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Table of Contents
REVIEW ARTICLE
Year : 2020  |  Volume : 28  |  Issue : 2  |  Page : 115-119

Increasing the flap viability: Truth or myth?


1 Department of Plastic, Reconstructive and Aesthetic Surgery, Ataturk Training and Research Hospital, Izmir Katip Celebi University, Izmir, Turkey
2 Department of Plastic, Reconstructive and Aesthetic Surgery, Kartal Training and Research Hospital, Istanbul, Turkey

Date of Submission01-Apr-2019
Date of Acceptance20-Jul-2019
Date of Web Publication18-Mar-2020

Correspondence Address:
Dr. Ersin Aksam
Izmir Katip Celebi University, Ataturk Training and Research Hospital, Plastic Surgery Department, Karabaglar, Izmir
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/tjps.tjps_30_19

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  Abstract 


Introduction: One question has led us to conduct this study: “Can we increase skin flap viability?” We found many published articles on flap viability in every journal about reconstructive surgery. However, we did not encounter any study on human subjects. The aim of this study is to evaluate the articles that have been published on flap viability in the last 10 years, to find potential agents or methods that can be used for flaps performed on humans. Materials and Methods: English articles published between 2008 and 2017 in the PubMed database were evaluated. The search terms used for this review included “flap viability” and “flap survival.” Details about the test subjects, sample sizes, and interventions and the effects on flap viability were recorded for each study. Results: A total of 995 articles were evaluated according to the inclusion and exclusion criteria; 231 studies were then included in the study and 764 were excluded from the study. No previous study on human subjects was encountered. An increase of flap viability was detected in 209 studies (90.5%), and a decrease was detected in 16 studies (6.9%). Six studies reported no effect on flap viability (2.6%). Conclusion: Although it is inevitable that animal experiments will be undertaken before human experiments, when researchers are planning animal experiments, they should consider how well the methods used can be adapted for human beings. We recommend planning human clinical trials with physical methods such as extracorporeal shockwave therapy, laser therapies, and the chemical agent botulinum toxin A. Physical methods are locally effective methods, and their side effects are well known.

Keywords: Animal experiments, botulinum toxin, extracorporeal shockwave therapy, laser therapy, surgical flaps


How to cite this article:
Aksam E, Cicek C, Dervis A. Increasing the flap viability: Truth or myth?. Turk J Plast Surg 2020;28:115-9

How to cite this URL:
Aksam E, Cicek C, Dervis A. Increasing the flap viability: Truth or myth?. Turk J Plast Surg [serial online] 2020 [cited 2020 May 27];28:115-9. Available from: http://www.turkjplastsurg.org/text.asp?2020/28/2/115/280987




  Introduction Top


The problems seen while treating patients in clinics prompted us to ask how we can solve them. The answers can be found through scientific research. A solid scientific research study evolves fromin vivo toin vitro and then to clinical trials. Asking the right question is one of the key points of designing a solid research study. The researcher should design the study with the clinical problem in mind. For plastic and reconstructive surgeons, decreased flap viability is always a clinical problem that needs to be addressed. Considerable research has been done over decades to find solutions for this problem, and some surgical delay procedures and flap planning techniques with regard to vascular anatomy have been proved to be effective.[1],[2] However, a substantial number of studies performed on animals, using a variety of biological, chemical, and physical methods to increase flap viability, were not applied to clinical practice. The aim of this study is to evaluate the articles that have been published in the last 10 years on flap viability, to find potential agents or methods that can be used for increasing flap viability in humans.


  Materials and Methods Top


The studies selected for this study were gathered from the articles published between 2008 and 2017, by searching the PubMed database. All the results were evaluated according to the inclusion and exclusion criteria. Only articles published in English were considered for inclusion in this study. The search terms used for this review included “flap viability” and “flap survival.” The inclusion criteria were defined as studies that analyze the viability of pedicled skin flaps, studies about the effects of biological or chemical agents on skin flap viability, and studies on the effects of physical intervention on skin flap viability. The exclusion criteria were defined as studies that did not analyze the skin flap viability, studies about free flap viability, studies on perforator scanning, studies that inspect the screening of flap viability without any intervention, and studies that did not give exact sample sizes. Details about the test subjects, sample sizes, and interventions and the effects on flap viability were recorded for each study. The types of interventions were placed into the following three major groups for better evaluation: those using chemical agents, those using biological agents, and those involving physical interventions. The effects on flap viability were also placed in the following three groups: those with increases in flap viability, those resulting in no differences, and those with decreases in flap viability. Each article was evaluated by all the authors to reduce the chances of any misinterpretation.


