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A large number of treatment approaches have been used for spinal cord injury improvement, a medically incurable disorder, and subsequently stem cell transplantation appears to be a promising strategy. The main objective of this study is to ascertain whether combinational therapy of human neural stem cells (hNSCs) together with lithium chloride improves cell survival, proliferation, and differentiation in a rat spinal contusion model, or not. Contusive spinal cord injury was implemented on Wistar male rats. Experimental groups comprised of: control, hNSCs transplanted, lithium chloride (Li), and hNSCs and lithium chloride (hNSCs + Li). In every experimental group, locomotor activity score and motor evoked potential (MEP) were performed to evaluate motor recovery as well as histological assessments to determine mechanisms of improvement. In accordance with our results, the hNSCs + Li and the Li groups showed significant improvement in locomotor scores and MEP. Also, Histological assessments revealed that transplanted hNSCs are capable of differentiation and migration along the spinal cord. Although NESTIN-positive cells were proliferated significantly in the Lithium group in comparison with control and the hNSCs + Li groups, the quantity of ED1 cells in the hNSCs + Li was significantly larger than the other two groups. Our results demonstrate that combinational therapy of hNSCs with lithium chloride and lithium chloride individually are adequate for ameliorating more than partial functional recovery and endogenous repair in spinal cord-injured rats., (© 2019 Wiley Periodicals, Inc.)

Purpose: This study was designed to assess the dose accumulation (DA) of bladder and rectum between brachytherapy fractions using hybrid-based deformable image registration (DIR) and compare it with the simple summation (SS) approach of GEC-ESTRO in cervical cancer patients., Material and Methods: Patients ( n = 137) with cervical cancer treated with 3D conformal radiotherapy and three fractions of high-dose-rate brachytherapy were selected. CT images were acquired to delineate organs at risk and targets according to GEC-ESTRO recommendations. In order to determine the DA for the bladder and rectum, hybrid-based DIR was done for three different fractions of brachytherapy and the results were compared with the standard GEC-ESTRO method. Also, we performed a phantom study to calculate the uncertainty of the hybrid-based DIR algorithm for contour matching and dose mapping., Results: The mean ± standard deviation (SD) of the Dice similarity coefficient (DICE), Jaccard, Hausdorff distance (HD) and mean distance to agreement (MDA) in the DIR process were 0.94 ±0.02, 0.89 ±0.03, 8.44 ±3.56 and 0.72 ±0.22 for bladder and 0.89 ±0.05, 0.80 ±0.07, 15.46 ±10.14 and 1.19 ±0.59 for rectum, respectively. The median (Q1, Q3; maximum) Gy EQD2 differences of total D 2cc between DIR-based and SS methods for the bladder and rectum were reduced by -1.53 (-0.86, -2.98; -9.17) and -1.38 (-0.80, -2.14; -7.11), respectively. The mean ± SD of DICE, Jaccard, HD, and MDA for contour matching were 0.98 ±0.008, 0.97 ±0.01, 2.00 ±0.70 and 0.20 ±0.04, respectively for large deformation. Maximum uncertainty of dose mapping was about 3.58%., Conclusions: The hybrid-based DIR algorithm demonstrated low registration uncertainty for both contour matching and dose mapping. The DA difference between DIR-based and SS approaches was statistically significant for both bladder and rectum and hybrid-based DIR showed potential to assess DA between brachytherapy fractions., Competing Interests: The authors report no conflict of interest., (Copyright: © 2019 Termedia Sp. z o. o.)

