One Versus Two Veins in Free Anterolateral Thigh Flap Reconstruction: A Systematic Review and Meta-Analysis

There is considerable debate in the literature as to whether one or two venous anastomoses are optimal in the anterolateral thigh (ALT) free-flap reconstruction. The literature is currently devoid of a systematic review and meta-analysis of studies evaluating these procedures. This review will therefore be the first to address this clinical question. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, two authors (EW and SR) independently searched the following electronic databases: MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL). Case-control, randomised control and observational studies were included. The authors did not include case reports, case series, letters or abstracts. All patients were included regardless of age, co-morbidity status, and the anatomical site of reconstruction. Venous congestion/thrombosis, flap take-back rate due to venous insufficiency, flap loss and operative time were the primary outcome measures. Secondary outcome measures included partial flap loss and haematoma formation. The Newcastle Ottawa Scale was used to assess the risk of bias in the included studies. Review Manager 5.4 data synthesis software was used for the analysis. The authors identified eight observational studies, with a total of 1741 patients reviewed, demonstrating a significantly lower flap take-back rate for a double venous anastomosis and a shorter operative time in the single venous anastomosis group. However, other reported measures, including venous congestion and flap loss, showed a non-significant difference (P>0.05). The limitations of the evidence included in this review were that all studies were observational in design. The flap take-back rate is significantly less when anastomosing two veins, and the authors recommend that utilising a second vein can circumvent the caveat of venous compromise.


Introduction And Background
In plastic surgery, the anterolateral thigh (ALT) flap is a recognised versatile perforator flap. Initially advocated by Song et al. [1], it has a wide variety of uses, including reconstruction of the head and neck [2][3][4], breast [4], as well as limb defects [4]. There is considerable debate in the literature, however, associated with techniques of microvascular anastomosis [3] and whether one or two venous anastomoses are better. Authors advocating one vein for ALT flaps have emphasised lower operative times, improved resource optimisation and a reduced risk of thrombosis from a theoretically decreased blood flow velocity when two veins are anastomosed [5][6][7]. Utilising a second vein has been reported by others to mitigate the risk of potential flap compromise from venous failure [8,9]. To the authors' knowledge, the literature is currently devoid of a systematic review and meta-analysis evaluating outcomes of studies comparing one versus two venous anastomoses in ALT-free flap reconstruction.

Review Methods
This meta-analysis and systematic review were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards (Appendices) [10]. The authors did not register the review protocol with the International Prospective Register of Systematic Reviews.

Eligibility Criteria
The aim was to include case-control, randomised control and observational studies that compared outcomes for one versus two venous anastomoses in ALT free-flap reconstruction. The authors did not include case reports, case series, letters or abstracts. Two venous anastomoses were the intervention of interest, with single venous anastomosis being the comparator as a control group. All patients were included regardless of age, co-morbidity status and the anatomical site of reconstruction. Studies not reported in English were excluded from the review.

Outcome Measures
Venous congestion/thrombosis, flap take-back rate due to venous insufficiency, flap loss and operative time were the primary outcome measures. Secondary outcome measures included partial flap loss as well as haematoma formation.

Literature Search
Two authors (EW and SR) independently searched the following electronic databases MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials (CENTRAL). The search strategy was developed by both authors and refined by the senior author (SR). Any discrepancies, at any stage, in the screening of the articles were resolved following discussion and re-evaluation by the authors. The last search was run on the 20th of September, 2022.
The search terminologies, as well as medical subject headings (MeSH), were combined with the adjuncts of "and" as well as "or" and included ("one vein"[All Fields] OR "single venous anastomosis"[All Fields]) AND ("two veins"[All Fields] OR "double venous anastomosis"[All Fields]) AND ("ALT flap"[All Fields} OR "anterolateral thigh flaps"[All Fields]) AND ("reconstruction"[All Fields]). Bibliographic lists of articles were also reviewed to enhance the screening process.

Study Selection
The titles and abstracts of articles that met the eligibility criteria within the literature were independently reviewed by two authors (EW and SR). Articles that met the eligibility criteria were then reviewed through their full text.

Data Collection
An electronic data extraction spreadsheet was created in accordance with Cochrane's data collection form concerning intervention reviews. Pilot testing was conducted in random articles and adjusted accordingly. Two authors (EW and SR) independently collated and entered the data into the spreadsheet.

Methodological Quality and Risk of Bias Assessment
Two authors (EW and SR) independently assessed the methodological quality and bias risk for included articles. The Newcastle Ottawa Scale was used to review the methodological quality and risk of bias for all non-randomised trials or observational studies [11]. It uses a star system with three domains: selection, comparability and exposure. Scores of nine are considered low risk of bias, those between seven and eight are regarded as medium risk and a score of six or lower is a high risk indicator of bias.

Data Synthesis and Statistical Analyses
The odds ratio (OR) was used for dichotomous variables representing the odds of an event in the double venous anastomosis group compared to the single vein group. Review Manager 5.4 data synthesis software (Review Manager (RevMan) (Computer program). Version 5.4, The Cochrane Collaboration, 2020) was used for the analysis. The senior author (SR) has experience in performing meta-analyses using Review Manager 5.4. Results were reported in a forest plot with 95% confidence intervals (CIs).
Heterogeneity among the studies was assessed using the Cochran Q test (χ2) as well as the I2 and interpreted as follows: 0% to 25% (low heterogeneity), 25% to 75% (moderate heterogeneity) and 75% to 100% (considerable heterogeneity).
Venous congestion/thrombosis: Four studies [13][14][15]17] reported venous congestion and thrombosis comparing one versus two veins, but no significant difference was seen between the two groups, as demonstrated in Figure 3 below.

