Pulmonary metastasectomy for soft tissue sarcoma--report from a dual institution experience at the Medical University of Vienna.

BACKGROUND: Pulmonary metastasectomy when possible has become therapeutic standard in soft tissue sarcoma patients. However, published reports frequently describe mixed series of patients with bone or soft tissue sarcoma. We report the outcome of 46 soft tissue sarcoma (STS) patients who underwent pulmonary metastasectomy (PM). METHODS: This current analysis includes retrospective survival data from 46 consecutive STS patients with pulmonary metastases who underwent PM at the Medical University of Vienna between January 2003 and December 2013. RESULTS: In total 72 pulmonary metastasectomies were performed. 322 metastatic nodules were resected with a median number of four nodules per intervention and the R0 resection rate was 97.2%. The postoperative complication rate as documented was low. Median follow-up (mFU) was 31.8 months (range 3.7-127.4). Median overall survival as calculated from first detection of metastatic disease was 47.1 months (95% confidence interval (CI)=36.2-58.1 months) and 45.3 months (95% CI=33.3-57.4 months) when calculated from first PM until death or last follow-up (n=46). Five-year overall survival calculated from primary diagnosis was 62% and 32% when estimated from first PM. Previous disease free interval (DFI) as calculated from date of surgery of the primary tumour until the date of diagnosis of lung metastasis was 12.2 months (range 0-140.1 months). Median relapse-free survival (mRFS) after first PM to the date of recurrence of lung metastasis, death or last follow-up was 13.4 months (95% CI=3-23.8 months). CONCLUSION: Median overall survival in this selected patient cohort is 45.3 months. Despite the lack of prospective randomised controlled trials, PM is a reasonable treatment strategy in selected patients.

Alignment does not influence cartilage T2 in asymptomatic knee joints.

PURPOSE: To investigate whether the static knee alignment affects articular cartilage ultrastructures when measured using T2 relaxation among asymptomatic subjects. METHODS: Both knee joints (n = 96) of 48 asymptomatic volunteers (26 females, 22 males; 25.4 ± 1.7 years; no history of major knee trauma or surgery) were evaluated clinically (Lysholm, Tegner) and by MRI (hip-knee-ankle angle, standard knee protocol, T2 mapping). Group (n = 4) division was as follows: neutral (<1° varus/valgus), mild varus (2°-4° varus), severe varus (>4° varus) and valgus (2°-4° valgus) deformity with n = 12 subjects/group; n = 24 knees/group. Regions of interest (ROI) for T2 assessment were placed within full-thickness cartilage across the whole joint surface and were divided respecting compartmental as well as functional joint anatomy. RESULTS: Leg alignment was 0.7° ± 0.5° varus among neutral, 3.0° ± 0.6° varus among mild varus, 5.0° ± 1.1° varus among severe varus and 2.5° ± 0.7° valgus among valgus group subjects and thus significantly different. No differences between the groups emerged from clinical measures. No morphological pathology was detected in any knee joint. Global T2 values (42.3 ± 2.3; 37.7-47.9 ms) of ROIs placed within every knee joint per subject were not different between alignment groups or between genders, respectively. CONCLUSION: Static frontal plane leg malalignment does not affect cartilage ultrastructure among young, asymptomatic individuals as measured by T2 quantitative imaging. LEVEL OF EVIDENCE: Cross-sectional study, Level II-III.

[Problems and complications of surgical techniques for treatment of full-thickness cartilage defects]. / Probleme und Komplikationen chirurgischer Verfahren zur Behandlung vollschichtiger Knorpeldefekte am Kniegelenk.

