline information and research quality evaluation are shown in Table 1 and Table 2 separately.

2.2 Univariate analysis

In terms of univariate analysis, there are 9 studies containing 2279 patients exploring the association between smoking and stricture recurrence after urethroplasty. According to the overall meta-analysis result, smoking can make patients more vulnerable to stricture recurrence (RR = 1.46, 95%CI: 1.11–1.93, P = 0.008) with no significant heterogeneity found (I2 = 28.6%, p = 0.190) (Fig. 2). No significant publication bias was found according to the Egger’s test (t = 0.92, P = 0.389) and Begg’s test (z = 0.00, P = 1.00) and was showed in funnel plot (Fig. 3). Sensitivity analysis showed that the results were not significantly changed by eliminating the study one by one (Fig. 4).

2.3 Multivariate analysis

Based on multivariate analysis, the the association between smoking and stricture recurrence after urethroplasty was explored in 7 studies containing 2074 studies. According to the overall meta-analysis result, smoking can make patients more vulnerable to stricture recurrence (RR = 1.39, 95%CI: 1.04–1.85, P = 0.026) with no significant heterogeneity found (I2 = 27.5%, p = 0.290) (Fig. 5). No significant publication bias was found according to the Egger’s test (t = 0.85, P = 0.427) and Begg’s test (z = 0.37, P = 0.711) and was showed in funnel plot (Fig. 3). Sensitivity analysis showed that the results may become non-significant by eliminating Benjamin N. Breyer (2010) or Jared M. Whitson (2007) (Fig. 4).

Urethral stricture is a kind of pathological stricture of urethra, which can limit fluid transportation. Since the male urethra is significantly longer than the female urethra, and the posterior urethra is hidden in the pelvis, urethral stricture can always bring many troubles to patients and urologists. Urethral stricture is a common urinary disease for the male. There are 229–627 cases in every 100000 people, and in some susceptible groups, such as elderly men, the prevalence rate is as high as 0.6%[18]. As one of the main methods to treat urethral stricture, there are many ways to implement urethroplasty, including primary anastomosis and substitution implantation. However, although many different surgical methods have been developed for different stricture degree, length and location, the total success rate is still only 72% − 94%[11, 14, 16]. Therefore, it is very important to find out the risk factors of recurrence of urethral stricture after urethroplasty and to prevent them. Some risk factors such as the length of stricture and etiology have attracted the attention of urologists, but other factors such as tobacco consumption has not been evaluated carefully [1, 3, 8, 19]

This meta-analysis revealed that tobacco consumption can make the chance of stricture recurrence significantly increased based on both univariate and multivariate analysis. In the multivariate analysis stage, the sensitivity analysis result was not exactly stable, this indicated that more multivariate analysis studies and adjusted estimate between smoking and stricture recurrence were required.

There are many proven relationships between smoking and urinary diseases. Smoking can promote the development of bladder cancer, which has been proved by many studies[20, 21]. The possible reasons why smoking is an independent risk factor for bladder cancer are various and some studies mentioned that the substances produced by tobacco burning, when metabolized into urine, will have a great influence on the DNA of bladder urothelial cells, which will lead to cell death and local inflammation[22]. This procedure may also be implied on urothelial cells. Persistent local inflammation in the epithelium of the urethra at the site of urethroplasty, caused by irritation of substances in the urine, may lead to recurrence of urethral stricture. Furthermore, for patients who receive oral mucosa graft Urethroplasty (OMGU), smoking history will make the general state of oral mucosa worse, leading to poor graft survival after OMGU operation, and ultimately leading to the increase of stenosis recurrence rate[9, 23].

In many current urological guidelines, the effect of smoking on the stricture recurrence after urethroplasty is not mentioned[24]. According to the results of this meta-analysis, urologists should guide urethroplasty patients to quit smoking before and after the operation to improve the overall success rate of the operation.

