ABSTRACT
The blood-brain barrier (BBB) poses a significant challenge to drug delivery for brain tumors, with most chemotherapeutics having limited permeability into non-malignant brain tissue and only restricted access to primary and metastatic brain cancers. Consequently, due to the drug's inability to effectively penetrate the BBB, outcomes following brain chemotherapy continue to be suboptimal. Several methods to open the BBB and obtain higher drug concentrations in tumors have been proposed, with the selection of the optimal method depending on the size of the targeted tumor volume, the chosen therapeutic agent, and individual patient characteristics. Herein, we aim to comprehensively describe osmotic disruption with intra-arterial drug administration, intrathecal/intraventricular administration, laser interstitial thermal therapy, convection-enhanced delivery, and ultrasound methods, including high-intensity focused and low-intensity ultrasound as well as tumor-treating fields. We explain the scientific concept behind each method, preclinical/clinical research, advantages and disadvantages, indications, and potential avenues for improvement. Given that each method has its limitations, it is unlikely that the future of BBB disruption will rely on a single method but rather on a synergistic effect of a combined approach. Disruption of the BBB with osmotic infusion or high-intensity focused ultrasound, followed by the intra-arterial delivery of drugs, is a promising approach. Real-time monitoring of drug delivery will be necessary for optimal results.
ABSTRACT
The paradigm is gradually shifting, with radiosurgery and endovascular embolization being increasingly chosen over surgical resection in the selected cases of brain arteriovenous malformations. Routinely used X-ray monitoring of liquid embolic infusion has very good spatial and temporal resolution but is not without significant drawbacks regarding poor visualization of the complex AVM angioarchitecture, especially after many embolizations in the past and therefore limiting the technical ability of the embocure-total occlusion of the feeding arteries, nidus, and draining veins. The purpose of this study was to evaluate the use of real-time MRI guidance in endovascular embolization with Onyx (instead of X-ray) in a single swine rete mirabile (RM) AVM model in order to provide the scaffolding for the real-time MRI guidance method. Onyx propagation was observed in real-time dynamic GE-EPI scan with initial ipsilateral RM filling followed by main cerebral arterial branch distribution. The relatively bright signal within RM and the brain prior to Onyx injection provided a good background for the dark, low signal of the embolic agent spreading in rete mirabile and brain arteries. X-ray picture confirmed Onyx cast distribution at the end of the procedure. In this initial experience, real-time MRI seems to be a promising method that may significantly improve liquid embolic agent infusion monitoring in the future, although requiring further development before clinical use.
ABSTRACT
As a significant cause of intracerebral hemorrhages, seizures, and neurological decline, brain arteriovenous malformations (bAVMs) are a rare group of complex vascular lesions with devastating implications for patients' quality of life. Although the concerted effort of the scientific community has improved our understanding of bAVM biology, the exact mechanism continues to be elucidated. Furthermore, to this day, due to the high heterogeneity of bAVMs as well as the lack of objective data brought by the lack of evaluative and comparative studies, there is no clear consensus on the treatment of this life-threatening and dynamic disease. As a consequence, patients often fall short of obtaining the optimal treatment. Endovascular embolization is an inherent part of multidisciplinary bAVM management that can be used in various clinical scenarios, each with different objectives. Well-trained neuro-interventional centers are proficient at curing bAVMs that are smaller than 3 cm; are located superficially in noneloquent areas; and have fewer, larger, and less tortuous feeding arteries. The transvenous approach is an emerging effective and safe technique that potentially offers a chance to cure previously untreatable bAVMs. This review provides the state of the art in all aspects of endovascular embolization in the management of bAVMs.
ABSTRACT
Background: Human papillomavirus targets the skin and mucous membranes, producing benign hyperplastic lesions and precancerous and cancerous lesions. An increasing number of head and neck cancersin particular, oropharyngeal squamous cell carcinoma, laryngeal squamous cell carcinoma, and oral squamous cell carcinoma, are attributable to HPV infection. HPV-induced HNCs typically affect younger, nonsmoking patients with no prior history of heavy alcohol use, more extensive sexual history, and higher socioeconomic status. Aim: The purpose of the review is to present the most recent and well-established findings concerning HPV-induced head and neck cancers and consequently to provide medical specialists with essential information regarding the epidemiology, the role of HPV in HNC cancerogenesis, prevention, diagnosis, and treatment. Material and Methods: All authors independently have searched The EMbase, Medline/Pubmed, and Cochrane databases by using the following keywords "head and neck cancer", "human papillomavirus", "HPV", "HPV biology", "oropharyngeal squamous cell carcinoma", "carcinogenesis", "transoral surgery", "robotic surgery". The last search was conducted in March 2022. The references of the publications of interest were also screened for relevant papers. There were no limitations in regard to the publication date. Conclusion: Aiming to avoid the epidemic of HPV-induced HNC, it is paramount to improve the access to vaccination as well as resolve parental concerns regarding vaccine safety. Physicians should rely on reduced-dose radiation and aim to reduce the overall treatment time. Thanks to a more elaborate understanding of the genomic background of HPV-induced HNC, precision medicine could become a relevant part of patients' management. In comparison to traditional techniques and non-operative treatment, transoral robotic surgery (TORS) offers similar oncologic and functional outcomes, with a possible benefit on long-term quality of life. However, more research is needed to establish clear guidelines indicating when TORS resections should be supported with adjuvant therapy.