Objective: In this study, the effects of vacuum (VP) and high-oxygen modified atmosphere (80% O2+20% CO2) packaging (HiOx-MAP) on physico-chemical and microbiological properties of minced water buffalo meat were investigated., Methods: After minced meat preparation, samples were packaged under VP and HiOx-MAP and stored at 2°C±0.5°C for 14 days. Samples taken on certain days were subjected to total aerobic mesophilic bacteria, total aerobic psychrotrophic bacteria, lactic acid bacteria, Pseudomonas, Enterobacteriaceae and yeast-mold counts as well as pH, color (L*, a*, and b*) and thiobarbituric acid reactive substances (TBARS) analyses., Results: In minced water buffalo meat packaged under HiOx-MAP, TBARS value exceeded 1 mg malondialdehyde/kg on the 4th day of the storage. In VP samples, TBARS value remained close to initial TBARS value during storage. According to the findings, a* value was determined to be high in the HiOx-MAP samples within initial days of the storage. However, no significant changes in a* value were observed in VP samples during storage. In contrast, the mean value of L* was detected as higher in HiOx-MAP sample than VP samples. The count of psychrotrophic bacteria increased more than that of mesophilic bacteria during storage. The growth of Enterobacteriaceae and Pseudomonas was delayed in both the packaging methods. However, lactic acid bacteria exhibited more growth in VP samples compared to MAP samples., Conclusion: The lipid oxidation proceeded faster than expected in minced water buffalo meat packed with HiOx-MAP method. This situation adversely affected the a* value. On the other hand, similar microbiological results were obtained in both packing methods.

Purpose: To examine the efficacy and safety of Ruthenium-106 plaque radiotherapy in the treatment of circumscribed choroidal hemangioma., Methods: Twenty-one eyes of 21 patients diagnosed with symptomatic circumscribed choroidal hemangioma who underwent Ruthenium-106 plaque radiotherapy were included in the study. Clinical response, ancillary tests finding improvement, and major side effects were evaluated., Results: From the initial to the 1-year follow-up visits, vision improved in 12 eyes (57%), was stable in 7 eyes (33%), and became worse in 2 eyes (10%). Based on fluorescein angiography and optical coherence tomography, subretinal fluid and cystoid macular edema resolved in all patients. Changes in logarithm of minimum angle of resolution visual acuity (P = 0.038); tumor thickness (P = 0.0001) and largest diameter (P = 0.007) on ultrasonography; and subfoveal thickness on optical coherence tomography (P < 0.0001), were statistically significant between the initial and the 1-year follow-up visits. Side effects as observed during the follow-up period included: radiation-related retinopathy in 5 (24%) eyes, radiation-related papillopathy in 1 eye (5%), and subretinal fibrosis in 2 eyes (10%). Subretinal fibrosis was the only permanent radiation-related side effect., Conclusion: Ruthenium-106 plaque radiotherapy is an effective and safe method of treatment for symptomatic circumscribed choroidal hemangiomas. The incidence of permanent visual loss is low with prompt treatment of complications.

Purpose: Skin cancers are the most common human malignancy with increasing incidence. Currently, surgery is standard of care treatment for non-melanoma skin cancers. However, brachytherapy is a growing modality in the management of skin cancers. Therefore, we aimed to assess the outcome of patients with non-melanoma skin cancers treated by high-dose-rate (HDR) brachytherapy with surface mold technique., Material and Methods: In this prospective study, we recruited patients with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin who were candidates for definitive or adjuvant brachytherapy during 2013-2014. Alginate was used for making the individualized surface molds for each patient. Patients were treated with afterloading radionuclide HDR brachytherapy machine, with a total dose of 30-52 Gy in 10-13 fractions. Participants were followed for 2 years for radiation toxicity, cosmetic results, and local failures., Results: A total of 60 patients (66.7% male; median age, 71 years) were included, of which 42 (70.0%) underwent definitive radiotherapy. Seventy-five percent of lesions were BCC. The mean total dose was 39.6 ± 5.4 Gy. Of patients in definitive group, 40/42 (95.2%) experienced complete clinical response after 3 months. The recurrence rate was 2/18 (11.11%) and 1/42 (2.38%) in adjuvant and definitive groups, respectively. The percentage of grade 3-4 acute (3-month post-treatment) and late toxicities (2 years post-treatment) was 6.7% and 0%, respectively. The cosmetic results were good/excellent in 96.2% of patients after 2 years of follow-up., Conclusions: With appropriate patient selection and choosing as lowest dose per fraction as possible, HDR brachytherapy with customized surface molds yields good oncological and cosmetic results for the treatment of localized skin BCC and SCC., Competing Interests: The authors report no conflict of interest.

