Prosthetic reconstruction of the trachea: A historical perspective.

This review discusses the history of tracheal reconstruction; from early work to future challenges. The focus is primarily on prosthetic tracheal reconstruction in the form of intraluminal stents, patch repairs, circumferential repairs and replacement of the trachea. A historical perspective of materials used such as foreign materials, autografts, allografts, xenografts and techniques, along with their advantages and disadvantages, is provided.

Core tip: Reconstruction of tracheal defects has historically been difficult, predominantly due to the lack of an intrinsic blood supply. Direct anastomosis is generally considered to be the best option. For larger defects, stenting and prosthetic reconstruction remain the primary methodologies. In light of the recent scandal surrounding tracheal replacement, this article aims to give a historical review of tracheal reconstruction methods.

INTRODUCTION

Tracheal reconstruction has been widely researched over the last 50 years. There are numerous indications for tracheal reconstruction, most frequently post-intubation injuries, idiopathic stenosis, neoplasia and re-stenosis following surgery[1].

Following tracheal resection, primary reconstruction with direct anastomosis of the patient’s own tracheobronchial tissue is generally accepted as the best option[2-7]. Anatomical studies suggest that up to half of the trachea can be resected in adults and directly anastomosed, without undue tension, by implementing mobilisation techniques such as suprahyoid release incisions and/or dissection of the hilum and pulmonary ligament[8]. This has been corroborated in large studies, with acceptable safety profiles and good long-term results, although the limits vary depending upon the patient’s age, body habitus, local anatomy, co-morbidities and previous treatments[1,9-12].

In patients with very extensive pathology, direct anastomosis following resection is not possible and as such, either stenting or replacement with a prosthesis remain the two principle options. This provides a sig–nificant subset of patients. For example, long-segment defects (greater than 50% of the trachea) constitute approximately half of tracheal stenosis cases, although more recently this has been innovatively and successfully managed via a slide tracheoplasty procedure[13,14]. A range of materials have been attempted and no ideal prosthesis has yet been developed. The ideal prosthesis is airtight, of adequate consistency to prevent collapse, well accepted by the host thus causing minimal inflammatory reaction, impervious to fibroblastic and bacterial invasion of the lumen and allows ingrowth of respiratory epithelium along the lumen[15,16].

In this review article we will provide a historical overview of tracheal reconstructive trends.

EARLY WORK

In the late 1890s and into the twentieth century, interest in tracheal reconstruction evolved[17-20]. Initially, as with many surgical specialities, a knowledge base was formed principally through isolated case reports. The focus at this time was autogenous replacements such as skin alone, or skin and fascial grafts[21,22]. Daniel et al[23] heralded the advent of a more scientific approach with experimental animal studies. Throughout this period there was a transition from autogenous materials to solid prostheses such as tantalum, polyethylene, acrylic and steel tubes[24-27]. No ideal prosthesis was found and outcomes were variable. Indeed, often composite approaches were taken, usually in the form of a solid prosthesis with fascia lata grafts. The level of evidence remained low.

