Skip to main content
NCBI home page
Annals of The Royal College of Surgeons of England logoLink to Annals of The Royal College of Surgeons of England
. 2007 Jan;89(1):6. doi: 10.1308/003588407X160792

Degenerative Disc Disease: Disc Replacement

Tom Dehn
PMCID: PMC1963555  PMID: 17316511

Disc replacement is an exciting and relatively new technique in the treatment of patients with discogenic back pain. Its advantages include a less destructive approach than posterior surgery, with the potential to maintain motion and protect the adjacent levels of the spine, by preventing a stress riser at the interface of the fusion.

Spinal fusion on the other hand is the gold standard by which new treatments must be measured. Spinal fusion has been used for more than 50 years and the long-term results are well understood and are generally reliable.

While disc replacement offers many potential advantages, it has not been shown to be superior to spinal fusion in randomised, controlled trials, although the postoperative recovery is certainly more rapid. The majority of the patients in this group are relatively young, certainly less than 60 years old, with many years to live. We have little idea about the long-term results of disc replacement and the possible complications which might occur in the future. We do know that revision surgery after disc replacement can be hazardous.

Surgeons and the public are inevitably enthusiastic about new developments, which have potential advantages, but caution needs to be exercised until long-term results of well-controlled trials are available.

James Wilson-MacDonald

Nuffield Orthopaedic Centre Headington, Oxford OX14 4LZ, UK; E: wil.mac@virgin.net

Ann R Coll Surg Engl. 2007 Jan;89(1):6–9. doi: 10.1308/003588406X114848

The Case for Disc Replacement

Nick Boeree 1

The lumbar disc is a complex and beautifully adapted structure that must meet several conflicting requirements. The spine is flexible and the disc must allow movement while at the same time promoting stability and maintaining normal alignment. It must absorb excessive stresses and loads while distributing and transmitting forces through the trunk. Over time, these repetitive mechanical stresses and the ageing process lead to a slow biochemical degradation of the disc. This is a natural process, occurring gradually in most people and usually goes largely unnoticed. However, for some, the process can result in pain and occasionally, neurological compromise. Most of these individuals can be treated successfully without recourse to surgery. For a few, however, their symptoms of back pain remain very intrusive and impose unacceptable functional restrictions. The spinal surgeon is then looked to for a response.

Traditionally, that response has been to fuse the affected part of the spine. Fusion has become, de facto, the gold standard in the surgical treatment of degenerative disease in the lumbar spine, although it is debatable whether it deserves such a lofty status.

Spinal fusion emerged early in the last century as a means of dealing with spinal infection, later being extended to fractures and tumours, and then to cases of spinal deformity. The intention was to restore segmental stability and spinal alignment. Spinal fusion for degenerative disease is a relatively recent extension of the indications for this technique. Nonetheless, it is one which became established by default, in the absence of any viable alternative. However, one might argue that if NICE approval for this procedure were sought now, this would be unlikely to be forthcoming.

Spinal fusion is an expensive procedure entailing a long hospital stay. It has a significant rate of complications and considerable morbidity. Recuperation is lengthy and slow, and return to work considerably delayed. The posterior approach to the spine inevitably causes damage to the paravertebral muscles which are so important in subsequent functional recovery. Harvesting autogenous bone from the pelvis, for which there is no satisfactory substitute, can cause chronic donor site pain. Failure of fusion remains a problem even with the use of sophisticated instrumentation.1 The use of screws and cages has appreciable neurological and vascular risks. The reported incidence of these complications varies, but a meta-analysis of 47 publications found a 9% risk of significant donor site pain and a pseudarthrosis rate of 14%.2

A particular concern with rigid fusion is the transfer of stress to adjacent segments. This may cause symptomatic degenerative disease in the long term, which can progress to a severity requiring further surgery in up to 20% of patients.3,4 and perhaps even 37%,5 within a decade following ‘successful’ lumbar fusion. This risk may lead to the exclusion of many very deserving patients from consideration for surgery if the adjacent segments show any existing sign of degeneration, even if this is asymptomatic. Success with spinal fusion certainly relies on robust and stringent patient selection, but for these patients this is effectively an admission of failure.

