Transorbital endoscopic approaches to the skull base: a systematic literature review and anatomical description.

Transorbital endoscopic approaches are increasing in popularity as they provide corridors to reach various areas of the ventral skull base through the orbit. They can be used either alone or in combination with different approaches when dealing with the pathologies of the skull base. The objective of the current study is to evaluate the surgical anatomy of transorbital endoscopic approaches by cadaver dissections as well as providing objective clinical data on their actual employment and morbidity through a systematic review of the current literature. Four cadaveric specimens were dissected, and step-by-step dissection of each endoscopic transorbital approach was performed to identify the main anatomic landmarks and corridors. A systematic review with pooled analysis of the current literature from January 2000 to April 2020 was performed and the related studies were analyzed. Main anatomical landmarks are presented based on the anatomical study and systematic review of the literature. With emphasis on the specific transorbital approach used, indications, surgical technique, and complications are reviewed through the systematic review of 42 studies (19 in vivo and 23 anatomical dissections) including 193 patients. In conclusion, transorbital endoscopic approaches are promising and appear as feasible techniques for the surgical treatment of skull base lesions. Surgical anatomy of transorbital endoscopic approaches can be mastered through knowledge of a number of anatomical landmarks. Based on data available in the literature, transorbital endoscopic approaches represent an important complementary that should be included in the armamentarium of a skull base team.

Retroesophageal right subclavian artery associated with a bicarotid trunk and an ectopic origin of vertebral arteries.

A rare branching pattern of the aortic arch in a female cadaver is reported. An aberrant right subclavian artery originated from the distal part of the aortic arch and following a retroesophageal course was recognized. Next to it, from the left to the right, the left subclavian artery and a short bicarotid trunk originating the left and the right common carotid artery were recognized. An unusual origin of the vertebral arteries was also identified. The left vertebral artery originated directly from the aortic arch, whereas the right vertebral artery originated directly from the right common carotid artery. Retroesophageal right subclavian artery associated with a bicarotid trunk and ectopic origin of vertebral arteries represents an exceptional and noteworthy case.

Epoxyeicosatrienoic intervention improves NAFLD in leptin receptor deficient mice by an increase in PGC1α-HO-1-PGC1α-mitochondrial signaling.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and is considered to be an inflammatory disorder characterized by fatty acid accumulation, oxidative stress, and lipotoxicity. We have previously reported that epoxyeicosatrienoic acid-agonist (EET-A) has multiple beneficial effects on cardiac, renal and adipose tissue function while exhibiting both anti-inflammatory and anti-oxidant activities. We hypothesized that EET-A intervention would play a central role in attenuation of obesity-induced steatosis and hepatic fibrosis that leads to NAFLD. METHODS: We studied the effect of EET-A on fatty liver using db/db mice as a model of obesity. Mice were fed a high fat diet (HFD) for 16 weeks and administered EET-A twice weekly for the final 8 weeks. RESULTS: db/db mice fed HFD significantly increased hepatic lipid accumulation as manifested by increases in NAS scores, hepatic fibrosis, insulin resistance, and inflammation, and decreases in mitochondrial mitofusin proteins (Mfn 1/2) and anti-obesity genes Fibroblast growth factor 21 (FGF21) and Cellular Repressor of E1A-Stimulated Genes 1 (CREG1). EET-A administration reversed the decrease in these genes and reduced liver fibrosis. Knockout of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in EET-A treated mice resulted in a reversal of the beneficial effects of EET-A administration. CONCLUSIONS: EET-A intervention diminishes fatty acid accumulation, fibrosis, and NFALD associated with an increase in HO-1-PGC1α and increased insulin receptor phosphorylation. A pharmacological strategy involving EETs may offer a potential therapeutic approach in preventing fibrosis, mitochondrial dysfunction, and the development of NAFLD.

Thymus-Pineal Gland Axis: Revisiting Its Role in Human Life and Ageing.

For years the thymus gland (TG) and the pineal gland (PG) have been subject of increasingly in-depth studies, but only recently a link that can associate the activities of the two organs has been identified. Considering, on the one hand, the well-known immune activity of thymus and, on the other, the increasingly emerging immunological roles of circadian oscillators and the rhythmically secreted main pineal product, melatonin, many studies aimed to analyse the possible existence of an interaction between these two systems. Moreover, data confirmed that the immune system is functionally associated with the nervous and endocrine systems determining an integrated dynamic network. In addition, recent researches showed a similar, characteristic involution process both in TG and PG. Since the second half of the 20th century, evidence led to the definition of an effectively interacting thymus-pineal axis (TG-PG axis), but much has to be done. In this sense, the aim of this review is to summarize what is actually known about this topic, focusing on the impact of the TG-PG axis on human life and ageing. We would like to give more emphasis to the implications of this dynamical interaction in a possible therapeutic strategy for human health. Moreover, we focused on all the products of TG and PG in order to collect what is known about the role of peptides other than melatonin. The results available today are often unclear and not linear. These peptides have not been well studied and defined over the years. In this review we hope to awake the interest of the scientific community in them and in their future pharmacological applications.

