Autologe Chondrozytenimplantation

Gallik, David (2023): Autologe Chondrozytenimplantation: Analyse der defektbezogenen Einflussfaktoren bei ACI im Kniegelenk. Dissertation, LMU München: Medizinische Fakultät

Abstract

In this document I present my two publications. Both publications are about autologous chondrocyte implantation of the third generation (ACI). This technique of cartilage regeneration has become very popular and showed excellent results in the past years. However, this complex therapy method involves immense costs. In this regard, it is necessary to know all the influencing factors of the ACI, which can be at the indication making benefited of. We concentrated us on the influence of defect localization, defect size and the effect of previous microfracture therapy on the ACI afterwards. In our two studies, we analysed our knee patients with ACI NOVOCART® 3D done between 2004 and 2018. A matched pair analysis was carried out in both of our studies. Thanks to this method, it was possible to eliminate the influencing factors, which we did not look at. The goal of matching was to find for every patient from one group another patient from the second group with similar observable characteristics. The criteria for matching were in both paper similar. The criteria were age, defect localization, body mass index, number of defects treated or in the first paper also the intraoperatively measured absolute defect size. The exact surgical and then the rehabilitative procedures are explained in the publications under "surgical technique and rehabilitation". Clinical data were gathered by a standardized scheme. The preoperative clinical state was carried out together with the indication. Subsequently, the gathering of the clinical data was performed by our questionnaire 6,12,24 and 36 months after the surgery. The questionnaires included the subjective evaluation by the IKDC score as well as the visual analog scale for pain (VAS). Furthermore, the patient-specific and the defect-specific data were documented. The imaging examinations were done by the MRI and for the statistical analysis was SPSS program used. The specific statistical tests and models that brought us to the corresponding results are mentioned individually in the paper. 6.2. Results of Paper 1 ”Effect of defect size and localization of third generation autologous chondrocyte implantation in the knee joint" The hypothesis of our first paper ”Effect of defect size and localization of third generation autologous chondrocyte implantation in the knee joint" was that defects at the patella and defects with a higher relative defect size lead to worst results. A matched pair analysis was carried out. There were 25 patellar and 25 femoral defects. The follow-up period lasted 3 years. The mean age in the femoral group was 34.6 years (15-53). The group consisted of 11 men and 14 women. The mean intraoperative absolute defect size was 4.8 cm2 (2-15). The average body mass index (BMI) of 27.3 kg/m2 (20-36) was recorded. In the other group of patellar ACI was it 33.3 years (13-56), BMI of 26.3 kg/m2 (19-35), 10 men and 15 women and intraoperative defect size of 4.6 cm2 (2-12). Initially, MRI images were used to do the computer-assisted segmentation of the defect and of the whole cartilage layer. The clinical result was measured before the surgery and 6, 12, 24 and 36 months after the surgery. As for the clinical assessment there were used the IKDC and VAS scores. In both groups could IKDC and VAS provide a significant difference compared to the preoperative condition. After 3 years we noticed in the femoral group an improvement from 33.9 (SD 18.1) preoperatively to 71.5 (SD 17.4) in IKDC and from 6.9 (SD 2.9) to 2.4 (SD 2.5) in VAS. The second group of the patellar defects showed after 3 years an increase in the IKDC from 36.1 (SD 12.6) to 54.7 (SD 20.3) and an improvement in the VAS from 6.7 (SD 2.8) to 3.4 (SD 2). After 1-3 years postoperatively the femoral IKDC score was significant better (p <0.05) than the patellar group, which confirmed part of our hypothesis. With the data from the MRI segmentation we could calculate the relative defect size. The calculation was done by the ratio between the absolute defect size and the whole cartilage layer of the relevant knee. The result was calculated in percentage. A comparison between the relative defects revealed a significant difference between femoral (6.7%) and patellar group (18.9%). Consequently, it implies that although the absolute defect size in both groups was the same, the share of the defect on the cartilage layer of the patella was higher than femoral. However, according to our data neither the absolute nor the relative defect size has a significant impact on the outcome. 6.3. Conclusion of Paper 1 ”Effect of defect size and localization of third generation autologous chondrocyte implantation in the knee joint" Thanks to our work, we were able to confirm that third generation of ACI offers benefits to the patients with cartilage defects. The patellar defects lead to a worse clinical result compared to the femoral defects. In terms of influence on the outcome the absolute and relative defect size showed itself as irrelevant. Despite this fact, our study was the first to look at the issue of the relative defect size and it would be worth further exploring this topic. 22 6.4. Results of Paper 2 “Third-generation autologous chondrocyte implantation after failed bone marrow stimulation leads to inferior clinical results” In our second published paper “Third‑generation autologous chondrocyte implantation after failed bone marrow stimulation leads to inferior clinical results” we observed the outcome of patients of the second line matrix-based ACI after failed microfracture therapy. The observation period was three years postoperatively. The hypothesis was that the second line ACI after unsuccessful microfracture provides inferior results compared to the first line ACI. Similar to the first paper, we did a matched pair analysis. We matched two groups with together 40 ACI patients. The first group of 20 patients represented first line ACI without pre-surgery or pre- treatment of the cartilage. The second matched group represented the second line ACI. It means the patients with a previous unsuccessful microfracture therapy. Clinical data collecting was carried out using IKDC and VAS scores. The first group had preoperatively an IKDC score of 37.0, which increased to 77.7 after two years. The postoperative IKDC increase was always statistically significant, comparing to preoperative values. Analysing the VAS at rest and in motion we noticed a significant improvement at all follow ups as well. In the second group was the subjective IKDC score preoperatively at 29.9 and then after six months at 44.3. After 12 months was it 50.1, as the further increase continued. A significant improvement compared to preoperative findings was observed at all times. The VAS begun at 6.8 in motion and 4.4 at rest. Both VAS scores improved significantly after 6 and 12 months, while the VAS at rest reached significant difference also after 3 years compared to preoperative results. When comparing our two groups in terms of IKDC and VAS in motion, a significant difference in favour of first line ACI was observed in all follow-ups. Similar was it in VAS at rest with only one exception after 6 months. The first line group of patients without previous microfracture treatment was always superior to the group of second line ACI. This confirmed our hypothesis. 6.5. Conclusion of Paper 2 “Third-generation autologous chondrocyte implantation after failed bone marrow stimulation leads to inferior clinical results” The matrix-based ACI as the third generation of this procedure confirmed itself as an appropriate approach in the therapy of full cartilage defects. The benefits of this method were significantly proven for the patient with and without previous microfracture surgery. However, the ACI therapy after previous failed microfracture procedure was clearly inferior to first line ACI. It implies, that the ACI should be initially preferred instead of microfracture in the larger defects.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Deutsch
• Datum der mündlichen Prüfung: 23. November 2023
• 1. Bericht­erstatter:in: Pietschmann, Matthias