Preservation Of Healthy Tissue Research Articles

Melatonin as a radioprotective agent against flattening filter and flattening filter-free beam in radiotherapy-induced lung tissue damage

Background Radiotherapy is a widely used treatment method in oncology, applied by delivering high-energy particles or waves to the tumor tissue. Although tumor cells are targeted with radiotherapy, it can cause acute or long-term damage to healthy tissues. Therefore, the preservation of healthy tissues has been an important subject of various scientific researches. Melatonin has been shown to have a radioprotective effect on many tissues and organs such as liver, parotid gland, brain, and testicles. This study aimed to evaluate the protective effect of melatonin against the radiation at various doses and rates administered to the lung tissue of healthy mice. Methods This study was a randomized case-control study conducted with 80 rats comprising 10 groups with eight animals per group. Of the 10 groups, first is the control group, which is not given any melatonin, and second is the group that does not receive RT, which is given only melatonin, and the other eight groups are RT groups, four with melatonin and four without melatonin. Results There was no statistical difference in terms of histopathological findings in the lung tissue between the second group, which did not receive radiotherapy and received only melatonin, and the control group. Lung damage due to radiotherapy was statistically significantly higher in the groups that did not receive melatonin compared to the groups that received melatonin. Conclusions This study revealed that melatonin has a protective effect against the cytotoxic damage of RT in rats receiving RT.

MOHS SURGERY

Mohs surgery is a highly specialized procedure used to treat skin cancer, especially basal cell carcinoma and squamous cell carcinoma. This technique is known for its high cure rate and preservation of healthy tissue around the affected area. This study aims to review and address the most recent updates in the Mohs surgery technique, including advances in equipment and instruments, improved treatment protocols and post-surgical reconstruction techniques, while also discussing the growing importance of this procedure in contemporary dermatological practice and its positive impact on patients’ quality of life. Mohs surgery involves the surgical removal of thin layers of cancerous tissue, followed by immediate microscopic analysis of the margins of the removed tissue. This allows precise identification of the tumor margins, ensuring complete removal of the cancer while preserving as much healthy tissue as possible. Recent updates to the technique include the use of advanced imaging techniques, such as dermoscopy and confocal microscopy, to aid in the precise identification of tumor margins prior to surgery. In addition, the development of more effective surgical reconstruction methods has improved aesthetic and functional results for patients. It is therefore concluded that Mohs surgery remains an effective option for the treatment of skin cancer, offering high cure rates and preservation of healthy tissue. Updates to the technique, including improvements in diagnostic accuracy and reconstruction options, have contributed to increasingly better results for patients undergoing this procedure.

Thoracic Proton Minibeam Radiation Therapy: Tissue Preservation and Survival Advantage Over Conventional Proton Therapy

PurposeProton Minibeam Radiotherapy (pMBRT) is an innovative radiation therapy approach that highly modulates the spatial dimension of the dose delivery using narrow, parallel, and submillimetric proton beamlets. pMBRT has proven its remarkable healthy tissue preservation in the brain and skin. This study assesses the potential advantages of pMBRT for thoracic irradiations compared to conventional radiotherapy in terms of normal tissue toxicity. The challenge here was the influence of respiratory motion on the typical peak and valley dose patterns of pMBRT and its potential biological impact. Methods and materialsthe whole thorax of naïve C57BL/6 mice received one fraction of high dose (18 Gy) pMBRT or conventional proton therapy (CPT) without any respiratory control. The development of radiation-induced pulmonary fibrosis was longitudinally monitored using cone-beam computed tomography. Anatomopathological analysis was carried out at 9 months post-irradiation and focused on the reaction of the lungs’ parenchyma and the response of cell types involved in the development of radiation-induced fibrosis and lung regeneration as Alveolar Type II (AT2) epithelial cells, club cells, and macrophages. ResultspMBRT has milder effects on survival, skin reactions, and lung fibrosis compared to CPT. The pMBRT-induced lung changes were more regional and less severe, with evidence of potential reactive proliferation of AT2 epithelial cells and less extensive depletion of club cells and macrophage invasion than the more damaging effects observed in CPT. ConclusionpMBRT appears suitable to treat moving targets, holding a significant ability to preserve healthy lung tissue, even without respiratory control or precise targeting.