AIM: There has been great progress concerning the surgical treatment of full-thickness cartilage defects within recent years. Surgical techniques such as arthroscopic microfracturing (MF), autologous osteochondral transplantation (OCT) and autologous chondrocyte implantation (ACI) have been introduced and, by using these techniques, reliable and satisfying clinical results can be achieved. Nevertheless, there are also technique-related problems and characteristic complications of all surgical techniques in the field of cartilage repair. Knowledge of these complications is essential for every surgeon using these techniques. The aim of the present article is to give an overview concerning technique-associated and characteristic complications of the most common cartilage repair techniques including arthroscopic microfracturing, autologous osteochondral transplantation and autologous chondrocyte implantation (ACI). METHODS: In order to identify relevant literature concerning complications following cartilage repair, medical databases including "medline", "ovid" and "web of science" were searched for the terms "autologous chondrocyte implantation", "autologous chondrocyte transplantation", "microfracture", "osteochondral transplantation", "cartilage repair", "cartilage defect" and "complications" in October 2009. The present publication represents a non-systematic review including publications which were considered relevant for describing charateristic complications and adverse events in surgical techniques used for cartilage repair. RESULTS: Although the number of studies describing complications and adverse events following surgical cartilage repair studies is limited, for all techniques included in the present review (arthroscopic microfracturing, autologous osteochondral transplantation and autologous chondrocyte implantation) technique-associated and characteristic complications could be identified. While regenerative tissue following microfracturing seems to be limited in terms of durability, intralesional bone formation and elevation of the subchondral bone plate seem to be characteristic problems of this technique. Harvest morbidity, degeneration of the surrounding cartilage, necrosis of the transplanted cylinders and a lack of integration of the cartilage into the surrounding cartilage seem to be related to the transplantation of osteochondral cylinders (OATS/OCT), while hypertrophic regenerative cartilage, disturbed fusion into the adjacent cartilage, delamination and insufficient cartilage regeneration are associated with the autologous chondrocyte implantation (ACI). CONCLUSION: The present paper identifies technique-associated complications for the most common surgical techniques used for cartilage repair. Even if the clinical relevance of the complications described in the current article has not been investigated to its fullest extent, the awareness of these characteristic complications is essential in order to avoid them whenever possible or to develop standardised treatment regimes for these problems. This needs to be addressed in further investigations.

Prognostic factors in nonoperative therapy for chronic symptomatic calcific tendinitis of the shoulder.

OBJECTIVE: To define prognostic factors in chronically symptomatic patients with calcific tendinitis of the shoulder. METHODS: We evaluated 420 patients (488 shoulders) in the context of a prospective cohort study. Epidemiologic data were assessed. The radiographic and sonographic appearance of the calcific deposits was classified. The mean period of nonoperative therapy was 4.4 years (range 0.5-13.7 years). After referral to our institution, standardized nonoperative therapy was continued for a minimum of 3 months. Failure of nonoperative therapy was defined as the persistence of symptomatic calcific tendinitis of the shoulder after a minimum of 6 months. Prognostic factors (determined at P < 0.05 by chi-square test) were analyzed by logistic regression. RESULTS: Of the 420 patients, 269 (64%) were women, 151 (36%) were men. The mean age of the patients was 51.3 years (range 28-84 years). Occurrence of calcific tendinitis of the shoulder was unilateral in 84% and bilateral in 16%. Gärtner type I calcific deposits were found in 37%, type II in 32%, and type III in 31%. Failure of nonoperative therapy was observed in 114 patients (27%). Negative prognostic factors were bilateral occurrence of calcific tendinitis of the shoulder, localization to the anterior portion of the acromion, medial (subacromial) extension, and high volume of the calcific deposit. Positive prognostic factors were a Gärtner type III deposit and a lack of sonographic sound extinction of the calcific deposit. CONCLUSION: Our findings demonstrate the existence of prognostic factors in the nonoperative treatment of chronic symptomatic calcific tendinitis of the shoulder. Guidelines for optimal treatment can be implemented according to these factors to avoid a long-term symptomatic disease course.

Trail-induced apoptosis and interaction with cytotoxic agents in soft tissue sarcoma cell lines.

