Radiotherapy of epicondylitis humeri : Analysis of 138 elbows treated with a linear accelerator.

BACKGROUND: Epicondylitis humeri is a common disease with a prevalence of 1.7%. One of the treatment options is radiotherapy. Most published cases were treated with the orthovoltage technique or with a telecobalt device. Many radiotherapy institutions are nowadays using linear accelerators for treatment of epicondylitis humeri. There is a discussion whether the treatment results with linear accelerators are comparable to the orthovoltage technique. The aim of this study was to analyze the results of radiotherapy with a linear accelerator for epicondylitis humeri. MATERIAL AND METHODS: The analysis was performed on patients of 2 German radiotherapy institutions and included 138 irradiated elbows. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy course as well as for the follow-up of 24 months. The median age of the patients was 49 years with 48.4% male and 51.6% female. In all, 81.0% were suffering from from epicondylitis humeri radialis while 16.7% were treated because of epicondylitis humeri ulnaris. In 65.4% the dominant arm was treated. RESULTS: A significant response to radiotherapy could be found. For the whole sample the median pain was 7 on the NRS before radiotherapy, 4 after 6 weeks and 0 after 12 and 24 months. The percentage of patients with 0 or 1 on the NRS was 64.6% 12 months after radiotherapy. All subgroups, notably those with epicondylitis humeri radialis and epicondylitis humeri ulnaris had a significant reduction of pain. CONCLUSION: Radiotherapy of epicondylitis humeri with a linear accelerator is an effective treatment without showing side effects. All analyzed subgroups showed a good response to radiotherapy for at least 24 months.

Re-irradiation for osteoarthritis-retrospective analysis of 217 joints.

PURPOSE: Osteoarthritis is a common disease with a prevalence of approximately 8.9% among the average population. One treatment option is low-dose radiotherapy. Some authors mention that they apply a second or third course of radiation for recurrent pain or partial or no response to the initial course. As the results of re-irradiation have not been analysed systematically, the aim of this study was to document the results of repeated radiation treatment and to identify those patients who will benefit. METHODS AND MATERIALS: The analysis was performed on patients of three German radiotherapy institutions and included 217 re-irradiated joints. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy as well as at the follow-up of 24 months. The median age of the patients was 67 years, with 40% male and 60% female patients. Re-irradiation was indicated because the initial radiotherapy resulted in no response in 21.2%, in partial response in 41.5%, and in recurrent pain in 37.3%. RESULTS: We found a significant response to re-irradiation. For the whole sample, the median pain was 6 before re-irradiation, 4 after 6 weeks, and 3 after 12 weeks, 6 months, 12 months, and 24 months. The percentage of patients being free of pain or with very little pain was approximately 25% 12 months after re-irradiation. All subgroups, notably those with no response to the first course versus partial response to the first course versus recurrent pain, had significant reduction of pain. CONCLUSION: Re-irradiation of osteoarthritis is an effective and safe treatment. All subgroups showed a good response to re-irradiation for at least 24 months.

Is low dose radiotherapy an effective treatment for Baker's cyst?

PURPOSE: Osteoarthritis of the knee is a common disease, often associated with a Baker's cyst. Besides osteoarthritis, also other joint pathologies of the knee can be causative for a Baker's cyst. Radiotherapy is known to be an effective treatment for osteoarthritis, with an anti-inflammatory effect. As the excessive production of synovia usually is associated with intraarticular inflammation, our hypothesis was that radiotherapy might positively influence the synovial production and reduce the volume of a Baker's cyst. MATERIALS AND METHODS: We performed a prospective trial, including 20 knees receiving radiotherapy for knee arthritis. Besides documentation of NRS (numeric rating scale), WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score and Knee Society Score, the volume of the Baker's cyst was calculated for a short- (6 to 12 weeks) and long-term (9 to 12 months) follow-up. Ultrasonic volumetry was performed using an ultrasound device with a high-resolution multifrequency linear probe (6-9 MHz). RESULTS: Low-dose radiotherapy improved NRS, WOMAC score and Knee Society Score significantly. The mean volume of Baker's cyst decreased from 22.3 ml to 10.7 respectively 3.1 ml during follow-up. A decrease in volume of more than 25% compared to the baseline could be achieved for 75% of the patients in the short-term and 79% of the patients in the long-term follow up. CONCLUSION: Radiotherapy of knee osteoarthritis is an effective treatment that decreases the volume of a Baker's cyst. Most patients respond to the treatment. Whether radiotherapy is an effective treatment for Baker's cyst without associated osteoarthritis has to be further examined.

