Next Article in Journal
Evaluating the Perceived Health-Related Effectiveness of ‘The Daily Mile’ Initiative in Irish Primary Schools
Next Article in Special Issue
Early Management for Fracture-Related Infection: A Literature Review
Previous Article in Journal
The Development and Content Validation of a Clinical Screening Scale to Identify Attention-Deficit Hyperactivity Disorder Cases Based on the Gender Perspective: An e-Delphi Study
Previous Article in Special Issue
Risk of Periprosthetic Joint Infection after Intra-Articular Injection: Any Difference among Shoulder, Knee and Hip?
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Healthcare
Volume 12
Issue 13
10.3390/healthcare12131283
healthcare-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Systematic Review

Characteristics and Epidemiology of Megaprostheses Infections: A Systematic Review

by
Luigi Cianni
1,2,
Francesco Taccari
3,
Maria Beatrice Bocchi
1,2,*,
Giulia Micheli
2,3,
Flavio Sangiorgi
2,3,
Antonio Ziranu
2,4,
Massimo Fantoni
2,3,
Giulio Maccauro
1,2 and
Raffaele Vitiello
1,2
1
Dipartimento di Scienze dell’invecchiamento, Ortopediche e Reumatologiche, Unità Operativa Complessa di Ortopedia e Traumatologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
2
Dipartimento di Sicurezza e Bioetica—Sezione di Malattie Infettive, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
3
Dipartimento di Scienze Mediche e Chirurgiche, Unità Operativa Complessa di Malattie infettive, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
4
Ospedale Isola Tiberina-Gemelli Isola, 00186 Rome, Italy
*
Author to whom correspondence should be addressed.
Healthcare 2024, 12(13), 1283; https://doi.org/10.3390/healthcare12131283
Submission received: 12 April 2024 / Revised: 18 May 2024 / Accepted: 18 June 2024 / Published: 27 June 2024
(This article belongs to the Special Issue Orthopedic Implant-Associated Infections: Unlocking the Secrets of Prevention and Treatment)
Browse Figure
Versions Notes

Abstract

:
Background: Megaprostheses were first employed in oncological orthopedic surgery, but more recently, additional applications have arisen. These implants are not without any risks and device failure is quite frequent. The most feared complication is undoubtedly the implants’ infection; however, the exact incidence is still unknown. This systematic review aims to estimate in the current literature the overall incidence of megaprosthesis infections and to investigate possible risk/protective factors. Methods: We conducted a systematic search for studies published from July 1971 to December 2023 using specific keywords. To be included, studies needed to report either the megaprosthesis anatomical site, and/or whether the megaprosthesis was coated, and/or the surgical indication as oncological or non-oncological reasons. Results: The initial literature search resulted in 1281 studies. We evaluated 10,456 patients and the overall infection rate was 12%. In cancer patients, the infection rate was 22%, while in non-oncological patients, this was 16% (trauma 12%, mechanical failure 17%, prosthetic joint infections 26%). The overall infection rates comparing coated and uncoated implants were 10% and 12.5%, respectively. Conclusions: The number of megaprosthesis implants is increasing considerably. In traumatological patients, the infection rate is lower compared to all the other subgroups, while the infection rate remains higher in the cancer patient group. As these devices become more common, focused studies exploring epidemiological data, clinical outcomes, and long-term complications are needed to address the uncertainties in prevention and management.

1. Introduction

Massive long bone defects pose significant challenges for reconstruction in the orthopedic field. Various techniques and strategies have been adopted to treat these bone defects, such as autograft and allogeneic bone grafting, bone transport, and the use of standard prostheses and megaprostheses (MP) [1]. Megaprostheses, also referred to as tumor endoprostheses, are systems that allow special segmental bone and joint replacement, which were initially developed for lower limb and then upper limb salvage. First employed in oncological orthopedic surgery in the 1960s [2], megaprostheses, along with the advent of adjuvant therapies, have dramatically changed the management of bone tumors, which previously condemned patients to limb amputation. Since the 1990s, megaprostheses have become the gold standard for reconstruction after the resection of primary malignant bone tumors. Occasionally, further oncological indications have come into place, such as reconstruction after the eradication of locally aggressive benign bone tumors, malignant soft tissue tumors, or bone metastasis [3,4]. More recently, additional applications have arisen for megaprostheses implants as a last resort for revision arthroplasty in selected cases, where extensive bone loss or poor bone quality jeopardizes the success of conventional joint arthroprosthesis, or for trauma/revision trauma surgery with severe soft tissue damage, severely comminuted fractures, or similar bone quality concerns [5,6]. As expected, however, the implant of a megaprostheses is not without any risks, and device failure is more frequent than in other primary joint arthroplasties [7,8]. Recently, Henderson et al. [9] proposed a classification system for megaprostheses failure. The latter can be divided into mechanical causes, such as soft tissue failure, aseptic loosening, and structural failure, and nonmechanical, such as infection and tumor progression. Mechanical challenges such as dislocation are quite common: the rate of hip dislocation after proximal femur replacement ranges from 6% to 42% [10,11]. Another major challenge lies in the recovery of good joint function, especially when the knee is involved. Scar tissue, joint problems from previous deformities or concomitant degeneration, and muscle loss with loss of contractile function are common in patients undergoing megaprostheses placement and have a deep impact in joint mobility recovery. Failure can also originate from the low quality of superficial soft tissue coverage, which can be compromised following trauma, septic conditions, or recurrent surgeries [12], or by adjuvant therapy in oncologic diseases, such as radiotherapy [13]. When the implant is placed for tumors, recurrence and progression are other possible causes of implant failure and reduced survival [9]. In addition, one of the most feared complications is megaprostheses infection, which is even more frequent than periprosthetic infections according to multiple studies. However, the exact incidence of periprosthetic infection in patients with megaprostheses is still unknown and may range from 3% [14] to higher than 30% [9,15]. Infections are facilitated by a longer surgery time and wider soft tissue dissection compared to other orthopedic procedures, along with a usually more immunocompromised host who may need multiple revision surgeries [16]. Although indications for the implantation of megaprostheses are increasing, this type of prostheses is still quite rare. Therefore, the exact epidemiology and incidence rate of megaprostheses infection are largely unknown due to a lack of literature. To date, it is also not yet known whether there are specific risk factors that may negatively influence the risk of infection for these implants. This systematic narrative review first and foremost aims to estimate in the current literature the overall incidence of megaprostheses infections. Furthermore, it aims to investigate possible risk/protective factors with respect to the onset of infections such as the impact of the anatomical location, the indications for placement, and the presence/absence of implant coating. Greater clarity in the matter could help to establish preventive measures and to give clues in terms of management and outcomes.

2. Materials and Methods

We conducted a comprehensive systematic search on four databases (PubMed, Embase, Scopus, and Web of Science) using the search keywords ((megaprostheses) OR (megaprosthesis) OR (resection arthroplasty) AND (infection)). No restrictions were applied to the publication dates. Therefore, the research included studies published from July 1971 until December 2023. The bibliographies of the selected studies were manually searched to identify additional papers not found through the ordinary search. The titles of the journal, authors’ names, and supporting institutions were known throughout the whole process. This systematic review was conducted according to the latest version of Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) [17], as reported in Figure 1. The 27-item PRISMA checklist of this systematic review can be found in the Supplementary Materials. This study was not registered in any protocol database; therefore, there is no registration number. Inclusion criteria were specified as follows: studies published in Italian, English, or French, describing the number of infected implants out of the total number of megaprostheses implanted. Moreover, studies had to report either the megaprostheses anatomical site (total femur, proximal tibia, distal femur, proximal femur, proximal humerus, custom megaprosthesis after hemipelvectomy, and other), and/or whether the megaprostheses were coated, and/or the surgical indication as oncological or non-oncological reasons. Exclusion criteria were established as follows: review articles (systematic or narrative), meta-analysis, letters, case reports, notes, conference papers, editorials, and conference abstracts; cadaveric and animal studies; full text not available; and finally, articles published in any language other than the previously stated ones. The primary outcome is to determine the overall incidence of infection per implanted megaprostheses. The secondary outcome is to establish the occurrence of megaprosthesis infection per implanted megaprostheses categorized by anatomy (total femur, proximal tibia, distal femur, proximal femur, proximal humerus, custom megaprostheses after hemipelvectomy), coating (presence or absence), and reason for implantation (oncological and non-oncological, with the latter further divided into trauma, periprosthetic joint infections (PJIs), and mechanical failure). Abstracts and full texts were independently screened by three authors (L.C., F.S., and G.M.), and any arising conflict was solved by consensus with a fourth author (F.T.). All the selected studies were retrospectively analyzed by two authors (M.B.B. and R.V.) who then extracted and entered the data in an Excel worksheet. The collected data included authors’ list, year of publication, and the number of infected prostheses out of the total number of megaprostheses implanted. In addition, the implanted and then infected megaprostheses were specifically studied according to the anatomical district involved, the presence or absence of coating of the megaprostheses, and indication for megaprostheses implantation. Lastly, the data sheet was reviewed by three authors (A.Z., M.F., and G.M.) who agreed and validated the extracted data.