MR-LINAC, a New Partner in Radiation Oncology: Current Landscape.

Technological advances in radiation oncology are oriented towards improving treatment precision and tumor control. Among these advances, magnetic-resonance-image-guided radiation therapy (MRgRT) stands out, with technological advances to deliver targeted treatments adapted to a tumor's anatomy on the day while minimizing incidental exposure to organs at risk, offering an unprecedented therapeutic advantage compared to X-ray-based IGRT delivery systems. This new technology changes the traditional workflow in radiation oncology and requires an evolution in team coordination to administer more precise treatments. Once implemented, it paves the way for newer indication for radiation therapy to safely deliver higher doses than ever before, with better preservation of healthy tissues to optimize patient outcomes. In this narrative review, we assess the technical aspects of the novel linear accelerators that can deliver MRgRT and summarize the available published experience to date, focusing on oncological results and future challenges.

Infero-Auricular Folded Flap for The Reconstruction of a Full-Thickness Defect of The Earlobe

Basal cell carcinoma is the most common type of malignant cutaneous tumor. Chronic exposure to sunlight is the main factor in its etiology. The main treatment goals in the management of BCC are total removal of the lesion, preservation of healthy tissue, preservation of function and obtaining aesthetically acceptable results. Posteroauricular/preauricular advancement flaps, biloble flaps, helical rim advancement flaps and revolving door flaps are among the flaps used in ear reconstruction. In this study, we present a case of the reconstruction of a full-thickness ear lobe defect with a postro-inferiorly based flap. The patient did not develop any recurrence within the 3 years follow-up period. .

Deep learning classification of deep ultraviolet fluorescence images toward intra-operative margin assessment in breast cancer.

Breast-conserving surgery is aimed at removing all cancerous cells while minimizing the loss of healthy tissue. To ensure a balance between complete resection of cancer and preservation of healthy tissue, it is necessary to assess themargins of the removed specimen during the operation. Deep ultraviolet (DUV) fluorescence scanning microscopy provides rapid whole-surface imaging (WSI) of resected tissues with significant contrast between malignant and normal/benign tissue. Intra-operative margin assessment with DUV images would benefit from an automated breast cancer classification method. Deep learning has shown promising results in breast cancer classification, but the limited DUV image dataset presents the challenge of overfitting to train a robust network. To overcome this challenge, the DUV-WSI images are split into small patches, and features are extracted using a pre-trained convolutional neural network-afterward, a gradient-boosting tree trains on these features for patch-level classification. An ensemble learning approach merges patch-level classification results and regional importance to determine the margin status. An explainable artificial intelligence method calculates the regional importance values. The proposed method's ability to determine the DUV WSI was high with 95% accuracy. The 100% sensitivity shows that the method can detect malignant cases efficiently. The method could also accurately localize areas that contain malignant or normal/benign tissue. The proposed method outperforms the standard deep learning classification methods on the DUV breast surgical samples. The results suggest that it can be used to improve classification performance and identify cancerous regions more effectively.

Gold-Enhanced Brachytherapy by a Nanoparticle-Releasing Hydrogel and 3D-Printed Subcutaneous Radioactive Implant Approach.

Brachytherapy (BT) is a widely used clinical procedure for localized cervical cancer treatment. In addition, gold nanoparticles (AuNPs) have been demonstrated as powerful radiosensitizers in BT procedures. Prior to irradiation by a BT device, their delivery to tumors can enhance the radiation effect by generating low-energy photons and electrons, leading to reactive oxygen species (ROS) production, lethal to cells. No efficient delivery system has been proposed until now for AuNP topical delivery to localized cervical cancer in the context of BT. This article reports an original approach developed to accelerate the preclinical studies of AuNP-enhanced BT procedures. First, an AuNP-containing hydrogel (Pluronic F127, alginate) is developed and tested in mice for degradation, AuNP release, and biocompatibility. Then, custom-made 3D-printed radioactive BT inserts covered with a AuNP-containing hydrogel cushion are designed and administered by surgery in mice (HeLa xenografts), which allows for measuring AuNP penetration in tumors (≈100µm), co-registered with the presence of ROS produced through the interactions of radiation and AuNPs. Biocompatible AuNPs-releasing hydrogels could be usedin the treatment of cervical cancer prior to BT, with impact on the total amount of radiation needed per BT treatment, which will result in benefits to the preservation of healthy tissues surrounding cancer.