Imaging of pH and pO2 gives insight in molecular processes of irradiated cells.

One of the major challenges in radiation therapy is the interference with tissue repair processes due to hypoxic characteristics and pH dysregulation. In this study, we present dual imaging of pH and oxygenation in vitro based on luminescent biocompatible sensor foils that allow studying the effects of irradiation on different cell types in culture. Different sensitivities of fibroblast and oral squamous carcinoma cells were observed by complementing oxygen and pH differences with proliferation assays. This study highlights especially the distinct role of oxygen after irradiation and the difference in proliferation processes of irradiated normal dermal cells in contrast to irradiated tumor cells.

Second cancer risk after radiation therapy of ependymoma using the flattening filter free irradiation mode of a linear accelerator.

Pediatric patients suffering from ependymoma are usually treated with cranial or craniospinal three-dimensional (3D) conformal radiotherapy (3DCRT). Intensity-modulated techniques spare dose to the surrounding tissue, but the risk for second malignancies may be increased due to the increase in low-dose volume. The aim of this study is to investigate if the flattening filter free (FFF) mode allows reducing the risk for second malignancies compared to the mode with flattening filter (FF) for intensity-modulated techniques and to 3DCRT. A reduction of the risk would be advantageous for treating pediatric ependymoma. 3DCRT was compared to intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) with and without flattening filter. Dose-volume histograms (DVHs) were compared to evaluate the plan quality and used to calculate the excess absolute risk (EAR) to develop second cancer in the brain. Dose verification was performed with a two-dimensional (2D) ionization chamber array and the out-of-field dose was measured with an ionization chamber to determine the EAR in peripheral organs. Delivery times were measured. Both VMAT and IMRT achieved similar plan quality in terms of dose sparing in the OAR and higher PTV coverage as compared to 3DCRT. Peripheral dose in low-dose region, which is proportional to the EAR in organs located in this region, for example, gonads, bladder, or bowel, could be significantly reduced using FFF. The lowest peripheral EAR and lowest delivery times were hereby achieved with VMATFFF . The EAR calculated based on DVH in the brain could not be reduced using FFF mode. VMATFFF improved the target coverage and homogeneity and kept the dose in the OAR similar compared to 3DCRT. In addition, delivery times were significantly reduced using VMATFFF . Therefore, for radiotherapy of ependymoma patients, VMATFFF may be considered advantageous for the combination of Elekta Synergy linac and Oncentra External Beam planning system used in this study.

Impact of Platelet-Rich Plasma on Viability and Proliferation in Wound Healing Processes after External Radiation.

Platelet-rich plasma is a current subject of studies on chronic wound healing therapy due to possible pro-angiogenic effects. Microvascular compromise represents the major component in radiogenic wound healing complications. The effects of platelet-rich plasma on irradiated cells of the cutaneous wound healing process are poorly understood so far. In this study, the interaction of endothelial cells and adipose-derived stem cells in conjunction with treatment with platelet-rich plasma is investigated in the context of radiation effects. Therefore, the expression of surface-marker CD90 and CD31 was determined. Moreover, cell proliferation and viability after external radiation was analyzed with and without treatment by platelet-rich plasma.

DEGRO practical guidelines for the radiotherapy of non-malignant disorders - Part IV: Symptomatic functional disorders.

PURPOSE: To summarize the updated DEGRO consensus S2e guideline recommendations for the treatment of benign symptomatic functional disorders with low-dose radiotherapy. MATERIALS AND METHODS: This overview reports on the role of low-dose radiotherapy in the treatment of functional disorders in cases of heterotopic ossification (HO) and Graves orbitopathy (GO). The most relevant aspects of the DEGRO S2e Consensus Guideline "Radiation Therapy of Benign Diseases 2014" regarding diagnostics, treatment decision, dose prescription, as well as performance of radiotherapy and results are summarized. RESULTS: For both indications (HO, GO), retrospective and some prospective analyses have shown remarkable effects in terms of symptom relief. Nevertheless, the level of evidence (LoE) and the grade of recommendation (GR) vary: LoE 1-2 and GR A-B (HO), LoE 2 and GR B (GO). CONCLUSION: Low-dose radiotherapy for benign symptomatic functional disorders has proven to be effective, according to different authors, for 25-100 % of the patients studied and therefore it may be a reasonable prophylactic and therapeutic option if noninvasive or invasive methods have been used without persistent success. For HO, a single-fraction dose of 7-8 Gy or fractionated radiation with five fractions of 3.5 Gy is recommended. For GO, single-fraction doses of 0.3-2.0 Gy, and total doses of 2.4-20 Gy/series, applied in one daily fraction are recommended.