3. Results

3.1. Search and Literature Selection

The initial literature search resulted in 1281 studies. After reviewing all the abstracts, the restricted research retrieved 959 studies. Once duplicates were removed and the articles were screened for inclusion and exclusion criteria, 138 studies remained, and full texts were assessed for eligibility (Figure 1). Finally, a total of 91 articles were included in this systematic review [15,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107].

3.2. Study Characteristics

We evaluated 10,456 patients who had undergone limb reconstruction with modular megaprosthesis. The infection rate was 12% (1277/10,456). Our results are summarized in Table 1.

3.3. The Initial Diagnosis

Most patients had an indication to implant a modular megaprosthesis after tumor resection (4283/10,456, 41%) including either primary tumors or metastatic disease. In cancer patients, the infection rate was 22% (941/4283). Among all patients who instead had a megaprosthesis implanted in a non-oncological setting, the infection rate was 16% (221/1377). More specifically, 652 modular megaprostheses were implanted for significant bone loss due to major trauma, failed osteosynthesis with a nonunion, or even periprosthetic fractures. The infection rate in this group of patients was 12% (76/652). Furthermore, 142 megaprostheses were implanted in the case of mechanical failure, and among them, 24 later became infected with an infection rate of 17%. Finally, 318 modular implants were used in periprosthetic joint infections (PJIs) and the re-infection rate was found to be 26% (84/318).

3.4. Anatomical Classification

Among all the modular megaprostheses included in the study, 7766 were implanted in the lower limbs and 265 in the upper limbs. The overall infection rates were 15% (1155/7766) and 10% (27/265), respectively. Among the lower limb implants, 139 were total femur replacements of which 39 became infected (28%), 5780 were either proximal tibia or distal femur replacements with 885 ending up being infected (15%), and finally, 1402 were proximal femur replacements with an infection rate of 13% (187/1402). Among the 142 megaprostheses of proximal humerus included, 13 became infected (9%). Hemipelvectomy and reconstruction with a custom megaprosthesis was performed in 21 patients and among them 8 became infected (38%).

3.5. Coated vs. Uncoated

Among the 10,456 modular megaprostheses implanted, 1407 were silver coated and 9049 were uncoated. The overall infection rates comparing the two groups were 10% (141/1407) and 12.5% (1135/9049), respectively.

4. Discussion

Megaprosthesis replacement was originally used for reconstructive treatment in limb salvage surgery following soft tissue and bone tumor resections [108]. To date, indications are becoming broader and megaprostheses are now used in the management of bone loss such as in severe trauma, periprosthetic fracture, and arthroplasty revision, or in the case of periprosthetic joint infection [109]. However, the patient selection in this type of surgery is crucial because a possible revision surgery could be technically challenging with a high clinical burden and low functional recovery, especially in the frail population [110,111]. Given its increasing frequency, orthopedic surgeons should be aware of the risk of infection of a megaprosthesis as this is a complication that can lead to adverse clinical and functional outcomes, and in some cases, even to the patient’s death [112].
As far as we know, no recent epidemiological reviews in the literature have fully addressed this problem. We recruited 91 articles for a total of 10,456 patients with different features of indications, anatomy, and coating. Among these, the overall megaprosthesis infection rate was 12%.
Our data showed different infection rates based on the different initial diagnosis.
Our study showed that there exists an important difference in terms of the infection rate between cancer patients (22%) and non-cancer patients (16%). The poor general clinical conditions of an oncological patient may explain such data. A recent review by Gonzalez MR et al. identified several modifiable and unmodifiable risk factors such as chemotherapy, radiation therapy, immunosuppression and sufficient soft tissue coverage, operative time, and length of stay, which have to be considered when a cancer patient has to undergo surgery [113]. Previous studies indicated an incidence of infections of approximately 8% in megaprostheses implanted for oncological reasons, far different from our data [9]. Certainly, the increased use of these prostheses even only in the oncological context together with the increased survival of these patients leads to an increase in complications and thus also infections. On the other hand, Vayhsa et al. instead recruited studies focusing on the implantation of lower limb megaprostheses in non-cancer patients finding an infection rate of 18.5%, comparable to our findings [114]. We can therefore conclude that cancer patients with megaprostheses have a higher risk of implant infections compared to non-oncological patients. Concerning more specifically the non-oncological group, the infection rate in patients with megaprostheses implanted for traumatological indication is 12%, which is higher than expected. Indeed, recent findings by Sambri et al. [109] showed instead an incidence of 8.2% that is explainable, however, by a difference in the sample. Considering mechanical failure as an indication for megaprosthesis implants, the infection incidence rate was 17%. Studies on the same indication in the lower limb described a similar rate (18%) [49,113], while few data exist concerning the upper limb, describing very few cases of infection [114,115]. In the subgroup with PJI as the lead indication for megaprosthesis implants, the infection rate was 26%; higher than the other two subgroups, as expected, although in line with the existing literature [20].
Furthermore, our data showed different infection rates based on the anatomical site.
Lower limb megaprostheses demonstrated an infection rate of 15% (1155/7766 patients), compared to 10% (27/265) in the upper limb. Similar values were found by Schmidt-Braekling et al. who showed a lower limb infection rate higher than 17% [116]. However, the data in the literature are not unique. Indeed, Windagher et al. reported a rate of infection in patients treated with a megaprosthesis after a distal femur periprosthetic fracture that ranged from 6.6% after 1 year to 45% after a mean follow-up of 34 months [117].
Going into further detail, we found a higher rate of infection in knee megaprostheses compared to hip megaprostheses. These data can be explained both by the greater number of knee megaprostheses implanted and also because the knee is a most insidious anatomical site, which often does not provide adequate soft tissue coverage [118].
Finally, considering the outcomes for coated or uncoated megaprostheses, we found a higher infection rate for uncoated megaprostheses. Unfortunately, to date there are no univocal results in the literature on this matter. Not all studies included specified whether the megaprostheses were coated or uncoated; however, we assumed that when unspecified, the implants were uncoated. A total of 9049 patients had uncoated megaprostheses implanted with an infection rate of 12.5% (1135/9049 patients). The infection rate appears to decrease for coated implants such that in this group the infection rate was 10% (141/1407 patients). Lex JR et al. performed a review on the different outcomes between coated or uncoated megaprostheses, investigating major anti-bacterial coatings currently in use, including 11 studies: only 2 studies demonstrated better outcomes in coated megaprostheses compared to uncoated ones [115]. Furthermore, Fiore M et al. did not find any statistically significant difference between the outcomes in coated megaprostheses compared to uncoated ones, concluding that coated megaprostheses should only be used in selected cases [119]. No clear conclusions could be drawn on the difference of outcomes between coated and uncoated; however, our findings seem to suggest a potential protective role of coated prostheses as already mentioned by other authors.
Our paper has several limitations. This is a systematic review that was not registered. Furthermore, the articles’ quality has not been assessed. Moreover, although it was possible to extrapolate the number of implanted megaprostheses and the rate of infections in all included works, unfortunately, it was not always possible, for instance, to trace the reasons why the prosthesis was implanted. Therefore, such detailed tables were purposely included. In addition, due to the wide heterogeneity of the articles included in this review, it was not possible to assess the follow-up and then relate all our data to it. This is mostly because too often the follow-up was not mentioned or, unfortunately, was not relatable to the individual groups.
The present literature review focuses on the significantly increasing number of megaprostheses implantations and, accordingly, the increasing number of implant failures due to infections. To the best of our knowledge, there is no review in the literature that includes more than 10,000 patients undergoing megaprosthesis replacement. However, the large number of works examined, and the wide variability in the examined data and outcomes do not allow us to draw clear conclusions. In the future, the opportunity to identify not only predisposing but also protective factors with respect to megaprostheses will make it possible to develop standardized treatment algorithms to reduce the risks for patients in general, and specifically the infectious one. These would enable us to select patients and thus associate each one with a specific device and surgical approach to optimize treatment and outcomes.

