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Authors’ Disclosure Statement: Dr. Philippon reports that he receives royalties from Smith & Nephew, Arthrosurface, Bledsoe, ConMed Linvatec, DonJoy, Slack, and Elsevier; is a consultant for Smith & Nephew; is a Stockholder/Owner in Arthrosurface, MJP Innovations, LLC, and MIS, and receives research funding from Smith & Nephew, Ossur, Siemens, and Vail Valley Medical Center. The other authors report no actual or potential conflict of interest in relation to this article.

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Take-Home Points

Repair the labrum when tissue quality is good.
Avoid overcorrection of acetabulum by measuring center edge angle.
Cam resection should be comprehensive and restore a smooth head-neck offset to restore the suction seal.
Chondral débridement for Outerbridge grade 0-3 and microfracture for grade 4.
Routine capsular closure to prevent postoperative instability.

Management of Acetabular Labrum

Osseous Deformity

Treatment of Cartilage Lesions

Capsule Management

This technique was recently developed and implemented, and short-term results are promising.

Biologics

Rehabilitation

Conclusion

Take-Home Points

Repair the labrum when tissue quality is good.
Avoid overcorrection of acetabulum by measuring center edge angle.
Cam resection should be comprehensive and restore a smooth head-neck offset to restore the suction seal.
Chondral débridement for Outerbridge grade 0-3 and microfracture for grade 4.
Routine capsular closure to prevent postoperative instability.

Management of Acetabular Labrum

Osseous Deformity

Treatment of Cartilage Lesions

Capsule Management

This technique was recently developed and implemented, and short-term results are promising.

Biologics

Rehabilitation

Conclusion

References

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Treatment of Femoroacetabular Impingement: Labrum, Cartilage, Osseous Deformity, and Capsule

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Evolution of Femoroacetabular Impingement Treatment: The ANCHOR Experience

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Evolution of Femoroacetabular Impingement Treatment: The ANCHOR Experience

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Jeffrey J. Nepple

MD; John C. Clohisy

Take-Home Points

Our understanding of FAI has evolved from cam-type and pincer-type impingement to much more complex disease patterns.
Most surgeons are performing less aggressive acetabular rim trimming.
Inadequate osseous correction is still the most common cause of the failed hip arthroscopy.
Labral preservation is important to maintaining suction seal effect.
Open surgical techniques have a role for more severe and complex FAI deformities.

Femoroacetabular impingement (FAI) was described by Ganz and colleagues¹ in 2003 as a refinement of concepts introduced decades earlier. This description advanced our understanding of FAI as a mechanism for prearthritic hip pain and secondary hip osteoarthritis¹ (OA) and allowed for treatment of FAI. The concept of proximal femoral and acetabular/pelvic deformity contributing to OA had been previously speculated by Smith-Petersen,² Murray,³ Solomon,⁴ and Stulberg.⁵ Early cases of overcorrection of dysplasia using the periacetabular osteotomy created iatrogenic FAI, which further stimulated early development of the FAI concept.⁶ Improved anatomical characterization of the proximal femoral blood supply (medial femoral circumflex artery) allowed for development of the open surgical hip dislocation.⁷ Through open surgical hip dislocation, an improved understanding of hip pathomechanics by direct visualization helped pave the way for a better understanding of FAI. Open surgical hip dislocation allows for global treatment of labrochondral pathology and deformity of the proximal femoral head–neck junction and/or acetabular rim in FAI.

Hip arthroscopy has further developed and improved our understanding of FAI. Early hip arthroscopy was generally limited to débridement of labral and chondral pathology, and management of the soft-tissue structures. Advances in the understanding of FAI through open techniques allowed for application of similar techniques to hip arthroscopy. Improvements in arthroscopic instrumentation and techniques have allowed for treatment of labrochondral and acetabular-sided rim deformity in the central compartment and cam morphologies in the peripheral compartment through arthroscopic surgery. Appropriate bony correction by arthroscopic techniques has always been a concern, but improved techniques, dynamic assessment, and accurate use of intraoperative imaging have made this feasible and more predictable. Treatment of cam deformities extending adjacent and proximal to the retinacular vessels is possible but more technically demanding. Inadequate bony correction of FAI by arthroscopic means remains one of the most common causes of failure.^8-10In 2013, the Academic Network of Conservational Hip Outcome Research (ANCHOR) Study Group reported the characteristics of a FAI cohort of 1130 hips (1076 patients) that underwent surgical treatment of FAI across 8 institutions and 12 surgeons.¹¹ At that time, most ANCHOR surgeons (or surgeon groups) performed both open and arthroscopic surgeries and had significant referral volumes of complex cases that may have overrepresented the proportion of complex FAI cases in the cohort. During the 2008 to 2011 study period, FAI was treated with arthroscopy in 56% of these cases, open surgical hip dislocation in 34%, and reverse periacetabular osteotomy in 9%. FAI was characterized as isolated cam-type in 48%, combined cam–pincer type in 45%, and isolated pincer-type in 8%. Fifty-five percent of the patients were female. Patient-reported outcome studies in this cohort of patients are ongoing.

The FAI Concept

In 2003, after treating more than 600 open surgical hip dislocations over the previous decade, Ganz and colleagues¹ coined the term femoroacetabular impingement to describe a “mechanism for the development of early osteoarthritis for most nondysplastic hips.” They reported surgical treatment focused on “improving the clearance for hip motion and alleviation of femoral abutment against the acetabular rim” with the goal of improving pain and possibly of halting progression of the degenerative process. FAI was defined as “abnormal contact between the proximal femur and acetabular rim that occurs during terminal motion of the hip” leading to “lesions of the acetabular labrum and/or the adjacent acetabular cartilage.” Subtle, previously overlooked deformities of the proximal femur and acetabulum were recognized as the cause of FAI, “including the presence of a bony prominence usually in the anterolateral head and neck junction that is seen best on the lateral radiographs, reduced offset of the femoral neck and head junction, and changes on the acetabular rim such as os acetabuli or a double line that is seen with rim ossification.” Ganz and colleagues¹ recognized that “normal or near normal” hips could also experience FAI in the setting of excessive or supraphysiologic range of motion. Cam-type and pincer-type FAI deformities were introduced as 2 distinct mechanisms of FAI. By 2003, arthroscopic hip surgery was increasingly being used as a treatment for labral tears but not bony abnormalities. These FAI concepts seemed to explain the prevalence of labral tears at the anterosuperior rim, which had been noted during hip arthroscopy, and paved the way for major changes in arthroscopic hip surgery during the next decade. The ANCHOR group reported the descriptive epidemiology of a cohort of more than 1000 patients with FAI.¹¹

Cam-Type FAI

Cam-type impingement results from femoral-sided deformities. The mechanism was described as inclusion-type impingement in which “jamming of an abnormal femoral head with increasing radius into the acetabulum during forceful motion, especially flexion.”¹ This results in outside-in abrasion of the acetabular cartilage of the anterosuperior rim with detachment of the “principally uninvolved labrum”¹ and potentially delamination of the adjacent cartilage from the subchondral bone. Ganz and colleagues¹ recognized in their initial descriptions of FAI that cam-type FAI could involve decreased femoral version, femoral head–neck junction asphericity, and decreased head–neck offset. The complexity and variability in the topography and geography of the cam morphology have been increasingly recognized. Accurate understanding and characterization of the proximal femoral deformity are important in guiding surgical correction of the cam deformity.

Advances in understanding the prevalence of the cam morphology and the association with OA have been important to our understanding of the pathophysiology of FAI. Several studies¹² have established that a cam morphology of the proximal femur (defined by a variety of different metrics) is common among asymptomatic individuals. In light of this fact, a description of the femoral anatomy as a “cam morphology” rather than a cam deformity is now favored. Similarly, FAI is better used to refer to symptomatic individuals and is not equivalent to a cam morphology. The cam morphology seems significantly more common among athletes. Siebenrock and colleagues¹³ demonstrated the correlation of high-level athletics during late stages of skeletal immaturity and development of a cam morphology. A recent systematic review of 9 studies found that elite male athletes in late skeletal immaturity were 2 to 8 times more likely to develop a cam morphology before skeletal maturity.¹⁴Several population-based studies^15,16 have quantified the apparent association of the cam morphology with hip OA. However, the studies were limited in their ability to adequately define the presence of cam morphology based on anteroposterior (AP) pelvis radiographs.

In a prospective study, Agricola and colleagues¹⁵ found the risk of OA was increased 2.4 times in the setting of moderate cam morphology (α angle, >60°) over a 5-year period. Thomas and colleagues¹⁶ found increased risk in a female cohort when the α angle was >65°.

Treatment of cam-type FAI is focused on adequate correction of the abnormal bone morphology. Inadequate or inappropriate bony correction of FAI is a common cause of treatment failure and is more common with arthroscopic techniques.^9,10,17 Inadequate bony resection may be the result of surgical inexperience, poor visualization, or lack of understanding of the underlying bony deformity. Modern osteoplasty techniques also focus on gradual bony contour correction that restores the normal concavity–convexity transition of the head–neck junction. Overresection of the cam deformity not only may increase the risk of femoral neck fracture but may result in early disruption of the hip fluid seal from loss of contact between the femoral head and the acetabular labrum earlier in the arc of motion. In addition, high range-of-motion impingement can be seen in various athletic populations (dance, gymnastics, martial arts, hockey goalies), and the regions of impingement tend to be farther away from classically described impingement. Impingement in these situations occurs at the distal femoral neck and subspine regions, adding a level of complexity and unpredictability from a surgical standpoint.

FAI can also occur in the setting of more complex deformities than the typical cam morphology. Complex cases of FAI caused by slipped capital femoral epiphysis (SCFE) and residual Legg-Calvé-Perthes disease are relatively common. Complex deformities may also result in extra-articular impingement of the proximal femur (greater/lesser trochanter, distal femoral neck) on the pelvis (ilium, ischium) in addition to typical FAI. Mild to moderate cases of residual SCFE may be adequately treated with osteoplasty by arthroscopic techniques. In the setting of more severe residual SCFE, presence of underlying femoral retroversion and retrotilt of the femoral epiphysis may prevent adequate deformity correction and motion improvement by arthroscopy. Surgical hip dislocation (with or without relative femoral neck lengthening) and/or proximal femoral flexion derotational osteotomy may be the best means of treatment in these more severe deformities but may be dependent on the chronicity of the deformity and associated compensatory changes occurring on the acetabular side. Similarly, in moderate to severe residual Legg-Calvé-Perthes disease, presence of coxa vara, high greater trochanter, short femoral neck, and ovoid femoral head may be better treated in open techniques to allow comprehensive deformity correction, including correction of acetabular dysplasia in some cases.

Pincer-Type FAI

Pincer-type FAI results from acetabular-sided deformities in which acetabular deformity leads to impaction-type impingement with “linear contact between the acetabular rim and the femoral head–neck junction.”¹ Pincer FAI causes primarily labral damage with progressive degeneration and, in some cases, ossification of the acetabular labrum that further worsens the acetabular overcoverage and premature rim impaction. Chondral damage in pincer-type FAI is generally less significant and limited to the peripheral acetabular rim.

Pincer-type FAI may be caused by acetabular retroversion, coxa profunda, or protrusio acetabuli. Our understanding of what defines a pincer morphology has evolved significantly. Through efforts to better define structural features of the acetabular rim that represent abnormalities, we have improved our understanding of how these features may influence OA development. One example of improved understanding involves coxa profunda, classically defined as the medial acetabular fossa touching or projecting medial to the ilioischial line on an AP pelvis radiograph. Several studies have found that this classic definition poorly describes the “overcovered” hip, as it is present in 70% of females and commonly present (41%) in the setting of acetabular dysplasia.^18,19 Acetabular retroversion was previously associated with hip OA. Although central acetabular retroversion is relatively uncommon, cranial acetabular retroversion is more common. Presence of a crossover sign on AP pelvis radiographs generally has been viewed as indicative of acetabular retroversion. However, alterations in pelvic tilt on supine or standing AP pelvis radiographs can result in apparent retroversion in the setting of normal acetabular anatomy²⁰ and potentially influence the development of impingement.²¹ Zaltz and colleagues²² found that abnormal morphology of the anterior inferior iliac spine can also lead to the presence of a crossover sign in an otherwise anteverted acetabulum. Larson and colleagues²³ recently found that a crossover sign is present in 11% of asymptomatic hips (19% of males) and may be considered a normal variant. A crossover sign can also be present in the setting of posterior acetabular deficiency with normal anterior acetabular coverage. Ultimately, acetabular retroversion might indicate pincer-type FAI or dysplasia or be a normal variant that does not require treatment. Global acetabular overcoverage, including coxa protrusio, may be associated with OA in population-based studies but is not uniformly demonstrated in all studies.^16,24,25 A lateral center edge angle of >40° and a Tönnis angle (acetabular inclination) of <0° are commonly viewed as markers of global overcoverage.

FAI Treatment

Improvements in hip arthroscopy techniques and instrumentation have led to hip arthroscopy becoming the primary surgical technique for the treatment of most cases of FAI. Hip arthroscopy allows for precise visualization and treatment of labral and chondral disease in the central compartment by traction. Larson and colleagues²⁶ reported complication rates for hip arthroscopy in a prospective series of >1600 cases. The overall complication rate was 8.3%, with higher rates noted in female patients and in the setting of traction time longer than 60 minutes. Nonetheless, major complications occurred in 1.1%, with only 0.1% having persistent disability. The most common complications were lateral femoral cutaneous nerve dysesthesias (1.6%), pudendal nerve neuropraxia (1.4%), and iatrogenic labral/chondral damage (2.1%).

The importance of preserving the acetabular labrum is now well accepted from clinical and biomechanical evidence.^27-29 As in previous studies in surgical hip dislocation,³⁰ arthroscopic labral repair (vs débridement) results in improved clinical outcomes.^31,32 Labral repair techniques currently focus on stable fixation of the labrum while maintaining the normal position of the labrum relative to the femoral head and avoiding labral eversion, which may compromise the hip suction seal. With continued technical advancements and biomechanical support, arthroscopic labral reconstruction is possible in the setting of labral deficiency, often resulting from prior resection. However, the optimal indications, surgical techniques, and long-term outcomes continue to be better defined. Open and arthroscopic techniques have shown similar ability to correct the typical mild to moderate cam morphology in FAI.³³ Yet, inadequate femoral bony correction of FAI seems to be the most common cause for revision hip preservation surgery.^9,10,17Mild to moderate acetabular rim deformities are commonly treated with hip arthroscopy. As our understanding of pincer-type FAI continues to improve, many surgeons are performing less- aggressive bone resection along the anterior rim. On the other hand, subspinous impingement was recently recognized as a form of extra-articular pincer FAI variant.³⁴ Subspine decompression without true acetabular rim resection has become a more common treatment for pincer lesions and may be a consideration even with restricted range of motion after periacetabular osteotomy. Severe acetabular deformities with global overcoverage or acetabular protrusion are particularly challenging by arthroscopy, even for the most experienced surgeons. Although some improvement in deformity is feasible with arthroscopy, even cases reported in the literature have demonstrated incomplete deformity correction. Open surgical hip dislocation may continue to be the ideal treatment technique for severe pincer impingement.