Platelet-Rich Plasma in Treatment of Temporomandibular Joint Dysfunctions: Narrative Review.

BACKGROUND: The aims of this narrative review were to examine up-to-date literature in order to evaluate the effectiveness of arthrocentesis or injections with platelet-rich plasma in temporomandibular affections and to compare them to arthrocentesis alone or with hyaluronic acid (HA) or to hyaluronic acid injections. METHODS: The search of international literature was made on the PMC, PubMed and Cochrane databases, including all full-length text of studies on humans focused on osteoarthritis and disc displacements and their treatment with platelet-rich plasma arthrocentesis or injections. All design studies were included in the review and they were examined for three different outcomes: pain, joint sound and mandibular motion. English papers were only selected. RESULTS: Even though the low number of studies in this field, arthrocentesis with platelet-rich plasma and platelet-rich plasma injections in temporomandibular disorders' management were found to be effective in reducing pain and joint sound as well as in improving mandibular motion in a maximum follow-up of 24 months. CONCLUSION: Comparison to arthrocentesis alone or to HA use in arthrocentesis or by injections provided encouraging results in terms of the effectiveness of platelet-rich plasma use.

In vitro treatment with concentrated growth factors (CGF) and sodium orthosilicate positively affects cell renewal in three different human cell lines.

The aim of this study was to investigate the in vitro effect of Silicon, in the soluble form of sodium orthosilicate, combined and not with the concentrated growth factors (CGF), a platelet-rich preparation, on three different human cell lines of fibroblasts (NHDF), endothelial cells (HUVEC), and osteoblasts (HOBs). Each cell type was treated with sodium orthosilicate at the final concentration of 0.5 mM and 1 mM, CGF, and sodium orthosilicate combined with CGF, for 72 h. At the end of the experimental period, the in vitro effect on cell growth, proliferation, and metabolic activity was evaluated by performing a simple cell count, using an automated cell counter and by evaluating the expression of the intracellular proliferation marker Ki-67, using Fluorescence-activated cell sorting (FACS) analysis. Moreover, the expression of other cell markers and active molecules, such as Collagen type I, Osteopontin, Vascular Endothelial Growth Factor, and endothelial Nitric Oxide Synthase, was evaluated, through immunohistochemistry. Results obtained showed that the combined use of CGF and sodium orthosilicate stimulates cell growth, proliferation, and metabolic activity, suggesting that this treatment could be effective in tissue regeneration.

Growth Factors Release From Concentrated Growth Factors: Effect of ß-Tricalcium Phosphate Addition.

BACKGROUND: Platelet concentrates represent a new approach to improve tissue regeneration and can be used alone or together with autogenous bone, recombinant human growth factors, and/or other biomaterials, to enhance tissue regeneration. Among platelet concentrates, concentrated growth factors (CGFs) exhibit an interesting clinical and biotechnological application potential. OBJECTIVE: The aim of this study was to evaluate the in vitro release of 4 growth factors (bone morphogenetic proteins [BMP] -2, BMP-7, transforming growth factor [TGF] -ß1, and insulin-like growth factor [IGF] -1) by the enzyme-linked immunosorbent assay (ELISA) technique, in CGFs mixed or not with ß-tricalcium phosphate (ß-TCP), using or not the Round-up device, at different times. METHODS: CGFs were obtained from healthy volunteers, mixed or not with ß-TCP, using or not the Round-up device. The release of 4 growth factors from these CGFs was then measured at 5 hours, 1, 3, 6, and 8 days, using the ELISA assay. RESULTS: Comparison of the results obtained with those achieved for CGFs alone showed that BMP2 and BMP-7 release, significantly increased in CGFs mixed with Round-up and ß-TCP, TGF-ß1 release was similar to CGFs alone, whereas IG-1 release was lower compared with CGFs alone. CONCLUSION: The present data suggest that ß-TCP addition to CGF could enhance and improve tissue regeneration, especially bone regeneration, increasing the release of some growth factors that play an important role in osteogenesis.

Acute mercury exposition of virgin, pregnant, and lactating rats: Histopathological kidney and liver evaluations.