5. Conclusions

In conclusion, the number of megaprosthesis implants is increasing considerably. While in the past megaprosthesis implants were exclusive to cancer patients, to date, they are increasing in number by increasing the indications. Nowadays, megaprostheses are mostly used for lower limb replacements, especially around the knee. Megaprostheses implanted as a consequence of severe trauma are increasing significantly, second only to cancer patients. In traumatological patients, the infection rate is lower than in both cancer patients and patients with PJI but also in patients with the mechanical failure of prostheses. Knee megaprostheses have a higher infection risk than hip megaprostheses, which can help the surgeon to decide on different perioperative management approaches for the hip and the knee. Coated implants have a slightly lower infection rate than uncoated implants and should be considered in patients at high risk of infection. As these devices become more common, focused studies exploring epidemiological data, clinical outcomes, and long-term complications are needed to address the uncertainties in prevention and management.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/healthcare12131283/s1, The 27-item PRISMA checklist.

Author Contributions

Conceptualization, L.C. and R.V.; methodology, M.B.B.; software, F.T.; validation, G.M.(Giulia Micheli), F.S. and L.C.; formal analysis, M.F. and A.Z.; investigation, R.V.; resources, G.M. (Giulio Maccauro); data curation, F.T.; writing—original draft preparation, L.C.; writing—review and editing, M.B.B.; visualization, M.F.; supervision, G.M. (Giulio Maccauro). All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No new data were created in this study. Data sharing is not applicable to this article.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Zekry, K.M.; Yamamoto, N.; Hayashi, K.; Takeuchi, A.; Alkhooly, A.Z.A.; Abd-Elfattah, A.S.; Elsaid, A.N.S.; Ahmed, A.R.; Tsuchiya, H. Reconstruction of intercalary bone defect after resection of malignant bone tumor. J. Orthop. Surg. 2019, 27, 230949901983297. [Google Scholar] [CrossRef]
  2. Buchman, J. Total femur and knee joint replacement with a vitallium endoprosthesis. Bull. Hosp. Joint Dis. 1965, 26, 21–34. [Google Scholar] [PubMed]
  3. Jeys, L.M.; Kulkarni, A.; Grimer, R.J.; Carter, S.R.; Tillman, R.M.; Abudu, A. Endoprosthetic Reconstruction for the Treatment of Musculoskeletal Tumors of the Appendicular Skeleton and Pelvis. J. Bone Jt. Surg. 2008, 90, 1265–1271. [Google Scholar] [CrossRef] [PubMed]
  4. Johnson, C.N.; Gurich, R.W.; Pavey, G.J.; Thompson, M.J. Contemporary Management of Appendicular Skeletal Metastasis by Primary Tumor Type. J. Am. Acad. Orthop. Surg. 2019, 27, 345–355. [Google Scholar] [CrossRef]
  5. Korim, M.T.; Esler, C.N.; Reddy, V.R.; Ashford, R.U. A systematic review of endoprosthetic replacement for non-tumour indications around the knee joint. Knee 2013, 20, 367–375. [Google Scholar] [CrossRef]
  6. Korim, M.T.; Esler, C.N.; Ashford, R.U. Systematic review of proximal femoral arthroplasty for non-neoplastic conditions. J. Arthroplast. 2014, 29, 2117–2121. [Google Scholar] [CrossRef]
  7. Wirganowicz, P.Z.; Eckardt, J.J.; Dorey, F.J.; Eilber, F.R.; Kabo, J.M. Etiology and results of tumor endoprosthesis revision surgery in 64 patients. Clin. Orthop. Relat. Res. 1999, 358, 64–74. [Google Scholar] [CrossRef]
  8. Zeegen, E.N.; Aponte-Tinao, L.A.; Hornicek, F.J.; Gebhardt, M.C.; Mankin, H.J. Survivorship Analysis of 141 Modular Metallic Endoprostheses at Early Followup. Clin. Orthop. Relat. Res. 2004, 420, 239–250. [Google Scholar] [CrossRef] [PubMed]
  9. Henderson, E.R.; Groundland, J.S.; Pala, E.; Dennis, J.A.; Wooten, R.; Cheong, D.; Windhager, R.; Kotz, R.I.; Mercuri, M.; Funovics, P.T.; et al. Failure Mode Classification for Tumor Endoprostheses: Retrospective Review of Five Institutions and a Literature Review. J. Bone Jt. Surg. 2011, 93, 418–429. [Google Scholar] [CrossRef]
  10. Mazurkiewicz, T.; Warda, E.; Kopacz, J.; Mazurkiewicz, M. Results of the megaprosthesis replacement reconstruction proximal femoral resection bone tumors. Ortop. Traumatol. Rehabil. 2005, 7, 595–599. [Google Scholar]
  11. Shih, S.-T.; Wang, J.-W.; Hsu, C.-C. Proximal femoral megaprosthesis for failed total hip arthroplasty. Chang. Gung. Med. J. 2007, 30, 73–80. [Google Scholar] [PubMed]
  12. Calori, G.; Colombo, M.; Malagoli, E.; Mazzola, S.; Bucci, M.; Mazza, E. Megaprosthesis in post-traumatic and periprosthetic large bone defects: Issues to consider. Injury 2014, 45 (Suppl. 6), S105–S110. [Google Scholar] [CrossRef] [PubMed]
  13. Theil, C.; Röder, J.; Gosheger, G.; Deventer, N.; Dieckmann, R.; Schorn, D.; Hardes, J.; Andreou, D. What is the Likelihood That Tumor Endoprostheses Will Experience a Second Complication After First Revision in Patients with Primary Malignant Bone Tumors and What Are Potential Risk Factors? Clin. Orthop. Relat. Res. 2019, 477, 2705–2714. [Google Scholar] [CrossRef]
  14. Eckardt, J.J.; Eilber, F.R.; Rosen, G.; Mirra, J.M.; Dorey, F.J.; Ward, W.G.; Kabo, J.M. Endoprosthetic replacement for stage IIB osteosarcoma. Clin. Orthop. Relat. Res. 1991, 270, 202–213. [Google Scholar] [CrossRef]
  15. Cho, W.H.; Song, W.S.; Jeon, D.-G.; Kong, C.-B.; Kim, J.I.; Lee, S.-Y. Cause of infection in proximal tibial endoprosthetic reconstructions. Arch. Orthop. Trauma Surg. 2012, 132, 163–169. [Google Scholar] [CrossRef]
  16. Müller, D.; Kaiser, D.; Sairanen, K.; Studhalter, T.; Uçkay, I. Antimicrobial Prophylaxis for the Prevention of Surgical Site Infections in Orthopaedic Oncology—A Narrative Review of Current Concepts. J. Bone Jt. Infect. 2019, 4, 254–263. [Google Scholar] [CrossRef] [PubMed]
  17. Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.; Brennan, S.E.; et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 2021, 372, n71. [Google Scholar] [CrossRef]
  18. Aebischer, A.S.; Hau, R.; de Steiger, R.N.; Holder, C.; Wall, C.J. Distal Femoral Replacement for Periprosthetic Fractures After TKA: Australian Orthopaedic Association National Joint Replacement Registry Review. J. Arthroplast. 2022, 37, 1354–1358. [Google Scholar] [CrossRef]
  19. Agarwal, M.; Gulia, A.; Ravi, B.; Ghyar, R.; Puri, A. Revision of broken knee megaprostheses: New solution to old problems. Clin. Orthop. Relat. Res. 2010, 468, 2904–2913. [Google Scholar] [CrossRef]
  20. Alvand, A.; Grammatopoulos, G.; de Vos, F.; Scarborough, M.; Kendrick, B.; Price, A.; Gundle, R.; Whitwell, D.; Jackson, W.; Taylor, A.; et al. Clinical Outcome of Massive Endoprostheses Used for Managing Periprosthetic Joint Infections of the Hip and Knee. J. Arthroplast. 2018, 33, 829–834. [Google Scholar] [CrossRef]