Cam-type FAI is commonly treated with hip arthroscopy (Figures A-F).

Dynamic examination during hip arthroscopy, similar to that performed with open techniques, can also be helpful in demonstrating FAI in the typical anterosuperior location. It may be crucial to perform an arthroscopic dynamic assessment in various positions (flexion-abduction, extension-abduction, flexion-internal rotation) in order to more accurately evaluate potential regions of impingement. Fluoroscopic imaging is generally used to guide and confirm appropriate deformity correction.³⁵ Anterior and anterolateral head–neck junction deformity is well accessed in 30° to 45° of hip flexion. Both interportal and T-type capsulotomies can be used, generally depending on surgeon preference. FAI deformity extending distal along the head–neck junction can be more challenging to access without a T-type capsulotomy. FAI deformities that extend laterally and are visible on an AP pelvis radiograph remain the most challenging aspect of arthroscopic FAI surgery. These areas of deformity can be better accessed with the hip in extension and sometimes even with traction applied. Access to the more cranial and posterior extensions of these deformities is more difficult in the setting of femoral retroversion or relative femoral retroversion, which can often coexist. Fabricant and colleagues³⁶ found relative femoral retroversion (<5° anteversion) was associated with poorer outcomes after arthroscopic treatment of FAI.

Open surgical techniques will continue to have an important role in the treatment of severe and complex FAI deformities in which arthroscopic techniques do not consistently achieve adequate bony correction (Figures A-F). Surgical hip dislocation remains a powerful surgical technique for deformity correction in FAI. Sink and colleagues³⁷reported rates of complications after open surgical hip dislocation in the ANCHOR study group. In a cohort of 334 hips (302 patients), trochanteric nonunion occurred in 1.8% of cases, and there were no cases of avascular necrosis. Overall major complications were observed in 4.8% of cases, with 0.3% having chronic disability. Excellent outcomes, including high rates of return to sports, have been reported after surgical hip dislocation for FAI.³⁸ Midterm studies from the early phase of surgical treatment of FAI have helped identify factors that may play a major role in optimizing patient outcomes.

Conclusion

Our understanding and treatment of FAI continue to evolve. Both open and arthroscopic techniques have demonstrated excellent outcomes in the treatment of FAI. Most cases of FAI are now amenable to arthroscopic treatment. Inadequate resection and underlying acetabular dysplasia remain common causes of treatment failure. Open surgical hip dislocation continues to play a role in the treatment of severe deformities that are poorly accessible by arthroscopy—including cam lesions with posterior extension, severe global acetabular overcoverage, or extra-articular impingement. The association of FAI with OA is most apparent for cam-type FAI. Future research will define the optimal treatment strategies and determine if they modify disease progression.

Am J Orthop. 2017;46(1):28-34. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

References

1. Ganz R, Parvizi J, Beck M, Leunig M, Nötzli H, Siebenrock KA. Femoroacetabular impingement: a cause for osteoarthritis of the hip. Clin Orthop Relat Res. 2003;(417):112-120.

2. Smith-Petersen MN. The classic: treatment of malum coxae senilis, old slipped upper femoral epiphysis, intrapelvic protrusion of the acetabulum, and coxa plana by means of acetabuloplasty. 1936. Clin Orthop Relat Res. 2009;467(3):608-615.

3. Murray RO. The aetiology of primary osteoarthritis of the hip. Br J Radiol. 1965;38(455):810-824.

4. Solomon L. Patterns of osteoarthritis of the hip. J Bone Joint Surg Br. 1976;58(2):176-183.

5. Stulberg SD. Unrecognized childhood hip disease: a major cause of idiopathic osteoarthritis of the hip. In: Cordell LD, Harris WH, Ramsey PL, MacEwen GD, eds. The Hip: Proceedings of the Third Open Scientific Meeting of the Hip Society. St. Louis, MO: Mosby; 1975:212-228.

6. Myers SR, Eijer H, Ganz R. Anterior femoroacetabular impingement after periacetabular osteotomy. Clin Orthop Relat Res. 1999;(363):93-99.

7. Ganz R, Gill TJ, Gautier E, Ganz K, Krügel N, Berlemann U. Surgical dislocation of the adult hip: a technique with full access to the femoral head and acetabulum without the risk of avascular necrosis. J Bone Joint Surg Br. 2001;83(8):1119-1124.

8. Ross JR, Larson CM, Adeoye O, Kelly BT, Bedi A. Residual deformity is the most common reason for revision hip arthroscopy: a three-dimensional CT study. Clin Orthop Relat Res. 2015;473(4):1388-1395.

9. Clohisy JC, Nepple JJ, Larson CM, Zaltz I, Millis M; Academic Network of Conservation Hip Outcome Research (ANCHOR) Members. Persistent structural disease is the most common cause of repeat hip preservation surgery. Clin Orthop Relat Res. 2013;471(12):3788-3794.

10. Heyworth BE, Shindle MK, Voos JE, Rudzki JR, Kelly BT. Radiologic and intraoperative findings in revision hip arthroscopy. Arthroscopy. 2007;23(12):1295-1302.

11. Clohisy JC, Baca G, Beaulé PE, et al; ANCHOR Study Group. Descriptive epidemiology of femoroacetabular impingement: a North American cohort of patients undergoing surgery. Am J Sports Med. 2013;41(6):1348-1356.

12. Frank JM, Harris JD, Erickson BJ, et al. Prevalence of femoroacetabular impingement imaging findings in asymptomatic volunteers: a systematic review. Arthroscopy. 2015;31(6):1199-11204.

13. Siebenrock KA, Ferner F, Noble PC, Santore RF, Werlen S, Mamisch TC. The cam-type deformity of the proximal femur arises in childhood in response to vigorous sporting activity. Clin Orthop Relat Res. 2011;469(11):3229-3240.

14. Nepple JJ, Vigdorchik JM, Clohisy JC. What is the association between sports participation and the development of proximal femoral cam deformity? A systematic review and meta-analysis. Am J Sports Med. 2015;43(11):2833-2840.

15. Agricola R, Waarsing JH, Arden NK, et al. Cam impingement of the hip: a risk factor for hip osteoarthritis. Nat Rev Rheumatol. 2013;9(10):630-634.

16. Thomas GE, Palmer AJ, Batra RN, et al. Subclinical deformities of the hip are significant predictors of radiographic osteoarthritis and joint replacement in women. A 20 year longitudinal cohort study. Osteoarthritis Cartilage. 2014;22(10):1504-1510.

17. Philippon MJ, Schenker ML, Briggs KK, Kuppersmith DA, Maxwell RB, Stubbs AJ. Revision hip arthroscopy. Am J Sports Med. 2007;35(11):1918-1921.

18. Nepple JJ, Lehmann CL, Ross JR, Schoenecker PL, Clohisy JC. Coxa profunda is not a useful radiographic parameter for diagnosing pincer-type femoroacetabular impingement. J Bone Joint Surg Am. 2013;95(5):417-423.

19. Anderson LA, Kapron AL, Aoki SK, Peters CL. Coxa profunda: is the deep acetabulum overcovered? Clin Orthop Relat Res. 2012;470(12):3375-3382.

20. Siebenrock KA, Kalbermatten DF, Ganz R. Effect of pelvic tilt on acetabular retroversion: a study of pelves from cadavers. Clin Orthop Relat Res. 2003;(407):241-248.

21. Ross JR, Nepple JJ, Philippon MJ, Kelly BT, Larson CM, Bedi A. Effect of changes in pelvic tilt on range of motion to impingement and radiographic parameters of acetabular morphologic characteristics. Am J Sports Med. 2014;42(10):2402-2409.

22. Zaltz I, Kelly BT, Hetsroni I, Bedi A. The crossover sign overestimates acetabular retroversion. Clin Orthop Relat Res. 2013;471(8):2463-2470.

23. Larson CM, Moreau-Gaudry A, Kelly BT, et al. Are normal hips being labeled as pathologic? A CT-based method for defining normal acetabular coverage. Clin Orthop Relat Res. 2015;473(4):1247-1254.

24. Gosvig KK, Jacobsen S, Sonne-Holm S, Palm H, Troelsen A. Prevalence of malformations of the hip joint and their relationship to sex, groin pain, and risk of osteoarthritis: a population-based survey. J Bone Joint Surg Am. 2010;92(5):1162-1169.

25. Agricola R, Heijboer MP, Roze RH, et al. Pincer deformity does not lead to osteoarthritis of the hip whereas acetabular dysplasia does: acetabular coverage and development of osteoarthritis in a nationwide prospective cohort study (CHECK). Osteoarthritis Cartilage. 2013;21(10):1514-1521.

26. Larson CM, Clohisy JC, Beaulé PE, et al; ANCHOR Study Group. Intraoperative and early postoperative complications after hip arthroscopic surgery: a prospective multicenter trial utilizing a validated grading scheme. Am J Sports Med. 2016;44(9):2292-2298.

27. Ferguson SJ, Bryant JT, Ganz R, Ito K. An in vitro investigation of the acetabular labral seal in hip joint mechanics. J Biomech. 2003;36(2):171-178.

28. Nepple JJ, Philippon MJ, Campbell KJ, et al. The hip fluid seal—part II: the effect of an acetabular labral tear, repair, resection, and reconstruction on hip stability to distraction. Knee Surg Sports Traumatol Arthrosc. 2014;22(4):730-736.

29. Philippon MJ, Nepple JJ, Campbell KJ, et al. The hip fluid seal—part I: the effect of an acetabular labral tear, repair, resection, and reconstruction on hip fluid pressurization. Knee Surg Sports Traumatol Arthrosc. 2014;22(4):722-729.

30. Espinosa N, Rothenfluh DA, Beck M, Ganz R, Leunig M. Treatment of femoro-acetabular impingement: preliminary results of labral refixation. J Bone Joint Surg Am. 2006;88(5):925-935.

31. Krych AJ, Thompson M, Knutson Z, Scoon J, Coleman SH. Arthroscopic labral repair versus selective labral debridement in female patients with femoroacetabular impingement: a prospective randomized study. Arthroscopy. 2013;29(1):46-53.

32. Larson CM, Giveans MR. Arthroscopic debridement versus refixation of the acetabular labrum associated with femoroacetabular impingement. Arthroscopy. 2009;25(4):369-376.

33. Bedi A, Zaltz I, De La Torre K, Kelly BT. Radiographic comparison of surgical hip dislocation and hip arthroscopy for treatment of cam deformity in femoroacetabular impingement. Am J Sports Med. 2011;39(suppl):20S–28S.

34. Larson CM, Kelly BT, Stone RM. Making a case for anterior inferior iliac spine/subspine hip impingement: three representative case reports and proposed concept. Arthroscopy. 2011;27(12):1732-1737.

35. Ross JR, Bedi A, Stone RM, et al. Intraoperative fluoroscopic imaging to treat cam deformities: correlation with 3-dimensional computed tomography [published correction appears in Am J Sports Med. 2015;43(8):NP27]. Am J Sports Med. 2014;42(6):1370-1376.

36. Fabricant PD, Fields KG, Taylor SA, Magennis E, Bedi A, Kelly BT. The effect of femoral and acetabular version on clinical outcomes after arthroscopic femoroacetabular impingement surgery. J Bone Joint Surg Am. 2015;97(7):537-543.

37. Sink EL, Beaulé PE, Sucato D, et al. Multicenter study of complications following surgical dislocation of the hip. J Bone Joint Surg Am. 2011;93(12):1132-1136.

38. Naal FD, Miozzari HH, Wyss TF, Nötzli HP. Surgical hip dislocation for the treatment of femoroacetabular impingement in high-level athletes. Am J Sports Med. 2011;39(3):544-550.

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ANCHOR Study Group Members who contributed to this article

Asheesh Bedi, MD, Etienne L. Belzile, MD, Christopher M. Larson, MD, Travis H. Matheney, MD, Michael B. Millis, MD, Christopher L. Peters, MD, David A. Podeszwa, MD, James R. Ross, MD, Wudbhav N. Sankar, MD, Perry L. Schoenecker, MD, Rafael J. Sierra, MD, Ernest L. Sink, MD, Michael D. Stover, MD, Daniel J. Sucato, MD, Yi-Meng Yen, MD, PhD, and Ira Zaltz, MD

Authors’ Disclosure Statement: Dr. Nepple reports that he is a consultant to, a speaker for, and receives research support from Smith & Nephew. Dr. Clohisy reports that he receives research support from the National Football League grant, the Curing Hip Disease Fund, the International Hip Dysplasia Institute, and the Washington University Institute of Clinical and Translational Sciences (National Institutes of Health grant UL1RR024992). ANCHOR Study Group Members report that they receive research support from Zimmer Biomet and ANCHOR Research Fund.

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Take-Home Points

Our understanding of FAI has evolved from cam-type and pincer-type impingement to much more complex disease patterns.
Most surgeons are performing less aggressive acetabular rim trimming.
Inadequate osseous correction is still the most common cause of the failed hip arthroscopy.
Labral preservation is important to maintaining suction seal effect.
Open surgical techniques have a role for more severe and complex FAI deformities.

The FAI Concept

Cam-Type FAI

Pincer-Type FAI

FAI Treatment

Conclusion

Take-Home Points

Our understanding of FAI has evolved from cam-type and pincer-type impingement to much more complex disease patterns.
Most surgeons are performing less aggressive acetabular rim trimming.
Inadequate osseous correction is still the most common cause of the failed hip arthroscopy.
Labral preservation is important to maintaining suction seal effect.
Open surgical techniques have a role for more severe and complex FAI deformities.

The FAI Concept

Cam-Type FAI

Pincer-Type FAI

FAI Treatment

Conclusion

References

Issue

The American Journal of Orthopedics - 46(1)

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The American Journal of Orthopedics - 46(1)

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28-34

Page Number

28-34

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Multicenter Outcomes After Hip Arthroscopy: Epidemiology (MASH Study Group). What Are We Seeing in the Office, and Who Are We Choosing to Treat?

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Benjamin R. Kivlan, PhD, PT

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Multicenter Outcomes After Hip Arthroscopy: Epidemiology (MASH Study Group). What Are We Seeing in the Office, and Who Are We Choosing to Treat?