Lip Reconstruction After Mohs Micrographic Surgery: A Guide on Flaps

The lips are commonly affected by skin cancer because of increased sun exposure over time. Even with early detection, many of these skin cancers require surgical removal with subsequent reconstruction. Mohs micrographic surgery is the preferred method of treatment for nonmelanoma skin cancers of the lip, as it has the lowest recurrence rates and allows for the maximum preservation of healthy tissue. After surgery, the remaining lip defect often requires reconstruction with skin grafts or a local cutaneous or myocutaneous flap. There are several local flap reconstruction options available, and some may be used in combination for more complex defects. We provide a succinct review of commonly utilized flaps and outline their indications, risks, and benefits.

Can Zeolite-Supporting Acridines Boost Their Anticancer Performance?

Acridine and its derivatives (9-chloroacridine and 9-aminoacridine) are investigated here, supported on FAU type zeolite Y, as a delivery system of anticancer agents. FTIR/Raman spectroscopy and electron microscopy revealed successful drug loading on the zeolite surface, while spectrofluorimetry was employed for drug quantification. The effects of the tested compounds on cell viability were evaluated using in vitro methylthiazol-tetrazolium (MTT) colorimetric technique against human colorectal carcinoma (cell line HCT-116) and MRC-5 fibroblasts. Zeolite structure remained unchanged during homogeneous drug impregnation with achieved drug loadings in the 18-21 mg/g range. The highest drug release, in the µM concentration range, with favourable kinetics was established for zeolite-supported 9-aminoacridine. The acridine delivery via zeolite carrier is viewed in terms of solvation energy and zeolite adsorption sites. The cytotoxic effect of supported acridines on HCT-116 cells reveals that the zeolite carrier improves toxicity, while the highest efficiency is displayed by zeolite-impregnated 9-aminoacridine. The 9-aminoacridine delivery via zeolite carrier favours healthy tissue preservation while accompanying increased toxicity toward cancer cells. Cytotoxicity results are well correlated with theoretical modelling and release study, providing promising results for applicative purposes.

A Handheld Visible Resonance Raman Analyzer Used in Intraoperative Detection of Human Glioma.

There is still a lack of reliable intraoperative tools for glioma diagnosis and to guide the maximal safe resection of glioma. We report continuing work on the optical biopsy method to detect glioma grades and assess glioma boundaries intraoperatively using the VRR-LRRTM Raman analyzer, which is based on the visible resonance Raman spectroscopy (VRR) technique. A total of 2220 VRR spectra were collected during surgeries from 63 unprocessed fresh glioma tissues using the VRR-LRRTM Raman analyzer. After the VRR spectral analysis, we found differences in the native molecules in the fingerprint region and in the high-wavenumber region, and differences between normal (control) and different grades of glioma tissues. A principal component analysis-support vector machine (PCA-SVM) machine learning method was used to distinguish glioma tissues from normal tissues and different glioma grades. The accuracy in identifying glioma from normal tissue was over 80%, compared with the gold standard of histopathology reports of glioma. The VRR-LRRTM Raman analyzer may be a new label-free, real-time optical molecular pathology tool aiding in the intraoperative detection of glioma and identification of tumor boundaries, thus helping to guide maximal safe glioma removal and adjacent healthy tissue preservation.

Banking Autologous Tarsus: A Simple Technique For Maximizing Preservation of Healthy Tissue.