Given the risks, morbidity and limited application of spinal fusion it is not surprising that spinal surgeons have looked over the shoulders of their colleagues undertaking successful hip and knee arthroplasty, and sought to emulate this success through more physiologically sound procedures. Various nonrigid stabilisation techniques and arthroplasty solutions have been developed, of which disc replacement is among the most important.

Surgical technique

Accurate central placement of the prosthesis is a critical determinant of outcome6 and requires midline anterior access to the appropriate level. This can be achieved through a 5–7 cm transverse incision, splitting the rectus muscles. Finger dissection around the retroperitoneal space quickly gains access to the appropriate level of the spine. The pre-sacral nerves come forwards with the peritoneum minimising the risk of retrograde ejaculation. The common iliac vessels can be retracted to give wide exposure of the lumbo-sacral disc. The L4/L5 disc is at or above the level at which the great vessels bifurcate and these must, therefore, be mobilised over to the right, after first ligating and dividing the ilio-lumbar vein.

The disc is excised, clearing particularly the posterior annulus to facilitate mobility of the artificial disc. The cartilaginous endplates are scraped clean, although preserving the bony endplates upon which the prosthesis will rest. Sizing of the prosthesis is established with trials and the prosthesis is then accurately positioned using radiographic guidance (Figs 1 and 2). Immediate fixation is achieved through teeth or a keel on the prosthetic endplates, and may be enhanced subsequently by bony in-growth into a porous coating.

Figure 1.

Figure 1

Open in a new tab

Charité artificial disc for degenerative disease L4/5, above a sacralised L5 vertebra. Flexion and extension radiographs show 9° of movement. Good positioning (central and posterior in the disc space) is vital for a good long-term prognosis.

Figure 2.

Figure 2

Open in a new tab

Charité artificial disc. The sliding central core is contained between the two concave endplates but closely reproduces normal physiological movement.

Following surgery, patients can be mobilised quickly and are remarkably comfortable from the outset. Physiotherapy helps to enhance muscle stability but no brace is required. The patient can go home after 3–4 days on light activities and generally returns to work within 3–4 weeks. Fitness training in a gymnasium is allowed from 6 weeks and patients can return to sports within 2–3 months.

Benefits for the patient

Several advantages of disc replacement are self-evident. No bone graft is taken so there is no risk of donor site pain. Similarly, none of the problems associated with failure of fusion will occur. These problems may require revision surgery, often with poor results.

Patients undergoing disc replacement improve substantially faster following surgery.7,8 This is perhaps because there is virtually no muscle trauma and indeed there is none of the other ‘collateral damage’ seen in spinal fusion. Their hospital stay is shorter and patients need little in the way of social and functional support following surgery. This is in stark contrast to the course after spinal fusion, and comes as quite a surprise to patients (and their GPs) who have often been ‘warned’ what to expect with spinal surgery. In terms of symptoms, it takes 6–12 months for fusion patients to achieve the same improvement seen by 6 weeks in those undergoing disc replacement.7,8 A similar pattern is seen in functional outcome. The importance of this very significant ‘head start’ should not be underestimated. Many of these patients have suffered for years from disabling back pain, often having tried, and failed, many forms of treatment. This rapid and dramatic improvement instils a belief and confidence that allows them to get their lives back on track.

Any exciting new procedure inevitably raises expectations of dramatically improved results. However, a well-performed spinal fusion can achieve a satisfactory medium-term clinical outcome in a good proportion of carefully selected patients. It is, therefore, perhaps unrealistic to expect a dramatic difference between the two techniques, at least in the first few years, once the early gains from the less damaging surgery of disc replacement are passed. Both procedures deal effectively with the patient's principal pain source. The movement allowed by disc replacement may confer some clinical benefit. Similarly, the long-term effects of ‘collateral damage’ may continue to mar the results from spinal fusion, and problems resulting from a failure of fusion may reduce the results for this group a little further. As such, the outcome measures from the various clinical trials at 2 years have shown either a moderate but significant benefit with total disc replacement,7 or comparable results8 with the two techniques. Even so, patient satisfaction is considerably greater: 92% of disc replacement patients indicated that they would definitely undergo the same procedure again. Only 55% of fusion patients felt the same.8

One of the principal potential advantages of disc replacement, the avoidance of adjacent level problems, must await longer term comparative studies. Several such studies have been commenced, comparing disc replacement with fusion in various guises. It may take over a decade for junctional changes to evolve following fusion and thus for this advantage of motion preservation to become apparent. Needless to say, a definitive answer to this question is keenly awaited.