Author(s)

Shane J. Nho, MD

John J. Christoforetti, MD

Geoffrey S. Van Thiel, MD, MBA

Allston J. Stubbs, MBA

Dominic S. Carreira, MD

Take-Home Points

MASH is a multicenter arthroscopic study of the hip that features a large prospective database of 10 separate institutions in the United States.
The mean patient demographic was age 34.6 years, BMI 25.9 kg/m², 62.8% females, and 97% white.
Most patients had anterior or groin pain, but 17.6% had lateral hip pain, 13.8% had posterior hip pain, and 2.9% had low back or sacral pain.
Patients typically had pain for about 1 year that was worsened with athletic activity as well as sitting.
The most common surgical procedures that were performed included labral surgery in 64.7%, femoroplasty in 49.9%, acetabuloplasty in 33.3%, and chondroplasty in 31.1%

Arthroscopic surgery of the hip has been growing over the past decade, with drastically increasing rates of arthroscopic hip procedures and increased education and interest in orthopedic trainees.^1-3 The rise of this minimally invasive surgical technique may be attributed to expanding knowledge of surgical management of morphologic hip disorders as a means of hip preservation. Many arthroscopic techniques have been developed to treat intra-articular hip joint pathologies, including femoroacetabular impingement (FAI), labral tears, and cartilage damage.^4-11 These hip pathologies are widely recognized as painful limitations to activities of daily living and sports as well as early indicators of hip osteoarthritis.^12,13 Limited evidence suggests that arthroscopic treatment of these intra-articular hip joint pathologies preserves the hip from osteoarthritis and progression to total hip arthroplasty.^13-15

FAI is the most common etiology of pathologies related to arthroscopic surgery of the hip, including both labral tears and cartilage damage.^4,7,14 FAI is a morphologic bone disorder characterized by impingement of the femur and the acetabulum on flexion or rotation. The etiology of FAI is not completely understood, but evidence suggests that stress to the proximal femoral physis during skeletal growth increases the risk of developing femoral head and neck deformations leading to cam-type FAI.^15-17 Understanding the characteristics of the patient population in which FAI occurs may shed light on the processes of intra-articular damage, such as labral tears and cartilage damage.

In the present study, we collected epidemiologic data, including demographics, pathologic entities treated, patient-reported measures of disease, and surgical treatment preferences, on a hip pathology population that elected to undergo arthroscopic surgery. These data are important in gaining a better understanding of the population and environment in which hip arthroscopy is performed across multiple centers throughout the United States and may help guide clinical practice and research to advance hip arthroscopy.

Methods

The Multicenter Arthroscopic Study of the Hip (MASH) Study Group conducts multicenter clinical studies in arthroscopic hip preservation surgery. Patients are enrolled in this large prospective longitudinal study at 10 sites nationwide by 10 fellowship-trained hip arthroscopists. Institutional Review Board approval was obtained from all institutions before patient enrollment. After enrollment, we collected comprehensive patient data, including demographics, common symptoms and their duration, provocative activities, patient-reported outcome measures (modified Harris Hip Score, International Hip Outcome Tool, 12-item Short Form Health Survey, visual analog scale pain rating, Hip Outcome Score), physical examination findings, imaging findings, diagnoses, surgical findings, and surgical procedures.

All study participants were patients undergoing arthroscopic hip surgery by one of the members of the MASH Study Group. Patients with incomplete preoperative information (needed for data analysis) were excluded. Data analysis was performed with SPSS Statistics Version 21.0 (SPSS Inc.) to obtain descriptive statistics of the quantitative data and frequencies of the nominal data.

Results

Between January 2014 and November 2016, we enrolled 1738 patients (647 male, 1091 female) in the study. Table 1 lists the demographics of the population.

Mean age was 34.6 years (range, 11-77 years); mean height, 67.1 inches (range, 54-180 inches); mean weight, 163.4 pounds (range, 62-325 pounds); and mean body mass index, 25.9 kg/m² (range, 7-57.1 kg/m²). Ninety-seven percent of the patients were white, 1.7% African-American, 1% Hispanic, and 0.30% Asian. In 55% of the cases, the right side was involved; in 43%, the left side; and in 2%, both sides. Only 1.2% of patients reported being a smoker, and 1.1% had services paid through worker’s compensation claims.

Regarding symptom location, 40.9% of patients described pain in the groin region, 24.2% in the anterior hip region, and 11.3% in a C-sign distribution (Table 2).

Lateral pain was reported by 17.6% of patients, and 13.8% of patients complained of pain in the posterior hip and buttock region.

Figure 1 shows that, before surgery, symptoms lasted more than 2 years in 38.4% of cases, between 1 and 2 years in 22%, between 4 and 12 months in 28.7%, and less than 4 months in 10.9%. Figure 2 shows that symptoms were provoked during sports in 47.1% of cases, while sitting in 46.8%, while walking in 39.5%, while standing in 26.4%, and while climbing stairs in 19%.

In addition, 22.3% of patients had a detectable limp, and catching, clicking, or locking occurred in 23.4% of patients.

Table 3 lists the results of the patient-reported outcome measures.

Mean visual analog scale pain rating was 51.8 (range, 0-100), mean modified Harris Hip Score was 53.8 (range, 0-91), mean Hip Outcome Score for activities of daily living was 62.3 (range, 5.9-100), mean Hip Outcome Score for sports was 39.4 (range, 0-100), and mean International Hip Outcome Tool was 33.9 (range, 0-99.3).

Of the 1738 patients enrolled, 424 (24.4%) had prior surgery related to current symptoms, 252 (14.5%) had 1 previous surgery, 120 (6.9%) had 2 previous surgeries, and 52 (3%) had 3 previous surgeries. Twenty-six patients (1.5%) had a previous revision hip arthroscopy on the ipsilateral side, and 14 (0.8%) had a previous hip arthroscopy on the contralateral side. Before surgery, 80% of patients received an intra-articular injection of corticosteroid and lidocaine. The peritrochanteric region was injected in 11.5% of patients and the psoas bursa in 2.2% (Table 4).

Eighty percent of patients attended physical therapy for their hip before electing to have surgery.

Of the 1011 patients who had magnetic resonance imaging (MRI) performed, 943 (93.3%) had abnormal acetabular labrum findings, and 163 (17.1%) had acetabular articular damage. According to radiographic evaluation, 953 patients had abnormal hip joint morphology consistent with FAI. Figure 3 shows the FAI classification percentages.

The combination of cam-type and pincer-type impingement was noted in 42.6% of cases, isolated cam-type impingement in 47%, and isolated pincer-type impingement in 29.5% (61 of the 107 isolated pincer cases had positive radiographic signs of focal acetabular overcoverage). Conversely, 84 patients (4.8%) had signs of hip dysplasia (lateral center edge angle, <25°). Of all 1738 patients, 1602 (92.5%) had Tönnis grade 0 osteoarthritis on radiographic evaluation, 6.3% had Tönnis grade 1, and 1.5% had Tönnis grade 2. The lateral joint space was the most common location for arthrosis (2.1%), followed by the medial joint space (1.3%) and the central joint space (1.1%).

On clinical examination, 1079 patients (62.1%) had a positive anterior impingement sign. The subspine impingement sign was positive in 447 patients (25.7%), and the trochanteric pain sign was positive in 400 (23%). Table 5 lists range-of-motion values for flexion and hip rotation from 90° of flexion.

Loss of motion for hip flexion (<110°) occurred in 57.3% of patients, hip internal rotation of <15° in 42%, external rotation of <45° in 47.3%, and total hip rotation of <60° in 41.7%.

As seen in Table 6, labral pathology was the most common diagnosis (1426/1738 patients, 82%).

Of the entire population, 354 (20.4%) had mild complexity labral tears, 288 (16.6%) had moderate complexity labral tears, and 130 (7.5%) had severe complexity labral tears. Of the 1738 cases total, 487 (28%) had labral bruising, and 167 (9.6%) had degenerative tears. Other diagnoses were 4 cases of septic arthritis (0.2%), 2 cases of avascular necrosis (0.1%), 36 cases of gluteus minimus/medius tears (2.1%), and 198 ligamentum teres tears (11.4%).

As seen in Table 7, the most common procedure was femoroplasty (867/1738, 49.9%).

Other common procedures were synovectomy (833, 47.9%), acetabuloplasty (579, 33.3%), and acetabular chondroplasty (541, 31.1%). Of the 1124 labral tears, 847 (75.3%) were repaired, 154 (13.7%) were reconstructed, and 81 (7.2%) were débrided.

Discussion

In this study, we collected epidemiologic data (demographics, pathologic entities treated, patient-reported measures of disease, surgical treatment preferences) from a large multicenter population of hip pathology patients who elected to undergo arthroscopic surgery. Our results showed these patients were most commonly younger to middle-aged white females with pain primarily in the groin region. Most had pain for at least 1 year, and it was commonly exacerbated by sitting and athletics. Patients reported clinically significant pain and functional limitation, which showed evidence of affecting general physical and mental health. It was not uncommon for patients to have undergone another, related surgery and nonoperative treatments, including intra-articular injection and/or physical therapy, before surgery. There was a high incidence of abnormal hip morphology suggestive of a cam lesion, but the incidence of arthritic changes on radiographs was relatively low. Labral tear was the most common diagnosis, and most often it was addressed with repair. Many patients underwent femoroplasty, acetabuloplasty, and chondroplasty in addition to labral repair.

According to patient-reported outcome measures administered before surgery, 40% to 65% of patients seeking hip preservation surgery reported functional deficits and pain—which falls within the range of results from other multicenter studies on the epidemiology of FAI.^18,19 There was, however, a high amount of variability in individual scores on the functional and pain measures; some patients rated their functional ability very high. These findings were supported by the general health forms measuring global physical and mental health. Mean Physical Health and Mental Health scores on the 12-item Short Form Health Survey indicated that patients seeking hip preservation surgery thought their hip condition affected their general well-being. This finding is consistent with research on FAI,¹⁸ hip arthritis,²⁰ and total hip arthroplasty.¹⁹Our results further showed that hip arthroscopists commonly prescribed alternative treatment measures ahead of surgery. Before elective surgery, 80% of patients received an intra-articular injection, underwent physical therapy, or both. This could suggest a high failure rate for patients who chose conservative treatment approaches for hip-related pathology. However, our study was limited in that it may have included patients who had improved significantly with conservative measures and decided to forgo arthroscopic hip surgery. Although conservative treatment often is recommended in an effort to potentially avoid surgery, there is a lack of research evaluating the efficacy of nonoperative care.^21,22Analysis of diagnostic imaging and clinical examination findings revealed some unique characteristics of patients undergoing elective hip preservation surgery. MRI showed labral pathology in an overwhelming majority of these patients, but few had evidence of articular damage. Previous research has found a 67% rate of arthritic changes on diagnostic imaging, but our rate was much lower (17%).²³ Radiograph evaluation confirmed the pattern: More than 90% of our patients had Tönnis grade 0 osteoarthritis. Tönnis grade 1 or 2 osteoarthritis is a predictor of acetabular cartilage degeneration,²³ and long-term studies have related these osteoarthritic changes to poorer hip arthroscopy outcomes.²⁴ Thus, the lower incidence of osteoarthritis in our study population may reflect current evidence-based practice and a contemporary approach to patient selection.

Most of our patients had isolated cam-type FAI as opposed to pincer-type FAI or a combination of cam and pincer—contrary to research findings that combination cam–pincer FAI is most prevalent.^25,26 Our results are more consistent with more recent research findings of a higher incidence of isolated cam lesion, particularly in female patients, and combination cam–pincer in male patients.^18,27,28 Similar distributions of surgical procedures and diagnoses exist between the present study and other multicenter evaluations of the epidemiologic characteristics of patients with hip pathology.¹⁸Our study had several limitations. First, the population consisted entirely of patients who sought evaluation by a hip arthroscopy specialist and underwent elective surgery. Therefore, the data cannot be applied to a more general orthopedic population or to patients who consult other medical specialists. Second, the population, which was 97% white and had small percentages of African-American, Latino, and Asian patients, lacked ethnic diversity. This finding is consistent with recent epidemiologic research in which ethnicity was identified as a factor in patterns of hip disease.^13,29,30 Access to specialists, however, was likely affected by multiple other factors. Fourth, the validity and the reliability of the imaging modalities used have been questioned.^31-33 There is controversy regarding ideal imaging modalities for assessment of articular cartilage damage^31,32 and FAI. However, the modalities that we used to determine diagnoses in this study are well supported²⁶ and represent common practice patterns.

Am J Orthop. 2017;46(1):35-41. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

References

1. Cvetanovich GL, Chalmers PN, Levy DM, et al. Hip arthroscopy surgical volume trends and 30-day postoperative complications. Arthroscopy. 2016;32(7):1286-1292.

2. Peters CL, Aoki SK, Erickson JA, Anderson LA, Anderson AE. Early experience with a comprehensive hip preservation service intended to improve clinical care, education, and academic productivity. Clin Orthop Relat Res. 2012;470(12):3446-3452.

3. Siebenrock KA, Peters CL. ABJS Carl T. Brighton workshop on hip preservation surgery: editorial comment. Clin Orthop Relat Res. 2012;470(12):3281-3283.

4. Parvizi J, Leunig M, Ganz R. Femoroacetabular impingement. J Am Acad Orthop Surg. 2007;15(9):561-570.

5. Poh SY, Hube R, Dienst M. Arthroscopic treatment of femoroacetabular pincer impingement. Oper Orthop Traumatol. 2015;27(6):536-552.

6. Javed A, O’Donnell JM. Arthroscopic femoral osteochondroplasty for cam femoroacetabular impingement in patients over 60 years of age. J Bone Joint Surg Br. 2011;93(3):326-331.

7. Groh MM, Herrera J. A comprehensive review of hip labral tears. Curr Rev Musculoskelet Med. 2009;2(2):105-117.

8. Philippon MJ, Nepple JJ, Campbell KJ, et al. The hip fluid seal—part I: the effect of an acetabular labral tear, repair, resection, and reconstruction on hip fluid pressurization. Knee Surg Sports Traumatol Arthrosc. 2014;22(4):722-729.

9. White BJ, Herzog MM. Labral reconstruction: when to perform and how. Front Surg. 2015;2:27.

10. Yen YM, Kocher MS. Chondral lesions of the hip: microfracture and chondroplasty. Sports Med Arthrosc. 2010;18(2):83-89.

11. Jordan MA, Van Thiel GS, Chahal J, Nho SJ. Operative treatment of chondral defects in the hip joint: a systematic review. Curr Rev Musculoskelet Med. 2012;5(3):244-253.

12. Griffin DW, Kinnard MJ, Formby PM, McCabe MP, Anderson TD. Outcomes of hip arthroscopy in the older adult: a systematic review of the literature [published online October 18, 2016]. Am J Sports Med. doi:10.1177/0363546516667915.

13. Ganz R, Leunig M, Leunig-Ganz K, Harris WH. The etiology of osteoarthritis of the hip. Clin Orthop Relat Res. 2008;466(2):264-272.

14. Kaya M, Suzuki T, Emori M, Yamashita T. Hip morphology influences the pattern of articular cartilage damage. Knee Surg Sports Traumatol Arthrosc. 2016;24(6):2016-2023.

15. Beck M, Leunig M, Parvizi J, Boutier V, Wyss D, Ganz R. Anterior femoroacetabular impingement: part II. Midterm results of surgical treatment. Clin Orthop Relat Res. 2004;(418):67-73.

16. Byrd JT. Hip arthroscopy in athletes. Oper Tech Sports Med. 2005;13(1):24-36.

17. Werner BC, Gaudiani MA, Ranawat AS. The etiology and arthroscopic surgical management of cam lesions. Clin Sports Med. 2016;35(3):391-404.

18. Clohisy JC, Baca G, Beaulé PE, et al; ANCHOR Study Group. Descriptive epidemiology of femoroacetabular impingement: a North American cohort of patients undergoing surgery. Am J Sports Med. 2013;41(6):1348-1356.