A Co-Culture Model of Fibroblasts and Adipose Tissue-Derived Stem Cells Reveals New Insights into Impaired Wound Healing After Radiotherapy.

External radiation seems to be associated with increased amounts of cytokines and other cellular modulators. Impaired microcirculation and fibrosis are examples of typical long term damage caused by radiotherapy. Adipose tissue-derived stem cells (ASC) are discussed to enhance wound healing, but their role in wounds due to radiotherapy is poorly understood. Normal human fibroblasts (NHF) and ASCs were co-cultured and external radiation with doses from 2-12 Gray (Gy) was delivered. Cell proliferation and mRNA levels of matrix metalloproteinases (MMP1, MMP2 and MMP13) were determined 48 h after irradiation of the co-cultures by qPCR. Additionally, tissue inhibitors of matrix metalloproteinases (TIMP1, TIMP2) were determined by enzyme-linked immunosorbent assay (ELISA). There was a reduction of cell proliferation after external radiation in mono-cultures of NHFs and ASCs compared to controls without irradiation. The co-culture of ASCs and NHFs showed reduced impairment of cell proliferation after external radiation. Gene expression of MMP1 and MMP13 was reduced after external irradiation in NHF. MMP2 expression of irradiated NHFs was increased. In the co-culture setting, MMP1 and MMP2 gene expression levels were upregulated. TIMP1 and TIMP2 protein expression was increased after irradiation in NHFs and their co-cultures with ASCs. ASCs seem to stimulate cell proliferation of NHFs and modulate relevant soluble mediators as well as proteinases after external radiation.

Mechanisms of apoptosis in irradiated and sunitinib-treated follicular thyroid cancer cells.

The multikinase inhibitor sunitinib (S) seems to have promising potential in the treatment of thyroid cancer. We focused on the impact of S and/or irradiation (R) on mechanisms of apoptosis in follicular thyroid cancer cells. The effects of R, S and their combination were evaluated 2 and 4 days after treatment, using the human thyroid cancer cell line CGTH W-1. The transcription of genes involved in the regulation of apoptosis was investigated using quantitative real-time PCR. Western blot analyses of caspases and survivin were also performed. S elevated BAX (day 4), CASP9, CASP3, BIRC5 (day 4) and PRKACA (day 4) gene expression, whereas the mRNAs of BCL2, CASP8, PRKCA, ERK1, and ERK2 were not significantly changed. S, R and R+S clearly induced caspase-9 protein and elevated caspase-3 activity. Survivin was down-regulated at day 4 in control cells and the expression was blunted by S treatment. R+S induced survivin expression at day 2 followed by a reduction at day 4 of treatment. Sunitinib and the combined application with radiation induced apoptosis in follicular thyroid cancer cells via the intrinsic pathway of apoptosis. In addition, sunitinib might induce apoptosis via decreased expression of the anti-apoptotic protein survivin. These findings suggest the potential use of sunitinib for the treatment of poorly differentiated follicular thyroid carcinomas.

Risk of infection due to medical interventions via central venous catheters or implantable venous access port systems at the middle port of a three-way cock: luer lock cap vs. luer access split septum system (Q-Syte).

BACKGROUND: Many cancer patients receive a central venous catheter or port system prior to therapy to assure correct drug administration. Even appropriate hygienic intervention maintenance carries the risk of contaminating the middle port (C-port) of a three-way cock (TWC), a risk that increases with the number of medical interventions. Because of the complexity of the cleaning procedure with disconnection and reconnection of the standard luer lock cap (referred as "intervention"), we compared luer lock caps with a "closed access system" consisting of a luer access split septum system with regard to process optimization (work simplification, process time), efficiency (costs) and hygiene (patient safety). METHODS: For determination of process optimization the workflow of an intervention according to the usual practice and risks was depicted in a process diagram. For determining the actual process costs, we analyzed use of material and time parameters per intervention and used the process parameters for programming the process into a simulation run (n = 1000) to determine the process costs as well as their differences (ACTUAL vs. NOMINAL) within the framework of a discrete event simulation.Additionally cultures were carried out at the TWC C-ports to evaluate possible contamination. RESULTS: With the closed access system, the mean working time of 5.5 minutes could be reduced to 2.97 minutes. The results for average process costs (labour and material costs per use) were 3.92 € for luer lock caps and 2.55 € for the closed access system. The hypothesis test (2-sample t-test, CI 0.95, p-value<0.05) confirmed the significance of the result.In 50 reviewed samples (TWC's), the contamination rate for the luer lock cap was 8% (4 out of 50 samples were positive), the contamination rate of the 50 samples with the closed access system was 0%.Possible hygienic risks (related to material, surroundings, staff handling) could be reduced by 65.38%. CONCLUSIONS: In the present research, the closed access system with a divided split septum was superior to conventional luer lock caps. The advantage of the closed access system lies in the simplified handling for staff, which results in a reduced risk of patient infection due to improved clinical hygiene.

Neoadjuvant radiotherapy in ER+, HER2+, and triple-negative -specific breast cancer based humanized tumor mice enhances anti-PD-L1 treatment efficacy.

Pre-operative radiation therapy is not currently integrated into the treatment protocols for breast cancer. However, transforming immunological "cold" breast cancers by neoadjuvant irradiation into their "hot" variants is supposed to elicit an endogenous tumor immune defense and, thus, enhance immunotherapy efficiency. We investigated cellular and immunological effects of sub-lethal, neoadjuvant irradiation of ER pos., HER2 pos., and triple-negative breast cancer subtypes in-vitro and in-vivo in humanized tumor mice (HTM). This mouse model is characterized by a human-like immune system and therefore facilitates detailed analysis of the mechanisms and efficiency of neoadjuvant, irradiation-induced "in-situ vaccination", especially in the context of concurrently applied checkpoint therapy. Similar to clinical appearances, we observed a gradually increased immunogenicity from the luminal over the HER2-pos. to the triple negative subtype in HTM indicated by an increasing immune cell infiltration into the tumor tissue. Anti-PD-L1 therapy divided the HER2-pos. and triple negative HTM groups into responder and non-responder, while the luminal HTMs were basically irresponsive. Irradiation alone was effective in the HER2-pos. and luminal subtype-specific HTM and was supportive for overcoming irresponsiveness to single anti-PD-L1 treatment. The treatment success correlated with a significantly increased T cell proportion and PD-1 expression in the spleen. In all subtype-specific HTM combination therapy proved most effective in diminishing tumor growth, enhancing the immune response, and converted non-responder into responder during anti-PD-L1 therapy. In HTM, neoadjuvant irradiation reinforced anti-PD-L1 checkpoint treatment of breast cancer in a subtype -specific manner. According to the "bench to bedside" principle, this study offers a vital foundation for clinical translating the use of neoadjuvant irradiation in the context of checkpoint therapy.

Subcellular localization of PD-L1 and cell-cycle-dependent expression of nuclear PD-L1 variants: implications for head and neck cancer cell functions and therapeutic efficacy.