Eliminating stress transfer to adjacent levels may also broaden the possible indications for intervention. Many patients who previously were denied surgery because of mild changes at other levels of the lumbar spine may now be candidates, while others, who might previously have been offered a multilevel spinal fusion, could benefit from less extensive motion preserving techniques.

Long-term studies are clearly of great importance in disc replacement, as with any new technique. Results at up to 17 years from early procedures in one study were not encouraging9 but much has been learned over the past few years,6,10 and other studies have shown sustained clinical benefits (75–90% good or excellent), continued movement and an absence of some of the feared complications such as wear or subsidence.11,12 Certainly, there are several issues to be resolved and it is fair to say that spinal surgeons as a group are still climbing the learning curve of this technique. Experience will help to refine clinical indications, identify key points of technique and lead to further improvements in prosthetic design. As disc replacement evolves and matures, further improvements in clinical outcomes can be expected. The era of motion preservation in spine surgery has arrived and the future of disc replacement looks exciting and promising.

References

  • 1.Kornblum MB, Fishgrund JS, Herkowitz HN, Abraham DA, Berkower DL, Ditkoff JS. Degenerative lumbar spondylolisthesis with spinal stenosis: a prospective long-term study comparing fusion and pseudarthrosis. Spine. 2004;29:726–33. doi: 10.1097/01.brs.0000119398.22620.92. (discussion 33–4) [DOI] [PubMed] [Google Scholar]
  • 2.Turner JA, Ersek M, Herron L, Haselkorn J, Kent D, Ciol MA, et al. Patient outcomes after lumbar spinal fusions. JAMA. 1992;268:907–11. [PubMed] [Google Scholar]
  • 3.Gillet P. The fate of the adjacent motion segments after lumbar fusion. J Spinal Disord Tech. 2003;16:338–45. doi: 10.1097/00024720-200308000-00005. [DOI] [PubMed] [Google Scholar]
  • 4.Etebar S, Cahill DW. Risk factors for adjacent segment failure following lumbar fixation with rigid instrumentation for degenerative instability. J Neurosurg. 1999;90:163–9. doi: 10.3171/spi.1999.90.2.0163. [DOI] [PubMed] [Google Scholar]
  • 5.Ghiselli G, Wang JC, Bhatia NN, Wellington KH, Dawson EG. Adjacent segment degeneration in the lumbar spine. J Bone Joint Surg Am. 2004;86:1497–503. doi: 10.2106/00004623-200407000-00020. [DOI] [PubMed] [Google Scholar]
  • 6.McAfee PC, Cunningham B, Holsapple G, Adams K, Blumenthal S, Guyer RD, et al. A prospective, randomized multicenter Food and Drug Administration Investigational Device Exemptions study of lumbar total disc replacement with the Charité artificial disc versus lumbar fusion. Part II: Evaluation of radiographic outcomes and correlation of surgical technical accuracy with clinical outcomes. Spine. 2005;30:1576–83. doi: 10.1097/01.brs.0000170561.25636.1c. [DOI] [PubMed] [Google Scholar]
  • 7.Blumenthal S, McAfee PC, Guyer RD, Hochschuler SH, Geisler FH, Holt RT, et al. A prospective, randomized multicenter Food and Drug Administration Investigational Device Exemptions study of lumbar total disc replacement with the Charité artificial disc versus lumbar fusion. Part I: Evaluation of clinical outcomes. Spine. 2005;30:1565–75. doi: 10.1097/01.brs.0000170587.32676.0e. [DOI] [PubMed] [Google Scholar]
  • 8.Delemarter RB, Bae HW, Pradhan BB. Clinical results of ProDisc-II lumbar total disc replacement: report from the United States clinical trial. Orthop Clin North Am. 2005;36:301–13. doi: 10.1016/j.ocl.2005.03.004. [DOI] [PubMed] [Google Scholar]
  • 9.Putzier M, Funk JF, Schneider SV, Gross C, Tohtz SW, Khodadadyan-Klostermann C, et al. Charité total disc replacement – clinical and radiographic results after an average follow-up of 17 years. Eur Spine J. 2006;15:183–95. doi: 10.1007/s00586-005-1022-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Huang RC, Girardi FP, Cammisa FP, Lim MR, Tropiano P, Marnay T. Correlation between range of motion and outcome after lumbar total disc replacement: 8.6 year follow-up. Spine. 2005;30:1407–11. doi: 10.1097/01.brs.0000166528.67425.0e. [DOI] [PubMed] [Google Scholar]
  • 11.Lemaire JP, Carrier H, Sari Ali el-H, Skalli W, Lavaste F. Clinical and radiological outcomes with the Charité artificial disc: a 10-year minimum follow-up. J Spinal Disord Tech. 2005;18:353–9. doi: 10.1097/01.bsd.0000172361.07479.6b. [DOI] [PubMed] [Google Scholar]
  • 12.Tropiano P, Huang RC, Girardi FP, Cammisa FP, Marnay MD. Lumbar total disc replacement; 7 to 11 year follow-up. J Bone Joint Surg Am. 2005;87:490–6. doi: 10.2106/JBJS.C.01345. [DOI] [PubMed] [Google Scholar]
Ann R Coll Surg Engl. 2007 Jan;89(1):9–11. doi: 10.1308/003588406X114848