  21. Apprich, S.R.; Nia, A.; Schreiner, M.M.; Jesch, M.; Böhler, C.; Windhager, R. Modular megaprostheses in the treatment of periprosthetic fractures of the femur. Wien. Klin. Wochenschr. 2021, 133, 550–559. [Google Scholar] [CrossRef] [PubMed]
  22. Artiaco, S.; Boggio, F.; Colzani, G.; Titolo, P.; Zoccola, K.; Bianchi, P.; Bellomo, F. Megaprostheses in the Revision of Infected Total Hip Arthroplasty. Clinical Series and Literature Review. Bull. Hosp. Jt. Dis. (2013) 2015, 73, 229–232. [Google Scholar]
  23. Asokan, A.; Ibrahim, M.S.; Thompson, J.W.; Haddad, F.S. Debridement, antibiotics, and implant retention in non-oncological femoral megaprosthesis infections: Minimum 5 year follow-up. J. Exp. Orthop. 2022, 9, 32. [Google Scholar] [CrossRef]
  24. Berger, C.; Parai, C.; Tillander, J.; Bergh, P.; Wennergren, D.; Brisby, H. High Risk for Persistent Peri-Prosthetic Infection and Amputation in Mega-Prosthesis Reconstruction. J. Clin. Med. 2023, 12, 3575. [Google Scholar] [CrossRef]
  25. Bertani, A.; Helix, M.; Louis, M.; Rochwerger, A.; Curvale, G. Total hip arthroplasty in severe segmental femoral bone loss situations: Use of a reconstruction modular stem design (JVC IX™). Retrospective study of 23 cases. Orthop. Traumatol. Surg. Res. 2009, 95, 491–497. [Google Scholar] [CrossRef]
  26. Bischel, O.E.; Suda, A.J.; Böhm, P.M.; Lehner, B.; Bitsch, R.G.; Seeger, J.B. En-Bloc Resection of Metastases of the Proximal Femur and Reconstruction by Modular Arthroplasty is Not Only Justified in Patients with a Curative Treatment Option—An Observational Study of a Consecutive Series of 45 Patients. J. Clin. Med. 2020, 9, 758. [Google Scholar] [CrossRef]
  27. Bruns, J.; Delling, G.; Gruber, H.; Lohmann, C.H.; Habermann, C.R.; Batta, V.; Coathup, M.J.; Parratt, M.T.; Pollock, R.C.; Cannon, S.R.; et al. Cementless fixation of megaprostheses using a conical fluted stem in the treatment of bone tumours. J. Bone Jt. Surgery. Br. Vol. 2007, 89, 1084–1087. [Google Scholar] [CrossRef] [PubMed]
  28. Calabró, T.; Van Rooyen, R.; Piraino, I.; Pala, E.; Trovarelli, G.; Panagopoulos, G.N.; Megaloikonomos, P.D.; Angelini, A.; Mavrogenis, A.F.; Ruggieri, P. Reconstruction of the proximal femur with a modular resection prosthesis. Eur. J. Orthop. Surg. Traumatol. 2016, 26, 415–421. [Google Scholar] [CrossRef] [PubMed]
  29. Cannon, S.R. The use of megaprosthesis in the treatment of periprosthetic knee fractures. Int. Orthop. 2015, 39, 1945–1950. [Google Scholar] [CrossRef]
  30. Capanna, R.; Scoccianti, G.; Frenos, F.; Vilardi, A.; Beltrami, G.; Campanacci, D.A. What was the survival of megaprostheses in lower limb reconstructions after tumor resections? Clin. Orthop. Relat. Res. 2015, 473, 820–830. [Google Scholar] [CrossRef]
  31. Chandler, H.; Clark, J.; Murphy, S.; Mccarthy, J.; Penenberg, B.; Danylchuk, K.; Roehr, B. Reconstruction of major segmental loss of the proximal femur in revision total hip arthroplasty. Clin. Orthop. Relat. Res. 1994, 298, 67–74. [Google Scholar] [CrossRef]
  32. Corona, P.S.; Vicente, M.; Lalanza, M.; Amat, C.; Carrera, L. Use of modular megaprosthesis in managing chronic end-stage periprosthetic hip and knee infections: Is there an increase in relapse rate? Eur. J. Orthop. Surg. Traumatol. 2018, 28, 627–636. [Google Scholar] [CrossRef] [PubMed]
  33. Crosby, S.N.; Polkowski, G.G.; Schwartz, H.S.; Shinar, A.A.; Holt, G.E. Metal-backed versus all-polyethylene tibias in megaprostheses of the distal femur. J. Arthroplast. 2011, 26, 451–457. [Google Scholar] [CrossRef] [PubMed]
  34. De Gori, M.; D’arienzo, A.; Andreani, L.; Beltrami, G.; Campanacci, D.A.; De Biase, P.; Frenos, F.; Giannotti, S.; Sacchetti, F.; Totti, F.; et al. Complications and survival of megaprostheses after resection of bone metastases. J. Biol. Regul. Homeost. Agents 2017, 31, 43–50. [Google Scholar]
  35. De Gori, M.; Scoccianti, G.; Frenos, F.; Bettini, L.; Familiari, F.; Gasparini, G.; Beltrami, G.; Cuomo, P.; De Biase, P.; Capanna, R. Modular Endoprostheses for Nonneoplastic Conditions: Midterm Complications and Survival. BioMed Res. Int. 2016, 2016, 2606521. [Google Scholar] [CrossRef] [PubMed]
  36. De Martino, I.; D’apolito, R.; Nocon, A.A.; Sculco, T.P.; Sculco, P.K.; Bostrom, M.P. Proximal femoral replacement in non-oncologic patients undergoing revision total hip arthroplasty. Int. Orthop. 2019, 43, 2227–2233. [Google Scholar] [CrossRef]
  37. Donati, F.; Di Giacomo, G.; D’adamio, S.; Ziranu, A.; Careri, S.; Rosa, M.; Maccauro, G. Silver-Coated Hip Megaprosthesis in Oncological Limb Savage Surgery. BioMed Res. Int. 2016, 2016, 9079041. [Google Scholar] [CrossRef] [PubMed]
  38. Döring, K.; Vertesich, K.; Martelanz, L.; Staats, K.; Böhler, C.; Hipfl, C.; Windhager, R.; Puchner, S. Proximal femoral reconstruction with modular megaprostheses in non-oncological patients. Int. Orthop. 2021, 45, 2531–2542. [Google Scholar] [CrossRef]
  39. Ercolano, L.B.; Christensen, T.; McGough, R.; Weiss, K. Treatment solutions are unclear for perimegaprosthetic infections. Clin. Orthop. Relat. Res. 2013, 471, 3204–3213. [Google Scholar] [CrossRef]
  40. Fiore, M.; Sambri, A.; Morante, L.; Bortoli, M.; Parisi, S.C.; Panzavolta, F.; Alesi, D.; Neri, E.; Neri, M.P.; Tedeschi, S.; et al. Silver-Coated Distal Femur Megaprosthesis in Chronic Infections with Severe Bone Loss: A Multicentre Case Series. J. Clin. Med. 2023, 12, 6679. [Google Scholar] [CrossRef]
  41. Glehr, M.; Leithner, A.; Friesenbichler, J.; Goessler, W.; Avian, A.; Andreou, D.; Maurer-Ertl, W.; Windhager, R.; Tunn, P.-U. Argyria following the use of silver-coated megaprostheses: No association between the development of local argyria and elevated silver levels. Bone Jt. J. 2013, 95-B, 988–992. [Google Scholar] [CrossRef] [PubMed]
  42. Gosheger, G.; Hillmann, A.; Lindner, N.; Rödl, R.; Hoffmann, C.; Bürger, H.; Winkelmann, W. Soft tissue reconstruction of megaprostheses using a trevira tube. Clin. Orthop. Relat. Res. 2001, 393, 264–271. [Google Scholar] [CrossRef] [PubMed]
  43. Grandhi, T.S.P.; Titus, V. The results of patellar stainless steel wire extensor mechanism reconstruction in proximal tibial tumour excision mega-prosthesis surgeries for proximal tibial sarcomas. Knee 2021, 29, 332–344. [Google Scholar] [CrossRef] [PubMed]
  44. Gulia, A.; Prajapati, A.; Gupta, S.; Exner, U.; Puri, A. Rotationplasty after failed limb salvage: An alternative to amputation. Eur. J. Orthop. Surg. Traumatol. 2023, 33, 1683–1689. [Google Scholar] [CrossRef] [PubMed]
  45. Gundavda, M.K.; Katariya, A.; Reddy, R.; Agarwal, M.G. Fighting Megaprosthetic Infections: What are the Chances of Winning? Indian J. Orthop. 2020, 54, 469–476. [Google Scholar] [CrossRef] [PubMed]
  46. Hardes, J.; Henrichs, M.P.; Hauschild, G.; Nottrott, M.; Guder, W.; Streitbuerger, A. Silver-Coated Megaprosthesis of the Proximal Tibia in Patients with Sarcoma. J. Arthroplast. 2017, 32, 2208–2213. [Google Scholar] [CrossRef] [PubMed]
