Influence of prereferral surgery in soft tissue sarcoma: 10 years' experience in a single institution

Soft tissue sarcomas are a group of rare mesenchymal neoplasms comprising 0.8% of all malignant tumors. Workup should include medical history, physical examination, magnetic resonance imaging, biopsy, and thoracoabdominal computed tomography scan, in that order. Centralized multimodality treatment in a cross-disciplinary setting is mandatory. Treatment not according to current clinical practice guidelines is a common problem before referral to a specialized institution. The purpose of this 10-year, single-institution review was to investigate the influence of curative surgery on outcome, with a special emphasis on surgery before referral.A cohort of 266 patients who underwent curative surgery for soft tissue sarcoma between 1998 and 2008 was analyzed. One hundred thirty-one (49%) patients underwent surgery contrary to current clinical guidelines before referral, most (73%) at primary care units. One hundred thirteen (86%) of these patients underwent surgery without previous biopsy with a higher rate of intralesional margins (P<.001), a smaller mean diameter of primary lesion (P<.001), a higher rate of subcutaneous situs (P<.001), a lower mean American Joint Committee on Cancer score (P=.008), a higher rate of additional plastic surgery after re-resection (eg, flap surgery) (P<.001), and a longer period before referral (P<.001). No influence on survival, local recurrence, or metastasis existed.Prereferral surgery necessitating re-resection has no influence on survival but leads to an unfavorable clinical course. More effort should be made to improve awareness and referral modalities for general practitioners and physicians at community hospitals.     

Should ‘typical’, first-generation antipsychotics no longer be generally used in the treatment of schizophrenia?

European Archives of Psychiatry and Clinical Neuroscience -     

Elution behavior of a 3D-printed,milled and conventional resin-based occlusal splint material

ObjectiveThe elution of unpolymerized (co-)monomers and additives from methacrylic resin-based materials like polymethyl methacrylate (PMMA) can cause adverse side effects, such as mutagenicity, teratogenicity, genotoxicity, cytotoxicity and estrogenic activity.The aim of this study was to quantify the release and the cytotoxicity of residual (co-)monomers and additives from PMMA-based splint materials under consideration of real splint sizes. Three different materials used for additive (3D printing), subtractive (milling) and conventional (powder and liquid) manufacturing were examined.MethodsThe splint materials SHERAprint-ortho plus (additive), SHERAeco-disc PM20 (subtractive) and SHERAORTHOMER (conventional) were analysed. 16 (n = 4) sample discs of each material (6 mm diameter and 2 mm height) were polished on the circular and one cross-section area and then eluted in both distilled water and methanol. The discs were incubated at 37 °C for 24 h or 72 h and subsequently analysed by gas chromatography/mass spectrometry (GC/MS) for specifying and quantifying released compounds. XTT-based cell viability assays with human gingival fibroblasts (HGFs) were performed for Tetrahydrofurfuryl methacrylate (THFMA), 1,4-Butylene glycol dimethacrylate (BDDMA) and Tripropylenglycol diacrylate (TPGDA). In order to project the disc size to actual splint sizes in a worst-case scenario, lower and upper jaw occlusal splints were designed and volumes and surfaces were measured.ResultsFor SHERAeco-disc PM20 and for SHERAORTHOMER no elution was determined in water. SHERAprint-ortho plus eluted the highest THFMA concentration of 7.47 μmol/l ±2,77 μmol/l after 72 h in water. Six (co-)monomers and five additives were detected in the methanol eluates of all three materials tested. The XTT-based cell viability assays resulted in a EC₅₀ of 3006 ± 408 μmol/l for THFMA, 2569.5 ± 308 μmol/l for BDDMA and 596.7 ± 88 μmol/l for TPGDA.SignificanceWith the solvent methanol, released components from the investigated splint materials exceeded cytotoxic concentrations in HGFs calculated for a worst-case scenario in splint size. In the water eluates only the methacrylate THFMA could be determined from SHERAprint-ortho plus in concentrations below cytotoxic levels in HGFs.     

The phosphodiesterase 3 inhibitor cilostazol does not stimulate growth of colorectal liver metastases after major hepatectomy

Liver failure after extended hepatectomy represents a major challenge in the surgery of hepatic colorectal metastasis. A previous study has indicated that inhibition of phosphodiesterase type 3 (PDE 3) stimulates liver regeneration. However, little is known whether PDE 3 inhibitors, such as cilostazol, also stimulate the growth of remnant metastases. Therefore, we herein studied the effect of cilostazol on engraftment, vascularization and growth of colorectal liver metastasis after major hepatectomy. WAG-rats underwent either major hepatectomy or sham operation. Metastases were induced by subcapsular implantation of 5 × 10⁵ CC531-colorectal cancer cells. Animals were daily treated with cilostazol (5 mg/kg body weight) or glucose solution. Tumor growth was measured by high-resolution ultrasound at days 7 and 14. Tumor vascularization and tumor cell proliferation were determined by immunohistochemistry and western blotting. High-resolution ultrasound analysis in hepatectomized and non-hepatectomized animals showed that cilostazol does not stimulate tumor growth. Accordingly, the number of PCNA-positive tumor cells did not differ between cilostazol-treated animals and sham-treated controls. Interestingly, cilostazol reduced tumor vascularization in both hepatectomized and non-hepatectomized animals. This was indicated by a significantly lower number of platelet-endothelial cell adhesion molecule (PECAM-1)-positive cells in tumors of cilostazol-treated animals compared to sham-treated controls. The PDE 3 inhibitor cilostazol does not stimulate the growth of colorectal metastases during liver regeneration after major hepatectomy.