The Case Against Disc Replacement

SN Khan 1, AJ Stirling 1

Disc arthroplasty can be used to treat patients with lower back pain where internal disc derangement, typically at L4/5 or L5/S1, is perceived as the pain source.

Currently, over 100 prostheses have been designed, with the Charité III disc and the ProDisc the most frequently used in Europe. Both are implanted through an anterior approach and comprise low friction sliding surfaces, consisting of metal end plates with a polyethylene spacer. A ‘press fit’ mechanism secures the prosthesis, with supplementary primary fixation provided by teeth or fins on the endplates which grip the adjacent vertebral surfaces.

As the number of artificial disc procedures performed in the UK quickly grows, proponents describe a revolutionary treatment that relieves pain, preserves motion at the operated level and protects against degeneration at adjacent levels. The wave of publicity in the mass media has been overwhelmingly favourable, with the experience of individual patients giving the impression that all patients will achieve similar results.

Such fashionable treatment has been rapidly adopted; nevertheless, significant concerns remain. Despite having been implanted for almost 20 years, there remains a lack of adequate clinical information. Although early results appear encouraging, to date these represent protected series from the originators of the devices. The second wave of results may identify failures and complications associated with the inevitable learning curve. Potential problems that may become apparent with long-term follow-up have yet to be addressed.

Patient selection

Patient selection is fundamental to a successful outcome. However, there is considerable doubt over our ability to select appropriate patients with an unambiguous pain source who are suitable for arthroplasty surgery. Our ability to diagnose spinal pathology continues to lag behind the progression of treatment options.

All studies report inconsistent results both from fusion and arthroplasty surgery for discogenic lower back pain. Whilst some patients report complete symptom resolution, the majority experience only partial pain relief. This variation is likely to be due to failures in patient selection.

Carragee et al.1 assessed the outcome of fusion spinal surgery in patients with single level discogenic pain as confirmed by a stringent discography protocol and compared the results with a ‘gold standard’ – fusion for patients with single level unstable spondylolisthesis. He concluded that even in what should represent the ‘ideal patient’, discography failed to identify a single segment pain generator in about 50% of patients.

Until we are better able to identify symptomatic discs, neither fusion nor disc replacement will consistently relieve symptoms; advances in technology may not result in better outcomes.

Comparison with alternative surgical options

Arthrodesis is held up as the ‘gold standard’ against which disc replacement is judged. However, two recent studies found no advantage of spinal fusion over state of the art non-operative treatment programmes involving aggressive exercise and cognitive therapy.2,3 Furthermore, the superiority of spinal fusion over physical therapy seen at 2 years in the Swedish Spine Study, disappeared at long-term follow-up.4 Thus, lumbar fusion would seem an inadequate ‘gold standard’ against which to compare disc replacement.

In their review of the literature, de Kleuver et al.5 concluded that although early results (0–68 months) appear comparable to results of arthrodesis, ‘the studies are of such limited quality that it is hard to justify such a comparison’.

The perceived disadvantages of arthrodesis are loss of motion and consequent adjacent segment degeneration. However, even the touted dual benefits of disc replacement surgery, namely preserved motion and reduction of adjacent level disease, are not supported by the literature. Although the operated segment does appear to move with a reported average range of movement of 5–12°, in many instances movement of the operated segment is lost, with several studies reporting complete loss of motion at the operated level (in one series 26%6) due either to spontaneous fusion or surgical revision.

There is not a single, rigorous, scientific study demonstrating that artificial discs reduce degeneration at adjacent levels. Adjacent segment degeneration may represent the natural history of the underlying disc disease and motion preserving surgery would, therefore, not reduce its incidence. Follow-up is simply too short. Indeed, in one series, re-operation at the adjacent segment was performed in 11 of 50 patients (22%) within 2 years.7

Comparison with conservative treatments

There is no evidence available from clinical trials that disc replacement leads to better outcome than non-operative care. A recent trial from France8 concluded that total disc replacement is more effective than rehabilitation in the treatment of very specific cases of low back pain. However, patients randomised to rehabilitation were given the option of converting to disc replacement surgery if their symptoms failed to improve significantly. Half opted for surgery at 6 months.

With both Fairbank et al.2 and Brox et al.3 finding similar outcomes between fusion and structured rehabilitation and the FDA trial reporting similar outcomes between fusion and total disc replacement, does it follow that disc replacement offers little beyond an aggressive rehabilitation regimen?

Complications

Complication rates are a concern, both of the artificial discs and the anterior spinal approach required to implant them. Early results from the originators of the devices suggest a low complication rate, but as other surgeons embark on their learning curves, complications are inevitable. In a recent review, Polly9 wrote: ‘there will be deaths from the procedure, due to thromboembolic phenomenon or due to uncontrolled haemorrhage from irreparable vascular injury… there will be prostheses that dislodge. There will be infections that require disc removal.’ Complication rates are variably reported. Of 411 patients gathered from a review of the literature,5 there were eight vascular injuries (six venous, two arterial) and six thrombotic complications, but no infections.

Disc replacement has been associated with heterotopic ossification, rendering the operated segment immobile. The prospective RCT of the Charité III disc reports a 6% incidence at 2 years.10

Subsidence of the prosthesis, similar to that seen with fusion cages, has been reported but has not yet been systematically reviewed. It can occur as a result of undersizing, intraoperative endplate violation or asymmetric implantation and may cause eccentric facet load, degeneration and back pain.

The Swedish fusion study4 emphasises the importance of long-term follow-up in patients undergoing back pain surgery. Such data for disc replacement surgery do not yet exist. Potential long-term complications of an artificial joint as experienced in total hip and knee arthroplasty cannot, therefore, be discounted. Polyethylene wear, a well-recognised mechanism of failure with hip arthrodesis, has not been accurately measured. The potential effect of granuloma formation around major blood vessels and neural structures remains unknown. This may preclude later implant removal. Similarly, radiological and clinical loosening has not yet been addressed. It has not been demonstrated that in-growth of these devices and true fixation to the vertebral endplate actually occurs.

Experience with anterior fusion surgery highlights the risk of retrograde ejaculation, reported in up to 5.9% of patients undergoing anterior interbody lumbar fusion (ALIF) procedure, increasing to 22% of patients with the transabdominal approach.11 An equivalent incidence following disc replacement surgery can be expected, especially as a greater exposure is often required.

In cases of failure, salvage procedures remain a concern. Whilst successful use of posterolateral fusion has been reported, implant removal may be required in cases such as dislocation, infection or polyethylene wear, but may be difficult due to fibrosis of the vena cava adjacent to the vertebral body. Supplementary fixation aids, such as fins and teeth, may further hinder removal to the extent that partial corpectomy may be required.

Conclusions

Despite nearly 20 years' experience of these devices, there is still no evidence that disc arthroplasty reliably and reproducibly meets the three primary aims of clinical efficacy, continued motion and fewer adjacent segment problems.

Boden et al.12 suggested eight criteria required to establish the efficacy and safety of disc replacement surgery:

  1. Long-term (greater than 10 years) follow-up demonstrating clinical outcomes equivalent or better than fusion.

  2. Motion preservation at the operated level.

  3. Reduced adjacent segment disease.

  4. Cost effectiveness.

  5. Predictable, safe implantation.

  6. Manageable wear-related problems.

  7. Safe and effective salvage procedures.

  8. Misuse of the devices can be adequately controlled.

There remains a lack of solid scientific evidence to support this major shift toward disc replacement. At best, disc replacement presently represents an unpredictable treatment for a condition that cannot yet be diagnosed with any precision. Until the criteria listed above are met, arthroplasty should be performed only as part of strictly controlled studies on adequately consented patients.

References

  • 1.Carragee E, Alamin T, Carragee J, Van der Haak E. Clinical outcomes after solid ALIF for presumed lumbar ‘discogenic’ pain in highly selected patients: an indirect indication of diagnostic failure. Annual meeting of the International Society for the Study of the Lumbar Spine; Porto: Portugal. 2004. [Google Scholar]
  • 2.Fairbank J, Frost H, Wilson-MacDonald J, Yu L-M, Barker K, Collins R. Randomised controlled trial to compare surgical stabilisation of the lumbar spine with an intensive rehabilitation programme for patients with chronic low back pain: the MRC spine stabilisation trial. BMJ. 2005;330:1233. doi: 10.1136/bmj.38441.620417.8F. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Brox JI, Sorensen R, Friis A, Nygaard O, Indahl AK, Ingebrigsten T, et al. Randomised clinical trial of lumbar instrumented fusion and cognitive intervention and exercises in patients with chronic low back pain and disc degeneration. Spine. 2003;28:1913–21. doi: 10.1097/01.BRS.0000083234.62751.7A. [DOI] [PubMed] [Google Scholar]
  • 4.Fritzell P, Hagg O, Wessberg P, Nordwall A. Swedish Lumbar Spine Study Group. Lumbar fusion versus non-surgical treatment for chronic low back pain: a multicentre randomized controlled trial from the Swedish Lumbar Spine Study Group. Spine. 2001;26:2521–32. doi: 10.1097/00007632-200112010-00002. [DOI] [PubMed] [Google Scholar]
  • 5.de Kleuver M, Oner FC, Jacobs W. Total disc replacement for chronic low back pain: background and a systematic review of the literature. Eur Spine J. 2003;12:108–16. doi: 10.1007/s00586-002-0500-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Cinotti G, David T, Postacchini F. Results of disc replacement prosthesis after a minimum follow up period of 2 years. Spine. 1996;21:995–1000. doi: 10.1097/00007632-199604150-00015. [DOI] [PubMed] [Google Scholar]
  • 7.Zeegers WS, Bohnen LM, Laaper M, Verhaegen MJA. Artificial disc replacement with the modular type SB Charité III: 2-year results in 50 prospectively studied patients. Eur Spine J. 1999;8:210–7. doi: 10.1007/s005860050160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Ilharreborde B. Efficiency of total disc replacement arthroplasty in the treatment of chronic low back pain. Annual meeting of the International Society for the Study of the Lumber Spine; New York: USA. 2005. [Google Scholar]
  • 9.Polly DW., Jr Adapting innovative motion-preserving technology to spinal surgical practice: What should we expect to happen? Spine. 2003;28(Suppl):S104–9. doi: 10.1097/01.BRS.0000092208.09020.16. [DOI] [PubMed] [Google Scholar]
  • 10.Guyer RD, McAfee PC, Hochschuler S, Blumenthal S, Fedder I, Ohnmeiss D, Cunningham B. Prospective randomized study of the Charité artificial disc: data from two investigational centers. Spine J. 2004;4(Suppl):252S–259S. doi: 10.1016/j.spinee.2004.07.019. [DOI] [PubMed] [Google Scholar]
  • 11.Tiusanen H, Seitsalo S, Österman K, Soini J. Retrograde ejaculation after anterior interbody lumbar fusion. Eur Spine J. 1995;4:339–42. doi: 10.1007/BF00300293. [DOI] [PubMed] [Google Scholar]
  • 12.Boden S, Balderston D, Heller RA, Hanley JG. An AOA critical issue. Disc replacements: this time will we really cure low back and neck pain? J Bone Joint Surg Am. 2004;86:411–22. [PubMed] [Google Scholar]

Articles from Annals of The Royal College of Surgeons of England are provided here courtesy of The Royal College of Surgeons of England

RESOURCES