  47. Hardes, J.; Henrichs, M.-P.; Gosheger, G.; Guder, W.; Nottrott, M.; Andreou, D.; Bormann, E.; Eveslage, M.; Hauschild, G.; Streitbürger, A. Tumour endoprosthesis replacement in the proximal tibia after intra-articular knee resection in patients with sarcoma and recurrent giant cell tumour. Int. Orthop. 2018, 42, 2475–2481. [Google Scholar] [CrossRef] [PubMed]
  48. Hardes, J.; von Eiff, C.; Streitbuerger, A.; Balke, M.; Budny, T.; Henrichs, M.P.; Hauschild, G.; Ahrens, H. Reduction of periprosthetic infection with silver-coated megaprostheses in patients with bone sarcoma. J. Surg. Oncol. 2010, 101, 389–395. [Google Scholar] [CrossRef] [PubMed]
  49. Höll, S.; Schlomberg, A.; Gosheger, G.; Dieckmann, R.; Streitbuerger, A.; Schulz, D.; Hardes, J. Distal femur and proximal tibia replacement with megaprosthesis in revision knee arthroplasty: A limb-saving procedure. Knee Surg. Sports Traumatol. Arthrosc. 2012, 20, 2513–2518. [Google Scholar] [CrossRef] [PubMed]
  50. Holm, C.E.; Bardram, C.; Riecke, A.F.; Horstmann, P.; Petersen, M.M. Implant and limb survival after resection of primary bone tumors of the lower extremities and reconstruction with mega-prostheses fifty patients followed for a mean of forteen years. Int. Orthop. 2018, 42, 1175–1181. [Google Scholar] [CrossRef]
  51. Hu, C.-C.; Chen, S.-Y.; Chen, C.-C.; Chang, Y.-H.; Ueng, S.W.-N.; Shih, H.-N. Superior Survivorship of Cementless vs Cemented Diaphyseal Fixed Modular Rotating-Hinged Knee Megaprosthesis at 7 Years’ Follow-Up. J. Arthroplast. 2017, 32, 1940–1945. [Google Scholar] [CrossRef] [PubMed]
  52. Hussmann, B.; Johann, I.; Kauther, M.D.; Landgraeber, S.; Jäger, M.; Lendemans, S. Measurement of the silver ion concentration in wound fluids after implantation of silver-coated megaprostheses: Correlation with the clinical outcome. BioMed Res. Int. 2013, 2013, 763096. [Google Scholar] [CrossRef] [PubMed]
  53. Ilyas, I.; Kurar, A.; Moreau, P.; Younge, D. Modular megaprosthesis for distal femoral tumors. Int. Orthop. 2001, 25, 375–377. [Google Scholar] [CrossRef] [PubMed]
  54. Innocenti, M.; Muratori, F.; Foschi, L.; Bartolini, S.; Scorianz, M.; Scoccianti, G.; Campanacci, D.A. Salvage of limb salvage in oncological reconstructions of the lower limb with megaprosthesis: How much to push the boundaries? Arch. Orthop. Trauma Surg. 2023, 143, 763–771. [Google Scholar] [CrossRef] [PubMed]
  55. Kamal, A.F.; Rubiansyah, P. Clinical outcome of various limb salvage surgeries in osteosarcoma around knee: Megaprosthesis, extracorporeal irradiation and resection arthrodesis. Ann. Med. Surg. 2019, 42, 14–18. [Google Scholar] [CrossRef] [PubMed]
  56. Kar, B.K.; Ojha, M.M.; Yadav, S.K.; Agrawal, A.C.; Sakale, H. Outcomes of Tumor Resection and Reconstruction by Megaprosthesis around Knee: Our Experience. J. Orthop. Case Rep. 2021, 11, 49–52. [Google Scholar] [CrossRef] [PubMed]
  57. Khakzad, T.; Karczewski, D.; Thielscher, L.; Reiter, K.; Wittenberg, S.; Paksoy, A.; Flörcken, A.; Rau, D.; Märdian, S. Prosthetic Joint Infection in Mega-Arthroplasty Following Shoulder, Hip and Knee Malignancy—A Prospective Follow-Up Study. Life 2022, 12, 2134. [Google Scholar] [CrossRef] [PubMed]
  58. Kostuj, T.; Streit, R.; Baums, M.H.; Schaper, K.; Meurer, A. Midterm Outcome after Mega-Prosthesis Implanted in Patients with Bony Defects in Cases of Revision Compared to Patients with Malignant Tumors. J. Arthroplast. 2015, 30, 1592–1596. [Google Scholar] [CrossRef] [PubMed]
  59. Lam, Y.-L.; Yau, R.; Ho, K.W.; Ho, P.-L. Antibiotic-laden cement wrap: A simple but effective way of treating patients with megaprosthesis infection. J. Orthop. Surg. 2019, 27, 2309499019825587. [Google Scholar] [CrossRef]
  60. Logoluso, N.; Pedrini, F.A.; Morelli, I.; De Vecchi, E.; Romanò, C.L.; Pellegrini, A.V. Megaprostheses for the revision of infected hip arthroplasties with severe bone loss. BMC Surg. 2022, 22, 68. [Google Scholar] [CrossRef]
  61. Lundh, F.; Sayed-Noor, A.S.; Brosjö, O.; Bauer, H. Megaprosthetic reconstruction for periprosthetic or highly comminuted fractures of the hip and knee. Eur. J. Orthop. Surg. Traumatol. 2014, 24, 553–557. [Google Scholar] [CrossRef]
  62. Marczak, D.; Kowalczewski, J.; Czubak, J.; Okoń, T.; Synder, M.; Sibiński, M. Short and mid term results of revision total knee arthroplasty with Global Modular Replacement System. Indian J. Orthop. 2017, 51, 324–329. [Google Scholar] [CrossRef]
  63. Mavrogenis, A.F.; Mitsiokapa, E.A.; Sakellariou, V.I.; Tzanos, G.; Papagelopoulos, P.J. Functional and radiographic outcome after tumor limb salvage surgery using STANMORE megaprostheses. J. BUON 2011, 16, 353–360. [Google Scholar]
  64. Mavrogenis, A.F.; Pala, E.; Angelini, A.; Ferraro, A.; Ruggieri, P. Proximal tibial resections and reconstructions: Clinical outcome of 225 patients. J. Surg. Oncol. 2013, 107, 335–342. [Google Scholar] [CrossRef] [PubMed]
  65. Mavrogenis, A.F.; Pala, E.; Angelini, A.; Calabro, T.; Romagnoli, C.; Romantini, M.; Drago, G.; Ruggieri, P. Infected Prostheses after Lower-Extremity Bone Tumor Resection: Clinical Outcomes of 100 Patients. Surg. Infect. 2015, 16, 267–275. [Google Scholar] [CrossRef] [PubMed]
  66. Mazaleyrat, M.; Le Nail, L.-R.; Auberger, G.; Biau, D.; Rosset, P.; Waast, D.; Gouin, F.; Bonnevialle, P.; Ehlinger, M.; Pasquier, G.; et al. Survival and complications in hinged knee reconstruction prostheses after distal femoral or proximal tibial tumor resection: A retrospective study of 161 cases. Orthop. Traumatol. Surg. Res. 2020, 106, 403–407. [Google Scholar] [CrossRef]
  67. Müller, P.; Dürr, H.; Wegener, B.; Pellengahr, C.; Refior, H.; Jansson, V. Internal hemipelvectomy and reconstruction with a megaprosthesis. Int. Orthop. 2002, 26, 76–79. [Google Scholar] [CrossRef]
  68. Murphy, E.P.; Conway, S.; Fenelon, C.; Dawson, P.H.; O’toole, G.C.; Molloy, A.P. Intermediate to Long-Term Follow-up of Distal Femoral Replacements in the Treatment of Neoplastic Disease About the Knee. Arthroplast. Today 2021, 9, 35–39. [Google Scholar] [CrossRef] [PubMed]
  69. Natarajan, M.V.; Mohanlal, P.; Bose, J.C. The role of limb salvage surgery and custom mega prosthesis in multiple myeloma. Acta Orthop. Belg. 2007, 73, 462–467. [Google Scholar]
  70. Natarajan, M.V.; Sivaseelam, A.; Ayyappan, S.; Bose, J.C.; Kumar, M.S. Distal femoral tumours treated by resection and custom mega-prosthetic replacement. Int. Orthop. 2005, 29, 309–313. [Google Scholar] [CrossRef]
  71. Ogura, K.; Yakoub, M.A.; Boland, P.J.; Healey, J.H. Finn/Orthopaedic Salvage System Distal Femoral Rotating-Hinge Megaprostheses in Oncologic Patients: Long-Term Complications, Reoperations, and Amputations. J. Bone Jt. Surg. Am. 2021, 103, 705–714. [Google Scholar] [CrossRef] [PubMed]