Some potential limitations of this study should be presented. First, although there were some prospective data involved, all the included studies are retrospective studies. Second, although it was recognized in statistical methodology[25, 26], it is still possible to bring some additional bias by combining HR and OR to get RR estimates. Third, since smoking can directly damage oral mucosa, so OMGU patients with smoking history may have higher recurrence ratio, however, in this meta-analysis, since many studies didn’t offer detailed information about OMGU technique, so OMGU subgroup analysis was not performed, further high-level evidences about smoking’s effect on OMGU are needed.

NOS

Newcastle-Ottawa Scale;

Hazard Ratio;

Odds Ratio;

Relative Risk;

Confidence Interval;

DVIU

Direct Visual Internal Urethrotomy;

PRISMA

Preferred Reporting Items for Systematic Reviews and Meta-analysis;

OMGU

Oral Mucosa Graft Urethroplasty;

RCS

Retrospective Cohort Study;

NRPCS

Non-Randomized Prospective Cohort Study

BMG

Buccal Mucosa Graft

Acknowledgements

Not applicable.

Declarations

Authors’ contributions

YCM and MHW were responsible for the design of the work, the acquisition and analysis of data and manuscript writing. ZYJ carried out the acquisition of data. WKJ and LH revised the manuscript. All authors read and approved the final manuscript.

Funding:

This article is supported by 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (ZY2016104, ZYGD18011 and ZYJC18015) for data-collecting (availability of database purchased and provided by west china hospital). Chengdu Science and Technology Bureau project 2016-HM02-00020-SF, Science and Technology Department of Sichuan Province project 2015SZ0230-2 for data-analysis.

Availability of data and materials

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Ethics approval and consent to participate

All analyses were based on previous published studies. Thus, no ethical approval and patient consent are required.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Table 1. Characteristics of studies included in the meta-analysis.

Author	Year	Country	Disease	Study design	Techniques applied	Median/Mean follow (months)	Sample size	Recurrence number	Mean age (year)	Definition of stricture recurrence	NOS score
Adam S. Kinnaird	2014	Canada	Anterior/posterior urethral stricture	RCS	NR	52	604	56(91%)	44.5	cystoscopic evaluation	5
Benjamin N. Breyer	2009	USA	Anterior/posterior urethral stricture/combined stricture	RCS	Anastomotic urethroplasty/ Buccal mucosa graft/ Fasciocutaneous flap/combined techniques	70	443	93(79%)	41.5	peak urinary flow less than 15 cc per second and/or the radiographic evidence of stricture and further need for urethral instrumentation	8
Boyd R. Viers	2017	USA	bulbar urethral stricture	RCS	Excision + primary anastomosis/Substitution	64	278	34(88%)	49	the need for recurrent urethral interventions such as endoscopic treatment, subsequent catheterization or repeat urethroplasty	5
Christopher G. Keith	2019	USA	bulbomembranous urethra	RCS	Primary anastomosis	30.7	116	22(81%)	72.3	Recurrence was defined by recurrent stricture ≤ 16F in caliber on cystoscopy, stricture on VCUG, and/or operative intervention for urethral stricture disease	7
David Chapman	2017	Canada	bulbar stricture	RCS	BMG Onlay/ Flap Onlay/ Augmented Anastomosis/ Anastomotic/ Combined Tissue plasty	65.4	596	40(93%)	44.3	cystoscopic evaluation (inability to easily pass a 16Fr cystoscope)	7
Jared M. Whitson	2007	USA	Anterior Urethral Stricture	RCS	fasciocutaneous flap urethroplasty	87.6	124	32(76%)	48	Subjective and objective improvement in urinary flow, absence of radiographic evidence of stricture, and no further need for urethral instrumentation.	5
Joceline S. Liu	2015	USA	Fossa navicularis/ Penile/ Bulbomembranous/ Panurethral strictures	RCS	Dorsal onlay/ Ventral onlay/ Staged urethroplasty	59.3	238	66(72%)	42.9	A stricture <16F in caliber was visually present in the reconstructed segment of urethra on cystoscopy	8
Justin S Han	2015	USA	Posterior urethral stricture	RCS	Excision/primary anastomosis/ Dorsal onlay (including augmented anastomotic)/ Ventral onlay/ Staged/ Combined/flap/miscellaneous	62	227	60(73%)	42.9	patient-reported recurrent urinary symptoms and urethral caliber less than 18-Fr on cystoscopy, and/or need for any subsequent intervention (including dilation, endoscopic urethrotomy or repeat urethroplasty)	5
Arman A. Kahokehr	2018	USA	bulbar urethral stricture	RCS	Excision + primary anastomosis/ Augmented anastomotic repair/ Onlay	28	395	25(94%)	43.41	Stricture recurrence was defined as the need for further intervention in the postoperative period as diagnosed with cystoscopy and/or RUG	5
Mya Levy	2017	USA	Bulbar/ Meatus/Fossa/ Membranous/ Penile stricture	RCS	Excision + primary anastomosis/BMG dorsal onlay	21.6	322	22(93%)	44.2	the freedom from additional procedures after urethroplasty	5
Raj Kumar Mathur	2014	India	Anterior (penile+ bulbar)/ Posterior (membranous/bulbomembranous)/ Panurethra strictures	RCS + prospective data	single-stage penile preputial flap urethroplasty	42	58	11(81%)	42.2	Patient reported symptoms and retrograde urethrography	5
Rahul Janak Sinha	2010	India	Penile/Bulbar/ Bulbopenile/ Pananterior stricture	NRPCS	Oral mucosa graft Urethroplasty	18.2	42	11(74%)	40.2	failure was defined as the need to carry out any intervention or invasive procedure in the urethra following the complaint of decreased urinary flow by the patient	5