Purpose: Intra-fractional organs at risk (OARs) deformations can lead to dose variation during image-guided adaptive brachytherapy (IGABT). The aim of this study was to modify the final accepted brachytherapy treatment plan to dosimetrically compensate for these intra-fractional organs-applicators position variations and, at the same time, fulfilling the dosimetric criteria., Material and Methods: Thirty patients with locally advanced cervical cancer, after external beam radiotherapy (EBRT) of 45-50 Gy over five to six weeks with concomitant weekly chemotherapy, and qualified for intracavitary high-dose-rate (HDR) brachytherapy with tandem-ovoid applicators were selected for this study. Second computed tomography scan was done for each patient after finishing brachytherapy treatment with applicators in situ. Artificial neural networks (ANNs) based models were used to predict intra-fractional OARs dose-volume histogram parameters variations and propose a new final plan., Results: A model was developed to estimate the intra-fractional organs dose variations during gynaecological intracavitary brachytherapy. Also, ANNs were used to modify the final brachytherapy treatment plan to compensate dosimetrically for changes in 'organs-applicators', while maintaining target dose at the original level., Conclusions: There are semi-automatic and fast responding models that can be used in the routine clinical workflow to reduce individually IGABT uncertainties. These models can be more validated by more patients' plans to be able to serve as a clinical tool.

Purpose: Brachytherapy is a cost-effective method for the management of oral cavity cancers in low to middle income countries. We aimed to evaluate the clinical outcomes of high-dose-rate interstitial brachytherapy (HDR-IBT) in patients with oral cavity cancer., Material and Methods: From 2009 to 2013, 78 patients (49 combined external beam radiotherapy [EBRT] plus IBT and 29 IBT monotherapy) with oral cavity cancers had been treated in our center. Slightly more than half the patients were male, and the median age was 54 years. The treatment was planned based on the Paris system. The main outcomes were disease-free and overall survival., Results: The median follow-up duration was 36.5 months (range, 1.17-54.23). The actuarial four-year overall and disease-free survival rates were 83% and 65%, respectively. The local and locoregional control was achieved among 89.74% and 87.17% of patients, respectively. None of the factors including tumor size, node status, gender, and radiation modality (IBT alone vs. IBT + EBRT) had a significant statistical correlation to the local control rate. All the patients tolerated the planned treatment in the IBT alone group. Late complications included a case of trismus and three cases of catheter insertion site fibrosis., Conclusions: HDR-IBT as a monotherapy or in combination with EBRT is an appropriate option for the management of oral cavity squamous cell carcinomas, and supports the improvement in treatment outcomes and toxicity profiles in adjuvant settings.

Aim: Verification of dose distributions for gynecological (GYN) brachytherapy implants using EBT Gafchromic film., Background: One major challenge in brachytherapy is to verify the accuracy of dose distributions calculated by a treatment planning system., Materials and Methods: A new phantom was designed and fabricated using 90 slabs of 18 cm × 16 cm × 0.2 cm Perspex to accommodate a tandem and Ovoid assembly, which is normally used for GYN brachytherapy treatment. This phantom design allows the use of EBT Gafchromic films for dosimetric verification of GYN implants with a cobalt-60 HDR system or a LDR Cs-137 system. Gafchromic films were exposed using a plan that was designed to deliver 1.5 Gy of dose to 0.5 cm distance from the lateral surface of ovoids from a pair of ovoid assembly that was used for treatment vaginal cuff. For a quantitative analysis of the results for both LDR and HDR systems, the measured dose values at several points of interests were compared with the calculated data from a commercially available treatment planning system. This planning system was utilizing the TG-43 formalism and parameters for calculation of dose distributions around a brachytherapy implant., Results: The results of these investigations indicated that the differences between the calculated and measured data at different points were ranging from 2.4% to 3.8% for the LDR Cs-137 and HDR Co-60 systems, respectively., Conclusion: The EBT Gafchromic films combined with the newly designed phantom could be utilized for verification of the dose distributions around different GYN implants treated with either LDR or HDR brachytherapy procedures.