  72. Ozaki, T.; Hoffmann, C.; Hillmann, A.; Gosheger, G.; Lindner, N.; Winkelmann, W. Implantation of hemipelvic prosthesis after resection of sarcoma. Clin. Orthop. Relat. Res. 2002, 396, 197–205. [Google Scholar] [CrossRef] [PubMed]
  73. Pala, E.; Trovarelli, G.; Angelini, A.; Ruggieri, P. Distal femur reconstruction with modular tumour prostheses: A single Institution analysis of implant survival comparing fixed versus rotating hinge knee prostheses. Int. Orthop. 2016, 40, 2171–2180. [Google Scholar] [CrossRef] [PubMed]
  74. Pala, E.; Trovarelli, G.; Calabrò, T.; Angelini, A.; Abati, C.N.; Ruggieri, P. Survival of modern knee tumor megaprostheses: Failures, functional results, and a comparative statistical analysis. Clin. Orthop. Relat. Res. 2015, 473, 891–899. [Google Scholar] [CrossRef] [PubMed]
  75. Pala, E.; Trovarelli, G.; Ippolito, V.; Berizzi, A.; Ruggieri, P. A long-term experience with Mutars tumor megaprostheses: Analysis of 187 cases. Eur. J. Trauma Emerg. Surg. 2022, 48, 2483–2491. [Google Scholar] [CrossRef] [PubMed]
  76. Parvizi, J.; Tarity, T.D.; Slenker, N.; Wade, F.; Trappler, R.; Hozack, W.J.; Sim, F.H. Proximal femoral replacement in patients with non-neoplastic conditions. J. Bone Jt. Surg. Am. 2007, 89, 1036–1043. [Google Scholar] [CrossRef]
  77. Piccioli, A.; Donati, F.; Di Giacomo, G.; Ziranu, A.; Careri, S.; Spinelli, M.S.; Giannini, S.; Giannicola, G.; Perisano, C.; Maccauro, G. Infective complications in tumour endoprostheses implanted after pathological fracture of the limbs. Injury 2016, 47 (Suppl. 4), S22–S28. [Google Scholar] [CrossRef] [PubMed]
  78. Puchner, S.E.; Döring, K.; Staats, K.; Böhler, C.; Lass, R.; Hirschl, A.M.; Presterl, E.; Windhager, R.; Holinka, J. Sonication culture improves microbiological diagnosis of modular megaprostheses. J. Orthop. Res. 2017, 35, 1383–1387. [Google Scholar] [CrossRef] [PubMed]
  79. Rajasekaran, R.B.; Palanisami, D.R.; Natesan, R.; Jayaramaraju, D.; Rajasekaran, S. Megaprosthesis in distal femur nonunions in elderly patients-experience from twenty four cases. Int. Orthop. 2020, 44, 677–684. [Google Scholar] [CrossRef]
  80. Ribera, J.; Payo-Ollero, J.; Serrano-Toledano, D.; del Río-Arteaga, M.; Montilla, F.J.; Muela, R. Megaprosthesis use in Paprosky III/IV femoral defects in non-oncological patients: Analysis of survival, clinical, and functional outcomes after an average follow-up of five years. Eur. J. Orthop. Surg. Traumatol. 2023, 34, 1183–1192. [Google Scholar] [CrossRef]
  81. Ruggieri, P.; Kasimatis, G.; Errani, C.; Bosco, G.; Mercuri, M. Desarthrodesis and prosthetic reconstruction of the knee after resection of bone tumors. J. Surg. Oncol. 2010, 102, 832–837. [Google Scholar] [CrossRef]
  82. Ruggieri, P.; Mavrogenis, A.F.; Pala, E.; Abdel-Mota’Al, M.; Mercuri, M. Long term results of fixed-hinge megaprostheses in limb salvage for malignancy. Knee 2012, 19, 543–549. [Google Scholar] [CrossRef] [PubMed]
  83. Sacchetti, F.; Kilian, R.; Muratori, F.; Cherix, S.; Foschi, L.; Morganti, R.; Campanacci, D.A.; Capanna, R. The Performances of Conventional Titanium and Silver-Coated Megaprostheses in Non-oncological and Post-oncological Patients: An Analysis of Infection Failures in 142 Patients. Arch. Bone Jt. Surg. 2022, 10, 439–446. [Google Scholar] [CrossRef] [PubMed]
  84. Sambri, A.; Zucchini, R.; Giannini, C.; Zamparini, E.; Viale, P.; Donati, D.M.; De Paolis, M. Silver-coated (PorAg®) endoprosthesis can be protective against reinfection in the treatment of tumor prostheses infection. Eur. J. Orthop. Surg. Traumatol. 2020, 30, 1345–1353. [Google Scholar] [CrossRef] [PubMed]
  85. Schmolders, J.; Koob, S.; Schepers, P.; Pennekamp, P.H.; Gravius, S.; Wirtz, D.C.; Placzek, R.; Strauss, A.C. Lower limb reconstruction in tumor patients using modular silver-coated megaprostheses with regard to perimegaprosthetic joint infection: A case series, including 100 patients and review of the literature. Arch. Orthop. Trauma Surg. 2017, 137, 149–153. [Google Scholar] [CrossRef] [PubMed]
  86. Schmolders, J.; Koob, S.; Schepers, P.; Kehrer, M.; Frey, S.P.; Wirtz, D.C.; Pennekamp, P.H.; Strauss, A.C. Silver-coated endoprosthetic replacement of the proximal humerus in case of tumour-is there an increased risk of periprosthetic infection by using a trevira tube? Int. Orthop. 2017, 41, 423–428. [Google Scholar] [CrossRef] [PubMed]
  87. Scoccianti, G.; Frenos, F.; Beltrami, G.; Campanacci, D.A.; Capanna, R. Levels of silver ions in body fluids and clinical results in silver-coated megaprostheses after tumour, trauma or failed arthroplasty. Injury 2016, 47 (Suppl. 4), S11–S16. [Google Scholar] [CrossRef] [PubMed]
  88. Sewell, M.D.; Hanna, S.A.; Carrington, R.W.; Pollock, R.C.; Skinner, J.A.; Cannon, S.R.; Briggs, T.W.R. Modular proximal femoral replacement in salvage hip surgery for non-neoplastic conditions. Acta Orthop. Belg. 2010, 76, 493–502. [Google Scholar] [PubMed]
  89. Sigmund, I.K.; Gamper, J.; Weber, C.; Holinka, J.; Panotopoulos, J.; Funovics, P.T.; Windhager, R. Efficacy of different revision procedures for infected megaprostheses in musculoskeletal tumour surgery of the lower limb. PLoS ONE 2018, 13, e0200304. [Google Scholar] [CrossRef]
  90. Şirin, E.; Sofulu, Ö.; Baysal, Ö.; Akgülle, A.H.; Erol, B. Staged Management of Infection with Adjustable Spacers After Megaprosthesis Implantation in Primary Sarcoma Patients. Indian J. Orthop. 2023, 57, 938–947. [Google Scholar] [CrossRef]
  91. Smith, E.L.; Shah, A.; Son, S.J.; Niu, R.; Talmo, C.T.; Abdeen, A.; Ali, M.; Pinski, J.; Gordon, M.; Lozano-Calderon, S.; et al. Survivorship of Megaprostheses in Revision Hip and Knee Arthroplasty for Septic and Aseptic Indications: A Retrospective, Multicenter Study with Minimum 2-Year Follow-Up. Arthroplast. Today 2020, 6, 475–479. [Google Scholar] [CrossRef] [PubMed]
  92. Smolle, M.A.; Friesenbichler, J.; Bergovec, M.; Gilg, M.; Maurer-Ertl, W.; Leithner, A. How is the outcome of the Limb Preservation SystemTM for reconstruction of hip and knee? Orthop. Traumatol. Surg. Res. 2020, 106, 409–415. [Google Scholar] [CrossRef] [PubMed]
  93. Sobol, K.R.; Fram, B.R.; Strony, J.T.; Brown, S.A. Survivorship, complications, and outcomes following distal femoral arthroplasty for non-neoplastic indications. Bone Jt. Open 2022, 3, 173–181. [Google Scholar] [CrossRef] [PubMed]
  94. Springer, B.D.; Sim, F.H.; Hanssen, A.D.; Lewallen, D.G. The modular segmental kinematic rotating hinge for nonneoplastic limb salvage. Clin. Orthop. Relat. Res. 2004, 421, 181–187. [Google Scholar] [CrossRef] [PubMed]
  95. Streitbuerger, A.; Henrichs, M.P.; Hauschild, G.; Nottrott, M.; Guder, W.; Hardes, J. Silver-coated megaprostheses in the proximal femur in patients with sarcoma. Eur. J. Orthop. Surg. Traumatol. 2019, 29, 79–85. [Google Scholar] [CrossRef] [PubMed]
  96. Sukhonthamarn, K.; Tan, T.L.; Strony, J.; Brown, S.; Nazarian, D.; Parvizi, J. The Fate of Periprosthetic Joint Infection Following Megaprosthesis Reconstruction. JBJS Open Access 2021, 6, e21.00003. [Google Scholar] [CrossRef] [PubMed]