19. Shia DS, Clohisy JC, Schinsky MF, Martell JM, Maloney WJ. THA with highly cross-linked polyethylene in patients 50 years or younger. Clin Orthop Relat Res. 2009;467(8):2059-2065.

20. Gandhi SK, Salmon JW, Zhao SZ, Lambert BL, Gore PR, Conrad K. Psychometric evaluation of the 12-item Short-Form Health Survey (SF-12) in osteoarthritis and rheumatoid arthritis clinical trials. Clin Ther. 2001;23(7):1080-1098.

21. Loudon JK, Reiman MP. Conservative management of femoroacetabular impingement (FAI) in the long distance runner. Phys Ther Sport. 2014;15(2):82-90.

22. Wall PD, Fernandez M, Griffin DR, Foster NE. Nonoperative treatment for femoroacetabular impingement: a systematic review of the literature. PM R. 2013;5(5):418-426.

23. Nepple JJ, Carlisle JC, Nunley RM, Clohisy JC. Clinical and radiographic predictors of intra-articular hip disease in arthroscopy. Am J Sports Med. 2011;39(2):296-303.

24. McCormick F, Nwachukwu BU, Alpaugh K, Martin SD. Predictors of hip arthroscopy outcomes for labral tears at minimum 2-year follow-up: the influence of age and arthritis. Arthroscopy. 2012;28(10):1359-1364.

25. Beck M, Kalhor M, Leunig M, Ganz R. Hip morphology influences the pattern of damage to the acetabular cartilage: femoroacetabular impingement as a cause of early osteoarthritis of the hip. J Bone Joint Surg Br. 2005;87(7):1012-1018.

26. Tannast M, Siebenrock KA, Anderson SE. Femoroacetabular impingement: radiographic diagnosis—what the radiologist should know. AJR Am J Roentgenol. 2007;188(6):1540-1552.

27. Kapron AL, Peters CL, Aoki SK, et al. The prevalence of radiographic findings of structural hip deformities in female collegiate athletes. Am J Sports Med. 2015;43(6):1324-1330.

28. Lee WY, Kang C, Hwang DS, Jeon JH, Zheng L. Descriptive epidemiology of symptomatic femoroacetabular impingement in young athlete: single center study. Hip Pelvis. 2016;28(1):29-34.

29. Dudda M, Kim YJ, Zhang Y, et al. Morphologic differences between the hips of Chinese women and white women: could they account for the ethnic difference in the prevalence of hip osteoarthritis? Arthritis Rheum. 2011;63(10):2992-2999.

30. Solomon L, Beighton P. Osteoarthrosis of the hip and its relationship to pre-existing in an African population. J Bone Joint Surg Br. 1973;55(1):216-217.

31. Keeney JA, Peelle MW, Jackson J, Rubin D, Maloney WJ, Clohisy JC. Magnetic resonance arthrography versus arthroscopy in the evaluation of articular hip pathology. Clin Orthop Relat Res. 2004;(429):163-169.

32. Schmid MR, Nötzli HP, Zanetti M, Wyss TF, Hodler J. Cartilage lesions in the hip: diagnostic effectiveness of MR arthrography. Radiology. 2003;226(2):382-386.

33. Chevillotte CJ, Ali MH, Trousdale RT, Pagnano MW. Variability in hip range of motion on clinical examination. J Arthroplasty. 2009;24(5):693-697.

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Author and Disclosure Information

Authors’ Disclosure Statement: Dr. Nho reports that he is Deputy Editor-in-Chief of The American Journal of Orthopedics; receives research support from Allosource, Arthrex, Athletico, DJ Orthopaedics, Linvatec, Miomed, Smith & Nephew, and Stryker; is a paid consultant to Ossur and Stryker; and receives publishing royalties and financial or material support from Springer. Dr. Christoforetti reports that he receives support from Arthrex and Breg. Dr. Ellis reports that he receives intellectual property royalties from Medacta and research support from Smith & Nephew and is a paid consultant to Stryker. Dr. Matsuda reports
that he receives intellectual property royalties from Arthrocare, Zimmer Biomet, and Smith & Nephew and is a paid consultant to Orthopedics Overseas and Zimmer Biomet. Dr. Salvo reports that he is a paid consultant to Stryker. Dr. Wolff reports that he is a consultant to Stryker. Dr. Van Thiel reports that he is a paid consultant to Smith & Nephew and Zimmer Biomet, receives royalties from Zimmer Biomet, and has equity ownership in Zimmer Biomet. Dr. Stubbs
reports that he is a consultant to Smith & Nephew; receives research support from Bauerfeind and departmental or divisional support from Arthrex, Mitek, and Smith & Nephew; and owns stock in Johnson & Johnson. Dr. Carreira reports that he is a paid consultant to Zimmer Biomet. Dr. Kivlan reports no actual or potential conflict of interest in relation to this article.

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Read more about Multicenter Outcomes After Hip Arthroscopy: Epidemiology (MASH Study Group). What Are We Seeing in the Office, and Who Are We Choosing to Treat?

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Benjamin R. Kivlan, PhD, PT

Author(s)

Shane J. Nho, MD

John J. Christoforetti, MD

Geoffrey S. Van Thiel, MD, MBA

Allston J. Stubbs, MBA

Dominic S. Carreira, MD

Author(s)

Benjamin R. Kivlan, PhD, PT

Shane J. Nho, MD

John J. Christoforetti, MD

Geoffrey S. Van Thiel, MD, MBA

Allston J. Stubbs, MBA

Dominic S. Carreira, MD

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Take-Home Points

MASH is a multicenter arthroscopic study of the hip that features a large prospective database of 10 separate institutions in the United States.
The mean patient demographic was age 34.6 years, BMI 25.9 kg/m², 62.8% females, and 97% white.
Most patients had anterior or groin pain, but 17.6% had lateral hip pain, 13.8% had posterior hip pain, and 2.9% had low back or sacral pain.
Patients typically had pain for about 1 year that was worsened with athletic activity as well as sitting.
The most common surgical procedures that were performed included labral surgery in 64.7%, femoroplasty in 49.9%, acetabuloplasty in 33.3%, and chondroplasty in 31.1%

Methods

Results

Between January 2014 and November 2016, we enrolled 1738 patients (647 male, 1091 female) in the study. Table 1 lists the demographics of the population.

Regarding symptom location, 40.9% of patients described pain in the groin region, 24.2% in the anterior hip region, and 11.3% in a C-sign distribution (Table 2).

Lateral pain was reported by 17.6% of patients, and 13.8% of patients complained of pain in the posterior hip and buttock region.

In addition, 22.3% of patients had a detectable limp, and catching, clicking, or locking occurred in 23.4% of patients.

Table 3 lists the results of the patient-reported outcome measures.

Discussion

Take-Home Points

MASH is a multicenter arthroscopic study of the hip that features a large prospective database of 10 separate institutions in the United States.
The mean patient demographic was age 34.6 years, BMI 25.9 kg/m², 62.8% females, and 97% white.
Most patients had anterior or groin pain, but 17.6% had lateral hip pain, 13.8% had posterior hip pain, and 2.9% had low back or sacral pain.
Patients typically had pain for about 1 year that was worsened with athletic activity as well as sitting.
The most common surgical procedures that were performed included labral surgery in 64.7%, femoroplasty in 49.9%, acetabuloplasty in 33.3%, and chondroplasty in 31.1%

Methods

Results

Between January 2014 and November 2016, we enrolled 1738 patients (647 male, 1091 female) in the study. Table 1 lists the demographics of the population.

Regarding symptom location, 40.9% of patients described pain in the groin region, 24.2% in the anterior hip region, and 11.3% in a C-sign distribution (Table 2).

Lateral pain was reported by 17.6% of patients, and 13.8% of patients complained of pain in the posterior hip and buttock region.

In addition, 22.3% of patients had a detectable limp, and catching, clicking, or locking occurred in 23.4% of patients.

Table 3 lists the results of the patient-reported outcome measures.

Discussion

References

33. Chevillotte CJ, Ali MH, Trousdale RT, Pagnano MW. Variability in hip range of motion on clinical examination. J Arthroplasty. 2009;24(5):693-697.

References

33. Chevillotte CJ, Ali MH, Trousdale RT, Pagnano MW. Variability in hip range of motion on clinical examination. J Arthroplasty. 2009;24(5):693-697.

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Current Concepts in Labral Repair and Refixation: Anatomical Approach to Labral Management

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Current Concepts in Labral Repair and Refixation: Anatomical Approach to Labral Management

Author(s)

Robert Kollorgen

DO; Richard Mather

Take-Home Points

Labral preservation is recommended when possible to ensure restoration of suction seal, stability, and contact pressure of the hip joint.
Over 95% of labral tears can be addressed with primary repair.
Consider using an accessory portal (ie, DALA) to allow for more anatomic placement of suture anchor.
Mattress stitch when labrum >3 mm and looped stitch when labrum <3 mm.

10Control labral repair to avoid excessive inversion or eversion.

Arthroscopic labral repair and refixation have garnered much attention over the past several years. Restoration of suction seal and native labral function has been an evolving focus for achieving excellent results in hip preservation surgery.^1-6 Given the superior results of labral repair, including level I evidence, repair or refixation should be pursued whenever possible.⁷ Authors have reported using several labral management techniques: débridement, labralization, looped suture fixation, base stitch fixation, inversion-eversion, and reconstruction.^7-13 The optimal technique is yet to be determined. When possible, steps should be taken to repair the labrum to an anatomical position. Absolute indications for labral repair are a confirmed intra-articular diagnosis with symptomatic pain, joint space >2 mm with or without femoroacetabular impingement (FAI), labral tear or instability, and failed conservative management.^{9,11,12,14,15} More important, the surgeon must have a clear etiology of the pathologic cause of the tear and be aware of the limitations of the procedure. Labral repair is relatively contraindicated in end-stage arthritis and has failed when used alone in undiagnosed dysplasia or hip instability.¹⁶ In this article, we discuss indications for labral repair; describe Dr. Mather’s preoperative planning, labral repair technique, and postoperative care; and review published outcomes and future trends in labral repair.

Indications

At our institution, anatomical labral repair is the preferred procedure for most primary and revision hip arthroscopy procedures. We aim to restore the suction seal, re-create the contact of the labrum and the femoral head to facilitate proprioception, and restore normal stability of the labrum. Indications for primary repair are labrum width >3 mm, no more than 2 repairs, and ability to hold a suture. Our indications for reconstruction or débridement are stage 3 irreparable labral tear, calcified/cystic labrum, and multiple failed labral repairs or reconstructions. The decision to perform labral débridement or reconstruction is made on a case-by-case basis but is primarily influenced by the stability of the hip joint and the activity goals of the patient. If preoperative presentation and intraoperative examination suggest labral instability as a major component of the pathology, or if the patient wants to return to high-demand activity, we more strongly favor reconstruction over débridement. In our experience, with the technique described in this article, more than 95% of all primary labral tears can be addressed with repair.

Preoperative Planning

The goals in hip preservation surgery are to identify and address the underlying cause of the labral tear, whether it be FAI syndrome, trauma, labral instability, or all 3, and to re-create the anatomy and biomechanics of the acetabular labrum. For repair, we prefer an inversion-eversion technique with independent control of the labrum. Our initial work-up includes a thorough history and physical examination with baseline patient-reported outcome scores. Standard erect anteroposterior pelvis, Dunn lateral, and false-profile radiographs are obtained. Standard measurements of lateral center edge angle, anterior center edge angle, Tönnis angle, Tönnis grade, lateral joint space, and head extrusion indices are evaluated. Selective in-office ultrasound-guided injections are used to confirm an intra-articular source of pain. At our institution, noncontrast 3.0 Tesla magnetic resonance imaging (MRI) with volumetric interpolated breath-hold examination (VIBE) sequencing and 3-dimensional rendering is obtained for evaluation of labral and FAI morphology.¹⁷ All advanced imaging is performed without arthrogram or radiation exposure (Figures 1A-1C).

Although the advanced MRI used is of benefit in preoperative planning, it is limited in detecting labral pathology. Although its results are valuable, they do not predict the operative treatment algorithm of débridement, repair, or reconstruction.¹⁸

With use of the radiographs and the MRI scans, we engage the patient in an informed discussion about the labral tear, FAI, and concomitant pathology. We discuss expected outcomes of conservative or operative management given the patient’s expected functional activities, and inform the patient that primary repair is indicated for many others in similar situations. The potential for possible labral reconstruction is discussed if the patient had prior intra-articular hip surgery, has a large calcified labrum or a cystic labrum, is an athlete with failed prior surgery, or is younger than 40 years.

Labral Repair Technique

The patient is taken to the surgical suite, and a general anesthetic is administered. A peripheral nerve block is not routinely used. The patient’s feet are padded, and boots for the traction table are applied. The patient is carefully placed on a Hana table in modified supine position. Balanced traction is used to achieve proper joint distraction. The C-arm is used to verify proper distraction, assess hip stability, and achieve standard anterolateral (AL) portal placement. A midanterior portal (MAP) is created and an interportal capsulotomy is performed. Capsular suspension is performed with the InJector II Capsule Restoration System (Stryker Sports Medicine) and typically 4 or 5 high-strength No. 2 sutures (Zipline; Stryker Sports Medicine).¹⁹ Diagnostic arthroscopy is performed to identify the tear type, measure the labral width, determine the impingement area, and identify the intra-articular pathology. After the intra-articular pathology is addressed, a radiofrequency Ambient HIPVAC 50 Coblation Wand (Smith & Nephew) is used to expose the acetabular rim and subspine as indicated. Acetabuloplasty or subspine decompression is performed, and then a primary repair or refixation of the labrum is performed. We do not routinely detach the labrum for acetabular rim trimming. A crucial step here is to expose a bleeding surface to which the labrum can be repaired. If the rim is sclerotic, or the rim cannot be removed because of underlying low acetabular coverage, we prefer to obtain the bleeding surface with a microdrilling device (Stryker) that is routinely used for acetabular microfracture.

Labrum quality is used to determine which repair method to use. A hypertrophic labrum is debulked. The acetabular rim is seldom resected >3 mm, but, when it is, the newly exposed cartilage is removed. We have found that >3 mm of residual cartilage prevents refixation of the labrum directly to the bone and may interfere with anatomical positioning. When a labrum is <3 mm in width or will not hold a base technique, repair stability is the priority, and a looped method is used. A knotless anchor with No. 1 permanent suture designed for hip labral repair (CinchLock; Stryker) is our first-line anchor choice. A distal anterolateral accessory (DALA) portal is created with an outside-in technique, and anchors are drilled through this portal into zones 2 to 4 (Figures 2A-2E).

