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Evidence-Based Orthopaedics   |    
Utility of Intraoperative Frozen Section Histopathology in the Diagnosis of Periprosthetic Joint InfectionA Systematic Review and Meta-Analysis
Geoffrey Tsaras, MBChB, MPH1; Awele Maduka-Ezeh, MBBS, MPH2; Carrie Y. Inwards, MD2; Tad Mabry, MD2; Patricia J. Erwin, MLS2; M. Hassan Murad, MD, MPH2; Victor M. Montori, MD, MSc2; Colin P. West, MD, PhD2; Douglas R. Osmon, MD, MPH2; Elie F. Berbari, MD2
1 Department of Medicine, University of Illinois College of Medicine at Rockford, 1601 Parkview Avenue, Rockford, IL 61107. E-mail address: gtsaras@uic.edu
2 Division of Infectious Diseases, Department of Medicine (A.M.-E., D.R.O, and E.F.B.); Department of Pathology (C.Y.I.); Department of Orthopedic Surgery (T.M.); Mayo Clinic Libraries (P.J.E.); Knowledge and Encounter Research Unit, Department of Medicine (M.H.M. and V.M.M.); Division of General Internal Medicine, Department of Medicine, and Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (C.P.W.), Mayo Clinic, 200 First Street S.W., Rochester, MN 55905
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Investigation performed at the Mayo Clinic, Rochester, Minnesota



Disclosure: None of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of any aspect of this work. One or more of the authors, or his or her institution, has had a financial relationship, in the thirty-six months prior to submission of this work, with an entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. No author has had any other relationships, or has engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

Copyright © 2012 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2012 Sep 19;94(18):1700-1711. doi: 10.2106/JBJS.J.00756
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Abstract

Background: 

The accuracy of intraoperative periprosthetic frozen section histologic evaluation in predicting a diagnosis of periprosthetic joint infection prior to microbiologic culture results is unknown.

Methods: 

We performed a systematic review and meta-analysis of all longitudinal studies that compared frozen section histologic results with simultaneously obtained microbiologic culture at the time of revision total hip or total knee arthroplasty. The data sources were Ovid MEDLINE, Ovid EMBASE, the Cochrane Library, ISI Web of Science, and SCOPUS, from the inception of each database to January 2010.

Results: 

Twenty-six studies involving 3269 patients undergoing revision hip or knee arthroplasty met the inclusion criteria. A culture-positive periprosthetic joint infection was confirmed in 796 (24.3%) of the patients. Frozen section results, using any of the diagnostic criteria chosen by the investigating pathologist, had a pooled diagnostic odds ratio of 54.7 (95% confidence interval [CI], 31.2 to 95.7), a likelihood ratio of a positive test of 12.0 (95% CI, 8.4 to 17.2), and a likelihood ratio of a negative test of 0.23 (95% CI, 0.15 to 0.35) for the diagnosis of periprosthetic joint infection. Fifteen studies utilizing a threshold of five polymorphonuclear leukocytes (PMNs) per high-power field to define a positive frozen section had a diagnostic odds ratio of 52.6 (95% CI, 23.7 to 116.2), and six studies utilizing a diagnostic threshold of ten PMNs per high-power field had a diagnostic odds ratio of 69.8 (95% CI, 33.6 to 145.0). There was no significant difference between the diagnostic odds ratio or likelihood ratios associated with these thresholds. The moderate to high heterogeneity among the included studies was unexplained by variability in the study design, diagnostic criteria for acute inflammation, reference standard for periprosthetic joint infection, or prevalence of infection. This heterogeneity could be due to differences in the inclusion and exclusion criteria, tissue sampling error, experience or technique of the pathologists, number of microscopic fields visualized, and field diameter examined.

Conclusions: 

Intraoperative frozen sections of periprosthetic tissues performed well in predicting a diagnosis of culture-positive periprosthetic joint infection but had moderate accuracy in ruling out this diagnosis. Frozen section histopathology should therefore be considered a valuable part of the diagnostic work-up for patients undergoing revision arthroplasty, especially when the potential for infection remains after a thorough preoperative evaluation. The optimum diagnostic threshold (number of PMNs per high-power field) required to distinguish periprosthetic joint infection from aseptic failure could not be discerned from the included studies. There was no significant difference between the diagnostic accuracy of frozen section histopathology utilizing the most common thresholds of five or ten PMNs per high-power field.

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    References

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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    Geoffrey Tsaras, Douglas R. Osmon, Elie F. Berbari
    Posted on November 05, 2012
    Response to the comments of Bauer et al.

    We have read the comments of Dr. Bauer et al. with deep interest. We thank them for their comments, and submit our response to the specific concerns raised.

    First of all, it is worth noting that our paper is a systematic review of all relevant published peer-reviewed longitudinal studies that assessed the accuracy of intraoperative frozen sections in the diagnosis of periprosthetic infections at the time of revision hip or knee surgery, in comparison to simultaneously obtained microbiologic cultures, as at January 2010. The literature review/methods section clearly states that.

    Secondly, the timeline between research and publication provides a clue to the unintended omissions noted by Bauer et al. The research was conducted between February and April 2010, with our original submission to the Journal on May 1st, 2010. The first revision was submitted on November 8, 2010 and the final revision on October 3rd, 2011. The paper was accepted for publication on October 28, 2011, and published in September 2012.

    The American Academy of Orthopedic Surgeons (AAOS) guidelines(1) were submitted to the Board of Directors on June 18, 2010 (after our original submission) and published later in J Am Acad Orthop Surg (2) and Journal of Bone and Joint Surgery(3).