  97. Tan, P.K.; Tan, M.H. Functional outcome study of mega-endoprosthetic reconstruction in limbs with bone tumour surgery. Ann. Acad. Med. Singap. 2009, 38, 192–196. [Google Scholar] [CrossRef] [PubMed]
  98. Theil, C.; Schneider, K.N.; Gosheger, G.; Dieckmann, R.; Deventer, N.; Hardes, J.; Schmidt-Braekling, T.; Andreou, D. Does the Duration of Primary and First Revision Surgery Influence the Probability of First and Subsequent Implant Failures after Extremity Sarcoma Resection and Megaprosthetic Reconstruction? Cancers 2021, 13, 2510. [Google Scholar] [CrossRef]
  99. Toepfer, A.; Harrasser, N.; Petzschner, I.; Pohlig, F.; Lenze, U.; Gerdesmeyer, L.; Pförringer, D.; Toepfer, M.; Beirer, M.; Crönlein, M.; et al. Short- to long-term follow-up of total femoral replacement in non-oncologic patients. BMC Musculoskelet. Disord. 2016, 17, 498. [Google Scholar] [CrossRef]
  100. Toepfer, A.; Harrasser, N.; Petzschner, I.; Pohlig, F.; Lenze, U.; Gerdesmeyer, L.; von Eisenhart-Rothe, R.; Mühlhofer, H.; Suren, C. Is total femoral replacement for non-oncologic and oncologic indications a safe procedure in limb preservation surgery? A single center experience of 22 cases. Eur. J. Med Res. 2018, 23, 5. [Google Scholar] [CrossRef]
  101. Toepfer, A.; Harrasser, N.; Schwarz, P.-R.; Pohlig, F.; Lenze, U.; Mühlhofer, H.M.L.; Gerdesmeyer, L.; von Eisenhart-Rothe, R.; Suren, C. Distal femoral replacement with the MML system: A single center experience with an average follow-up of 86 months. BMC Musculoskelet. Disord. 2017, 18, 206. [Google Scholar] [CrossRef]
  102. Torner, F.; Segur, J.M.; Ullot, R.; Soldado, F.; Domenech, P.; DeSena, L.; Knorr, J. Non-invasive expandable prosthesis in musculoskeletal oncology paediatric patients for the distal and proximal femur. First results. Int. Orthop. 2016, 40, 1683–1688. [Google Scholar] [CrossRef]
  103. Ueda, T.; Kakunaga, S.; Takenaka, S.; Araki, N.; Yoshikawa, H. Constrained total hip megaprosthesis for primary periacetabular tumors. Clin. Orthop. Relat. Res. 2013, 471, 741–749. [Google Scholar] [CrossRef]
  104. Vertesich, K.; Puchner, S.E.; Staats, K.; Schreiner, M.; Hipfl, C.; Kubista, B.; Holinka, J.; Windhager, R. Distal femoral reconstruction following failed total knee arthroplasty is accompanied with risk for complication and reduced joint function. BMC Musculoskelet. Disord. 2019, 20, 47. [Google Scholar] [CrossRef] [PubMed]
  105. Yang, P.; Evans, S.; Khan, Z.; Abudu, A.; Jeys, L.; Grimer, R. Reconstruction of the distal tibia following resection of aggressive bone tumours using a custom-made megaprosthesis. J. Orthop. 2017, 14, 406–409. [Google Scholar] [CrossRef] [PubMed]
  106. Zhang, H.-R.; Zhao, Y.-L.; Wang, F.; Yang, X.-G.; Xu, M.-Y.; Qiao, R.-Q.; Li, J.-K.; Pang, C.-G.; Yu, X.-C.; Hu, Y.-C. Establishment and validation of a nomogram model for periprosthetic infection after megaprosthetic replacement around the knee following bone tumor resection: A retrospective analysis. Orthop. Traumatol. Surg. Res. 2020, 106, 421–427. [Google Scholar] [CrossRef]
  107. Zoccali, C.; Scoccianti, G.; Biagini, R.; Daolio, P.A.; Giardina, F.L.; Campanacci, D.A. Antibacterial hydrogel coating in joint mega-prosthesis: Results of a comparative series. Eur. J. Orthop. Surg. Traumatol. 2021, 31, 1647–1655. [Google Scholar] [CrossRef]
  108. Smolle, M.A.; Bergovec, M.; Scheipl, S.; Gössler, W.; Amerstorfer, F.; Glehr, M.; Leithner, A.; Friesenbichler, J. Long-term changes in serum silver concentrations after extremity reconstruction with silver-coated megaprostheses. Sci. Rep. 2022, 12, 13041. [Google Scholar] [CrossRef]
  109. Sambri, A.; Parisi, S.C.; Zunarelli, R.; Di Prinzio, L.; Morante, L.; Lonardo, G.; Bortoli, M.; Montanari, A.; De Cristofaro, R.; Fiore, M.; et al. Megaprosthesis in Non-Oncologic Settings—A Systematic Review of the Literature. J. Clin. Med. 2023, 12, 4151. [Google Scholar] [CrossRef] [PubMed]
  110. Vitiello, R.; Ziranu, A.; Oliva, M.S.; Meluzio, M.C.; Cauteruccio, M.; Maccauro, G.; Liuzza, F.; Saccomanno, M.F. The value of megaprostheses in non-oncological fractures in elderly patients: A short-term results. Injury 2022, 53, 1241–1246. [Google Scholar] [CrossRef]
  111. Vitiello, R.; Smimmo, A.; De Fazio, A.; Bocchi, M.B.; Oliva, M.S.; Perna, A.; Maccauro, G.; Ziranu, A. Megaprosthesis in articular fractures of the lower limbs in fragile patients: A proposal for the therapeutic algorithm. Eur. Rev. Med. Pharmacol. Sci. 2022, 26, 84–91. [Google Scholar] [CrossRef] [PubMed]
  112. El Ezzo, O.; Oliva, M.S.; Cauteruccio, M.; Saracco, M.; Vitiello, R.; Maccauro, G.; Perisano, C. Innovations in prevention of infections in oncological megaprostheses: A narrative review. J. Biol. Regul. Homeost. Agents 2020, 34, 275–278. [Google Scholar]
  113. Gonzalez, M.R.; Pretell-Mazzini, J.; Lozano-Calderon, S.A. Risk Factors and Management of Prosthetic Joint Infections in Megaprostheses—A Review of the Literature. Antibiotics 2023, 13, 25. [Google Scholar] [CrossRef]
  114. Vaishya, R.; Thapa, S.S.; Vaish, A. Non-neoplastic indications and outcomes of the proximal and distal femur megaprosthesis: A critical review. Knee Surg. Relat. Res. 2020, 32, 18. [Google Scholar] [CrossRef]
  115. Lex, J.R.; Koucheki, R.; Stavropoulos, N.A.; Di Michele, J.; Toor, J.S.; Tsoi, K.; Ferguson, P.C.; Turcotte, R.E.; Papagelopoulos, P.J. Megaprosthesis anti-bacterial coatings: A comprehensive translational review. Acta Biomater. 2022, 140, 136–148. [Google Scholar] [CrossRef] [PubMed]
  116. Schmidt-Braekling, T.; Streitbuerger, A.; Gosheger, G.; Boettner, F.; Nottrott, M.; Ahrens, H.; Dieckmann, R.; Guder, W.; Andreou, D.; Hauschild, G.; et al. Silver-coated megaprostheses: Review of the literature. Eur. J. Orthop. Surg. Traumatol. 2017, 27, 483–489. [Google Scholar] [CrossRef]
  117. Windhager, R.; Schreiner, M.; Staats, K.; Apprich, S. Megaprostheses in the treatment of periprosthetic fractures of the knee joint: Indication, technique, results and review of literature. Int. Orthop. 2016, 40, 935–943. [Google Scholar] [CrossRef] [PubMed]
  118. Rovere, G.; Smakaj, A.; De Mauro, D.; Marino, S.; Vitiello, R.; Meschini, C.; Ziranu, A.; Liuzza, F.; Maccauro, G.; Pataia, E. Medial gastrocnemius flap for the treatment of infected knee prostheses. Eur. Rev. Med. Pharmacol. Sci. 2022, 26 (Suppl. 1), 60–65. [Google Scholar] [CrossRef] [PubMed]
  119. Fiore, M.; Sambri, A.; Zucchini, R.; Giannini, C.; Donati, D.M.; De Paolis, M. Silver-coated megaprosthesis in prevention and treatment of peri-prosthetic infections: A systematic review and meta-analysis about efficacy and toxicity in primary and revision surgery. Eur. J. Orthop. Surg. Traumatol. 2021, 31, 201–220. [Google Scholar] [CrossRef]
Healthcare 12 01283 g001