For far medial anchor placement, the anchor drill guide is offset in an attempt to avoid iatrogenic psoas irritation or medial wall penetration. The socket is visually inspected before anchor insertion to confirm complete bony insertion. In the rare case in which a small part of the medial aspect of the anchor is exposed toward the psoas, this part of the anchor is carefully resected with a burr without disrupting anchor fixation or the suture in the anchor. For posterior anchor placement, the AL portal is cannulated and used for far lateral drilling. The MAP and the DALA portal traditionally are cannulated for repairs in zones 2 to 4. With visualization through the AL portal, the probe is used to apply tension on the labral segment being repaired for reduction. A suture-passing device (NanoPass; Stryker) is used to pass (with base stitch technique) the No. 1 suture for the anchor, and the acetabular (base) side of the No. 1 suture is marked with a methylene blue marker. The key is to make the first pass of suture at the base of the chondrolabral junction. The probe is then used to apply tension on the labrum and to reduce the labrum to the chondrolabral junction through the MAP. The second pass of the suture-passing device is through the labrum apex, and the suture is retrieved. Care is taken to make sure the suture is on equal sides of the labral apex to avoid labrum distortion (Figures 2A-2E).

A 2.4-mm drill guide is advanced through the DALA portal and placed in the appropriate position for drilling. We aim for 1 mm to 2 mm from the chondrolabral junction. Next, the probe is placed intra-articular and medial to the anchor insertion site, and the anchor is loaded and then inserted around the probe (Figures 3A-3E).

The probe allows the suture to remain free for independent tensioning. We then remove the probe and independently tension the suture ends. Gentle pulling on the marked suture end and then on the unmarked side allows for proper labrum inversion-eversion as needed, and the device is deployed.

If the capsular side of the labrum does not lie flat against the bone, the nonmarked end is tightened to position the labrum so that, when the base stitch is tightened, the tissue is compressed against the bone to maximize healing. For a standard 3-cm repair, it is routine to use 3 or 4 anchors placed 6 mm to 8 mm apart (Figures 4A-4D).

The hip is then reduced. If indicated, a T-capsulotomy is performed for femoral osteochondroplasty.

Routinely, the capsule is anatomically repaired with the Injector II Capsule Restoration System and No. 2 permanent suture. The Table presents our technical pearls.

Postoperative Care

Patients are placed in a postoperative hip brace and use a continuous passive motion machine 6 hours a day for 2 weeks, and an ice machine. They maintain 30 lb of foot-flat weight-bearing for 3 weeks, and begin a standard labral repair protocol on postoperative days 3 to 7.

Discussion

Hip labral preservation has evolved over the past 10 years, and current options for labral management include excision, débridement, labralization, repair, and reconstruction.^1-13 Labral excision was studied by Miozzari and colleagues,⁸ who postulated on the basis of animal models that the labrum may regenerate. In their series of 9 patients treated with surgical hip dislocation and labral excision at average 4-year follow-up, repeat magnetic resonance angiography revealed no regeneration of tissue—modified Harris Hip Score was 83. The hip scores were less than those of patients treated with the same procedure with repair, and the authors concluded that defining labral débridement versus excision in the literature, and treating patients with primary repair or reconstruction techniques, may lead to better results. Their study used a small sample and was limited to an open procedure. Arthroscopic labral débridement in isolation was also a poor option for treatment of a labral tear. In a 2-year follow-up of 59 isolated labral débridement procedures, Krych and colleagues⁹ found 47% combined poor results.

There is level I evidence of the importance of labral repair. In 2013, Krych and colleagues⁷ conducted a randomized control trial of 38 female patients who underwent hip arthroscopy for FAI. At time of surgery, patients were randomly assigned to either débridement or repair. At 1-year follow-up, activities of daily living and Sports specific Hip Outcome Scores were statistically significantly superior in the repair group. On a subjective scale, 94% vs 78% of patients reported normal or near normal hips in the repair versus débridement groups respectively. Ayeni and colleagues²⁰ performed a systematic review of 6 studies in an attempt to develop labral management recommendations. Five of the studies (N = 490 patients total) had improved results with labral repair over reconstruction. Although the studies had a low level of evidence, they found a trend toward improved results with labral repair. These studies highlight the importance of labral preservation and proper FAI management.

Techniques for labrum repair have advanced as well—from a looped suture technique to a base stitch and knotless independent tensioning.^11-13 Restoration of the hip labrum function as a suction seal, fluid circulator and anatomic capsular repair is paramount to excellent results and stresses the importance of performing an anatomic labral repair.^1-6 Knotless anchor repair is not novel and has been previously described. Fry and Domb¹² reported on a knotless labral repair technique that uses push-lock devices (Arthrex) that do not allow for independent tensioning. Inversion-eversion was introduced to the literature by Moreira and colleagues,¹³ who described an independent tensioning technique that uses speed-lock anchors (Smith & Nephew). Our technique differs in that it involves a DALA portal; labral reduction and tensioning with a probe assist to ensure the second pass of the base stitch is at the apex of the labrum; and use of No. 1 instead of No. 2 suture. Although seemingly subtle, these differences allow for proper anchor placement nearer the rim, additional support in achieving precise suture placement, and less disruption of small labra. These differences are particularly relevant for smaller labra.

Evaluating repair techniques on the basis of high-evidence literature is challenging. In a matched-cohort study of 220 patients, Jackson and colleagues²¹ compared 2 techniques: looped and base stitch. At 2-year follow-up, patients in both groups showed improvement, and there was no statistically significant difference in patient-reported outcome measures between the groups. Sawyer and colleagues²² studied the outcomes of 326 consecutive patients who underwent looped, pierced, or combined labral repair at an average 32-month follow-up. The groups’ revision rates were comparable, each group improved in postoperative patient-reported outcomes, and the pierced group had significantly higher preoperative scores on the Western Ontario and McMaster Universities Osteoarthritis Index. These studies described a base or pierce repair that did not differ from a looped repair, though the techniques did not allow for independent tensioning to re-create an anatomical inversion-eversion repair and may have altered the reported outcomes.

Our current technique uses independent tensioning of the repair to allow control of labrum inversion-eversion to give an anatomical repair with restoration of the suction seal. Preoperative planning, addressing the FAI appropriately, proper suture-passing technique, controlling the labrum in inversion-eversion fashion, and anatomical labral repair are the elements of Dr. Mather’s preferred method for preserving the native labrum and allowing it to assume its native function.

Future Directions

As our understanding of FAI and labral function evolves, labral preservation surgery continues to advance. With surgeons continually developing new techniques and following up on previous techniques, the ability to preserve the native hip with lasting procedures evolves as well. Proper identification of the underlying cause of the labral tear and proper anatomical repair are paramount to the success of FAI surgery.

References

1. Philippon MJ, Nepple JJ, Campbell KJ, et al. The hip fluid seal—part I: the effect of an acetabular labral tear, repair, resection and reconstruction on hip fluid pressurization. Knee Surg Sports Traumatol Arthrosc. 2014;22(4):722-729.

2. Nepple JJ, Philippon MJ, Campbell KJ, et al. The hip fluid seal—part II: the effect of an acetabular labral tear, repair, resection and reconstruction on hip stability to distraction. Knee Surg Sports Traumatol Arthrosc. 2014;22(4):730-736.

3. Dwyer MK, Jones HL, Hogan MG, Field RE, McCarthy JC, Noble PC. The acetabular labrum regulates fluid circulation of the hip joint during functional activities. Am J Sports Med. 2014;42(4):812-819.

4. Greaves LL, Gilbart MK, Yung AC, Kozlowski, Wilson DR. Effect of acetabular labral tears, repair and resection on hip cartilage strain: a 7T MR study. J Biomech. 2010;43(5):858-863.

5. Freehill MT, Safran MR. The labrum of the hip: diagnosis and rationale for surgical correction. Clin Sports Med. 2011;30(2):293-315.

6. Myers CA, Register BC, Lertwanich P, et al. Role of the acetabular labrum and the iliofemoral ligament in hip stability: an in vitro biplane fluoroscopy study. Am J Sports Med. 2011;39(suppl):85S-91S.

7. Krych AJ, Thompson M, Knutson Z, Scoon J, Coleman SH. Arthroscopic labral repair versus selective labral debridement in female patients with femoroacetabular impingement: a prospective randomized study. Arthroscopy. 2013;29(1):46-53.

8. Miozzari HH, Celia M, Clark JM, Werlen S, Naal FD, Nötzli HP. No regeneration of the human acetabular labrum after excision to bone. Clin Orthop Relat Res. 2015;473(4):1349-1357.

9. Krych AJ, Kuzma SA, Kovachevich R, Hudgens JL, Stuart MJ, Levy BA. Modest mid-term outcomes after isolated arthroscopic debridement of acetabular labral tears. Knee Surg Sports Traumatol Arthrosc. 2014;22(4):763-767.

10. Matsuda DK. Arthroscopic labralization of the hip: an alternative to labral reconstruction. Arthrosc Tech. 2014;3(1):e131-e133.

11. Philippon MJ, Faucet SC, Briggs KK. Arthroscopic hip labral repair. Arthrosc Tech. 2013;2(2):e73-e76.

12. Fry D, Domb B. Labral base refixation in the hip: rationale and technique for an anatomic approach to labral repair. Arthroscopy. 2010;26(9 suppl):S81-S89.

13. Moreira B, Pascual-Garrido C, Chadayamurri V, Mei-Dan O. Eversion-inversion labral repair and reconstruction technique for optimal suction seal. Arthrosc Tech. 2015;4(6):e697-e700.

14. Mook WR, Briggs KK, Philippon MJ. Evidence and approach for management of labral deficiency: the role for labral reconstruction. Sports Med Arthrosc. 2015;23(4):205-212.

15. Gupta A, Suarez-Ahedo C, Redmond JM, et al. Best practices during hip arthroscopy: aggregate recommendations of high-volume surgeons. Arthroscopy. 2015;31(9):1722-1727.

16. Yeung M, Kowalczuk M, Simunovic N, Ayeni OR. Hip arthroscopy in the setting of hip dysplasia: a systematic review. Bone Joint Res. 2016;5(6):225-231.

17. Hash TW. Magnetic resonance imaging of the hip. In: Nho SJ, Leunig M, Larson CM, Bedi A, Kelly BT, eds. Hip Arthroscopy and Hip Joint Preservation Surgery, Vol. 1. New York, NY: Springer; 2015:65-113.

18. Sutter R, Zubler V, Hoffmann A, et al. Hip MRI: how useful is intraarticular contrast material for evaluating surgically proven lesions of the labrum and articular cartilage? AJR Am J Roentgenol. 2014;202(1):160-169.

19. Federer AE, Karas V, Nho S, Coleman SH, Mather RC 3rd. Capsular suspension technique for hip arthroscopy. Arthrosc Tech. 2015;4(4):e317-e322.

20. Ayeni OR, Adamich J, Farrokhyar F, et al. Surgical management of labral tears during femoroacetabular impingement surgery: a systematic review. Knee Surg Sports Traumatol Arthrosc. 2014;22(4):756-762.

21. Jackson TJ, Hammarstedt JE, Vemula SP, Domb BG. Acetabular labral base repair versus circumferential suture repair: a matched-paired comparison of clinical outcomes. Arthroscopy. 2015;31(9):1716-1721.

22. Sawyer GA, Briggs KK, Dornan GJ, Ommen ND, Philippon MJ. Clinical outcomes after arthroscopic hip labral repair using looped versus pierced suture techniques. Am J Sports Med. 2015;43(7):1683-1688.

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Authors’ Disclosure Statement: Dr. Mather reports that he has received research support from and been a paid consultant to Stryker. Dr. Kollmorgen reports no actual or potential conflict of interest in relation to this article.

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Take-Home Points

Labral preservation is recommended when possible to ensure restoration of suction seal, stability, and contact pressure of the hip joint.
Over 95% of labral tears can be addressed with primary repair.
Consider using an accessory portal (ie, DALA) to allow for more anatomic placement of suture anchor.
Mattress stitch when labrum >3 mm and looped stitch when labrum <3 mm.

10Control labral repair to avoid excessive inversion or eversion.

Indications

Preoperative Planning

Labral Repair Technique

Routinely, the capsule is anatomically repaired with the Injector II Capsule Restoration System and No. 2 permanent suture. The Table presents our technical pearls.

Postoperative Care

Discussion

Future Directions

Take-Home Points

Labral preservation is recommended when possible to ensure restoration of suction seal, stability, and contact pressure of the hip joint.
Over 95% of labral tears can be addressed with primary repair.
Consider using an accessory portal (ie, DALA) to allow for more anatomic placement of suture anchor.
Mattress stitch when labrum >3 mm and looped stitch when labrum <3 mm.

10Control labral repair to avoid excessive inversion or eversion.

Indications

Preoperative Planning

Labral Repair Technique

Routinely, the capsule is anatomically repaired with the Injector II Capsule Restoration System and No. 2 permanent suture. The Table presents our technical pearls.

Postoperative Care

Discussion

Future Directions

References

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CASE A 59-year-old man with a remote history of seizures is transported to the emergency department (ED) by ambulance after a witnessed tonic-clonic seizure. At the time of arrival he is postictal and confused, but his vital signs are stable. A left eyebrow laceration indicating a possible fall is observed on physical exam, as is a left shoulder displacement with no obvious signs of neurovascular compromise. The patient is not currently taking anticonvulsant medication, stating that he has been “seizure free” for five years, and therefore chose to discontinue taking phenytoin against medical advice.

An anteroposterior (AP) bilateral shoulder x-ray is obtained in the ED (see Figures 1a and 1b). The image shows the humeral head to be anteriorly dislocated and reveals a large impaction fracture of the posterior superior humeral head. For a more detailed view of the fracture and to further assess any associated deformities, CT of the left shoulder is performed. The fracture has a depth of 11.6 mm and a length of 24.1 mm, with no additional pathology noted (see Figure 1c).

The shoulder is a large joint capable of moving in many directions and therefore is inherently unstable. The glenoid fossa is shallow, and stability of the joint is provided by both the fibrocartilaginous labrum and varying muscles of the rotator cuff. Because the shoulder joint is poorly supported, dislocations are not uncommon (see the illustrations).

The first step in evaluating a suspected shoulder dislocation is to order an AP radiographic view of the shoulder (known as the Grashey view). A transcapular view (known as the scapular “Y” view) is also sufficient.¹ While diagnostic studies, such as CT or MRI arthrography, are excellent for evaluating the glenohumeral ligaments and labrum, they generally are not done in an acute setting.¹ For patients who present to the ED, some would recommend taking a CT scan, especially if a posterior dislocation is suspected.²

The three types of shoulder dislocations include anterior, posterior, and inferior.

Anterior dislocations account for 95% of all presented cases of shoulder dislocation, making them the most common type.³ They may be caused by a fall on an outstretched arm, trauma to the posterior humerus, or—more frequently—trauma to the arm while it is extended, externally rotated, and abducted (eg, blocking a shot in basketball).

A patient with an anterior dislocation will enter the ED with a slightly abducted and externally rotated arm (see illustration) and will resist any movement by the examiner. Typically, the shoulder loses its rounded appearance, and in thin individuals, the acromion may be prominent. A detailed neurovascular examination of the arm must be performed.