The programmed cell death 1 ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) axis is primarily associated with immunosuppression in cytotoxic T lymphocytes (CTLs). However, mounting evidence is supporting the thesis that PD-L1 not only functions as a ligand but mediates additional cellular functions in tumor cells. Moreover, it has been demonstrated that PD-L1 is not exclusively localized at the cellular membrane. Subcellular fractionation revealed the presence of PD-L1 in various cellular compartments of six well-characterized head and neck cancer (HNC) cell lines, including the nucleus. Via Western blotting, we detected PD-L1 in its well-known glycosylated/deglycosylated state at 40-55 kDa. In addition, we detected previously unknown PD-L1 variants with a molecular weight at approximately 70 and > 150 kDa exclusively in nuclear protein fractions. These in vitro findings were confirmed with primary tumor samples from head and neck squamous cell carcinoma (HNSCC) patients. Furthermore, we demonstrated that nuclear PD-L1 variant expression is cell-cycle-dependent. Immunofluorescence staining of PD-L1 in different cell cycle phases of synchronized HNC cells supported these observations. Mechanisms of nuclear PD-L1 trafficking remain less understood; however, proximity ligation assays showed a cell-cycle-dependent interaction of the cytoskeletal protein vimentin with PD-L1, whereas vimentin could serve as a potential shuttle for nuclear PD-L1 transportation. Mass spectrometry after PD-L1 co-immunoprecipitation, followed by gene ontology analysis, indicated interaction of nuclear PD-L1 with proteins involved in DNA remodeling and messenger RNA (mRNA) splicing. Our results in HNC cells suggest a highly complex regulation of PD-L1 and multiple tumor cell-intrinsic functions, independent of immune regulation. These observations bear significant implications for the therapeutic efficacy of immune checkpoint inhibition.

Impact of sunitinib on human thyroid cancer cells.

BACKGROUND/AIMS: Thyroid cancer accounts for about 1% of all cancer cases. Multikinase inhibitors like sunitinib (S) have a promising potential in thyroid cancer therapy. Therefore, the principal aim of this study was to investigate the impact of sunitinib on the secretion of cytokines of follicular thyroid cancer cells. METHOD: The effects of irradiation (R), S, and their combination (R+S) on cytokine secretion by the human thyroid cancer cell lines ML-1 and CGTH W-1 were evaluated after two (d2) and four days (d4) of treatment. RESULTS: Multi-Analyte Profiling of cytokine release showed a decrease after S treatment (CGTH W-1: IFN-γ, IL-4, IL-8 d2, MIP-1a, MMP-2, TNF-α and TNF-ß; ML-1: IFN-γ, IL-4, IL-6, IL-7, IL-8; MIP-1α, MMP-2, MCP-1, TNF-α and TNF-ß). R elevated significantly the release of cytokines (exception ML-1: MCP-1, MMP-2; CGTH W-1: IL-4, TNF-ß). In contrast, R+S treatment resulted in a reduction of IFN-γ, IL-4, and MMP-2 in both cell lines. IL-6, IL-8 and MCP-1 proteins in the supernatant correlated with the data obtained by quantitative RT-PCR. VEGFD mRNAs were significantly elevated by R+S. CONCLUSION: A target-based therapy with R+S changed VEGFD, IL-6 and IL-8 in follicular thyroid cancer cells. These in vitro-experiments suggest IL-6, IL-8, VEGFD and TNF-α as interesting biomarkers to be investigated in vivo. Different reactions of the cell lines under equal treatment might be due to their different origin and characteristics.

The unusual (syn-/anti-)2 conformation of a di-meth-oxy-pyrimidyl-based tennimide.

The tennimide macrocycle, (I) (C52H40N16O16.0.167H2O), was synthesized from 2-amino-4,6-di-meth-oxy-pyrimidine and pyridine-2,6-dicarbonyl dichloride. Compound (I) represents the first tennimide incorporating pyridine rings in the macrocycle scaffold. In the macrocycle ring, the carbonyl groups at each successive dicarbon-yl(pyridine) moiety adopt the (syn/anti)2 conformation. This contrasts with all previously reported tetra-imide macrocycles, which exhibit the (syn)4 conformation. The effect is to close any potential cavity or niche by having two of the central pyridine C5N rings aligned close to each other [with closest pyridine Cg⋯Cg ring centroid separations of 3.5775 (19) Å; closest C⋯C = 3.467 (5) Å]. A partial occupancy water mol-ecule (with s.o.f. = 0.167), resides with its oxygen atom on a twofold axis at hydrogen-bonding distances to the carbonyl O atom, in a mol-ecular niche between two pyridine rings. Macrocyles of (I) have all six C=O groups and all eight meth-oxy O atoms present on the macrocycle surface. However, all twelve N atoms are effectively shielded on steric grounds from any potential inter-molecular inter-actions. The remaining two C=O O atoms inter-act with the partial occupancy water mol-ecule via two O-H⋯O=C hydrogen bonds. Macrocycles of (I) stack as one-dimensional chains along the b-axis direction with primary inter-molecular inter-actions involving weak C-H⋯O=C/OCH3/H2O contacts. Chains inter-lock weakly via meth-oxy-meth-oxy C-H⋯O inter-actions into two-dimensional sheets.