Five human soft tissue sarcoma (STS) cell lines (HTB-82 rhabdomyosarcoma, HTB-91 fibrosarcoma, HTB-92 liposarcoma, HTB-93 synovial sarcoma and HTB-94 chondrosarcoma) were analysed for their sensitivity to tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and the function of the TRAIL apoptotic pathway in these cells. TRAIL induced significant apoptosis (>90%) in HTB-92 and HTB-93 cells, whereas no effect was observed in HTB-82, HTB-91 and HTB-94 cells. TRAIL-Receptor 1 (TRAIL-R1) was expressed in TRAIL-sensitive HTB-92 and HTB-93 cell lines, but not in TRAIL-resistant HTB-91 and HTB-94 cells. HTB-82 cells, which expressed the long (c-FLIP(L)) and short (c-FLIP(S)) splice variants of the FLICE-like inhibitory protein (FLIP), were resistant to TRAIL in spite of the presence of TRAIL-R1. TRAIL-R2,-R3,-R4 and osteoprotegerin (OPG) expression did not correlate with TRAIL sensitivity. Coincubation of TRAIL and doxorubicin led to the overexpression of TRAIL-R2 resulting in a synergistic effect of doxorubicin and TRAIL in TRAIL-sensitive cell lines and in the overcoming of TRAIL-resistance in all of the TRAIL-resistant cell lines, except HTB-91, which lacked caspase 8 expression. These data suggest that TRAIL, either as a single agent or in combination with cytotoxic agents, might represent a new treatment option for advanced STS, which constitutes a largely chemotherapy-resistant disease.

Anti-Her-2/neu antibody induces apoptosis in Her-2/neu overexpressing breast cancer cells independently from p53 status.

Anti-Her-2/neu antibody is known to induce apoptosis in HER-2/neu overexpressing breast cancer cells. However, exact regulatory mechanisms mediating and controlling this phenomenon are still unknown. In the present study, we have investigated the effect of anti-Her-2/neu antibody on apoptosis of HER-2/neu overexpressing human breast cancer cell lines SK-BR-3, HTB-24, HTB-25, HTB-27, HTB-128, HTB-130 and HTB-131 in relation to p53 genotype and bcl-2 status. SK-BR-3, HTB-24, HTB-128 and HTB-130 cells exhibited mutant p53, whereas wild type p53 was found in HTB-25, HTB-27 and HTB-131 cells. All seven cell lines weakly expressed bcl-2 protein (10-20%). Anti-Her-2/neu antibody, irrespective of p53 and bcl-2 status, induced apoptosis in all 7 cell lines dose- and time-dependently and correlated with Her-2/neu overexpression. In addition, incubation of cell lines with anti-Her-2/neu antibody did not alter p53 or bcl-2 expression. Anti-HER-2/neu antibody did not induce apoptosis in HER-2/neu negative HBL-100 and HTB-132 cell lines. Our results indicate that within the panel of tested breast cancer cell lines, anti-Her-2/neu antibody-induced apoptosis was independent from the presence of intact p53.

Monotherapy with docetaxel in second- or third-line treatment of anthracycline-resistant metastatic breast cancer.

Nineteen breast cancer patients pretreated with one or two anthracycline-containing regimens for visceral metastases received i.v. docetaxel 100 mg/m2 on day 1, q 21d. Docetaxel was administered as second-line therapy in 11 patients, whereas eight patients received docetaxel in a third-line setting. In the second-line setting, complete response (CR) was achieved in two (18%), partial response (PR) in four (36%) and stable disease (SD) in three (27%) patients resulting in a response rate (RR) of 54%. In the third-line setting three (38%) patients experienced PR (RR 38%) and two (25%) SD. In the second-line setting, median time to progression was 6.5+/-3.9 months (range 2.1-15.8) versus 4.7+/-5.5 months (range 0.6-15.9) in the third-line setting. Median overall survival was 9.6+/-8.0 months (range 2.7-25.8) versus 11.2-6.1 months (range 4.8-18.7). Overall, no patient experienced treatment-limiting toxicities. We conclude that docetaxel induced responses in 48% of anthracycline-resistant patients enrolled into the present study. The safety profile of docetaxel was manageable and tolerable. Docetaxel represented efficacious treatment in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy.