The Effect of chemo- and radiotherapy on tumor necrosis in soft tissue sarcoma- does it influence prognosis?

BACKGROUND: Soft tissue sarcomas (STSs) are a heterogeneous group of tumors. Wide surgical resection is standard, often combined with neoadjuvant chemotherapy, radiotherapy, or both. Studies have shown the predictive value of tumor necrosis in bone sarcoma (BS); however, the role of necrosis in STS after neoadjuvant therapies is still unclear. This study aimed to investigate the role of chemo- and radiotherapy in the formation of tumor necrosis and to evaluate the influence of tumor necrosis on overall survival and local recurrence-free survival. Data from BS patients and patients who did not receive neoadjuvant therapy were compared. METHODS: A total of 779 patients with STS or BS were treated surgically. In all patients, tumor-specific factors such as type, size, or grading and the type of adjuvant therapy were documented. Local recurrence (LR), the diagnosis of metastatic disease, and survival during follow-up were evaluated. RESULTS: A total of 565 patients with STS and 214 with BS were investigated. In STS, 24.1% G1 lesions, 34.1% G2 lesions, and 41.8% G3 lesions were observed. Two hundred twenty-four of the patients with STS and neoadjuvant therapy had either radiotherapy (RTx) (n = 80), chemotherapy (CTx) (n = 93), or both (n = 51). Three hundred forty-one had no neoadjuvant therapy at all. In STS, tumor necrosis after neoadjuvant treatment was significantly higher (53.5%) than in patients without neoadjuvant therapy (15.7%) (p < 0.001). Patients with combined neoadjuvant chemo-/radiotherapy had substantially higher tumor necrosis than those with radiotherapy alone (p = 0.032). There was no difference in tumor necrosis in patients with combined chemo-/radiotherapy and chemotherapy alone (p = 0.4). The mean overall survival for patients with STS was 34.7 months. Tumor necrosis did not influence survival in a subgroup of G2/3 patients. In STS with no neoadjuvant therapy and grading of G2/3, the correlation between necrosis and overall survival was significant (p = 0.0248). There was no significant correlation between local recurrence (LR) and necrosis. CONCLUSION: STS shows a broad spectrum of necrosis even without neoadjuvant chemo- or radiotherapy. After CTx or/and RTx necrosis is enhanced and is significantly pronounced with a combination of both. There is a trend toward higher necrosis with CTx than with RTx. Grading substantially influences the necrosis rate, but necrosis in soft-tissue sarcoma following neoadjuvant therapy does not correlate with better survival or a lower local recurrence rate, as in bone sarcomas.

Electrospun PLA-Based Biomaterials Loaded with Melissa officinalis Extract with Strong Antioxidant Activity.

In the present study, the plant extract Melissa officinalis (M. officinalis) was successfully loaded in polymer fibrous materials on the basis of a biodegradable polyester-poly(L-lactide) (PLA) and biocompatible polyether-polyethylene glycol (PEG) by applying the electrospinning method. The optimal process conditions for the preparation of hybrid fibrous materials were found. The extract concentration was varied-0, 5 or 10 wt% in respect of the polymer weight, in order to study its influence on the morphology and the physico-chemical properties of the obtained electrospun materials. All the prepared fibrous mats were composed of defect-free fibers. The mean fiber diameters of the PLA, PLA/M. officinalis (5 wt%) and PLA/M. officinalis (10 wt%) were 1370 ± 220 nm, 1398 ± 233 nm and 1506 ± 242 nm, respectively. The incorporation of the M. officinalis into the fibers resulted in slight increase of the fiber diameters and in increase of the water contact angle values to 133°. The presence of the polyether in the fabricated fibrous material assisted the wetting of the materials imparting them with hydrophilicity (the value of the water contact angle become 0°). Extract-containing fibrous materials displayed strong antioxidant activity as determined by the 2,2-diphenyl-1-picryl-hydrazyl-hydrate free radical method. The DPPH solution color changed to yellow and the absorbance of the DPPH radical dropped by 88.7% and 91% after being in contact with PLA/M. officinalis and PLA/PEG/M. officinalis mats, respectively. These features revealed the M. officinalis-containing fibrous biomaterials promising candidates for pharmaceutical, cosmetic and biomedical use.

Amputation for Extremity Sarcoma: Indications and Outcomes.

BACKGROUND: Sarcomas are rare, malignant tumors of soft tissues or bone. Limb salvage surgery (LSS) is the standard treatment, but amputation is still an option, especially in local recurrence or complications after LSS. METHODS: We retrospectively reviewed indications and oncological outcomes in patients who underwent an amputation. Two groups with either primary amputations (n = 120) or with secondary amputations after failed LSS with local recurrence or complications (n = 29) were compared with the main end points of LRFS and OS. RESULTS: Five-year LRFS was 84% with 17 (16%) patients developing local recurrence, of which 16 (13%) occurred in group I. Forty-two (28%) patients developed metastatic disease and overall survival at five years was 44%. Overall survival (OS) was the same in both groups. In those group II patients who had a secondary amputation due to LR or insufficient margins after LSS (n = 12) the five-year OS was 33% compared to 48% in patients with amputation due to complications (n = 17) (n.s.). CONCLUSIONS: This study indicates the worse oncological outcomes with respect to OS of sarcoma patients requiring an amputation as compared to LSS. Patients with primary amputation or those who had a secondary amputation after failed LSS for whatever reason showed the same oncological results.

Discovery of anxiolytic 2-ferrocenyl-1,3-thiazolidin-4-ones exerting GABAA receptor interaction via the benzodiazepine-binding site.

Herein, we report on the synthesis, spectral, crystallographic and electrochemical properties of a small library of N-substituted 2-ferrocenyl-1,3-thiazolidin-4-ones, designed as novel GABAA benzodiazepine-binding site ligands. The anxiolytic properties of the title compounds were evaluated in several different in vivo models, whereas the involvement of the GABAA receptor complex in the activity of the most potent compound, 2-ferrocenyl-3-(4-methoxyphenylethyl)-1,3-thiazolidin-4-one, was inferred from experiments with known GABAA-targeting agents. Ligand docking experiments revealed that the high, dose-dependent, anxiolytic activity of the new compounds might be due to their favorable interactions with the benzodiazepine-binding site of the GABAA receptor complex. The incorporation of the ferrocene core and fine tuning of the distance between the thiazolidinone core and an additional aromatic ring were judged to be crucial structural requirements for the observed anxiolytic effect.