Spinal meningiomas.

Spinal meningiomas (SM) are lesions with a mostly favorable oncological and surgical prognosis and a low incidence of tumor recurrence. SM account for approximately 1.2-12.7% of all meningiomas and 25% of all spinal cord tumors. Typically, SM are located in the intradural extramedullary space. SM grow slowly and spread laterally into the subarachnoid space, stretching and sometimes incorporating the surrounding arachnoid but rarely the pia. Standard treatment is surgery with the primary aims of achieving complete tumor resection as well as improving and recovering neurologic function. Radiotherapy may be considered in case of tumor recurrence, for challenging surgical cases, and for patients with higher-grade lesions (World Health Organization grade 2 or 3); however, radiotherapy is mostly used as an adjuvant therapy for SM. New molecular and genetic profiling increases the understanding of SM and may uncover additional treatment options.

Cross-Reactivity of IgG Antibodies and Virus Neutralization in mRNA-Vaccinated People Against Wild-Type SARS-CoV-2 and the Five Most Common SARS-CoV-2 Variants of Concern.

The rapid development, approval, and production of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in less than 1 year after the first reports of a new infectious disease was a real game changer, providing 80%-90% efficacy in preventing severe etiopathologies of the coronavirus disease 2019 (COVID-19). These vaccines induce an immune response against the SARS-CoV-2 spike (S) protein located on the surface of the virus particle. Antibodies (Abs) recognizing the S-protein can inhibit binding of the virus via the S-protein to the angiotensin-converting enzyme-2 (ACE-2) receptor expressed on different human cells, especially when these Abs bind to the interaction site, the so-called receptor-binding domain (RBD). We have expressed the RBDs of wild-type SARS-CoV-2 and five variants of concern (VOCs) to test the immune response in people before vaccination with mRNA vaccines BNT162b2 and mRNA-1273 and after up to three vaccinations using in-house ELISA and inhibition assays. The methods of both assays are provided. Both vaccines initiated similarly high IgG titers after two vaccinations against the wild-type and even two VOC-RBDs (alpha and delta) and strongly inhibited the corresponding RBD-ACE-2 binding. The IgG titers and inhibition of ACE-2 binding were lower for beta and gamma RBDs and much lower for omicron RBD. The third vaccination after 6 months strongly increased both the IgG titers and the neutralizing effect against all variants, especially for omicron, leading to 63% ± 13% neutralization potential. Importantly, neutralization linearly increased with the IgG titers.

Recurrence in childhood medulloblastoma.

Thirty-eight consecutive children treated according to the HIT2000 and HIT91 studies for medulloblastoma who suffered 40 recurrence events were identified from a neuroradiological database. Relapse was associated with younger median age compared with all children treated on HIT2000. Eight patients relapsed with isolated local recurrence. There was no correlation with incomplete surgical removal or violation of the respective treatment protocol. Four patients were younger than 4 years at time of initial presentation and thus were not treated primarily with radiotherapy, suggesting that delayed radiotherapy might be a contributing factor. Meningeal dissemination was present in 32 events; 16 were located in the frontal region, 8 of which were isolated nodular frontal and frontobasal meningeal disease. Circumscribed meningeal recurrences were associated with better overall survival (OS) compared with diffuse, widespread recurrences. Isolated frontobasal meningeal relapses are a well-known phenomenon in medulloblastomas even years after treatment and have been correlated to an underdose of radiation in many literature reports. However, in our patients there was no correlation to possible treatment violations, indicating that inadequate radiation dose to the frontobasal region was unlikely to be a causative factor. Surgical technique varied due to the multicentric nature of our study, so position during surgery was not recognized as a predisposing factor for frontobasal recurrence.

A novel titanium implant surface modification by plasma electrolytic oxidation (PEO) preventing tendon adhesion.

