The most important finding of this study was that high TTT values before ACL reconstruction may be a potential risk factor for developing cyclops nodule formation. Many researchers have reported that the cause of cyclops syndrome (due to an impinged cyclops nodule) is multi-factorial, and therefore, the pathological condition is not completely understood [1, 7, 8]. In fact, although surgical procedures corresponding to the causative disease condition have been reported [19, 20], surgical procedures still fail to prevent the occurrence of cyclops lesions. We believe the cyclops nodule formation that occurs after surgery is related to the individual’s immune response. This is because the patterns observed during cyclops nodule formation cannot be explained by the potential causes that have been reported so far. The clinical problem of cyclops syndrome (due to an impinged cyclops nodule) is to cause loss of irreversible knee extension that does not improve without surgery. Furthermore, nodule formation is considered to be completed by about 6 weeks after surgery [7]. On the other hand, it has been reported that resection of cyclops nodule formation improves symptoms without recurrence. This suggests that acute vital tissue reactions occurring after ACL injury or in the early phase after reconstruction may be involved in development of cyclops nodules. The continuous contact between the graft and intercondylar notch may produce an irritating stimulus, which may induce an inflammatory response with the production of granulation tissue, which would be transformed into fibrocartilaginous and cartilaginous tissue [21]. However, because all knees in our cohort achieved full extension at the end of surgery, failure to regain full extension may be due the wound healing process after surgery. Intra- or post-operative factors may promote the process, but they are not the key factors. Injury to the ligament and the reparative processes occurring as a result of vital tissue reactions are the main triggering factors for cyclops nodule formation [9]. The response of living tissue in this reparative process varies from individual to individual, and it is possible that an immune response is involved.
We discovered that TTT values associated with the risk of developing cyclops nodule formation following ACL reconstruction. TTT was reported as an indicator of hepatic injury in the mid-twentieth century [13]. Basically, this examination reflects a decrease in serum albumin and an increase in globulin. γ globulin has a tendency to precipitate, and this increases the amount of sedimentation; however, if hydrophilic albumin increases, γ globulin does not precipitate. The TTT value is relatively high even with lower albumin levels associated with chronic hepatitis and chronic inflammation. Although, we did evaluate AST, ALT, and CRP, and there were no differences at the different time points (before reconstruction, at 3 months, and 1 year after reconstruction) (Table 3). Previous reports have shown that TTT is associated with immune reaction [11, 21, 22]. Our findings are clinically relevant, since the pathophysiological effect of the presence of a cyclops nodule formation is not fully understood to date.
We performed cyclops resection in the cyclops group 3 months after reconstruction. Interestingly, the high pre-operative TTT values were reduced following cyclops resection. Furthermore, the TTT values did not return to the pre-reconstruction values before second-look arthroscopy, but they were higher than the no-cyclops group (Table 3). It may be suggested that resection of the cyclops using the arthroscope suppressed the reaction that occurs in the body of a living organism when the body rejects something. Furthermore, the gradually increasing TTT values after nodule resection may indicate that the patients who developed cyclops nodule formation originally had high immunoglobulin levels.
There was no difference in TTT values in the group that developed cyclopoids and the no-cyclops group. The cyclopoid is the displaced portion of the ACL with an angulated fold at the anterior end, giving it a tongue-like appearance [1, 23]. Histologically, cyclopoid scar formations are made up of fibrous tissue, showing elements of granulation tissue [6]. Similar to these reports, the cyclopoid scars observed during second-look arthroscopy in our study were recognized as soft, scar-like tissue in front of the ACL graft impinging on the intercondylar region during knee extension (Fig. 2). Regarding range of motion in the cyclopoid group, extension loss was observed at 3 months (Table 4), and 10 patients showed extension loss of more than 10 degrees 3 months after reconstruction. However, due to no palpable “clunk” with terminal extension, we did not perform surgery on the cyclopoid group. As a result, in the cyclopoid group, range of motion recovered to that of the contralateral knee 1 year after reconstruction in all cases. Extension loss in the early phase after reconstruction prevents closure of the intercondylar notch and allows local organization of the post-operative hemarthrosis [24]. Soft tissues such as cyclopoid scars may not be the result of an individual’s immune reaction, but due to extension loss in the early post-reconstruction phase.
Given that this was a retrospective case control study, we did not examine other joint abnormalities. Given that flexion was also limited in the cyclops group, we further believe that the development of this nodulous scar formation is merely the expression of a generalized inclination to fibrotic healing. We showed that the occurrence of cyclops nodule formation may be involved in the response of living tissue, which is a potential factor that varies between individuals. Given this, low-dose steroids administered for the treatment of arthrofibrosis may be effective for patients with high TTT values.
Limitations
Although we have shown that the development of cyclops nodule formation depends on TTT values, TTT values are said to vary depending on the amount of immunoglobulin; however, we did not evaluate antibody-producing lymphocytes or antigen-presenting dendritic cells. Further evaluations using immunostaining of cyclops tissue are necessary. In addition, further studies are required to investigate the secretion of cytokines, growth factors, chemokines, inflammatory mediators, and matrix molecules and proteins that contribute to motility, proliferation, and differentiation of fibroblasts and myofibroblasts involved in the growth phase during wound healing.