ABSTRACT
Objective: To provide a comprehensive review of intra-arterial cerebral infusions of chemotherapeutics in glioblastoma multiforme treatment and discuss potential research aims. We describe technical aspects of the intra-arterial delivery, methods of blood-brain barrier disruption, the role of intraoperative imaging and clinical trials involving intra-arterial cerebral infusions of chemotherapeutics in the treatment of glioblastoma multiforme. Method: 159 articles in English were reviewed and used as the foundation for this paper. The Medline/Pubmed, Cochrane databases, Google Scholar, Scielo and PEDro databases have been used to select the most relevant and influential papers on the intra-arterial cerebral infusions of chemotherapeutics in the treatment of glioblastoma multiforme. Additionally, we have included some relevant clinical trials involving intra-arterial delivery of chemotherapeutics to other than GBM brain tumours. Conclusion: Considering that conventional treatments for glioblastoma multiforme fall short of providing a significant therapeutic benefit, with a majority of patients relapsing, the neuro-oncological community has considered intra-arterial administration of chemotherapeutics as an alternative to oral or intravenous administration. Numerous studies have proven the safety of IA delivery of chemotherapy and its ability to ensure higher drug concentrations in targeted areas, simultaneously limiting systemic toxicity. Nonetheless, the scarcity of phase III trials prevents any declaration of a therapeutic benefit. Given that the likelihood of a single therapeutic agent which will be effective for the treatment of glioblastoma multiforme is extremely low, it is paramount to establish an adequate multimodal therapy which will have a synergistic effect on the diverse pathogenesis of GBM. Precise quantitative and spatial monitoring is necessary to guarantee the accurate delivery of the therapeutic to the tumour. New and comprehensive pharmacokinetic models, a more elaborate understanding of glioblastoma biology and effective methods of diminishing treatment-related neurotoxicity are paramount for intra-arterial cerebral infusion of chemotherapeutics to become a mainstay treatment for glioblastoma multiforme. Additional use of other imaging methods like MRI guidance during the procedure could have an edge over X-ray alone and aid in selecting proper arteries as well as infusion parameters of chemotherapeutics making the procedure safer and more effective.
ABSTRACT
PURPOSE: To create a systematic overview of the available reconstructive techniques, facial nerve grading scales, physical evaluation, the reversibility of paralysis, non-reconstructive procedures and medical therapy, physical therapy, the psychological aspect of facial paralysis, and the prevention of facial nerve injury in order to elucidate the gaps in the knowledge and discuss potential research aims in this area. A further aim was to propose an algorithm simplifying the selection of reconstructive strategies, given the variety of available reconstructive methods and the abundance of factors influencing the selection. METHODOLOGICAL APPROACH: A total of 2439 papers were retrieved from the Medline/Pubmed and Cochrane databases and Google Scholar. Additional research added 21 articles. The primary selection had no limitations regarding the publication date. We considered only papers written in English. Single-case reports were excluded. Screening for duplicates and their removal resulted in a total of 1980 articles. Subsequently, we excluded 778 articles due to the language and study design. The titles or abstracts of 1068 articles were screened, and 134 papers not meeting any exclusion criterion were obtained. After a full-text evaluation, we excluded 15 papers due to the lack of information on preoperative facial nerve function and the follow-up period. This led to the inclusion of 119 articles. CONCLUSIONS: A thorough clinical examination supported by advanced imaging modalities and electromyographic examination provides sufficient information to determine the cause of facial palsy. Considering the abundance of facial nerve grading scales, there is an evident need for clear guidelines regarding which scale is recommended, as well as when the postoperative evaluation should be carried out. Static procedures allow the restoral of facial symmetry at rest, whereas dynamic reanimation aims to restore facial movement. The modern approach to facial paralysis involves neurotization procedures (nerve transfers and cross-facial nerve grafts), muscle transpositions, and microsurgical free muscle transfers. Rehabilitation provides patients with the possibility of effectively controlling their symptoms and improving their facial function, even in cases of longstanding paresis. Considering the mental health problems and significant social impediments, more attention should be devoted to the role of psychological interventions. Given that each technique has its advantages and pitfalls, the selection of the treatment approach should be individualized in the case of each patient.
ABSTRACT
BACKGROUND: Despite the vivid progress in molecular and genetic profiling, extensive diagnosis and multiple therapeutic modalities, cancers of unknown primary in the head and neck region continue to be a formidable challenge. AIM: The purpose of the review is to present the most recent and well-established findings concerning cancers of unknown primary (CUPs) in the head and neck patients and consequently to provide medical specialists with essential information regarding the biology, pathology, histology, diagnosis and treatment of CUP in the head and neck region. MATERIAL AND METHODS: The Medline/PubMed database was searched by using the following keywords "CUP", "cancer of unknown primary", "CUP biology", "head and neck". The references of the publications of interest were also screened for relevant papers. There were no limitations in regard to the publication date. CONCLUSION: Unique biology and pathophysiology prompt the management of CUP to be demanding. The vivid rise in HPV-related CUPs during the last 20 years has put more focus on this phenomenon. New findings concerning the enigmatic biology of CUP provide fundaments for targeted therapy. Despite the availability of various diagnostic methods, the diagnosis of CUP continues to be a time-consuming, strenuous process that eventually provides answers. It remains controversial as to what combination of treatment methods is the most effective. There is no consensus on the value of combining chemotherapy with radiotherapy. Highly specific surgical treatments for particular histological types of CUP produce more satisfactory results. It is paramount to establish reliable guidelines concerning the diagnosis and treatment of CUP patients.