Titanium is one of the most commonly used materials for implants in trauma applications due to its low density, high corrosion resistance and biocompatibility. Nevertheless, there is still a need for improved surface modifications of Titanium, in order to change surface properties such as wettability, antibacterial properties or tissue attachment. In this study, different novel plasma electrolytic oxidation (PEO) modifications have been investigated for tendon adhesion to implants commonly used in hand surgery. Titanium samples with four different PEO modifications were prepared by varying the electrolyte composition and analyzed with regards to their surface properties. Unmodified titanium blanks and Dotize® coating served as controls. Samples were examined using scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), contact angle measuring system and analyzed for their biocompatibility and hemocompatibility (according to DIN ISO 10993-5 and 10,993-4). Finally, tendon adhesion of these specific surfaces were investigated by pull-off tests. Our findings show that surface thickness of PEO modifications was about 12-20 µm and had porous morphology. One modification demonstrated hydrophilic behavior accompanied by good biocompatibility without showing cytotoxic properties. Furthermore, no hemolytic effect and no significant influence on hemocompatibility were observed. Pull-off tests revealed a significant reduction of tendon adhesion by 64.3% (35.7% residual adhesion), compared to unmodified titanium (100%). In summary, the novel PEO-based ceramic-like porous modification for titanium surfaces might be considered a good candidate for orthopedic applications supporting a more efficient recovery.

Orientation-Dependent Deformation Behavior of 316L Steel Manufactured by Laser Metal Deposition and Casting under Local Scratch and Indentation Load.

This study analyzes the local deformation behavior of austenitic stainless steel 316L, manufactured conventionally by casting and additively by laser metal deposition (LMD). We produced directionally solidified 316L specimens with most grains showing (001) orientations parallel to the longitudinal specimen axis. We conducted nanoindentation and scratch experiments for local mechanical characterization and topography measurements (atomic force microscopy and confocal laser scanning microscopy) of indentation imprints and residual scratch grooves for the analysis of the deformation behavior and, in particular, of the pile-up behavior. The local mechanical properties and deformation behavior were correlated to the local microstructure investigated by scanning electron microscopy with energy dispersive X-ray spectroscopy and electron backscatter diffraction analysis. The results show that the local mechanical properties, deformation behavior, and scratch resistance strongly depend on the crystallographic orientation. Nearly (001)-oriented grains parallel to the surface show the lowest hardness, followed by an increasing hardness of nearly (101)- and (111)-oriented grains. Consequently, scratch depth is the greatest for nearly (001)-oriented grains followed by (101) and (111) orientations. This tendency is seen independently of the analyzed manufacturing route, namely Bridgman solidification and laser metal deposition. In general, the laser metal deposition process leads to a higher strength and hardness, which is mainly attributed to a higher dislocation density. Under the investigated loading conditions, the cellular segregation substructure is not found to significantly and directly change the local deformation behavior during indentation and scratch testing.

Lymphatic and vascular invasion in oral squamous cell carcinoma: Implications for recurrence and survival in a population-based cohort study.

OBJECTIVE: Numerous studies analyzed lymphovascular invasion (LVI) in various malignant diseases, however, little is known about the role of lymphatic invasion (LI) as well as vascular invasion (VI) in oral squamous cell carcinoma (OSCC). The aim of this study is to illuminate the role of LI and VI in a population-based cohort study. METHODS: We retrospectively analyzed 745 primarily resected OSCC patients in Eastern Bavaria for histopathologically verified LI and VI. Overall survival (OS) and recurrence-free survival (RFS) were calculated, whereas analysis was performed by uni- and multivariate statistics. Mean follow-up time was 7.4 years. RESULTS: LI was found in 115 patients (15.4%), VI was diagnosed in 23 cases (3.1%). LI correlated significantly with distinct anatomical sites (p = 0.004), increasing pT-classification (p < 0.001), lymph node involvement (p < 0.001), higher grading (p < 0.001), advanced UICC-stages (p < 0.001) and adjuvant therapies (p < 0.001). Similar results were found for VI. Survival analysis resulted in a significantly decreased five-year OS and RFS in patients with diagnosed LI (OS: 41.1%, RFS: 38.3%) in contrast to LI-negative cases (OS: 66.8%, RFS: 59.7.7%, p < 0.001). Analogous outcomes were seen for patients with VI. Additionally, LI was identified as a predictive parameter, indicating individual patients' response to adjuvant therapies. CONCLUSION: This population-based cohort study underlines the unfavorable aspect of LI and VI on outcome in OSCC. Including LI and VI in existing staging systems could help to stratify patients' risk for adverse outcome and consecutively determine adjuvant treatment in malignant disease.