RCS = Retrospective Cohort Study; NRPCS =Non-Randomized Prospective Cohort Study; NR = Not Reported; NOS = Newcastle-Ottawa Scale; BMG = buccal mucosa graft.

Table 2. Newcastle-Ottawa scale score of the reviewed studies

Study	Selection (4 stars)				Comparability (2 stars)	Outcome (3 stars)			Total score
Study	Representativeness score of the stricture recurrence	Selection of the stricture recurrence	Ascertainment of stricture recurrence	Demonstration that outcome of interest was not present at start of study	Comparability of cohorts based on the design or analysis	Assessment of outcome	Was follow up long enough for outcomes to occur?	Adequacy of follow up of cohort	Total score
Adam S. Kinnaird (2014)	/	★	/	★	★	/	★	★	5
Benjamin N. Breyer (2009)	★	★	★	★	★	★	★	★	8
Boyd R. Viers (2017)	/	★	/	★	★	/	★	★	5
Christopher G. Keith (2019)	/	★	★	★	★	★	★	★	7
David Chapman (2017)	/	★	★	★	★	★	★	★	7
Jared M. Whitson (2007)	/	★	/	★	★	/	★	★	5
Joceline S. Liu (2015)	★	★	★	★	★	★	★	★	8
Justin S Han (2015)	/	★	/	★	★	/	★	★	5
Arman A. Kahokehr (2018)	/	★	/	★	★	/	★	★	5
Mya Levy (2017)	★	★	/	★	★	/	/	★	5
Raj Kumar Mathur (2014)	★	★	/	★	/	/	★	★	5
Rahul Janak Sinha (2010)	★	★	/	★	★	/	/	★	5

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You are reading this latest preprint version

Is There a Relationship Between Smoking and Stricture Recurrence After the Urethroplasty? a Systematic Review and Meta-Analysis

Status:

Version 1

Abstract

Figures

Background

Method

1.1 Literature search and inclusion criteria

1.2 Research Quality Evaluation

1.3 Meta-analysis

Result

2.1 Study selection

2.2 Univariate analysis

2.3 Multivariate analysis

Discussion

Conclusion

Abbreviations

Declarations

References

Tables

Supplementary Files

Status:

Version 1