  Results Top


A total of 995 studies were evaluated according to the inclusion and exclusion criteria; 231 studies were included in the study and 764 were excluded from the study. Experimental animals were the test subjects in all the 231 studies. No study on human subjects was encountered [Figure 1]. The preferred experimental animal was rat (8676 rats in 204 studies). Mice were the second experimental animal in terms of preference (558 mice in 16 studies), and rabbits were the third preferred animal (90 rabbits in five studies). Pigs (55 pigs in three studies), hamsters (24 hamsters in one study), and dogs (18 dogs in two studies) were the other preferred animals [Figure 2]. The average sample size was 407 subjects (ranging between two and 344 subjects). A total of 9421 experimental animals were used for these studies. Administration of chemical agents was the leading intervention and was used in 119 studies. Biological agents were tried in 67 studies, physical interventions were chosen for 39 studies, and a combination of the two methods was selected for six studies [Figure 3]. The most commonly used chemical agent was botulinum toxin A (BtxA) (nine studies). The other commonly used chemical agents were hirudin (five studies) and sildenafil (five studies). Adipose-derived stem cells (ADSCs) were the biological agent that were most preferred (10 studies), and vascular endothelial growth factor (VEGF) (nine studies) and platelet-rich plasma (five studies) were the other commonly used biological agents. Extracorporeal shockwave therapy (ESWT) (nine studies) and laser therapies (seven studies) were the leading physical interventions. An increase of flap viability was detected in 209 studies (90.5%), and a decrease was detected in 16 studies (6.9%). Six studies reported no effect on flap viability (2.6%). Positive effects of chemical agents on flap viability were seen in 89.9% of the studies (107 of 119 studies), and 91% of those using biological agents and 89.1% of those using physical agents resulted with increased flap viability.
Figure 1: PubMed search for flap viability

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Figure 2: The distribution of used experimental animals in performed studies

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Figure 3: The distribution of used modalities for evaluating flap viability

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  Discussion Top


A simple question has led us to conduct this study: “How can we increase random skin flap viability?” “Is there any clinically used method or substance that can increase flap viability?” We encountered a lot of published articles about experimental studies that examined the effects of agents or methods on skin flap viability. However, in clinical practice, only basic surgical delay procedures are used to increase flap viability. None of the experimentally used substances or procedures have been used in clinical practice and not even tried in clinical trials. When we searched the PubMed database for flap viability studies over the last 10 years, we encountered 231 published articles. All the articles were performed on experimental animals and aimed to evaluate the effects of chemical, biological, and physical agents on flap viability. We encountered no clinical trials done on human subjects. This striking result has led to many new questions: “What is the reason behind this huge number of experimental studies that are not involved in clinical studies?”, “Do we not need a procedure to increase skin flap viability in humans?”, “Are the results of these experimental studies not good enough to try on human subjects?”, “Are the chemical and biological agents or physical methods not applicable to humans?”, “If some of the methods or substances mentioned have been used in clinical practice, why have there been no clinical trials to evaluate the effects of these methods and substances?”, “If the substances or methods that have been tried are not applicable to humans, how can researchers get institutional ethical board approval?”, and, finally, “What are the most suitable methods that can be tried on humans?”

Do we need to increase skin flap viability? The answer is obviously yes. The dreams of plastic surgeons will come true if an injection can increase the flap viability. Of the experiments mentioned above, 90% have resulted in an increase in flap viability. A full 89.9% of the studies performed with chemical agents resulted in increased flap viability. The chemicals that were used most commonly were BtxA, hirudin, and sildenafil, and all of these substances resulted in increased flap viability. BtxA has been found to have an effect on the vascular smooth muscle function, which may increase the vascular supply to the flap.[3],[4],[5],[6] Injecting BtxA around the vascular pedicle and subdermal plexus of the flap may increase blood supply by decreasing the tension in the vascular smooth muscles. Hirudin is an anticoagulant, antioxidant, and anti-inflammatory agent that can be obtained naturally with leech therapy or can be used as recombinant hirudin. However, leech therapy may cause uncontrolled bleeding and anemia, and leeches can transmit infectious diseases.[7],[8],[9] Sildenafil is a phosphodiesterase-5 inhibitor and exhibits antioxidant and pro-angiogenic effects.[10],[11],[12] Although these substances can be used on flaps for humans, the route of administration needs to be decided carefully. Using a chemical orally and taking high doses for long periods of time can cause far more important problems than necrosis of the distal part of a flap. In addition, some substances that provoke neovascularization have side effects such as hypotension, and the regulation of drug doses may be complicated when used systemically.

VEGF and ADSC are the most commonly used biological agents in these studies. VEGF mediates angiogenesis in 24–72 h and increases inducible nitric oxide synthase and nitric oxide, thus causing vasodilatation.[13],[14] In addition, stem cells can differentiate to various cell lines and can produce growth factors and cytokines that induce neovascularization.[15],[16],[17] However, biological agents such as VEGF and ADSC are not easy to obtain, and using these agents may lead to unexpected results such as immune problems.[18] Many techniques have been tried for delivering biological agents to surgical sites, which involves viral vectors such as adenovirus, nonviral gene therapy, and hollow fibers.[18],[19],[20],[21],[22] Furthermore, the use of biological agents may result in much more complicated side effects.

Many physical methods have been tried to increase flap viability, and ESWT and lasers are the attention grabbers. Considerable research has been conducted into evaluating the effects of these methods and then adjusting the treatment modalities of the methods.[23],[24],[25],[26],[27],[28],[29] The physical methods that have the most potential for use in human trials are ESWT and lasers. These are commonly used in clinical practice for other problems, and both the limitations of their use and the side effects are well known. However, they can only be used locally for the sites of the planned flap areas. A clinical trial on humans can be designed with one of these methods.

Pentoxifylline is used for increasing flap viability in clinical practice, but no clinical trial has yet been undertaken to evaluate the efficiency of pentoxifylline with respect to the viability of flaps performed on humans. Without randomized controlled trials, how can we be sure about the effects of pentoxifylline on flap viability? How can we determine the optimal dosage of pentoxifylline that promotes flap viability and avoids side effects? Randomized controlled studies are the cornerstone elements of evidence-based medicine. As professional health-care providers, we should treat our patients with modalities that are found on evidence-based medicine. In other words, if we want to use a method or substance on humans, we should perform randomized controlled studies. However, performing randomized controlled studies on humans is not easy. The approval of ethical boards is difficult to obtain. The patients must provide consent to participate in the trial. Huge amounts of funding should be arranged to cover patients' health insurance. There are multiple factors that make it difficult to create homogenized trial groups, such as age, sex, comorbidities, smoking, and trauma. On the other hand, it is not impossible to perform a well-designed clinical trial.

The critical standpoint for performing a scientific research study is to find a solution to a problem. The following problem is examined in this article: “Can we increase the skin flap viability?” Many animal experiments have been done to address this problem, and numerous solutions have been offered. However, not one of these solutions has been tried on human subjects. If an animal experiment is done to find a solution for a problem that occurs in humans, then the solution that is offered should be able to be used for humans. Otherwise, the animals that were used and the efforts that were made were done for nothing. One of the primary duties of the institutional ethical boards is to check how well the methods used can be adapted for human beings. The strict control of ethical boards may restrict the number of pointless experiments that are done. Research theses are done compulsorily to complete plastic surgery residency programs in some countries, and this may be responsible for the high numbers of pointless experiments. Performing a flap viability experiment is very easy, and the protocols are well defined. Testing a substance that has never been tried before, regardless of its adaptability to human subjects, is a guaranteed way of completing a research thesis in a very short time. However, these researchers should be mindful of the fact that the animals used in these experiments are living beings, and their lives should be sacrificed only for good reasons.

Our study has some limitations: only articles published in English in the last 10 years have been evaluated. It would be better to evaluate articles published in other languages and that extend back over a longer time period.


  Conclusion Top


This study provides several critical conclusions. First, it is imperative to execute animal experiments before human experiments, but researchers should consider how well the methods used can be adapted to human beings, while also planning the animal experiments. Second, the research should try these experimentally proven methods on human beings as soon as possible. Our recommendation is to begin with physical methods such as ESWT and laser therapies, which have resulted in increased flap viability in experimental animals. In addition, these methods are currently used on humans with different indications. They are locally effective methods, and their side effects are well known. BtxA is a chemical agent that is worth investigating in flaps performed on humans. Furthermore, plastic and reconstructive surgeons are very familiar with the application of BtxA and well acquainted with its side effects.

Acknowledgment

We thank Prof. Dr. Erol Demirseren for his inspiring personality about being a great instructor.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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