Ethinylestradiol is beneficial for postmenopausal patients with heavily pre-treated metastatic breast cancer after prior aromatase inhibitor treatment: a prospective study.

BACKGROUND: Oestrogens usually stimulate the progression of oestrogen receptor (ER)-positive breast cancer. Paradoxically, high-dose oestrogens suppress the growth of these tumours in certain circumstances. METHODS: We prospectively examined the efficacy and safety of ethinylestradiol treatment (3 mg per day oral) in postmenopausal patients with advanced or recurrent ER-positive breast cancer who had previously received endocrine therapies, especially those with resistance to aromatase inhibitors. RESULTS: Eighteen patients were enrolled with the median age of 63 years and the mean observation time of 9.2 months. Three cases withdrew within 1 week due to oestrogen flare reactions with nausea, fatigue and muscle-skeletal pain. The response rate was 50% (9 out of 18), and the clinical benefit rate was 56% (10 out of 18). The stable disease (<6 months) was 17% (3 out of 18) and another 2 cases were judged as progressive disease. Time-to-treatment failure including 2 on treatment was a median of 5.6 months (range 0.1 to 14.5(+)). Although vaginal bleeding or endometrial thickening was observed in patients receiving long-term treatment, there were no severe adverse events, such as deep venous thrombosis or other malignancies. CONCLUSION: Although the mechanism of this treatment has not been fully understood, our data may contribute to change the common view of late-stage endocrine therapy.

Does joint effusion on T2 magnetic resonance images reflect synovitis? Comparison of arthroscopic findings in internal derangements of the temporomandibular joint.

OBJECTIVE: The purpose of this study was to clarify the characteristics of joint effusion (JE) in the temporomandibular joint by comparing T2-weighted magnetic resonance (MR) images with arthroscopic findings. STUDY DESIGN: MR images of 47 symptomatic temporomandibular joints (47 patients) with internal derangement associated with painful hypomobility were taken to evaluate the degree of JE on a scale of 0 to 3. Within 2 months after MR images, arthroscopic findings with respect to the severity of synovitis, adhesion, and degenerative change in the superior compartment were each quantitatively assessed on a scale of 0 to 10. The arthroscopic scores were compared among the 4 JE grades, as well as between 2 groups, effusion-present (grades 2 and 3) and effusion-absent (grades 0 and 1), by using the Spearman correlation coefficient and the Mann-Whitney U test. RESULTS: The distribution of JE was as follows: 10 joints had grade 0, 5 joints had grade 1, 19 joints had grade 2, and 13 joints had grade 3. The synovitis score had a significant relationship to the degree of effusion (P =.0012) and was higher in the effusion-present group (6.4 +/- 2.0) than in the effusion-absent group (4.2 +/- 1.6) (P =.0005) On the other hand, there was no statistically significant correlation between either adhesion or degenerative change and effusion. CONCLUSIONS: JE may reflect synovitis; however, the nature of JE itself needs to be further elucidated by additional studies.

Outcome of arthroscopic surgery to the temporomandibular joint correlates with stage of internal derangement: five-year follow-up study.

We studied the 5-year long-term outcome of arthroscopic surgery, and also investigated whether outcome correlates with stage of internal derangement of the temporomandibular joint (TMJ). A consecutive group of 41 patients (56 joints) who had been followed up for between 3 and 5 years were involved in this study. The result was excellent in 22 patients (54%) and fair in 15 (37%). 7/14 were excellent and 5/14 were fair in stage III, 7/12 were excellent and 4/12 were fair in stage IV, and 8/15 were excellent and 6/15 were fair in stage V. Arthroscopic surgery of the TMJ is an effective and minimally invasive technique for various stages of internal derangement.

Intra-articular levels of prostaglandin E2, hyaluronic acid, and chondroitin-4 and -6 sulfates in the temporomandibular joint synovial fluid of patients with internal derangement.

PURPOSE: This study was conducted to measure the intra-articular levels of prostaglandin E2 (PGE2), hyaluronic acid, and chondroitin-4 and -6 sulfate in patients with temporomandibular joint (TMJ) internal derangement involving a closed lock, and to see if these levels correlate with the clinical or arthroscopic findings. PATIENTS AND METHODS: Fifteen female patients (16 joints) with a mean age of 36.7 years were diagnosed as having a closed lock by clinical examination and diagnostic MR imaging. The patient's subjective pain was assessed by a visual analog scale (VAS) and a pain questionnaire (pain score), and the interincisal opening was measured. TMJ aspirates were obtained by washing of the joint with saline containing vitamin B12 as a marker for calibration of data. The samples were assayed for PGE2 with a radioimmunoassay, and the concentrations of unsaturated disaccaride isomers of hyaluronic acid (delta di-HA), chondroitin-4 sulfate (delta di-4S), and chondroitin-6 sulfate (delta di-6S) were measured by high-performance liquid chromatography. Immediately after collection of the synovial aspirates, diagnostic arthroscopy was performed on all but three joints to evaluate the severity of synovitis and cartilage degeneration. The degree of arthroscopic pathology was scored quantitatively. Intra-articular levels of PGE2, delta di-HA(HA), delta di-4S(C4S), and delta di-6S(C6S) were compared with patient's age, mouth opening, VAS rating, pain scores, and arthroscopic scores for synovitis and cartilage degeneration. RESULTS: The PGE2 level did not correlate with the clinical or arthroscopic parameters. HA had a weak correlation with mouth opening (0.54). C4S and C6S were correlated with arthroscopic scores of TMJ degeneration (0.97, 0.89) and with age (0.75, 0.62). The ratio of C4S and C6S to HA was also correlated with the arthroscopic indices of degeneration (0.93, 0.8) and PGE2 level (0.74, 0.69), but not with age. CONCLUSION: The PGE2 level in the TMJ synovial fluid does not specifically reflect the intensity of pain or synovitis, but the detection of high concentrations of C4S and C6S, compared with the amount of HA, is a possible marker of proteoglycan degradation in the TMJ.

Synovial fluid cytokines and proteinases as markers of temporomandibular joint disease.

PURPOSE: In this article, biochemical markers in the synovial fluid (SF) for detecting intraarticular inflammation and early cartilage degradation of the temporomandibular joint (TMJ) disease were examined. PATIENTS AND METHODS: SF was obtained from 25 TMJs in 22 patients with internal derangement (ID) or osteoarthritis (TMJ-OA), 15 asymptomatic TMJs in 11 normal volunteers, and 10 osteoarthritic knee joints (KNEE-OA). Cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA), and the proteinase activities were detected by enzymography. RESULTS: SF from TMJs with ID and OA showed higher (P < .05) levels (330.1 +/- 347.7 pg/100 microg SF protein) of IL-1beta than the asymptomatic control TMJs (76.7 +/- 95.3 pg/100 microg of SF protein). SF from TMJs with OA contained significantly (P < .05) higher levels of IL-1beta (531.8 +/- 379.6 pg/100 microg of SF protein) and IL-6 (979 +/- 552 pg/100 microg SF protein) than those with ID (IL-1beta: 216.7 +/- 280.1 pg, IL-6: 293 +/- 434 pg). Two matrix metalloproteinases (MMPs) with gelatinolytic activities at 92 kDa and 72 kDa were consistently detected in both the TMJ-SF (either normal or disease) and SF from KNEE-OA. Also detected were weak bands with molecular weight of 83 and 66 kDa. These bands were clearly shown, particularly in knee joints with advanced stages of OA. Western blot analysis delineated that these were active forms of MMP-9 (83 kDa) and MMP-2 (66 kDa). The same bands were also detected in TMJs with OA that showed high levels of IL-1beta and IL-6. CONCLUSION: These findings suggest that concomitant increases in the levels of cytokines (IL-1 and IL-6) and active forms of MMPs could be potential catabolic markers for cartilage degradation in the TMJ.

Glycosaminoglycan components in temporomandibular joint synovial fluid as markers of joint pathology.

PURPOSE: This study investigated the correlation between temporomandibular joint (TMJ) disease and the composition of glycosaminoglycans (GAGs) components in the synovial fluid (SF). MATERIALS AND METHODS: Synovial fluid (SF) was obtained from 30 TMJs of 28 female patients diagnosed as having a displaced disc with reduction (WR) (seven joints), a displaced disc without reduction (WOR) (13 joints), osteoarthritis (OA) (five joints), or rheumatoid arthritis (RA) (five joints) by MR imaging and clinical examination. After the SF was directly aspirated, It was digested with chondroitinase ABC and hyaluronidase, and the concentration of unsaturated disaccharide isomers of chondroitin 6-sulfate (delta di-6S), chondroitin 4-sulfate (delta di-4S) and hyaluronic acid (delta di-HA) were measured by high-performance liquid chromatography (HPLC) combined with fluorometry. The ratio of delta di-6S or delta di-4S to delta di-HA, and delta di-6S to delta di-4S, were calculated. RESULTS: There were no significant differences in concentrations of delta di-6S, delta di-4S, or delta di-HA among the groups. The ratio of delta di-6S to delta di-4S was 2.7 +/- 1.4 in OA, 2.6 +/- 0.9 in joints with WOR, 2.9 +/- 1.2 in joints with WR, and 1.3 +/- 0.4 in RA synovial fluid. Differences in the delta di-6S: delta di-4S ratio between RA and the other conditions were statistically significant (P < .05). CONCLUSION: These results suggest that the delta di-6S:delta di-4S ratio in the synovial fluid of the TMJ reflects the proteoglycan metabolism of the joint tissues, particularly of the articular cartilage and synovial tissue. This ratio could be used to diagnose joint diseases and to predict articular cartilage destruction or synovial proliferation caused by these diseases.

The indications of arthroscopic sweep for the patient with internal derangements of the temporomandibular joint (T.M.J.).

The arthroscopy of the temporomandibular joint (TMJ) is recently recognized as the useful diagnostic manner as well as the alternative surgical procedures in the treatment of TMJ internal derangements. Arthroscopic surgery of the TMJ, which consists of arthroscopic sweep with lysis of adhesion and lavage of the upper joint compartment, is simple and less surgical invasive manner for the patient with closed lock. The instrumentation, procedure, patient management, and clinical evaluation are described.