A 28-year-old female with congenital left-sided ptosis presented after 3 prior surgeries elsewhere. Although centrally her margin to reflex distance1 was 3 mm, persistent ptosis was noted laterally. In an effort to improve the symmetry of her eyelid contour, a lateral tarsectomy was performed. As the authors worried this might worsen her dryness, the decision was made to bank the excised tarso-conjunctival tissue in case additional revision surgery is required at a later date. To accomplish this, a conjunctival incision was created at the inferior tarsal margin in the ipsilateral lower lateral eyelid and the excised upper eyelid tarso-conjunctival tissue was secured in this pocket. Four months postoperatively, the banked tissue appeared healthy and the upper eyelid contour was improved. This technique may be most helpful in multi-operated situations, where the chance of future revision is not insignificant.

Effect of Quercetin and Fingolimod, Alone or in Combination, on the Sphingolipid Metabolism in HepG2 Cells.

Combinations of anti-cancer drugs can overcome resistance to therapy and provide new more effective treatments. In this work we have analyzed the effect of the polyphenol quercetin and the anti-cancer sphingosine analog fingolimod on the sphingolipid metabolism in HepG2 cells, since sphingolipids are recognized as mediators of cell proliferation and apoptosis in cancer cells. Treatment of hepatocellular carcinoma HepG2 cells with quercetin and fingolimod, alone or in combination, induced different degrees of sphingomyelin (SM) reduction and a corresponding activation of neutral sphingomyelinase (nSMase). Western blot analysis showed that only treatments containing quercetin induced up-regulation of nSMase expression. The same treatment caused elevation of ceramide (CER) levels, whereas the observed alterations in sphingosine (SPH) content were not statistically significant. The two tested drugs induced a reduction of the pro-proliferative sphingolipid, sphingosine 1 phosphate (S1P), in the following order: quercetin, fingolimod, quercetin + fingolimod. The activity of the enzyme responsible for CER hydrolysis, alkaline ceramidase (ALCER) was down-regulated only in the incubations involving quercetin and fingolimod did not affect this activity. The enzyme, maintaining the balance between apoptosis and proliferation, sphingosine kinase 1 (SK1), was down-regulated by incubations in the following order: quercetin, fingolimod, quercetin + fingolimod. Western blot analysis showed down-regulation in SK1 expression upon quercetin but not upon fingolimod treatment. Studies on the effect of quercetin and fingolimod on the two proteins associated with apoptotic events, AKT and Bcl-2, showed that only quercetin, alone or in combination, down-regulated the activity of the two proteins. The reported observations provide information which can be useful in the search of novel anti-tumor approaches, aiming at optimization of the therapeutic effect and maximal preservation of healthy tissues.

89Zr-panitumumab PET imaging for preoperative assessment of ameloblastoma in a PDX model

Accurate assessment of tumor margins with specific, non-invasive imaging would result in the preservation of healthy tissue and improve long-term local tumor control, thereby reducing the risk of recurrence. Overexpression of epidermal growth factor receptor (EGFR) has been used in other cancers as an imaging biomarker to identify cancerous tissue. We hypothesize that expression of EGFR in ameloblastomas may be used to specifically visualize tumors. The aims of this study are to measure the specificity of radiolabeled 89Zr-panitumumab (an EGFR antibody) in vivo using patient-derived xenograft (PDX) models of ameloblastoma and positron emission tomography/computed tomography (PET/CT) scans. In PDX of ameloblastomas from four patients (AB-36, AB-37, AB-39 AB-53), the biodistribution of 89Zr-panitumumab was measured 120 h post-injection and was reported as the injected dose per gram of tissue (%ID/g; AB-36, 40%; AB-37, 62%; AB-39 18%; AB-53, 65%). The radiolabeled %ID/g was significantly greater in tumors of 89Zr-panitumumab-treated mice that did not receive unlabeled panitumumab as a blocking control for AB-36, AB-37, and AB-53. Radiolabeled anti-EGFR demonstrates specificity for ameloblastoma PDX tumor xenografts, we believe 89Zr-panitumumab is an attractive target for pre-surgical imaging of ameloblastomas. With this technology, we could more accurately assess tumor margins for the surgical removal of ameloblastomas.