1950s TO THE POROUS PROSTHESIS

Following this initial interest and in vivo work (Table 1), Gebauer was amongst the first to develop porous prostheses to counteract some of the drawbacks of solid prostheses[28,29]. It was found that a porous prosthesis more closely approximates the function of tracheal cartilages as compared to a solid prosthesis[30]. However complications including strictures, granulation formation, chronic infection, pressure necrosis from the prosthesis and dislodgement remained problematic. Erosion of the brachiocephalic artery was also not infrequent. The porous structure was calculated to permit ingrowth of host connective tissue thus incorporating the prosthesis into the tracheal site; it was found that a minimal porosity of 40 to 60 μm is necessary for capillary ingrowth[31]. There was a proliferation of literature and animal studies in this field during the 1950s and 1960s[32-36]. This culminated in a better understanding of an ideal prosthesis in that the graft should be airtight, have adequate consistency, be well accepted by the host, cause minimal inflammatory reaction, be impervious to fibroblastic and bacterial invasion into the lumen but ideally allow ingrowth of respiratory epithelium along the lumen[15,33,35]. The decision of material to trial was often dependent upon industrial and commercial advances and availability, ranging from steel wire, tantalum, marlex, PTFE, dacron and teflon[2,29-36]. Combinations of materials were often employed. Towards the end of this period, as a result, prosthetic reconstruction of the trachea was being performed in human patients[37,38]. The most promising outcomes were with Silicone prostheses. The Neville group pioneered this approach and developed the Neville prosthesis, a silicone based mould under high compression available as straight or bifurcated tubes[15,16]. In this series of 62 patients, outcomes were reported to be good and the use of silicone was explicated by its resilience, non-reactivity, smooth inner surface and ability to be readily moulded[15,39]. This, therefore, fulfilled all the criteria for an ideal graft except for ciliated epithelium traversing the inner surface. Suture line granulomas remained problematic and were treated endoscopically[15,16,37]. This connective tissue ingrowth initially serves to fix and integrate the porous prostheses but this continued proliferation leads to scar tissue, obstruction and stenosis alongside with resultant chronic infection[31].