ALT: anterolateral thigh
Operative time: The operative time was significantly lower in the single venous anastomosis group, as reported in Figure 4, for ALT free-flap reconstruction [12,15,17]. A statistically significant mean difference (p<0.05) was evidenced favouring the use of one vein.

FIGURE 4: Operative time (minutes) of single versus double venous anastomoses in ALT flap reconstruction
Data reported by Lee, Abdelaal and Chen et al. [12,15,17].

ALT: anterolateral thigh
Flap take back: The flap take-back rate was significantly lower in the double venous anastomosis group [12,14,16,17] as demonstrated in Figure 5 with a significant P value (P = 0.01).

Secondary Outcome Measures
Miscellaneous complications: Additional complications reported included partial dehiscence and partial flap loss, which have been referenced as 11.4% versus 12% in one and two veins, respectively, by Abdelaal [15]. Chen [17] reports a partial flap loss rate of 7.2% (one vein) and 4.2% (two veins). Ehrl [13] and Heidekrueger [16] did not have any incidences of partial flap loss in either group. The rates of haematoma were comparable in the study by Chen [17], 5.1% (one vein) and 5% (two veins) for ALT flaps. Ehrl [13] did not report any haematoma in the one vein group but had a 1% incidence in the double venous anastomosis cohort. Heidekrueger [16] had near-similar incidences of haematoma formation in each group, 6.9% (one vein) versus 5.26% (two veins), as did Lee [12], 4.2% (one vein) and 3.1% (two veins).
Methodological quality review: The Newcastle-Ottawa scale was used to assess the methodological quality of all observational studies within this review [11] ( Table 2). Most studies scored poorly in the "Selection" domain due to no precise stratification method for patients undergoing single or double anastomoses. In the "Comparability" domain, however, most studies scored well, reporting both primary and secondary outcome measures homogenously to an extent. In the "Exposure" domain, studies scored poorly due to not stating the length of follow-up and no reports of whether any patients were lost to follow-up.

Discussion
There are many debatable factors regarding whether one or two venous anastomoses are preferred in ALT flap reconstruction. Surgeons who advocate the use of a single vein stress the importance of lower operative times, better use of resources and reduced risk of thrombosis from decreased blood flow velocity [5][6][7], whereas surgeons who encourage the use of two veins believe this reduces the risk of venous failure and mitigates flap compromise [8,9].
This review demonstrated a significantly lower flap take-back rate for a double venous anastomosis and a shorter operative time. Other reported measures, including venous congestion and flap loss, showed an insignificant difference (P>0.05).
Abdelaal [15] and Lin et al. [18] advocate using a single vein anastomosis, as there were no significant differences in most of their outcome measures when comparing one versus two veins. Outcome measures included flap loss and complications such as infection and venous thrombosis, none of which demonstrated any statistical differences.
In contrast, Ross [8], Lee [12], Iamaguchi [14], Chen [ [17] found that, in general, there was no significant difference between the groups; however, when vascular insufficiency was analysed, there was a considerable difference between the groups, with a higher proportion of these being in the single vein group.
Ehrl [13] and Heidekrueger et al. [16] reported, although the success of the flap was independent of the number of anastomoses used, they still suggested performing a double vein anastomosis. They both demonstrated no statistical difference when measuring surgical complications, specifically venous thrombosis rates.
Riot et al. [5] reviewed all free flaps in general; they found that using two veins decreased the risk of flap failure, venous thrombosis and the need for revision surgery. This meta-analysis has deduced comparable results for lower flap take-back rates in the double vein group. The authors of this review found no significant difference between venous thrombosis rates and the risk of flap loss. In addition, Chaput et al. [20] favoured double vein anastomosis, as there was a decrease in venous thrombosis and the need for surgical revision. Chaput et al. [20] identified that performing a two-vein anastomosis increased the operative time by 30 minutes. Analysing the results of this study, although the operative time is significantly less when performing a single venous anastomosis, the authors would still recommend double venous anastomosis be performed. Doing so will decrease the rate of return to theatre, which will inherently reduce the overall cost.

Conclusions
The ALT flap continues to be an effective reconstructive option; however, the microvascular dilemma of one versus two veins continues to divide opinions. Primary outcome measures showed comparable results between one versus two venous anastomoses for flap loss rate, venous congestion, and thrombosis, however, the flap take-back rate was lower in the double vein group. Secondary outcome measures, including partial flap loss and haematoma formation, showed no significant difference between the groups. This review suggests that the flap take-back rate is significantly less when anastomosing two veins, and the authors recommend that utilising a second vein can circumvent the caveat of venous compromise. More high-quality studies are needed to further the current evidence base. Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process.

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Data collection process 9 Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process. List and define all other variables for which data were sought (e.g. participant and intervention characteristics, funding sources). Describe any assumptions made about any missing or unclear information.

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Study risk of bias assessment 11 Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process. Describe the processes used to decide which studies were eligible for each synthesis (e.g. tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item #5)).

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Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions. Page 2 13c Describe any methods used to tabulate or visually display results of individual studies and syntheses. Page 2 13d Describe any methods used to synthesize results and provide a rationale for the choice(s). If metaanalysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used.

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Describe any methods used to explore possible causes of heterogeneity among study results (e.g. subgroup analysis, meta-regression). Page 2 13f Describe any sensitivity analyses conducted to assess robustness of the synthesized results. N/A Reporting bias assessment 14 Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from reporting biases

Conflicts of interest:
In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.