    In anticipation that any new studies, narrative reviews or guidelines could have been issued between our original submission and actual date of publication, perhaps we should have explicitly prefaced the two statements “the overall performance of intraoperative frozen sections in the diagnostic algorithm for periprosthetic joint infection has not been systematically reviewed” and "There is currently no published practice guideline from the Infectious Disease Society of America (IDSA) or the American Academy of Orthopedic Surgeons (AAOS) regarding a diagnostic algorithm for peri-prosthetic joint infection" with "At the time of this study..."

    Those statements were not inaccurate at the time of our original submission. Subsequent revisions did not capture intervening events. We submit that the omission was inadvertent, and we regret the error.

    References

    1. http://www.aaos.org/research/guidelines/PJIguideline.pdf

    2. Della Valle C, Parvizi J, Bauer TW, DeCesare PE, Evans RP, Segreti J, Spangehl M, Watters WC, Keith M, Turkelson CM, Weis JL, Slulka P, Hitchcock K. Diagnosis of periprosthetic joint infections of the hip and knee. AAOS Clinical Practice Guideline summary. J Am Acad Orthop Surg 2010;18:760- 770.

    3 . Della Valle C, Parvizi J, Bauer TW, DeCesare PE, Evans RP, Segreti J, Spangehl M, Watters WC, Keith M, Turkelson CM, Weis JL, Slulka P, Hitchcock K. Diagnosis of periprosthetic joint infections of the hip and knee. AAOS Clinical Practice Guideline summary. JBJS(A) 2011;93:355-1357.

    Thomas W. Bauer MD, PhD; Javad Parvizi MD, FRCS; Craig J. Della Valle, MD
    Posted on October 11, 2012
    Surprised by some of the comments made by the authors
    Departments of Pathology, Orthopedic Surgery and The Spine Center, The Cleveland Clinic Foundation; Rothman Institute at Thomas Jefferson University; Midwest orthopaedics at Rush

    We would like to offer a few comments regarding this article. We were surprised by some of the comments that were made by the authors. The authors claim that “the overall performance of intraoperative frozen sections in the diagnostic algorithm for periprosthetic joint infection has not been systematically reviewed” and further state: "There is currently no published practice guideline from the Infectious Disease Society of America (IDSA) or the American Academy of Orthopaedic Surgeons (AAOS) regarding a diagnostic algorithm for peri-prosthetic joint infection." The latter statement is clearly not accurate as there is a AAOS Practice Guidelines entitled: “The Diagnosis of Periprosthetic Joint Infections of the Hip and Knee; Guideline and Evidence Report” that was approved by the AAOS Board of Directors in 2010, summarized in JBJS (2), summarized in J Am Acad Orthop Surg (3), and is available in detail on the AAOS web site (4).

    The formulation of those guidelines included a comprehensive meta-analysis of many diagnostic tests, including frozen sections, and yielded 15 recommendations. The guideline strongly recommended “the use of frozen sections of peri-implant tissues in patients who are undergoing reoperation for whom the diagnosis of periprosthetic joint infection has not been established or excluded”. Further, four distinct diagnostic algorithms are included as part of the guideline. The Tsaras article identified adequate peer review literature to support thresholds of either 5, or 10 or more neutrophils per high power field in at least 5 microscopic fields as suggesting the diagnosis of infection, but did not find sufficient information to distinguish between 5 and 10 neutrophils as the best threshold. Not surprisingly, the AAOS Practice Guideline reported identical findings in 2010 (4).

    The authors of the Tsaras article also note that they "uncovered several research gaps that need addressing". These areas as well as clinical and morphologic settings that may lead to false positive frozen section interpretations have also been thoroughly discussed in other publications (e.g. 5-7).

    We do not disagree with the results and conclusions of the Tsaras article, it is just surprising given their expertise in the field and their extensive review of the literature, that work so similar to their own was neither referenced nor discussed.

    References

    1. Tsaras G, Maduka-Ezeh A, Inwards CY, Mabry T, Erwin PJ, Murad MH, Montori VM, West CP, Osmon DR, Berbari EF. Utility of intraoperative frozen section histopathology in the diagnosis of periprosthetic joint infection: A systematic review and meta-analysis. J Bone Joint Surg 2012;94:1700-1711.

    2. Della Valle C, Parvizi J, Bauer TW, DeCesare PE, Evans RP, Segreti J, Spangehl M, Watters WC, Keith M, Turkelson CM, Weis JL, Slulka P, Hitchcock K. Diagnosis of periprosthetic joint infections of the hip and knee. AAOS Clinical Practice Guideline summary. JBJS(A) 2011;93:355-1357.

    3. Della Valle C, Parvizi J, Bauer TW, DeCesare PE, Evans RP, Segreti J, Spangehl M, Watters WC, Keith M, Turkelson CM, Weis JL, Slulka P, Hitchcock K. Diagnosis of periprosthetic joint infections of the hip and knee. AAOS Clinical Practice Guideline summary. J Am Acad Orthop Surg 2010;18:760-770.

    4. http://www.aaos.org/research/guidelines/PJIguideline.pdf

    5. Bauer TW, Parvizi J, Krebs V, Kobayashi N. Current Concepts Review: Diagnosing periprosthetic infections. J Bone Joint Surg 2006;878:869-888.

    6. Workgroup Convened by the Musculoskeletal Infection Society. New definition for periprosthetic joint infection. J Arthroplasty 2011;26:1136-1138.

    7. Bauer TW, Hayashi R. The role of the pathologist in diagnosing periprosthetic infection. Surgical Pathology 2011;5:67-77.

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