Table 1

Tracheal reconstruction methodology over time

Year	First author	Category1	Material	Study type (number)
1898	Bruns[17]		Prosthesis unknown	Human
1911	Hohmeier[18]	Autogenous	Fascia lata	Animal
1912	Levit[19]	Autogenous	Fascia	Human (1)
1927	Fairchild[20]	Autogenous	Skin	Human (1)
1935	LeJeune[21]	Autogenous	Split thickness skin graft	Human (2)
1945	Crafoord[22]	Autogenous	Cutaneous and costal cartilage	Human (1)
1946	Belsey[24]	Solid prosthesis	Steel with fascia lata	Human (1)
1948	Clagett[25]	Solid prosthesis	Polyethylene	Human (1)
1948	Daniel[23]	Solid prosthesis	Fascia, Metal Tube	Animal
1948	Longmire[26]	Solid prosthesis	Acrylic tube	Human (1)
1949	Rob[27]	Solid prosthesis	Tantalum with fascia lata	Human (4)
1949	Kergin	Autogenous	Pericardium and bronchus	Human (1)
1950	Jarvis	Solid prosthesis	Stainless Steel	Human (1)
1950	Gebauer[29]	Porous prosthesis	Wire-enforced dermal graft	Human (11)
1951	Bucher[30]	Porous prosthesis	Stainless steel wire mesh	Animal
1952	Cotton[2]	Solid prosthesis	Stainless steel tube	Human (2)
1953	Edgerton	Solid prosthesis	Split grafts with foam rubber	Human (12)
1953	Pressman[32]	Autogenous	Decalcified bone	Animal
1955	Morfit	Solid prosthesis	Polyethylene	Animal
1962	Beall[35]	Solid prosthesis	Polyethylene	Animal
1964	Aletras	Solid prosthesis	Teflon frame with pericardium	Animal
1967	Graziano[33]	Porous prosthesis	Silicon with dacron	Animal
1968	Pearson[34]	Porous prosthesis	Marlex (Polyethylene)	Animal
1973	Monk	Autogenous	Dermal grafts	Human (6)
1973	Demos	Porous prosthesis	Silicone	Animal
1974	Montgomery[38]	Porous prosthesis	Silicone t tube	Human (94)
1974	Pearson	Porous prosthesis	Marlex (Polyethylene)	Human (6)
1976	Neville[37]	Porous prosthesis	Silicone	Human (26)
1977	Lindholm	Autogenous	Bone/periosteum/muscle	Human (2)
1982	Neville[15]	Porous prosthesis	Neville prosthesis (silicon with dacron rings)	Human (54)
1982	Westaby	Porous prosthesis	Bifurcated silicone stent	Human (1)
1985	Toomes[6]	Porous prosthesis	Neville prosthesis (silicon with dacron rings)	Human (9)
1986	Scherer[67]	Tissue engineering	Bioprosthesis	Animal
1989	Har-El	Autogenous	Alloplast implanted muscle flap	Animal
1990	Neville[39]	Porous prosthesis	Silicone tubes	Human (62)
1990	Cull	Porous prosthesis	PTFE	Animal
1990	Jorge	Porous prosthesis	PTFE	Animal
1990	Kato[66]	Autogenous	Oesophagus and Silicone T tube	Animal
1990	Letang[65]	Homograft	Jejunum and Silicone T tube	Animal
1990	Varela	Porous prosthesis	Stainless steel wire mesh	Human (5)
1992	East[64]	Autogenous	Composite fascia, septum	Human (1)
1994	Okumura[63]	Porous prosthesis	Collagen and Marlex mesh	Animal
1996	Sharpe	Porous prosthesis	Marlex and pericardium	Human (1)
1996	Elliott[62]	Homograft	Homograft	Human (5)
1997	Kiriyama[61]	Homograft	Oesophageal autograft	Animal
1997	Teramachi[60]	Porous prosthesis	Marlex with collagen	Animal
2000	Sekine[59]	Porous prosthesis	Marlex	Animal
2003	Pfitzmann[58]	Homograft	Oesophagus	Human (1)
2004	Kim[57]	Porous prosthesis	Skin and polypropylene mesh	Animal
2005	Martinod[56]	Homograft	Allogenic aorta	Animal
2005	Shi[55]	Porous prosthesis	Polyprophyelene mesh with polyurethane/collagen	Animal
2006	Jaillard[54]	Homograft	Allograft aorta	Animal
2008	Sato[53]	Porous prosthesis	Polyprophyelene mesh with collagen	Animal
2008	Macchiarini[79]	Homograft	Stem cell seeded homograft	Human
2009	Nakamura[51]	Porous prosthesis	Polyprophlene with additional collagen, stem cells	Animal
2010	Makris[50]	Homograft	Allograft aorta	Animal
2010	Sato[49]	Tissue engineering	Bioprosthesis	Animal
2010	Tsukada[74]	Tissue engineering	Bioprosthesis	Animal
2011	Yu[47]	Autogenous/prosthesis	Radial forearm flap with PTFE or polyethlene	Human (7)
2011	Jungebluth[48]	Tissue engineering	Stem cell bioartificial scaffold	Human (1)
2012	Elliott[46]	Tissue engineering	Stem cell bioartificial scaffold	Human (1)
2012	Gray[45]	Tissue engineering	Stem cell bioartificial scaffold	Animal
2012	Tani	Tissue engineering	Collagen scaffold with FGF	Animal
2012	Wurtz[77]	Homograft	Allograft aorta with fascial graft and external cartilage	Animal
2014	Chang[40]	Tissue engineering	Stem cell bioartificial (3D Printed) scaffold	Animal
2016	Delaere[78]	Allotransplant	Vascularised allograft	Human

A number of these are composite strategies. PTFE: Polytetrafluoroethylene; FGF: Fibroblast growth factor.

At this time, progress was also being made in surgical techniques, led by Grillo’s team in Boston. Anatomic studies indicated that up to half the trachea in adults can be resected and closed primarily with an end to end anastomosis[8]. The same group has validated this with resulting large case series with low morbidity and mortality[3,4,9-11,13,31]. Slide tracheoplasty and other mobilisation techniques including suprahyoid release incisions, dissection of the hilum and pulmonary ligament have all been successfully used to achieve primary closure. Undoubtedly this remains the gold standard management of tracheal resection. However, it is not always possible and is dependent upon the patient’s age, body habitus, local anatomy, extent of disease, co-morbidities and previous treatments such as radiotherapy[3,4,9-11,13,31].

These studies therefore established that primary repair remains the method of choice and should be employed wherever possible. In addition, it was concluded that an entirely satisfactory tracheal graft will never be available[31,35]. The silicone airway is at least as satisfactory as any prosthesis yet fashioned for tracheal replacement and any alternative must be wholly dependable with minimal morbidity and mortality[31]. This remains the case today.

1990s ONWARDS

Further avenues of research have evolved in the last few decades. This has focussed on homografts, various composite strategies (including further work on porous prostheses) and latterly, tissue engineering[1,5,9,10,12,14,40-67].

Scherer et al[67] were first to experiment with bioprostheses by transplanting tracheas from various animals as autografts, allografts and xenografts. Rejection seemed to be avoided[31,67]. This preceded a plethora of animal studies, particularly transplantation studies, and in the last few years, attempts to translate this to patients[40,41,43,44,49,50,54,56,61]. Recently, research has focused on tracheal stem cell regeneration. Despite initial positive results, the outcomes have been generally poor and as such should be used with caution[42]. Pedicled flaps may serve to implant and maintain the stem cell generated trachea prior to reconstruction[41]. A recent pilot study has used three-dimensional printing of an artificial tracheal graft[40]. In addition, there has been some focus on the use of intestinal (either jejunal or oesophageal) tubes to replace the trachea[66]. This autogenous tissue reconstruction can be categorised into free grafts with and without foreign material support (e.g., the composite wire and fascia or dermal grafts); vascularised tissue flaps (e.g., pedicled intercostal muscle) and autogenous tube construction (e.g., oesophagus)[31]. Autologous tracheal replacement using radial forearm fasciocutaneous free flap has also demonstrated positive outcomes[68].

Further homografts include pericardium and aorta[50,54,56]. Patch repair of the trachea using pericardial allografts[69] and xenografts[70] have been shown to have good outcomes[71]. More recently, aortic homografts used as a bioprosthetic device for patch repair have also shown favourable results[72,73]. Circumferential replacement of the trachea using aortic allografts has shown poorer results, in both animal[74] and human[75] models. Wurtz demonstrated that silicone-stented aortic allografts have no cartilage regeneration, probably due to ischaemia prior to neoangiogenesis[76]. This led to proposals of a composite, fascial flap-wrapped allogeneic aortic graft with external cartilage ring support[77]. Again, no reconstruction has been as successful as direct anastomosis, or even silicone prostheses alone.

CONTROVERSIES AND FUTURE DEVELOPMENTS

The intriguing yet unsolved surgical dilemma of tracheal replacement remains a challenge to clinicians. Currently, work from the Leuven group (Delaere et al[78]) have shown promising results with the judicious use of allotransplants. Surgical ingenuity will lead to novel approaches to these problems[3]. However, it is important to note that these techniques should not create more problems than they solve and patients are to be treated as an individual with a duty of care attached to that. As a corollary to this, it is worth highlighting that where a series of animal experiments are successful, application of these procedures to humans almost inevitably presents greater issues and a higher failure rate[3]. Work on tracheal regeneration using stem-cell implanted scaffolds[44,48,79], which has been the centre of recent controversy, showed questionable data and ultimately poor results.

CONCLUSION

Direct revascularisation of the trachea is unsuitable due to its lack of an intrinsic blood supply. Its anatomical features (proximity to major vessels, segmental blood supply) and the presence of a variety of different tissue types (respiratory epithelium, cartilage, blood vessels) make reconstruction difficult. Recent attempts with tissue-engineered transplants have all failed due to this reason[80]. Tracheal reconstruction is optimal when primary anastomosis is possible with undue tension. Patients requiring reconstruction should be managed in a multidisciplinary team at a high volume tertiary referral centre to optimise treatment. Tracheal replacement can be divided into prosthesis, homograft and autogenous tissue reconstruction, or a combinatorial methodology. None have proven ideal conduits as tracheal replacements. The most convincing evidence has historically been silicone based prostheses, and more recently revascularised tracheal homografts and allotransplants. Stenting of the trachea has shown poor results. In emergent situations, endobronchial debulking and laser is preferable over stenting as this may prevent primary surgery.