Purpose: To demonstrate the utility of "3D Slicer" for easy treatment verification by comparing dose-volume histograms (DVHs) calculated on pretreatment and posttreatment images., Methods and Materials: Thirty cervical cancer patients were CT scanned twice: first for treatment planning and a second time after the dose delivery. The initial plan was manually duplicated on the posttreatment image set in Flexiplan treatment planning system, and DVH parameters were calculated. Pretreatment and posttreatment images, organ structures, and plan data were exported from the treatment planning system to 3D Slicer to validate DVH parameter calculation with 3D Slicer. The gamma analysis was used to compare Flexiplan and 3D Slicer DVHs. Posttreatment images were rigidly fused on the initial CT to automatically transfer the data of the pretreatment plan onto the posttreatment images. DVH parameters were calculated in 3D Slicer for both image sets, and their relative variations were compared., Results: In calculating DVH parameter variations, no significant differences were observed between Flexiplan and 3D Slicer. Where the registration accuracy was better than 0.03, they returned similar results for D2 cm(3) of bladder, rectum, and sigmoid. Mean and standard deviation of DVH parameters were calculated on pretreatment and posttreatment images for several organs; both the manually duplicated plan and the automatically registered plan in SlicerRT returned comparable relative variations of these parameters. For 88% of the organs, more than 95% of the DVH dose bins passed the gamma analysis., Conclusions: We tested an automated DVH assessment method with an imaging freeware, 3D Slicer, for use in image-guided adaptive brachytherapy. SlicerRT is a viable verification tool to report and detect DVH variations between different contoured images series., (Copyright © 2016 American Brachytherapy Society. All rights reserved.)

The purpose of this study was to investigate the concurrent effects of tandem length and bladder volume on dose to pelvic organs at risk (OARs) in HDR intracavitary brachytherapy treatment of cervical cancer. Twenty patients with locally advanced cervical cancer were selected for brachytherapy using Rotterdam applicators. The patients were CT scanned twice with empty and full bladder. Two treatment plans were prepared on each of the image sets. Patients were categorized into two groups; those treated with a tandem length of 4 cm or smaller (T ≤ 4 cm) and those with tandem length larger than 4 cm (T > 4 cm). Only one tandem tip angle of 30° was studied. Dose-volume histograms (DVHs) of OARs were calculated and compared. Bladder dose was significantly affected by both bladder volume and tandem physical length for T ≤ 4 cm. This was reflected on the values obtained for D2cm³, D1cm³, and D0.1cm³ for both empty and full bladder cases. When T > 4 cm, no correlation could be established between variations in bladder dose and blad-der volume. Rectum dose was generally lower when the bladder was empty and T > 4 cm. Dose to sigmoid was increased when T > 4 cm; this increase was larger when the bladder was full. Our results suggest that, for tandems longer than 4 cm, keeping the bladder empty may reduce the dose to rectum and sigmoid. This is contrary to cases where a shorter than 4 cm tandem is used in which a full bladder (about 50-120 cm³) tends to result in a lower dose to rectum and sigmoid. Attention should be given to doses to sigmoid with long tandem lengths, as a larger tandem generally results in a larger dose to sigmoid.

Purpose: To evaluate the anatomical outcomes of corneal patch grafts in patients with progressive scleral necrosis secondary to plaque radiotherapy used for uveal malignant melanoma management., Methods: In this case series, 4 patients with progressive scleral necrosis after Ru-106 plaque radiotherapy underwent corneal patch grafts with the anterior corneal button from Descemet stripping automated endothelial keratoplasty donor tissue to strengthen the sclera and to improve appearance of the eye., Results: Ciliary body involvement was evident in all cases. All 4 patients had received radiation doses of 400 Gy or more to the tumor base. The mean time interval between plaque radiotherapy and scleral necrosis was 24.5 ± 7.5 months (range, 18-34 months). Successful results were achieved in all patients with tectonic graft. No patients experienced graft thinning, rejection, infection, or tumor recurrence in a mean follow-up of 28.5 ± 7.9 months (range, 20-39 months)., Conclusions: Corneal patch graft by anterior corneal button from Descemet stripping automated endothelial keratoplasty donor tissue results in successful restoration of globe integrity and satisfactory cosmetic appearance in patients with scleral necrosis secondary to plaque radiotherapy.

Purpose: To analyze the optimum organ filling point for organs at risk (OARs) dose in cervical cancer high-dose-rate (HDR) brachytherapy., Material and Methods: In a retrospective study, 32 locally advanced cervical cancer patients (97 insertions) who were treated with 3D conformal external beam radiation therapy (EBRT) and concurrent chemotherapy during 2010-2013 were included. Rotterdam HDR tandem-ovoid applicators were used and computed tomography (CT) scanning was performed after each insertion. The OARs delineation and GEC-ESTRO-based clinical target volumes (CTVs) contouring was followed by 3D forward planning. Then, dose volume histogram (DVH) parameters of organs were recorded and patients were classified based on their OARs volumes, as well as their inserted tandem length., Results: The absorbed dose to point A ranged between 6.5-7.5 Gy. D0.1cm(3) and D2cm(3) of the bladder significantly increased with the bladder volume enlargement (p value < 0.05). By increasing the bladder volume up to about 140 cm(3), the rectum dose was also increased. For the cases with bladder volumes higher than 140 cm(3), the rectum dose decreased. For bladder volumes lower than 75 cm(3), the sigmoid dose decreased; however, for bladder volumes higher than 75 cm(3), the sigmoid dose increased. The D2cm(3) of the bladder and rectum were higher for longer tandems than for shorter ones, respectively. The divergence of the obtained results for different tandem lengths became wider by the extension of the bladder volume. The rectum and sigmoid volume had a direct impact on increasing their D0.1cm(3) and D2cm(3) , as well as decreasing their D10, D30, and D50., Conclusions: There is a relationship between the volumes of OARs and their received doses. Selecting a bladder with a volume of about 70 cm(3) or less proved to be better with regards to the dose to the bladder, rectum, and sigmoid.

Purpose: To evaluate the outcomes of ruthenium-106 ((106)Ru) brachytherapy in terms of radiation parameters in patients with thick uveal melanomas., Material and Methods: Medical records of 51 patients with thick (thickness ≥ 7 mm and < 11 mm) uveal melanoma treated with (106)Ru brachytherapy during a ten-year period were reviewed. Radiation parameters, tumor regression, best corrected visual acuity (BCVA), and treatment-related complications were assessed., Results: Fifty one eyes of 51 consecutive patients including 25 men and 26 women with a mean age of 50.5 ± 15.2 years were enrolled. Patients were followed for 36.1 ± 26.5 months (mean ± SD). Mean radiation dose to tumor apex and to sclera were 71 (± 19.2) Gy and 1269 (± 168.2) Gy. Radiation dose rates to tumor apex and to sclera were 0.37 (± 0.14) Gy/h and 6.44 (± 1.50) Gy/h. Globe preservation was achieved in 82.4%. Preoperative mean tumor thickness of 8.1 (± 0.9) mm decreased to 4.5 (± 1.6) mm, 3.4 (± 1.4) mm, and 3.0 (± 1.46) mm at 12, 24, and 48 months after brachytherapy (p = 0.03). Four eyes that did not show regression after 6 months of brachytherapy were enucleated. Secondary enucleation was performed in 5 eyes because of tumor recurrence or neovascular glaucoma. Tumor recurrence was evident in 6 (11.8%) patients. Mean Log MAR (magnification requirement) visual acuity declined from 0.75 (± 0.63) to 0.94 (± 0.5) (p = 0.04). Best corrected visual acuity of 20/200 or worse was recorded in 37% of the patients at the time of diagnosis and 61.7% of the patients at last exam (p = 0.04). Non-proliferative and proliferative radiation-induced retinopathy was observed in 20 and 7 eyes., Conclusions: Thick uveal melanomas are amenable to (106)Ru brachytherapy with less than recommended apex radiation dose and dose rates.

Purpose: This study was performed to evaluate the role of in vivo dosimetry with semiconductor detectors in gynaecological medium dose rate brachytherapy, and to compare the actual doses delivered to organs at risk (as measured using in vivo dosimetry) with those calculated during treatment planning., Materials and Methods: Doses to the rectum and bladder were measured in a group of patients with cervical carcinoma using semiconductor detectors and compared to the doses calculated using a treatment planning system. 36 applications of brachytherapy at dose rates of 1.8-2.3 Gy/h were performed in the patients., Results: The mean differences between the measured and calculated doses were 3 % for the rectum and 11 % for the bladder., Conclusions: The main reason for the differences between the measured and calculated doses was patient movement. To reduce the risk of large errors in the dose delivered, in vivo dosimetry should be performed in addition to treatment planning system computations.