Computational Modeling of Microwave Tumor Ablation.

Microwave ablation is recognized as a minimally invasive, fast-recovery treatment for destroying cancer cells using the heat generated by microwave energy. Despite the unquestionable benefits of microwave ablation, the interaction of the microwave applicator with the tissue may result in localized heating and damage to the surrounding tissue. The majority of the tissue damage can be removed by clarifying the conditions for their development. In addition to experimental methods, computer modeling has proven to be an effective tool for optimizing the performance of microwave ablation. Furthermore, because the thermal spread in biological tissue is difficult to measure, developing a predictive model from procedural planning to execution may have a substantial influence on patient care. The comprehension of heat transport in biological tissues plays a significant role in gaining insight into the mechanisms underlying microwave ablation. Numerical methods that enable ablation size control are required to guarantee tumor destruction and minimize damage to healthy tissues. Various values of input power and ablation time correspond to different tumor shapes ensuring the preservation of healthy tissues. The optimal conditions can be estimated by performing full three-dimensional simulations. This topical review recapitulates numerous computational studies on microwave tumor ablation. Novel areas emerging in treatment planning that exploit the advantages of numerical methods are also discussed. As an illustration, the results of the three-dimensional simulations of real liver tumors in the 3D-IRCADb-01 database are presented and analyzed. The simulation results confirm that numerical methods are very useful tools for modeling microwave tumor ablation with minimal invasiveness and collateral damage.

Chemical Overview of Gel Dosimetry Systems: A Comprehensive Review.

Advances in radiotherapy technology during the last 25 years have significantly improved both dose conformation to tumors and the preservation of healthy tissues, achieving almost real-time feedback by means of high-precision treatments and theranostics. Owing to this, developing high-performance systems capable of coping with the challenging requirements of modern ionizing radiation is a key issue to overcome the limitations of traditional dosimeters. In this regard, a deep understanding of the physicochemical basis of gel dosimetry, as one of the most promising tools for the evaluation of 3D high-spatial-resolution dose distributions, represents the starting point for developing new and innovative systems. This review aims to contribute thorough descriptions of the chemical processes and interactions that condition gel dosimetry outputs, often phenomenologically addressed, and particularly formulations reported since 2017.

Cirugía micrográfica de Mohs en carcinomas cutáneos: primeros 250 casos en la Unidad de Cirugía Dermatológica

IntroductionMohs micrographic surgery (CMM) it’s a surgical technique for treatment of skin carcinomas, indicated in high-risk tumors. It allows control of 100% of the tumor margins, achieving the best healing rates and the biggest healthy tissue preservation compared with conventional techniques. ObjectivesLearn the epidemiologic characteristics of the first 250 patients treated with CMM at the clinical hospital “Dr. Manuel Quintela”. Patients and methodsA retrospective observational study was performed collecting epidemiological data and linked data of the first 250 patients treated with MMS at the Dermatology department between November 2013 and May 2018. Results58.4% of the patients were male, 41.6% were female. The average age was 68 years. We found equitative distribution between Montevideo (52.8%) and the rest of the country (47.2%). The basal cell carcinoma represented 67.2% of the treated carcinomas. The spinocellular carcinoma represented the 31.2%. The most frequent location was the head. Simple closure was the more common reconstruction method used. The vast majority of the cases corresponded to primary tumors (91.6%). DiscusionThe epidemiologic characteristics founded in our study our study were similar to those described in similar studies on other geographic areas. The CMM its the gold standard for the high-risk non-melanoma skin cancer treatment, allowing to control 100% of the surgical margins, achieving better oncologic, functional and esthetic results.

Intraoperative dyes, fluorescence and enhanced imaging in benign gynaecologic surgery.

We review the literature regarding the use of dyes and fluorescence-guided visualization techniques in gynaecological surgery. We also discuss advances in imaging that may enhance surgery by incorporating real-time visual feedback through augmented reality and preoperative planning with patient-specific, three-dimensional printed surgical fields. Methylene blue is one of the most commonly used dyes, while indocyanine green is the most used agent in fluorescence-guided surgery. Augmented reality and three-dimensional printing are also being increasingly used in gynaecology. Dyes and fluorescence-based surgeries are commonly utilized to improve anatomic identification, preservation of healthy tissue and excision of disease. In addition, we explore how augmented reality and three-dimensional printing are used in gynaecology.

The use of individual instruments in the surgical treatment of malignant bone tumors created by 3D printing

Introduction. Computer modeling and additive technologies are increasingly used in medicine. Oncoorthopedics is no exception. Careful preoperative planning and the creation of individual instruments make it possible to perform radical operations, which allows maximum preservation of healthy tissues and leads to an increase in the functional potential of patients in the postoperative period.Objective – to improve the results of surgical treatment of patients with malignant bone tumors of complex anatomical localizations using computer modeling and additive technologies.Materials and methods. This study included 44 patients (26 men and 18 women) with malignant bone tumors. The mean age of the patients was 39 ± 15.57 years (range 14 to 66 years). In 39 cases, the anatomical location of PSI application was the pelvis, in four cases it was the distal femur, and in one case the femoral shaft. The most common histological type of tumor was chondrosarcoma (47.7 %).Results. In the case of primary resection of the pelvic bone tumor (26 patients), according to the histological examination, radical resection margins (R0) were observed in 25 cases. In one case, after removal of the tumor, a discrepancy between the preoperative histological conclusion (G2 chondrosarcoma) and postoperative (dedifferentiated G3 chondrosarcoma) was revealed. During operations to remove tumors of the distal segment of the femur and resection of the tumor of the diaphysis of the femur, in all cases, the radicality was R0.Conclusion. Individual navigation devices have proven themselves in clinical practice. The results obtained in our study demonstrate their effectiveness in the treatment of malignant bone tumors.

An Analysis of Microwave Ablation Parameters for Treatment of Liver Tumors from the 3D-IRCADb-01 Database.

Simulation techniques are powerful tools for determining the optimal conditions necessary for microwave ablation to be efficient and safe for treating liver tumors. Owing to the complexity and computational resource consumption, most of the existing numerical models are two-dimensional axisymmetric models that emulate actual three-dimensional cancers and the surrounding tissue, which is often far from reality. Different tumor shapes and sizes require different input powers and ablation times to ensure the preservation of healthy tissues that can be determined only by the full three-dimensional simulations. This study aimed to tailor microwave ablation therapeutic conditions for complete tumor ablation with an adequate safety margin, while avoiding injury to the surrounding healthy tissue. Three-dimensional simulations were performed for a multi-slot microwave antenna immersed in two tumors obtained from the 3D-IRCADb-01 liver tumors database. The temperature dependence of the dielectric and thermal properties of healthy and tumoral liver tissues, blood perfusion, and water content are crucial for calculating the correct ablation time and, thereby, the correct ablation process. The developed three-dimensional simulation model may help practitioners in planning patient-individual procedures by determining the optimal input power and duration of the ablation process for the actual shape of the tumor. With proper input power, necrotic tissue is placed mainly in the tumor, and only a small amount of surrounding tissue is damaged.

Potential Utility of Adjunct Imaging with Wide-Field Optical Coherence Tomography for Gross and Microscopic Evaluation of Breast Specimens in Real-Time in the Operating Suite

One challenge in the surgical management of breast cancer is maximizing the preservation of healthy tissue while achieving acceptable negative margins. Tools capable of assessing disease-margin involvement intraoperatively and in real-time could provide clinically useful guidance regarding the adequacy of margin resection before the surgery is over. Here we report the intraoperative use of optical coherence tomography (OCT) in 3 patients with DCIS. In all 3 cases, additional lesions identified by OCT during surgery were also noted in histopathology reports 3 to 5 days post-surgery, suggesting that intraoperative use of OCT is a valuable tool for margin determination in real-time.