Dislocation of the humerus in any direction may compromise the axillary nerve, artery, or both. The axillary nerve and artery run parallel to each other, beneath and in close proximity to the humeral head. The axillary artery is located upstream from the radial artery; compression of the artery may lead to a diminution or complete absence of the radial pulse and/or coolness of the hand.⁴ The axillary nerve is both a sensory and motor nerve. If injured, a 2- to 3-cm area over the lateral deltoid may have complete sensory loss, which can be tested for with a light touch and pinprick.⁵ The patient may also have difficulty abducting the arm, but limitations of movement are difficult to measure with a new dislocation and a patient in pain.⁴

Any patient presenting with an anterior shoulder dislocation should also be screened for two other potential abnormalities. Hill-Sachs lesion, which occurs in up to 40% of anterior dislocations and 90% of all dislocations, is a cortical depression occurring in the humeral head. Bankart lesions, which occur in less than 5% of all dislocations, are avulsed bone fragments that occur when there is a glenoid labrum disruption.⁶ Both can be seen on plain films, although Bankart lesions are best seen on CT.⁴

The combination of an anterior dislocation and a humeral fracture, as seen in this case, is rare.⁷

POSTERIOR

Posterior shoulder dislocations occur far less frequently than anterior dislocations, representing 2% to 5% of all shoulder dislocations.² They often result from blows to the anterior portion of the shoulder (ie, motor vehicle accidents or sports-related collisions) or violent muscle contractions (eg, electrocution, electroconvulsive therapy, or seizures).

Unable to externally rotate the shoulder, patients with posterior dislocations present with the arm in adduction and internal rotation, making the coracoid process prominent (see illustration).⁸ This position is sometimes misdiagnosed as a “frozen shoulder.”²

INFERIOR

Inferior dislocation of the shoulder is the rarest type, accounting for only 0.5% of all cases of shoulder dislocation. The mechanism of injury is forceful hyperabduction and extension of the shoulder during a fall.

Patients present with the affected arm hyperadducted, flexed at the elbow, with the hand positioned above or behind the head in fixed abduction: a “hands up” position of the affected arm (see illustration). These dislocations are best identified via the transcapular “Y” radiographs. Inferior dislocations are often associated with neurovascular compromise, and there are often related tears of the infraspinatus, supraspinatus, and teres minor muscles.⁹

ASSOCIATION WITH SEIZURES

Any patient who has had a seizure is subject to a variety of injuries, including lacerations, contusions, long bone and skull fractures, and dislocations. Seizures with a fall are associated with a 20% chance of injury.¹⁰

Shaw et al were the first to note that, during an active convulsion, the patient’s shoulder is in adduction, internal rotation, and flexion. This positioning predisposes to injury: With sustained contraction of the surrounding shoulder girdle muscles, the humeral head is forced superiorly and posteriorly against the acromion andmedially against the glenoid fossa. The glenoid fossa is shallow; therefore, the humeral head is forced posteriorly and dislocates.¹¹

Researchers at the Mayo Clinic followed 247 patients who were diagnosed with seizures over nine years; 16% of the cohort experienced seizure-related injuries. Of the seizures recorded, 82% were tonic-clonic seizures. The singular predictive factor for injury was seizure frequency: Patients who had more seizures were more susceptible to injury.¹²

In an evaluation of outpatients with epilepsy, 25% of recorded seizures involved a fall. Among those who sustained an orthopedic injury, one injury occurred for every 178.6 generalized tonic-clonic seizures (0.6%)—a number that doubled for generalized tonic-clonic seizure associated with a fall (1.2%).¹⁰

The collective evidence from these and other studies suggests that patients who have poorly controlled tonic-clonic seizures have a higher incidence of seizures and, therefore, falls and injuries.^10,12 In the absence of known trauma, a posterior shoulder dislocation is almost pathognomonic of a seizure. In high-risk populations (ie, individuals who have poorly controlled diabetes or who are experiencing alcohol or drug withdrawal), suspicion for posterior shoulder dislocation should be elevated.⁸

After evaluation in the ED, the patient immediately underwent a nonsurgical closed reduction of the shoulder and suturing of the laceration. He was admitted overnight for further evaluation and was started on an anticonvulsant (levetiracetam). An orthopedic consult was obtained; the dislocation/fracture was managed conservatively with a sling for immobilization. No surgical intervention was recommended, since the patient had a manageable fracture without neurovascular compromise. He was discharged home within 36 hours and scheduled for follow-up appointments with both the neurologist and orthopedic surgeon.

CONCLUSION

This patient had a seizure with an associated fall; both the laceration and the anterior shoulder dislocation with a humeral fracture were associated with the fall and not with tonic-clonic activity from the seizure. Because injuries vary widely from soft tissue to joint dislocations, with possible axillary nerve and/or artery damage, clinicians must do a comprehensive examination of patients entering the ED who have had seizures. Each injury must be addressed individually.

References

1. Omoumi P, Teixeira P, Lecouvet F, Chung CB. Glenohumeral joint instability. J Magn Reson Imaging. 2010;33(1):2-16.
2. Rouleau DM, Hebert-Davies J. Incidence of associated injury in posterior shoulder dislocation: systematic review of the literature. J Orthop Trauma. 2012;26(4):246-251.
3. Sachit M, Shekhar A, Shekhar S, Joban SH. Acute spontaneous atraumatic bilateral anterior dislocation of the shoulder joint with Hill-Sach’s lesions: a rare case. J Orthop Case Rep. 2015;5(1):55-57.
4. Cutts S, Prempeh M, Drew S. Anterior shoulder dislocation. Ann R Coll Surg Engl. 2009;91(1):2-7.
5. Magee DJ. Orthopedic Physical Assessment. 5th ed. St. Louis, MO. Saunders Elsevier; 2008.
6. Greenspan A. Orthopedic Imaging: A Practical Approach. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011.
7. Karimi-Nasab MH, Shayesteh-Azar M, Sajjadi-Saravi M, Mehdi Daneshpoor SM. Anterior shoulder dislocation and ipsilateral humeral shaft fracture. Iran J Med Sci. 2012; 37(3):202-204.
8. Robinson CM, Aderinto J. Posterior shoulder dislocations and fracture-dislocations. J Bone Joint Surg Am. 2005; 87(3):639-650.
9. Cacioppo E, Waymack JR. Bilateral inferior shoulder dislocation. West J Emerg Med. 2015;16(1):157.
10. Tiamkao S, Shorvon SD. Seizure-related injury in an adult tertiary epilepsy clinic. Hong Kong Med J. 2006;12(4):260-263.
11. Shaw JL. Bilateral posterior fracture-dislocation of the shoulder and other trauma caused by convulsive seizures. J Bone Joint Surg Am. 1971;53(7):1437-1440.
12. Lawn ND, Bamlet WR, Radhakirshnan K, et al. Injuries due to seizures in persons with epilepsy: a population-based study. Neurology. 2004;63(9):1565-1570.

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CONCLUSION

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Current Therapeutic Approaches to Renal Cell Carcinoma

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Current Therapeutic Approaches to Renal Cell Carcinoma

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Jessica M. Clement, MD

INTRODUCTION

Renal cell carcinoma (RCC) is the most common malignancy arising in the kidney, comprising 90% of all renal tumors.¹ Approximately 55,000 new RCC cases are diagnosed each year.² Patients with RCC are often asymptomatic, and most cases are discovered as incidental findings on abdominal imaging performed during evaluation of nonrenal complaints. Limited-stage RCC that is found early can be cured surgically, with estimated 5-year survival rates approaching 90%; however, long-term survival for metastatic disease is poor, with rates ranging from 0% to 20%.² Advanced RCC is resistant to conventional chemotherapy and radiotherapy, and outcomes for patients with metastatic or unresectable RCC remain poor. However, the recent development of new therapeutic modalities that target tumor molecular pathways has expanded the treatment options for these patients and changed the management of RCC.

EPIDEMIOLOGY AND CLASSIFICATION

Median age at diagnosis in the United States is 64 years. Men have a higher incidence of RCC than women, with the highest incidence seen in American Indian and Alaska Native men (30.1 per 100,000 population). Genetic syndromes account for 2% to 4% of all RCCs.² Risk factors for RCC include smoking, hypertension, obesity, and acquired cystic kidney disease that is associated with end-stage renal failure.³ Longer duration of tobacco use is associated with a more aggressive course.

The 2004 World Health Organization (WHO) classification of renal tumors summarizes the previous classification systems (including the Heidelberg and Mainz classification systems) to describe different categories of RCC based on histologic and molecular genetics characteristics.² Using the WHO classification criteria, RCC comprises 90% of all renal tumors, with clear cell being the most common type (80%).² Other types of renal tumors include papillary, chromophobe, oncocytoma, and collecting-duct or Bellini duct tumors. Approximately 3% to 5% of tumors are unclassified. Oncocytomas are generally considered benign, and chromophobe tumors typically have an indolent course and rarely metastasize. Sarcomatoid differentiation can be seen in any histologic type and is associated with a worse prognosis. While different types of tumors may be seen in the kidney (such as transitional cell or lymphomas), the focus of this review is the primary malignancies of the renal parenchyma.

FAMILIAL SYNDROMES

Several genetic syndromes have been identified by studying families with inherited RCC. Among these, von Hippel-Lindau (VHL) gene mutation is the most commonly found inherited genetic defect. Table 1 summarizes the incidence of gene mutations and the corresponding histologic appearance of the most common sporadic and hereditary RCCs.⁴

VHL disease is an autosomal dominant familial syndrome. Patients with this mutation are at higher risk for developing RCC (clear cell histology), retinal angiomas, pheochromocytomas, as well as hemangioblastomas of the central nervous system (CNS).⁴ Of all the genetic mutations seen in RCC, the somatic mutation in the VHL tumor-suppressor gene is by far the most common.⁵ VHL targets hypoxia–inducible factor-1 alpha (HIF-α) for ubiquitination and subsequent degradation, which has been shown to suppress the growth of clear-cell RCC in mouse models.^6–8 HIF expression under hypoxic conditions leads to activation of a number of genes important in blood vessel development, cell proliferation, and glucose metabolism, including vascular endothelial growth factor (VEGF), erythropoietin, platelet-derived growth factor beta (PDGF-β), transforming growth factor alpha (TGF-α), and glucose transporter-1 (GLUT-1). Mutation in the VHL gene prevents degradation of the HIF-α protein, thereby leading to increased expression of these downstream proteins, including MET and Axl. The upregulation of these angiogenic factors is thought to be the underlying process for increased vascularity of CNS hemangioblastomas and clear-cell renal tumors in VHL disease.^4–8

Other less common genetic syndromes seen in hereditary RCC include hereditary papillary RCC, hereditary leiomyomatosis, and Birt-Hogg-Dubé (BHD) syndrome.⁹ In hereditary papillary RCC, the MET gene is mutated. BHD syndrome is a rare, autosomal dominant syndrome characterized by hair follicle hamartomas of the face and neck. About 15% of patients have multiple renal tumors, the majority of which are of the chromophobe or mixed chromophobe-oncocytoma histology. The BHD gene encodes the protein folliculin, which is thought to be a tumor-suppressor gene.

DIAGNOSIS AND STAGING

CASE PRESENTATION

A 74-year-old man who works as an airplane mechanic repairman presents to the emergency department with sudden worsening of chronic right upper arm and shoulder pain after lifting a jug of orange juice. He does not have a significant past medical history and initially thought that his pain was due to a work-related injury. Upon initial evaluation in the emergency department he is found to have a fracture of his right humerus. Given that the fracture appears to be pathologic, further work-up is recommended.

• What are common clinical presentations of RCC?

Most patients are asymptomatic until the disease becomes advanced. The classic triad of flank pain, hematuria, and palpable abdominal mass is seen in approximately 10% of patients with RCC, partly because of earlier detection of renal masses by imaging performed for other purposes.¹⁰ Less frequently, patients present with signs or symptoms of metastatic disease such as bone pain or fracture (as seen in the case patient), painful adenopathy, and pulmonary symptoms related to mediastinal masses. Fever, weight loss, anemia, and/or varicocele often occur in young patients (≤ 46 years) and may indicate the presence of a hereditary form of the disease. Patients may present with paraneoplastic syndromes seen as abnormalities on routine blood work. These can include polycythemia or elevated liver function tests (LFTs) without the presence of liver metastases (known as Stauffer syndrome), which can be seen in localized renal tumors. Nearly half (45%) of patients present with localized disease, 25% present with locally advanced disease, and 30% present with metastatic disease.¹¹ Bone is the second most common site of distant metastatic spread (following lung) in patients with advanced RCC.

• What is the approach to initial evaluation for a patient with suspected RCC?

Initial evaluation consists of a physical exam, laboratory tests including complete blood count (CBC) and comprehensive metabolic panel (calcium, serum creatinine, LFTs, lactate dehydrogenase [LDH], and urinalysis), and imaging. Imaging studies include computed tomography (CT) scan with contrast of the abdomen and pelvis or magnetic resonance imaging (MRI) of the abdomen and chest imaging. A chest radiograph may be obtained, although a chest CT is more sensitive for the presence of pulmonary metastases. MRI can be used in patients with renal dysfunction to evaluate the renal vein and inferior vena cava (IVC) for thrombus or to determine the presence of local invasion.¹² Although bone and brain are common sites for metastases, routine imaging is not indicated unless the patient is symptomatic. The value of positron emission tomography in RCC remains undetermined at this time.

Staging is done according to the American Joint Committee on Cancer (AJCC) staging classification for RCC; the Figure summarizes the staging and 5-year survival data based on this classification scheme.^4,13

Figure. Staging overview and 5-year survival rates for renal cancer. (Adapted from Cohen H, McGovern F. Renal-cell carcinoma. N Engl
J Med 2005;353:2477–90.)

LIMITED-STAGE DISEASE

• What are the therapeutic options for limited-stage disease?

For patients with nondistant metastases, or limited-stage disease, surgical intervention with curative intent is considered. Convention suggests considering definitive surgery for patients with stage I and II disease, select patients with stage III disease with pathologically enlarged retroperitoneal lymph nodes, patients with IVC and/or cardiac atrium involvement of tumor thrombus, and patients with direct extension of the renal tumor into the ipsilateral adrenal gland if there is no evidence of distant disease. While there may be a role for aggressive surgical intervention in patients with distant metastatic disease, this topic will not be covered in this review.

SURGICAL INTERVENTION

Once patients are determined to be appropriate candidates for surgical removal of a renal tumor, the urologist will perform either a radical nephrectomy or a nephron-sparing nephrectomy, also called a partial nephrectomy. The urologist will evaluate the patient based on his or her body habitus, the location of the tumor, whether multiple tumors in one kidney or bilateral tumors are present, whether the patient has a solitary kidney or otherwise impaired kidney function, and whether the patient has a history of a hereditary syndrome involving kidney cancer as this affects the risk of future kidney tumors.

A radical nephrectomy is surgically preferred in the presence of the following factors: tumor larger than 7 cm in diameter, a more centrally located tumor, suspicion of lymph node involvement, tumor involvement with renal vein or IVC, and/or direct extension of the tumor into the ipsilateral adrenal gland. Nephrectomy involves ligation of the vascular supply (renal artery and vein) followed by removal of the kidney and surrounding Gerota’s fascia. The ipsilateral adrenal gland is removed if there is a high-risk for or presence of invasion of the adrenal gland. Removal of the adrenal gland is not standard since the literature demonstrates there is less than a 10% chance of solitary, ipsilateral adrenal gland involvement of tumor at the time of nephrectomy in the absence of high-risk features, and a recent systematic review suggests that the chance may be as low as 1.8%.¹⁴ Preoperative factors that correlated with adrenal involvement included upper pole kidney location, renal vein thrombosis, higher T stage (T3a and greater), multifocal tumors, and evidence for distant metastases or lymph node involvement. Lymphadenectomy previously had been included in radical nephrectomy but now is performed selectively. Radical nephrectomy may be performed as

either an open or laparoscopic procedure, the latter of which may be performed robotically.¹⁵ Oncologic outcomes appear to be comparable between the 2 approaches, with equivalent 5-year cancer-specific survival (91% with laparoscopic versus 93% with open approach) and recurrence-free survival (91% with laparoscopic versus 93% with open approach).¹⁶The approach ultimately is selected based on provider- and patient-specific input, though in all cases the goal is to remove the specimen intact.^16,17

Conversely, a nephron-sparing approach is preferred for tumors less than 7 cm in diameter, for patients with a solitary kidney or impaired renal function, for patients with multiple small ipsilateral tumors or with bilateral tumors, or for radical nephrectomy candidates with comorbidities for whom a limited intervention is deemed to be a lower-risk procedure. A nephron-sparing procedure may also be performed open or laparoscopically. In nephron-sparing procedures, the tumor is removed along with a small margin of normal parenchyma.¹⁵

In summary, the goal of surgical intervention is curative intent with removal of the tumor while maintaining as much residual renal function as possible to limit long-term morbidity of chronic kidney disease and associated cardiovascular events.¹⁸ Oncologic outcomes for radical nephrectomy and partial nephrectomy are similar. In one study, overall survival was slightly lower in the partial nephrectomy cohort, but only a small number of the deaths were due to RCC.¹⁹

ADJUVANT THERAPY

Adjuvant systemic therapy currently has no role following nephrectomy for RCC because no systemic therapy has been able to reduce the likelihood of relapse. Randomized trials of cytokine therapy (eg, interferon, interleukin 2) or tyrosine kinase inhibitors (TKIs; eg, sorafenib, sunitinib) with observation alone in patients with locally advanced completely resected RCC have shown no delay in time to relapse or improvement of survival with adjuvant therapy.²⁰ Similarly, adjuvant radiation therapy has not shown benefit even in patients with nodal involvement or incomplete resection.²¹ Therefore, observation remains the standard of care after nephrectomy.

RENAL TUMOR ABLATION

For patients who are deemed not to be surgical candidates due to age, comorbidities, or patient preference and who have tumors less than 4 cm in size (stage I tumors), ablative techniques may be considered. The 2 most well-studied and effective techniques at present are cryoablation and radiofrequency ablation (RFA). Microwave ablation may be an option in some facilities, but the data in RCC are limited. An emerging ablative technique under investigation is irreversible electroporation. At present, the long-term efficacy of all ablative techniques is unknown.

Patient selection is undertaken by urologists and interventional radiologists who evaluate the patient with ultrasound, CT, and/or MRI to determine the location and size of the tumor and the presence or absence of metastatic disease. A pretreatment biopsy is recommended to document the histology of the lesion to confirm a malignancy and to guide future treatment for recurrent or metastatic disease. Contraindications to the procedure include the presence of metastatic disease, a life expectancy of less than 1 year, general medical instability, or uncorrectable coagulopathy due to increased risk of bleeding complications. Tumors in close proximity to the renal hilum or collecting system are a contraindication to the procedure because of the risk for hemorrhage or damage to the collecting system. The location of the tumor in relation to the vasculature is also important to maximize efficacy because the vasculature acts as a “heat sink,” causing dissipation of the thermal energy. Occasionally, stenting of the proximal ureter due to upper tumor location is necessary to prevent thermal injury that could lead to urine leaks.

Selection of the modality to be used primarily depends on operator comfort, which translates to good patient outcomes, such as better cancer control and fewer complications. Cryoablation and RFA have both demonstrated good clinical efficacy and cancer control of 89% and 90%, respectively, with comparable complication rates.²² There have been no studies performed directly comparing the modalities.

Cryoablation

Cryoablation is performed through the insertion of a probe into the tumor, which may be done through a surgical or percutaneous approach. Once the probe is in place, a high- pressure gas (argon, nitrogen) is passed through the probe and upon entering a low pressure region the gas cools. The gas is able to cool to temperatures as low as –185°C. The tissue is then rewarmed through the use of helium, which conversely warms when entering a low pressure area. The process of freezing followed by rewarming subsequently causes cell death/tissue destruction through direct cell injury from cellular dehydration and vascular injury. Clinically, 2 freeze-thaw cycles are used to treat a tumor.^23,24

RFA

Radiofrequency ablation, or RFA, targets tumors via an electrode placed within the mass that produces intense frictional heat from medium-frequency alternating current (approximately 500 kHz) produced by a connected generator that is grounded on the patient. The thermal energy created causes coagulative necrosis. Due to the reliance on heat for tumor destruction, central lesions are less amenable to this approach because of the “heat sink” effect from the hilum.²⁴

Microwave Ablation

Microwave ablation, like RFA, relies on the generation of frictional heat to cause cell death by coagulative necrosis. In this case, the friction is created through the activation of water molecules; because of the different thermal kinetics involved with microwave ablation, the “heat sink” effect is minimized when treatment is employed near large vessels, in comparison to RFA.²⁴ The data on this mechanism of ablation are still maturing, with varied outcomes thus far. One study demonstrated outcomes comparable to RFA and cryoablation, with cancer-specific survival of 97.8% at 3 years.²⁵ However, a study by Castle and colleagues²⁶ demonstrated higher recurrence rates. The overarching impediment to widespread adoption of microwave ablation is inconclusive data gleaned from studies with small numbers of patients with limited follow up. The role of this modality will need to be revisited.

Irreversible Electroporation

Irreversible electroporation (IRE) is under investigation. IRE is a non-thermal ablative technique that employs rapid electrical pulses to create pores in cell membranes, leading to cell death. The postulated benefits of IRE include the lack of an effect from “heat sinks” and less collateral damage to the surrounding tissues, when compared with the thermal modalities. In a human phase 1 study of patients undergoing IRE prior to immediate surgical resection, the procedure appeared feasible and safe.²⁷ Significant concerns for this method of ablation possibly inducing cardiac arrhythmias, and the resultant need for sedation with neuromuscular blockade and associated electrocardiography monitoring, may impede its implementation in nonresearch settings.²⁴

ACTIVE SURVEILLANCE

Due to the more frequent use of imaging for various indications, there has been an increase in the discovery of small renal masses (SRM); 85% of RCC that present in an asymptomatic or incidental manner are tumors under 4 cm in diameter.^28,29 The role of active surveillance is evolving, but is primarily suggested for patients who are not candidates for more aggressive intervention based on comorbidities. A recent prospective, nonrandomized analysis of data from the Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry evaluated outcomes for patients with SRM looking at primary intervention compared with active surveillance.³⁰ The primary intervention selected was at the discretion of the provider; treatments included partial nephrectomy, RFA, and cryoablation, and active surveillance patients were followed with imaging every 6 months. Progression of SRM, with recommendation for delayed intervention, was defined as a growth rate of mass greater than 0.5 cm/year, size greater than 4 cm, or hematuria. Thirty-six of 158 patients on active surveillance met criteria for progression; 21 underwent delayed intervention. Of note, even the patients who progressed but did not undergo delayed intervention did not develop metastatic disease during the follow-up interval. With a median follow-up of 2 years, cancer-specific survival was noted to be 99% and 100% at 5 years for primary intervention and active surveillance, respectively. Overall survival at 2 years for primary intervention was 98% and 96% for active surveillance; at 5 years, the survival rates were 92% and 75% (P = 0.06). Of note, 2 patients in the primary intervention arm died of RCC, while none in the active surveillance arm died. As would be expected, active surveillance patients were older, had a worse performance status, and had more comorbidities. Interestingly, 40% of patients enrolled selected active surveillance as their preferred management for SRM. The DISSRM results were consistent with data from the Renal Cell Consortium of Canada and other retrospective reviews.^31–33

• What is the approach to follow-up after treatment of localized RCC?

After a patient undergoes treatment for a localized RCC, the goal is to optimize oncologic outcomes, monitor for treatment sequelae, such as renal failure, and focus on survivorship. At this time, there is no consensus in the literature or across published national and international guidelines with regards to the appropriate schedule for surveillance to achieve these goals. In principle, the greatest risk for recurrence occurs within the first 3 years, so many guidelines focus on this timeframe. Likewise, the route of spread tends to be hematogenous, so patients present with pulmonary, bone, and brain metastases, in addition to local recurrence within the renal bed. Symptomatic recurrences often are seen

with bone and brain metastases, and thus bone scans and brain imaging are not listed as part of routine surveillance protocols in asymptomatic patients. Although there is inconclusive evidence that surveillance protocols improve outcomes in RCC, many professional associations have outlined recommendations based on expert opinion.³⁴ The American Urological Association released guidelines in 2013 and the National Comprehensive Cancer Network (NCCN) released their most recent set of guidelines in 2016.^21,35These guidelines use TNM staging to risk-stratify patients and recommend follow-up.

METASTATIC DISEASE

CASE CONTINUED

CT scan with contrast of the chest, abdomen, and pelvis as well as bone scan are done. CT of the abdomen and pelvis demonstrates a 7.8-cm left renal mass arising from the lower pole of the left kidney. Paraesophageal lymphadenopathy and mesenteric nodules are also noted. CT of the chest demonstrates bilateral pulmonary emboli. Bone scan is significant for increased activity related to the pathological fracture involving the right humerus. The patient undergoes surgery to stabilize the pathologic fracture of his humerus. He is diagnosed with metastatic RCC (clear cell histology) and undergoes palliative debulking nephrectomy.

• How is prognosis defined for metastatic RCC?

PROGNOSTIC MODELS

Limited-stage RCC that is found early can be cured surgically, with estimated 5-year survival rates for stage T1 and T2 disease approaching 90%; however, long-term survival for metastatic disease is poor, with rates ranging from 0% to 20%.¹³ Approximately 30% of patients have metastatic disease at diagnosis, and about one-third of patients who have undergone treatment for localized disease experience relapse.^36,37Common sites of metastases include lung, lymph nodes, bone, liver, adrenal gland, and brain.

Prognostic scoring systems have been developed to define risk groups and assist with determining appropriate therapy in the metastatic setting. The most widely used validated prognostic factor model is that from the Memorial Sloan-Kettering Cancer Center (MSKCC), which was developed using a multivariate analysis derived from data of patients enrolled in clinical trials and treated with interferon alfa.³⁸ The factors included in the MSKCC model are Karnofsky performance status less than 80, time from diagnosis to treatment with interferon alfa less than 12 months, hemoglobin level less than lower limit of laboratory’s reference range, LDH level greater than 1.5 times the upper limit of laboratory’s reference range, and corrected serum calcium level greater than 10 mg/dL. Risk groups are categorized as favorable (0 risk factors), intermediate (1 to 2 risk factors), and poor (3 or more risk factors).³⁹ Median survival for favorable-, intermediate-, and poor-risk patients was 20, 10, and 4 months, respectively.⁴⁰

Another prognostic model, the International Metastatic RCC Database Consortium, or Heng, model was developed to evaluate prognosis in patients treated with VEGF-targeted therapy.⁴¹This model was developed from a retrospective study of patients treated with sunitinib, sorafenib, and bevacizumab plus interferon alfa or prior immunotherapy. Prognostic factors in this model include 4 of the 5 MSKCC risk factors (hemoglobin level, corrected serum calcium level, Karnofsky performance status, and time to initial diagnosis). Additionally, this model includes both absolute neutrophil and platelet counts greater than the upper limit of normal. Risk groups are identified as favorable (0 risk factors), intermediate (1 to 2 risk factors), and poor (3 or more risk factors). Median survival for favorable-, intermediate-, and poor-risk patients was not reached, 27 months, and 8.8 months, respectively. The University of California, Los Angeles scoring algorithm to predict survival after nephrectomy and immunotherapy (SANI) in patients with metastatic RCC is another prognostic model that can be used. This simplified scoring system incorporates lymph node status, constitutional symptoms, metastases location, histology, and thyroid stimulating hormone (TSH) level.⁴²

The role of debulking or cytoreductive nephrectomy in treatment of metastatic RCC is well established. Large randomized studies have demonstrated a statistically significant median survival benefit for patients undergoing nephrectomy plus interferon alfa therapy compared with patients treated with interferon alfa alone (13.6 months versus 7.8 months, respectively).⁴³ The role of cytoreductive nephrectomy in combination with antiangiogenic agents is less clear. While a retrospective study investigating outcomes of patients with metastatic RCC receiving anti-VEGF agents showed a prolonged survival with nephrectomy, results of large randomized trials are not yet available.^44,45 Patients with lung-only metastases, good prognostic features, and a good performance status are historically the most likely to benefit from cytoreductive surgery.

CASE CONTINUED

Based on the MSKCC prognostic factor model, the patient is considered to be in the intermediate-risk group (Karnofsky performance status of 80, calcium 9.5 mg/dL, LDH 204 U/L, hemoglobin 13.6 g/dL). He is started on treatment for his bilateral pulmonary emboli and recovers well from orthopedic surgery as well as palliative debulking nephrectomy.

• What is the appropriate first-line therapy in managing this patient’s metastatic disease?

