Klaus Huch

Osteoarthritis in ankle and knee joints

Ankle and knee joints differ in their susceptibility to osteoarthritis (OA). This article reviews literature on differences between these joints. A Medline search and search of bibliographies of review articles was conducted. Knee cartilage degeneration leads to the development of OA with clinical symptoms, whereas the ankle cartilage develops fissures that do not appear to progress to later stages of OA. Epidemiological studies support these findings. Factors that might explain this phenomena include differences in joint motion, cartilage thickness, congruency, mechanical forces, and even evolutionary changes. Data suggest that chondrocytes from the two joints may respond differently to stimuli. Comparisons of cartilage from the knee and ankle joint of the same donor may provide a better understanding of the biochemical and molecular processes that induce the pathogenesis of OA and may provide new approaches to early detection and treatment.

The Tokuhashi Score: Significant Predictive Value for the Life Expectancy of Patients With Breast Cancer With Spinal Metastases

Study Design. Retrospective study of 55 consecutive patients with spinal metastases secondary to breast cancer who underwent surgery. Objective. To evaluate the predictive value of the Tokuhashi score for life expectancy in patients with breast cancer with spinal metastases. Summary of Background Data. The score, composed of 6 parameters each rated from 0 to 2, has been proposed by Tokuhashi and colleagues for the prognostic assessment of patients with spinal metastases. Methods. A total of 55 patients surgically treated for vertebral metastases secondary to breast cancer were studied. The score was calculated for each patient and, according to Tokuhashi, the patients were divided into 3 groups with different life expectancy according to their total number of scoring points. In a second step, the grouping for prognosis was modified to get a better correlation of the predicted and definitive survival. Results. Applying the Tokuhashi score for the estimation of life expectancy of patients with breast cancer with vertebral metastases provided very reliable results. However, the original analysis by Tokuhashi showed a limited correlation between predicted and real survival for each prognostic group. Therefore, our patients were divided into modified prognostic groups regarding their total number of scoring points, leading to a higher significance of the predicted prognosis in each group (P < 0.0001), and a better correlation of the predicted and real survival. Conclusion. The modified Tokuhashi score assists in decision making based on reliable estimators of life expectancy in patients with spinal metastases secondary to breast cancer.

Interleukin-1β Induces Different Gene Expression of Stromelysin, Aggrecan and Tumor-Necrosis-Factor-Stimulated Gene 6 in Human Osteoarthritic Chondrocytes in vitro

Objective: To analyze the gene expression of osteoarthritic chondrocytes cultured in alginate after stimulation with interleukin (IL)-1β. Methods: Chondrocytes were isolated from osteoarthritic cartilage obtained during total knee replacement by sequential enzymatic digestion. After suspension in alginate, cells were cultured with and without 100 pg/ml IL-1β. Quantitative RT-PCR reaction was used to estimate the messenger RNA (mRNA) of three different metabolites [tumor-necrosis-factor-stimulated gene 6 (TSG-6), stromelysin-1 (MMP-3) and aggrecan (AGG)]. Results: After having shown the precision of quantitative PCR, this method allowed us to detect IL-1β-induced changes in mRNA of TSG-6, MMP-3 and AGG. MMP-3 was found to be the most abundant transcript, IL-1β induced a 12-fold upregulation of MMP-3 levels compared to control, and 7-fold of TSG-6. The AGG transcript level, indicating anabolic events, was found to be downregulated by between 2- and 3-fold. Conclusions: In our culture system, the response of osteoarthritic chondrocytes to IL-1β is preserved. Therefore, this system might be helpful for further investigation of the influences of drugs, cytokines and growth factors, for example, on the metabolism of chondrocytes at the level of gene transcription as the most basic level of regulation.

Gene Expression by Human Articular Chondrocytes Cultured in Alginate Beads

Culture of articular chondrocytes in alginate beads offers several advantages over culture in monolayer; cells retain their phenotype for 8 months or longer. Earlier studies of chondrocytes cultured in alginate concentrated on collagen and proteoglycan synthesis. However, gene expression by in situ hybridization (ISH) has not been investigated. The purposes of the present study on human chondrocytes were (a) to modify the ISH procedure for the alginate beads to examine the mRNA expression of α1 (II) procollagen, aggrecan, and two matrix metalloproteinases (MMP-3 and MMP-8) thought to be involved in cartilage matrix degradation, and (b) to compare expression in cultured chondrocytes with that in chondrocytes of intact human cartilage. The modifications made for ISH include the presence of CaCl2 and BaCl2 in the fixation and washing steps and exclusion of cetyl pyridinium chloride. By ISH we show that aggrecan, MMP-3, and MMP-8 are continuously expressed during 8 months of culture. The α1 (II) procollagen gene is expressed only during the first 2 months of culture and after 3 months its expression is undetectable, which is consistent with its absence in adult articular cartilage. By Western blotting, Type II collagen protein had been synthesized and deposited in both the cell-associated and further-removed matrix compartments at 7 and 14 days of culture. These data indicate that chondrocytes cultured in alginate beads could be preserved for immunohistochemistry and ISH and that culture of human chondrocytes in alginate beads may serve as a good model for studying cartilage-specific phenotype as well as factors that influence cartilage matrix turnover.

Prognosis Scores of Tokuhashi and Tomita for Patients With Spinal Metastases of Renal Cancer

BackgroundRetrospective evaluation of the prognosis scores of Tokuhashi and Tomita for life expectancy in 37 consecutive patients with spinal metastases secondary to renal cancer who underwent surgery. The score of Tokuhashi, composed of six parameters, each rated from zero to two, has been proposed in 1990 for the prognostic assessment of patients with spinal metastases. In 2001, Tomita et al. created another prognostic score, composed of three parameters, growth behaviour of the primary tumor (slow, moderate and rapid) and the evidence of visceral and bony metastases.MethodsThirty-seven patients, surgically treated for vertebral metastases secondary to renal cancer were studied. The scores according to Tokuhashi and Tomita were calculated for each patient.ResultsApplying the Tokuhashi Score for the estimation of life expectancy of renal cancer patients with vertebral metastases was found to provide very reliable results with a statistically high significance. The analysis according to Tomita showed no correlation between predicted and real survival. The statistical analysis did not show any significance.ConclusionFor surgical decisions in renal cancer patients with spinal metastases, the prognostic score of Tokuhashi appears to be much more valuable than the Tomita score.

Effects of hyaluronan on proteoglycan content of osteoarthritic chondrocytes in vitro.

Purpose: To investigate the effect of hyaluronic acid (HA) on proteoglycan (PG) concentration in alginate cultures of human osteoarthritic chondrocytes and to analyze whether HA exhibit anti‐degradative effects in the presence of the cytokine IL‐1β.

Dynamic stabilization of the lumbar spine.

This study analyzed the outcome of patients treated with total disk replacement and posterior dynamic stabilization. For pathologies of different origin, dynamic stabilization of the lumbar spine is a novel alternative to fusion surgery. Although a physiological reconstruction of the sagittal profile was not always achieved, improvement was seen in all subscales of the clinical outcome measures in both treatment groups. Posterior dynamic stabilization and total disk replacement are promising alternatives to fusion with acceptable morbidity for strictly defined indications.

Gene Expression of Stromelysin and Aggrecan in Osteoarthritic Cartilage

Objective: To analyze cartilage gene expression of patients with osteoarthritis (OA) in correlation with radiographic and histological findings. Materials and Methods: Twenty-one patients with OA of the knee admitted for total knee replacement were analyzed clinically and radiographically by the Kellgren and Lawrence system. During surgery, cartilage samples from the medial and lateral condyles and tibial plateaus were harvested separately. Specimens were analyzed histologically (Mankin score) and total RNA was extracted directly from cartilage tissue. Steady state levels of stromelysin (MMP-3), aggrecan (AGG) and the house-keeping gene β-actin were measured using quantitative PCR. Results: Histology of medial and lateral knee compartments corresponded to radiographic changes (Spearman correlation coefficient: r = 0.7 (p < 0.01)). There was a positive correlation between MMP-3 and AGG gene expression (r = 0.4; p < 0.01). We found considerable variation of expression levels of MMP-3 and AGG and no correlation of gene expression with histological or radiographic scoring. Conclusion: The positive correlation between AGG and MMP-3 suggests a common regulation of anabolic and catabolic metabolism. There was no simple dependency between gene expression and histological and radiological findings in cartilage.

Classical and atypical location of adamantinomas--presentation of two cases.

Background: Adamantinomas are rare low-grade primary bone tumors of unknown histological origin. They typically develop in the diaphyses and metaphyses of long bones, prevalently the tibia. Case Reports: The cases of 2 female patients, one with localized swelling of the lateral metatarsals and one with pain of the tibia are being reported. The diagnostic work-up including biopsy verified an adamantinoma in both cases. In the younger patient, the tumor was located in the metatarsals 4 and 5, in the older patient in the left tibial diaphyses. In both patients, an en-bloc resection of the tumor with wide surgical margins was performed. Further follow-ups 73 and 36 months after surgery showed no local recurrence or metastatic spread. Conclusion: Adamantinomas of the short bones are rarely reported. In accordance to the literature, an en-bloc resection with wide surgical margins seems to reduce the risk of local recurrence and metastatic spread.

Osteoblastoma of the sacrum: report of 18 cases and analysis of the literature

Study Design. Retrospective case series. Objective. (1) To analyze clinical and radiographical characteristics, treatment, and outcome in patients with sacral osteoblastoma, (2) to evaluate progression-free survival and local recurrence rate, and (3) to identify prognostic factors. Summary of Background Data. Osteoblastoma is a rare tumor that has been reported to affect the sacrum from 7% to 17%. Symptoms are various and the diagnosis is often delayed. Methods. From 1980 to 2010, 18 patients with sacral osteoblastoma (16 males and 2 females) were treated at Rizzoli Institute. Lesion involved S1 (2 cases), S1–S2 (3 cases), S2 (1 case), S2–S3 (1 case), S2–S4 (1 case), S3 (2 cases), S3–S4 (5 cases), S4 (1 case), and almost the entire sacrum in 2 cases. According to Enneking classification for benign bone tumors, 13 (72%) were diagnosed at stage 2 and 5 (28%) at stage 3. Mean tumor volume was 64 cm3 (range, 2–441 cm3). Nine patients had preoperative magnetic resonance imaging. Five patients had a previous inadequate intralesional surgery elsewhere. Treatment consisted in intralesional surgery (16 cases), intralesional surgery and radiotherapy (1 case), and wide resection (1 case). Local adjuvants used were phenol (7 patients), cryocoagulation with “iceball” technique (1 case). Embolizations were performed in 7 patients. Results. At a mean of 8.4 years (range, 1–28 yr), 15 patients (83%) remained continuously disease free, whereas 3 patients had local recurrence (17%). Progression-free survival was 87% at 5 years and 74% at 10 years. No statistical difference was found between patients who received or not local adjuvants (P = 1.254), older or younger than 20 years (P = 0.970), at stage 2 or 3 (P = 0.826), evaluated preoperatively with or without magnetic resonance imaging (P = 0.160), primarily treated versus patients with previous intralesional surgery elsewhere (P = 0.131). Conclusion. In our series, curettage was successful in most of the patients. Local adjuvants did not seem to reduce the risk of local recurrence when combined with intralesional surgery. Level of Evidence: 4