Aims: This study investigates to what extent the dose received by lungs from a commercially available treatment planning system, Ir-192 high-dose-rate (HDR), in breast brachytherapy, is accurate, with the emphasis on tissue heterogeneities, and taking into account the presence of ribs, in dose delivery to the lung., Materials and Methods: A computed tomography (CT) scan of a breast was acquired and transferred to the 3-D treatment planning system and was also used to construct a patient-equivalent phantom. An implant involving 13 plastic catheters and 383 programmed source dwell positions were simulated, using the Monte Carlo N-Particle eXtended (MCNPX) code. The Monte Carlo calculations were compared with the corresponding commercial treatment planning system (TPS) in the form of percentage isodose and cumulative dose-volume histogram (DVH) in the breast, lungs, and ribs., Results: The comparison of the Monte Carlo results and the TPS calculations showed that a percentage of isodose greater than 75% in the breast, which was located rather close to the implant or away from the breast curvature surface and lung boundary, were in good agreement. TPS calculations overestimated the dose to the lung for lower isodose contours that were lying near the breast surface and the boundary of breast and lung and were relatively away from the implant., Conclusions: Taking into account the ribs and entering the actual data for breasts, ribs, and lungs, revealed an average overestimation of the dose by a factor of 8% in the lung for TPS calculations. Therefore, the accuracy of the TPS results may be limited to regions near the implants where the treatment is planned, and is a more conservative approach for regions at boundaries with curvatures or tissues with a different material than that in the breast.

The aim of this study was to assess the actual dose delivered to the rectum and compare it with the treatment planning system (TPS) reports. In this study, the dose delivered to the rectum was measured by semiconductor diode detectors (PTW, Germany). The factors that influence diode response were investigated as well. Calibration factors of diodes were measured weekly to investigate the effect of time interval on the accuracy of calibration. Then 40 applications of patients with cervix carcinoma were evaluated. Rectum dose was measured by means of rectal dosemeter and compared with the TPS-calculated dose. In this research, the differences between the measured and the calculated dose were investigated. The mean difference between the TPS-calculated dose and the measured dose was 6.5% (range: -22 to +39) for rectum. The TPS-calculated maximum dose was typically higher than the measured maximum dose. The study showed that the main reason for the difference was due to the movements of the patient and applicator shift in the elapsed time between the imaging and treatment stage. It is recommended that in vivo dosimetry should be performed in addition to treatment planning computation. In vivo dosimetry is a reliable solution to compare the planned and actual dose delivered to organs at risk.

High dose rate (HDR) brachytherapy is one of the accepted treatment modalities in gastro-intestinal tract and bladder carcinomas. Considering the shortcoming of contact brachytherapy routinely used in gastrointestinal tract in treatment of big tumors or invasive method of bladder treatment, an intraluminal applicator with the capability of insertion into the tumor depth seems to be useful. This study presents some dosimetric evaluations to introduce this applicator to the clinical use. The radiation attenuation characteristics of the applicator were evaluated by means of two dosimetric methods including well-type chamber and radiochromic film. The proposed 110 cm long applicator has a flexible structure made of stainless steel for easy passage through lumens and a needle tip to drill into big tumors. The 2mm diameter of the applicator is thick enough for source transition, while easy passage through any narrow lumen such as endoscope or cystoscope working channel is ensured. Well-chamber results showed an acceptably low attenuation of this steel springy applicator. Performing absolute dosimetry resulted in a correlation coefficient of R = 0.9916 (p-value ≈ 10-7) between standard interstitial applicator and the one proposed in this article. This study not only introduces a novel applicator with acceptable attenuation but also proves the response independency of the GAFCHROMIC EBT films to energy. By applying the dose response of the applicator in the treatment planning software, it can be used as a new intraluminal / interstitial applicator.