Several approaches to systemic therapy for advanced RCC have been taken based on the histologic type of the tumor. Clear-cell is by far the predominant histologic type in RCC. Several options are available as first-line treatment for patients with metastatic clear-cell RCC (Table 2).^46–54 These include biologic agents such as high-dose interleukin-2 (IL-2) immune therapy, as well as targeted therapies including TKIs and anti-VEGF antibodies. The mammalian target of rapamycin (mTOR) inhibitor temsirolimus is recommended as first-line therapy in patients with poor prognosis only. Second-line therapies for clear-cell RCC following antiangiogenic therapy include TKIs, mTOR inhibitors, nivolumab (PD-1 inhibitor), and the combination of the TKI lenvatinib and mTOR inhibitor everolimus.⁵⁵ In addition, after initial cytokine therapy, TKIs, temsirolimus, and the anti-VEGF antibody bevacizumab are other treatment options available to patients. Best supportive care should always be provided along with initial and subsequent therapies. Clinical trials are also an appropriate choice as first-line or subsequent therapies. All of these therapies require periodic monitoring to prevent and quickly treat adverse effects. Table 3 lists recommended monitoring parameters for each of these agents.⁵⁶

Based on several studies, TKIs seem to be less effective in patients with non–clear-cell type histology.^57,58 In these patients, risk factors can guide therapy. In the ASPEN trial, where 108 patients were randomly assigned to everolimus or sunitinib, patients in the good- and intermediate-risk groups had longer overall and median progression-free survival (PFS) on sunitinib (8.3 months versus 5.3 months, respectively). However, those in the poor-risk group had a longer median overall survival with everolimus.⁵⁹Given that the role of targeted therapies in non–clear-cell RCCs is less well established, enrollment in clinical trials should be considered as a first-line treatment option.²¹

Sarcomatoid features can be observed in any of the histologic types of RCC, and RCC with these features has an aggressive course and a poor prognosis. Currently, there is no standard therapy for treatment of patients with metastatic or unresectable RCC with sarcomatoid features.⁶⁰Chemotherapeutic regimens used for soft tissue sarcomas, including a trial of ifosfamide and doxorubicin, did not show any objective response.⁶¹ A small trial of 10 patients treated with doxorubicin and gemcitabine resulted in complete response in 2 patients and partial response in 1 patient.⁶²

Enrollment in a clinical trial remains a first-line treatment option for these patients. More recently, a phase 2 trial of sunitinib and gemcitabine in patients with sarcomatoid (39 patients) and/or poor-risk (33 patients) metastatic RCC showed overall response rates (ORR) of 26% and 24%, respectively. A higher clinical benefit rate (defined as ORR plus stable disease) was seen in patients with tumors containing more than 10% sarcomatoid histology, as compared with patients whose tumors contained less than 10% sarcomatoid histology. Neutropenia (n = 20), anemia (n = 10), and fatigue (n = 7) were the most common grade 3 toxicities seen in all the patients. Although this was a small study, the results showed a trend towards better efficacy of the combination therapy as compared with the single-agent regimen. Currently, another study is underway to further investigate this in a larger group of patients.⁶³

BIOLOGICS

Cytokine therapy, including high-dose IL-2 and interferon alfa, had long been the only first-line treatment option for patients with metastatic or unresectable RCC. Studies of high-dose IL-2 have shown an ORR of 25% and durable response in up to 11% of patients with clear-cell histology.⁶⁴ Toxicities were similar to those previously observed with high-dose IL-2 treatment; the most commonly observed grade 3 toxicities were hypotension and capillary leak syndrome. IL-2 requires strict monitoring (Table 3). It is important to note that retrospective studies evaluating the safety and efficacy of using IL-2 as second-line treatment in patients previously treated with TKIs demonstrated significant toxicity without achieving partial or complete response in any of the patients.⁶⁵

Prior to the advent of TKIs in the treatment of RCC, interferon alfa was a first-line treatment option for those who could not receive high-dose IL-2. It has been shown to produce response rates of approximately 20%, with maximum response seen with a higher dose range of 5 to 20 million units daily in 1 study.^66,67 However, with the introduction of TKIs, which produce a higher and more durable response, interferon alfa alone is no longer recommended as a treatment option.

VEGF MONOCLONAL ANTIBODIES

Bevacizumab is a recombinant humanized monoclonal antibody that binds and neutralizes VEGF-A. Given overexpression of VEGF in RCC, the role of bevacizumab both as a single agent and in combination with interferon alfa has been investigated. In a randomized phase 2 study involving patients with cytokine-refractory disease, bevacizumab produced a 10% response rate and PFS of 4.8 months compared to patients treated with placebo.⁶⁸ In the AVOREN trial, the addition of bevacizumab (10 mg/kg intravenously [IV] every 2 weeks) to interferon alfa (9 million units subcutaneously [SC] 3 times weekly) was shown to significantly increase PFS compared with interferon alfa alone (10.2 months versus 5.4 months; P = 0.0001).^47,48 Adverse effects of this combination therapy include fatigue and asthenia. Additionally, hypertension, proteinuria, and bleeding occurred.

TYROSINE KINASE INHIBITORS

TKIs have largely replaced IL-2 as first-line therapy for metastatic RCC. Axitinib, pazopanib, sorafenib, and sunitinib and can be used as first-line therapy. All of the TKIs can be used as subsequent therapy.

Sunitinib

Sunitinib is an orally administered TKI that inhibits VEGF receptor (VEGFR) types 1 and 2, PDGF receptors (PDGFR) α and β, stem cell factor receptor (c-Kit), and FLT-3 and RET kinases. Motzer and colleagues^52,53compared sunitinib 50 mg daily orally for 4 weeks with 2 weeks off to the then standard of care, interferon alfa 9 million units SC 3 times weekly. Sunitinib significantly increased the overall objective response rate (47% versus 12%; P < 0.001), PFS (11 versus 5 months; P < 0.001), and overall survival (26.4 versus 21.8 months; hazard ratio [HR], 0.821). The most common side effects are diarrhea, fatigue, nausea/vomiting, anorexia, hypertension, stomatitis, and hand-foot syndrome, occurring in more than 30% of patients. Often patients will require dose reductions or temporary discontinuations to tolerate therapy. Alternative dosing strategies (eg, 50 mg dose orally daily for 2 weeks alternating with 1-week free interval) have been attempted but not prospectively evaluated for efficacy.^69–71

Pazopanib

Pazopanib is an oral multi-kinase inhibitor of VEGFR types 1 and 2, PDGFR, and c-KIT. Results of a phase 3 trial comparing pazopanib (800 mg orally daily) to placebo favored the TKI, with a PFS of 9.2 months versus 4.2 months. A subset of treatment-naïve patients had a longer PFS of 11.1 versus 2.8 months and a response rate of 32% versus 4%.⁷² This led to a noninferiority phase 3 trial comparing pazopanib with sunitinib as first-line therapy.⁵⁰ In this study, PFS was similar (8.4 versus 9.5 months; HR 1.05), and overall safety and quality-of-life endpoints favored pazopanib. Much less fatigue, stomatitis, hand-foot syndrome, and thrombocytopenia occurred with pazopanib, whereas hair color changes, weight loss, alopecia, and elevations of LFT enzymes occurred more frequently with pazopanib. Hypertension is common with the administration of pazopanib as well.

Sorafenib

Sorafenib is an orally administered inhibitor of Raf, serine/threonine kinase, VEGFR, PDGFR, FLT-3, c-Kit, and RET. The pivotal phase 3 Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) compared sorafenib (400 mg orally twice daily) with placebo in patients who had progressed on prior cytokine-based therapy.⁷³ A final analysis, which excluded patients who were allowed to cross over therapies, found improved overall survival times (14.3 versus 1.8 months, P = 0.029).⁵¹Sorafenib is associated with lower rates of diarrhea, rash, fatigue, hand-foot syndrome, alopecia, hypertension, and nausea than sunitinib, although these agents have not been compared to one another.

Axitinib

Axitinib is an oral inhibitor of VEGFRs 1, 2, and 3. Results of the phase 3 AXIS trial comparing axitinib (5 mg orally twice daily) with sorafenib (400 mg orally twice daily) in patients receiving 1 prior systemic therapy showed axitinib was more active than sorafenib in improving ORR (19% versus 9%; P = 0.001) and PFS (6.7 versus 4.7 months; P < 0.001), although no difference in overall survival times was noted.⁷⁴In a subsequent phase 3 trial comparing these drugs in the first-line setting, axitinib showed a nonsignificantly higher response rate and PFS. Despite this, the National Comprehensive Cancer Network guidelines consider axitinib an acceptable first-line therapy because activity with acceptable toxicity was demonstrated (Table 2).⁴⁶The most common adverse effects of axitinib are diarrhea, hypertension, fatigue, decreased appetite, dysphonia, hypothyroidism, and upper abdominal pain.

CABOZANTINIB

Given that resistance eventually develops in most patients treated with standard treatments, including bevacizumab and TKIs, the need to evaluate the safety and efficacy of novel agents targeting VEGFR and overcoming this resistance is of vital importance. Cabozantinib is an oral small-molecule inhibitor of VEGFR, Met, and Axl, all tyrosine kinases implicated in metastatic RCC. Overexpression of Met and Axl, which occurs as a result of inactivation of the VHL gene, is associated with a poor prognosis in patients with RCC. In a

randomized, open label, phase 3 trial of cabozantinib versus everolimus in advanced RCC, Choueiri and colleagues⁷⁵ compared the efficacy of cabozantinib with everolimus in patients with metastatic RCC who had progressed on previous VEGFR-targeted therapies. In this study, 658 patients were randomly assigned to receive cabozantinib (60 mg orally daily) or everolimus (10 mg orally daily). Results of the study found that PFS was longer with cabozantinib in patients who had previously been treated with other TKIs (median PFS of 7.4 months versus 3.8 months; HR 0.58), corresponding to a 42% reduction in the rate of disease progression or death. The most common grade 3 and 4 toxicities seen with cabozantinib were similar to its class effect and consisted of hypertension, diarrhea, and fatigue. In the final analysis of the data, the median overall survival was 21.4 months (95% confidence interval [CI] 18.7–not estimable) with cabozantinib and 16.5 months (95% CI 14.7 to 18.8) with everolimus (HR 0.66 [95% CI 0.53 to 0.83]; P = 0.00026). The median follow-up for overall survival and safety was 18.7 months. These results highlight the importance of cabozantinib as a first line option in treatment of previously treated patients with advanced RCC.⁷⁶

MTOR INHIBITORS

The mTOR inhibitors, temsirolimus and everolimus, are also approved for the treatment of metastatic or advanced RCC. These drugs block mTOR’s phosphorylation and subsequent translation of mRNA to inhibit cell proliferation, cell growth, and angiogenesis.⁷⁷ Temsirolimus can be used as first-line therapy for patients with a poor prognosis, and everolimus is appropriate as a subsequent therapy.

Temsirolimus is an intravenous prodrug of rapamycin. It was the first of the class to be approved for metastatic RCC for treatment-naïve patients with a poor prognosis (ie, at least 3 of 6 predictors of poor survival based on MSKCC model).⁵⁴ The pivotal ARCC trial compared temsirolimus (25 mg IV weekly) alone, interferon alfa (3 million units SC 3 times weekly) alone, or the combination (temsirolimus 15 mg IV weekly plus interferon alfa 6 million units SC 3 times weekly). In this trial, temsirolimus monotherapy produced a significantly longer overall survival time than interferon alfa alone (10.9 versus 7.3 months; P = 0.008) and improved PFS time when administered alone or in combination with interferon alfa (3.8 and 3.7 months, respectively, versus 1.9 months). Because no real efficacy advantage of the combination was demonstrated, temsirolimus is administered alone. The most common adverse effects of temsirolimus are asthenia, rash, anemia, nausea, anorexia, pain, and dyspnea. Additionally, hyperglycemia, hyper-cholesterolemia, and hyperlipidemia occur with these agents. Noninfectious pneumonitis is a rare but often fatal complication.

Everolimus is also an orally administered derivative of rapamycin that is approved for use after failure of VEGF-targeted therapies. The results of the landmark trial RECORD-1 demonstrated that everolimus (10 mg orally daily) is effective at prolonging PFS (4 versus 1.9 months; P < 0.001) when compared with best supportive care, a viable treatment option at the time of approval.⁷⁸ The most common adverse effects of everolimus are stomatitis, rash, fatigue, asthenia, and diarrhea. As with temsirolimus, elevations in glucose, lipids, and triglycerides and noninfectious pneumonitis can occur.

TKI + MTOR INHIBITOR

Lenvatinib is also a small molecule targeting multiple tyrosine kinases, primarily VEGF2. Combined with the mTOR inhibitor everolimus, it has been shown to be an effective regimen in patients with metastatic RCC who have failed other therapies. In a randomized phase 2 study involving patients with advanced or metastatic clear-cell RCC, patients were randomly assigned to receive either lenvatinib (24 mg/day), everolimus (10 mg/day), or lenvatinib plus everolimus (18 mg/day and 5 mg/day, respectively). Patients received the treatment continuously on a 28-day cycle until progression or inability to tolerate toxicity. Patients in the lenvatinib plus everolimus arm had median PFS of 14.6 months (95% CI 5.9 to 20.1) versus 5.5 months (95% CI 3.5 to 7.1) with everlolimus alone (HR 0.40 [95% CI 0.24 to 0.68]; P = 0.0005). PFS with levantinib alone was 7.4 months (95% CI 5.6 to 10.20; HR 0.66 [95% CI 0.30 to 1.10]; P = 0.12). In addition, PFS with levantinib alone was significantly prolonged in comparison with everolimus alone (HR 0.61 [95% CI 0.38 to 0.98]; P = 0.048). Grade 3 or 4 toxicity were less frequent in the everolimus only arm and the most common grade 3 or 4 toxicity in the lenvatinib plus everolimus arm was diarrhea. The results of this study show that the combination of lenvatinib plus everolimus is an acceptable second-line option for treatment of patients with advanced or metastatic RCC.⁵⁵

CASE CONTINUED

The patient is initially started on pazopanib and tolerates the medication well, with partial response to the treatment. However, on restaging scans he is noted to have small bowel perforation. Pazopanib is discontinued until the patient has a full recovery. He is then started on everolimus. Restaging scans done 3 months after starting everolimus demonstrate disease progression.

• What is the appropriate next step in treatment?

PD1 BLOCKADE

Programmed death 1 (PD-1) protein is a T-cell inhibitory receptor with 2 ligands, PD-L1 and PD-L2. PD-L1 is expressed on many tumors. Blocking the interaction between PD-1 and PD-L1 by anti-PD-1 humanized antibodies potentiates a robust immune response and has been a breakthrough in the field of cancer immunotherapy.⁷⁹ Previous studies have demonstrated that overexpression of PD-L1 leads to worse outcomes and poor prognosis in patients with RCC.⁸⁰ Nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor, blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. In a randomized, open-label, phase 3 study comparing nivolumab with everolimus in patients with RCC who had previously undergone treatment with other standard therapies, Motzer and colleagues⁸¹ demonstrated a longer overall survival time and fewer adverse effects with nivolumab. In this study, 821 patients with clear-cell RCC were randomly assigned to receive nivolumab (3 mg/kg of body weight IV every 2 weeks) or everolimus (10 mg orally once daily). The median overall survival time with nivolumab was 25 months versus 19.6 months with everolimus (P < 0.0148). Nineteen percent of patients receiving nivolumab experienced grade 3 or 4 toxicities, with fatigue being the most common adverse effect. Grade 3 or 4 toxicities were observed in 37% of patients treated with everolimus, with anemia being the most common. Based on the results of this trial, on November 23, 2015, the U.S. Food and Drug Administration approved nivolumab to treat patients with metastatic RCC who have received a prior antiangiogenic therapy.

CASE CONCLUSION

Both TKI and mTOR inhibitor therapy fail, and the patient is eligible for third-line therapy. Because of his previous GI perforation, other TKIs are not an option. The patient opts for enrollment in hospice due to declining performance status. For other patients in this situation with a good performance status, nivolumab would be a reasonable option.

FUTURE DIRECTIONS

With the approval of nivolumab, multiple treatment options are now available for patients with metastatic or unresectable RCC. Development of other PD-1 inhibitors and immunotherapies as well as multi-targeted TKIs will only serve to expand treatment options for these patients. Given the aggressive course and poor prognosis of non-clear cell renal cell tumors and those with sarcomatoid features, evaluation of systemic and targeted therapies for these subtypes should remain active areas of research and investigation.

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Issue

Hospital Physician: Hematology/Oncology 12(1)a

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MDedge Hematology and Oncology

Hospital Physician: Hematology/Oncology

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Renal Cell Carcinoma

Genitourinary Cancer

Page Number

16-32

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