Figure 1. Search and literature selection.
Figure 1. Search and literature selection.
Healthcare 12 01283 g001
Table 1. Infection rate in relation to principal diagnosis, anatomy, and implant characteristics.
Table 1. Infection rate in relation to principal diagnosis, anatomy, and implant characteristics.
AuthorsYear of
Publication		MegaprosthesesInfectionsInfections/
Knee Replacement		Infections/
Hip Replacement		Infections/
Total Femur Replacement		Infections/
Shoulder Replacement		Infections/
Other		Infections/
Coated		Infections/
Uncoated		Infections/
Oncological		Infections/
Trauma		Infections/
PJI		Infections/
Mechanical Failure
Berger C et al. [24]20211163520/527/300/34/154/16-35/11625/116---
Şirin E et al. [90]20235533224/247/7-1/1--32/55332/553---
Khakzad T et al. [57]202282149/322/301/12/19-3/5710/2513/82---
Gulia A et al. [44]2023141010/14-----10/1410/14---
Sacchetti F et al. [83]202214229-----9/3820/104----
Asokan A et al. [23]202214145/56/63/3---14/14-7/73/34/4
Pala E et al. [75]2022187139/770/38-4/50-8/1185/6913/1800/7--
Innocenti M et al. [54]20234441917/172/2----19/44419/444---
Theil C et al. [98]20215685844/445 *14/123 **-58/568-58/568---
Murphy EP et al. [68]2021721212/77-----12/7212/72---
Grandhi TSP et al. [43]20212666/26----6/26-6/26---
Zoccali C et al. [107]2021866-----0/436/43----
Ogura K et al. [71]2021214112112/214-----112/214112/214---
Gundavda MK et al. [45]2020353526/269/9----35/3535/35---
Sambri A et al. [84]2020681313/68----3/2910/3913/68---
Mazaleyrat M et al. [66]20201612525/161-----25/16125/161---
Bischel OE et al. [26]2020451-1/45----1/451/45---
Zhang HR et al. [106]20201772121/77-----21/17721/177---
Kamal AF et al. [55]20201922/19-----2/192/19---
Smolle MA et al. [92]202057116/265/31----11/57----
Kamal AF et al. [55]2019811/8-----1/81/8---
Lam YL et al. [59]20195862/61/6-1/61/6-6/586/58---
Sigmund IK et al. [89]20186218370/7012/121/1---83/62183/621---
Aebischer AS et al. [18]20223061010/306-----10/306-10/306--
Apprich SR et al. [21]20213353/140/122/7---5/33-5/33--
Vertesich K et al. [104]20193088/30-----8/30--5/9-
Sobol KR et al. [93]2022751616/75-----16/75-5/275/232/25
Logoluso N et al. [60]2022212-2/21---2/120/9--2/21-
Sukhonthamarn K et al. [96]20212193318/14615/73----33/219-8/8120/635/67
Smith EL et al. [91]202042109/291/13----10/42-2/136/192/10
Rajasekaran RB et al. [79]20202411/24-----1/24-1/24--
Döring K et al. [38]2021286-6/28----6/28--6/11-
De Martino I et al. [36]2019313-3/31----3/31-3/31 ***
Streitbuerger A et al. [95]20199911-11/99---6/645/3511/99---
Hardes J et al. [47]2018981515/98----7/568/4215/98---
Holm CE et al. [50]2018506------6/506/50---
De Gori M et al. [34]20171692------2/1692/169---
Yang P et al. [105]201781----1/8-1/81/8---
Toepfer A et al. [101]2017361313/36-----13/366/207/16 ***
Piccioli A et al. [77]2016305-----2/173/13----
Schmolders J et al. [85]2016301---1/30-1/30-1/30---
Schmolders J et al. [86]2016100102/318/520/14-0/310/100-10/100---
Donati F et al. [37]2016688-8/68---3/385/30----
Pala E et al. [73]20166875757/687-----57/68757/6750/12 ***
Calabró T et al. [28]20161096-6/109----6/1096/109---
Torner F et al. [102]2016711/60/1----1/71/7---
Capanna R et al. [30]20152001917/1312/69----19/20019/200---
Pala E et al. [75]20152472323/247-----23/24723/247---
Ercolano LB et al. [39]20152823115/1511/113/3-2/2-31/28210/1016/16-5/5
Ueda T et al. [103]2016258-8/25----8/258/25---
Mavrogenis AF et al. [64]20132252727/225-----27/22527/225---
Cho WH et al. [15]2012621616/62-----16/6216/62---
Ruggieri P et al. [82]20126696060/669-----60/66960/669---
Mavrogenis AF et al. [63]20113322/33-----2/332/33---
Bertani A et al. [25]2009233-3/23----3/232/15--1/8
Kostuj T et al. [58]201368156/322/187/17-0/1-15/682/2213/46--
Hardes J et al. [48]2010125169/707/55---3/5113/7416/125---
Mavrogenis AF et al. [65]201511611008/97810/1541/29---100/1161100/1161---
Toepfer A et al. [100]2018225--5/22---5/221/94/13 ***
Puchner SE et al. [78]2016312312/195/66/6---23/31----
Ruggieri P et al. [81]20101655/16-----5/165/16---
Toepfer A et al. [99]2016188--8/18---8/18-3/11-5/7
Hussman B et al. [52]2013181-----1/18-0/8-1/10-
Höll S et al. [49]20122166/21----3/113/10-6/21 ***
Cannon SR et al. [29]20152711/27----0/21/25-1/27--
Lundh F et al. [61]20141732/101/50/2---3/17-3/17--
Agarwal M et al. [19]20102622/26-----2/26-2/26--
Ribera J et al. [80]2023161-1/16----1/16-1/16 ***
Fiore M et al. [40]20234588/45----8/45---8/45-
Alvand A et al. [20]2018691912/357/40----19/69--19/69-
Marczak S et al. [62]2017911/9-----1/9-0/71/2-
De Gori M et al. [35]201687104/435/401/4---10/87-10/87 ***
Glehr M et al. [41]2013314-----4/31-----
Hu CC et al. [51]201710677/106-----7/106----
Scoccianti G et al. [87]20163330/192/131/1--3/33-----
Corona PS et al. [32]20192953/122/140/3---5/29--5/29-
Sewell MD et al. [88]2010152-2/15----2/15-0/22/90/4
Artiaco S et al. [22]201551-1/5----1/5--1/5-
Crosby SN et al. [33]20117233/72-----3/723/580/2-0/12
Tan PK et al. [97]2009196------6/196/19---
Natarajan MV et al. [69]200791------1/91/9---
Bruns J et al. [27]2007251------1/251/25---
Harde J et al. [48]20102010/31/9-0/50/31/20-1/20---
Natarajan MV et al. [70]20052461717/246-----17/24617/246---
Müller P et al. [67]200295----5/9-5/95/9---
Ozaki T et al. [72]2002123----3/12-3/123/12---
Ilyas I et al. [53]20014844/48-----4/484/48---
Parvizi J et al. [76]2007431-1/43----1/43-1/43 ***
Springer BD et al. [94]20042655/26-----5/26-5/26 ***
Gosheger G et al. [42]20016963/153/330/50/16--6/696/69---
Chandler H et al. [31]1994301-1/30----1/30----
91 10,4561277 (12%)885/5780 (15%)187/1402 (13%)39/139 (28%)13/142 (9%)16/60 (27%)141/1407 (10%)1135/9049 (12.5%)941/4283 (22%)76/652 (12%)84/318 (26%)24/142 (17%)
* Infections/“lower limb” replacement; ** Infections/“upper limb” replacement; *** Infections/“non-oncological” (including trauma, PJI and mechanical failure).
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Cianni, L.; Taccari, F.; Bocchi, M.B.; Micheli, G.; Sangiorgi, F.; Ziranu, A.; Fantoni, M.; Maccauro, G.; Vitiello, R. Characteristics and Epidemiology of Megaprostheses Infections: A Systematic Review. Healthcare 2024, 12, 1283. https://doi.org/10.3390/healthcare12131283

AMA Style

Cianni L, Taccari F, Bocchi MB, Micheli G, Sangiorgi F, Ziranu A, Fantoni M, Maccauro G, Vitiello R. Characteristics and Epidemiology of Megaprostheses Infections: A Systematic Review. Healthcare. 2024; 12(13):1283. https://doi.org/10.3390/healthcare12131283

Chicago/Turabian Style

Cianni, Luigi, Francesco Taccari, Maria Beatrice Bocchi, Giulia Micheli, Flavio Sangiorgi, Antonio Ziranu, Massimo Fantoni, Giulio Maccauro, and Raffaele Vitiello. 2024. "Characteristics and Epidemiology of Megaprostheses Infections: A Systematic Review" Healthcare 12, no. 13: 1283. https://doi.org/10.3390/healthcare12131283

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop