Protocol for a systematic review of outcomes from microsurgical free-tissue transfer performed on short-term collaborative surgical trips in low-income and middle-income countries

Five billion people around the world are living without access to adequate surgical care [1]. Short-term collaborative surgical trips (STCSTs) provide an opportunity for surgical teams from higher income nations to collaborate with surgeons from low-income and middle-income countries (LMICs) to treat those most in need. Historically, some STCSTs have been criticised for an unsustainable ‘fly-in-fly-out’ model of surgical care delivery in LMICs, with limited patient follow-up after discharge. One consequence of this is that surgeons working in resource-limited settings have a poor context-specific evidence base to work from [2]. However, many STCSTs return annually to the same centre, building lasting relationships, offering sustainable education and training and treating patients who would otherwise have no access to healthcare. This model offers greater opportunity for thorough follow-up. Indeed, new methods of long-term patient follow-up after discharge are emerging that aim to improve patient safety after STCSTs in LMICs [3, 4]. Historically, such trips were often referred to as ‘missions’. However, there is a growing consensus that the model described above is better captured by the term ‘collaboration’ [5].

Free-tissue transfer can be considered the gold-standard method of reconstruction after significant composite tissue defects from cancer, trauma and infections [6‐9]. In the largest series from high volume centres, flap failure rates as low as 0.6%, and take back rates of 1.5% (66% successful salvage rate) have been published [10]. For surgeons operating in LMICs, that do not have funding and access to the required equipment and training to facilitate independent microsurgical practice, treatment options are restricted to those used 50 years ago in countries that now perform regular free-tissue transfer. For select advanced pathology, this may be the difference between amputation and lower limb salvage after trauma and sarcoma resection, or poorer functional outcomes following head and neck cancer reconstruction [11‐15]. Performing microsurgery in LMICs is challenging, even for experienced teams. However, a select few centres in LMICs are undertaking these procedures as part of standard practice [16‐18]. Local and regional reconstructive alternatives do exist (e.g. transposition or pedicled flaps); however, many of these are also technically demanding, and even with extensive training, microsurgical equipment and techniques, they are vulnerable to complications requiring further surgery [19‐22]. However, there is also some data in support of successful local reconstructive alternatives being used effectively in low-resource contexts [22].

There are existing reviews of STCSTs, but none provide the reader with a detailed account of microsurgical free-tissue transfer performed on this basis, and many combine surgical trips with medical ones in their analysis. There have been studies on socioeconomic/political impact, cost-effectiveness, sustainability and quality of follow-up [2, 23‐25]. However, it has been difficult to draw any firm conclusions due to the paucity of high-quality quantitative data, and the heterogeneity of these interventions, which are often organised on a departmental basis [2]. The closest review to our proposed study assessed a number of outcomes from ‘short-term reconstructive missions’, although the majority of patients in their analysis underwent cleft surgery (without microsurgical free tissue transfer) [26]. They cite substantial reporting bias when it comes to operative complications, and highly variable estimates of cost effectiveness for the same intervention depending on local context.

There are some fundamental challenges to providing microsurgery in LMICs. Amongst those reported are a lack of specialist equipment, trained staff and appropriate level three post-operative monitoring facilities [27]. STCSTs, which can provide additional staff and resources, can directly address these challenges. However, these are usually short-term interventions, and patients may not be afforded the same degree of follow-up provided by the home institutions of the visiting surgeons. In addition, it is traditionally held that reconstructive surgeons should stick to ‘simple’ surgery on STCSTs [28]. Therefore, it is important to establish the safety of delivering free-tissue transfer on STCSTs. Identification of common complications and constraints will inform organisations engaged in STCSTs where to focus their training and fundraising efforts in order to improve patient outcomes. The highly specialised nature of this surgery means that it is difficult to draw on the existing review articles in the literature to make any firm conclusions about this technique performed during STCSTs.

The aim of this study is to publish a robust systematic review protocol to establish the safety and efficacy of microsurgical free tissue transfer performed on STCSTs in low-income and middle-income countries. A meta-analysis of key outcomes will be undertaken with the aim of developing potentially life-changing microsurgical practice in resource-limited settings.

This protocol is registered on the PROSPERO international prospective register of systematic reviews (submitted 15/12/20 ID: 225613) and is written in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) guidelines [29, 30]. The methodology applied to the final systematic review and meta-analysis is derived from, and in line with, the Cochrane Handbook for Systematic Review of Interventions [31] and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [32].

This will be the first systematic review and meta-analysis of the outcomes of free-tissue transfer performed on STCSTs to low-income and middle-income countries. Our pilot searches indicate that the majority of data will be published in case series’; it is difficult to form a conclusion from any one of these alone. This underlines the importance of a thorough synthesis of these studies into a unifying review article. However, lack of randomised allocation and control groups increase the risk of bias, and this has led to concerns regarding the quality of evidence in this field [26]. We cannot remedy this, but will provide the reader with an open appraisal of the body of evidence according to the GRADE approach. From this, they will be able to form their own conclusions about their confidence in our findings.

We predict considerable clinical heterogeneity between the studies included in this paper. STCSTs are often based on relationships between specific institutions, sometimes individual surgeons, and thus there is no ‘one size fits all approach’. Another source of heterogeneity will come from the inclusion of all flap types. We will try to mitigate this through sub-group analysis if possible, but there may be insufficient data available.

Nutritional status has been identified as a determinant of free flap outcome [44]. STCSTs treat a diverse population of patients, many of whom will have poor nutritional status. This may be a confounding factor in reconstructive outcomes, but is unlikely to be well documented in a standardised manner across the literature. We will collect nutritional and other preoperative assessments where possible, but there may not be sufficient data to adjust for these variables.

We hope to equip surgeons undertaking STCSTs with the relevant data to offer appropriate treatment to their patients in order to achieve the best possible outcomes. In addition, this will ensure patients are able to give informed consent with an understanding of the risks specific to their situation. These impacts will improve patient safety, reconstructive outcomes and follow-up.

Finally, with appropriately strict governance surrounding distribution of funds designed to provide healthcare in low- and middle-income countries, it is essential that actors in this field are able to provide evidence supporting their work. Through identifying the nature and severity of complications, we hope to inform surgeons and funders of the challenges and barriers to free tissue transfer in LMICs. This should encourage investment in areas that are most likely to improve patient outcomes. This study will assist those funding global surgery to allocate resources to appropriate interventions with proven patient benefit.