This work investigated the effects of mercury chloride (HgCl2 ) acute exposure on virgin, pregnant and lactating rats by determination of renal and hepatic morphological and ultrastructural parameters and the expression of oxidative stress and stress tolerance markers, due to kidney and liver are the organs that more accumulate inorganic mercury. Adult Wistar rats virgin (90 days old), pregnant (18th gestation day) and lactating (7th lactation day) were injected once with HgCl2 (5 mg/kg) or saline (controls). We observed that HgCl2 exposure of virgin rats caused significant inflammatory infiltration and severe morphological variations, like glomeruli atrophy, dilatation of Bowman's capsule, tubular degeneration and hepatocytes alteration. Moreover, virgin rats presented mitochondrial modification, important oxidative stress and increase in stress tolerance proteins at both kidney and liver level, compared with virgin controls. In detail, virgin rats exposed to HgCl2 presented significantly elevated level of inducible nitric oxide synthase, heat shock protein 27 and glucose regulated proteins 75 expressions at both renal tubular and hepatocytes level, respect untreated virgin rats. Interestingly, pregnant and lactating rats exposed to HgCl2 presented weak renal and liver morphological alterations, showing weak inflammatory infiltration and no significant difference in structural mitochondrial transmembrane protein, oxidative stress markers and stress tolerance proteins expressions respect controls (virgin, pregnant and lactating rats). Although, both control and HgCl2 -exposed pregnant and lactating rats showed renal glomeruli greater in diameter respect virgin rats. In conclusion, we believe that virgin rats are more sensitive to HgCl2 toxicity respect pregnant and lactating rats. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1500-1512, 2017.

Oral Supplementation of Melatonin Protects against Fibromyalgia-Related Skeletal Muscle Alterations in Reserpine-Induced Myalgia Rats.

Fibromyalgia is a chronic syndrome characterized by widespread musculoskeletal pain and an extensive array of other symptoms including disordered sleep, fatigue, depression and anxiety. Important factors involved in the pathogenic process of fibromyalgia are inflammation and oxidative stress, suggesting that ant-inflammatory and/or antioxidant supplementation might be effective in the management and modulation of this syndrome. Recent evidence suggests that melatonin may be suitable for this purpose due to its well known ant-inflammatory, antioxidant and analgesic effects. Thus, in the current study, the effects of the oral supplementation of melatonin against fibromyalgia-related skeletal muscle alterations were evaluated. In detail, 90 Sprague Dawley rats were randomly treated with reserpine, to reproduce the pathogenic process of fibromyalgia and thereafter they received melatonin. The animals treated with reserpine showed moderate alterations at hind limb skeletal muscles level and had difficulty in moving, together with significant morphological and ultrastructural alterations and expression of inflammatory and oxidative stress markers in the gastrocnemius muscle. Interestingly, melatonin, dose and/or time dependently, reduced the difficulties in spontaneous motor activity and the musculoskeletal morphostructural, inflammatory, and oxidative stress alterations. This study suggests that melatonin in vivo may be an effective tool in the management of fibromyalgia-related musculoskeletal morphofunctional damage.

The ethmoidal arteries: a cadaveric study based on cone beam computed tomography and endoscopic dissection.

PURPOSE: To describe the anatomical variability of the ethmoidal arteries (EAs). To evaluate the reliability of cone beam computed tomography (CBCT) in preoperative assessment of EAs. METHODS: Fourteen cadaver heads underwent CBCT and endoscopic dissection. The following anatomical features were evaluated for anterior (AEA), middle (MEA), and posterior (PEA) EAs: presence, cranio-caudal position, antero-posterior position, and dehiscence of the bony canal. Accuracy of radiological assessment was calculated. RESULTS: AEA, MEA, and PEA were identified in 100, 28.6, and 100% of sides. They were caudal to the skull base in 60.7, 25, and 17.9%, respectively. CBCT showed a high accuracy in identifying these features. The antero-posterior position of EAs, which was highly variable, was correctly assessed by CBCT. A dehiscent bony canal of AEA, MEA, and PEA was found in 46.4, 12.5, and 28.6% of sides, respectively. Accuracy of CBCT in picking up this feature was poor but negative predictive value was high. CONCLUSIONS: CBCT was adequate in identifying and localizing EAs. In addition, it can be used to exclude the presence of MEA and dehiscence of ethmoidal canals, whereas the accuracy in detecting these anatomic variants was low.

Ophthalmic artery originating from the anterior cerebral artery: anatomo-radiological study, histological analysis, and literature review.

The ophthalmic artery has an anomalous origin in 2-3 % of cases and rarely arises from the anterior cerebral artery. Herein, we provide the first anatomical, radiological, and histological description of such an anomalous origin, together with a literature review. During the anatomical dissection of an 81-year-old Caucasian male, the absence of the right ophthalmic artery in its usual location was evident from an endonasal transsphenoidal perspective. The specimen was then studied in detail, through multiple dissections, corrosion casting, high-resolution CT, and histological analysis. The English literature on anomalous origins of the ophthalmic artery was reviewed, together with reported associated pathologies. Anatomo-radiological analysis documented that the right ophthalmic artery arose from the inferior surface of A1 tract of the anterior cerebral artery (A1) and passed over the optic nerve in its subarachnoid tract. A meningo-ophthalmic artery was evident on the same side and reached the orbit through the superior orbital fissure. Histological examination of both internal carotid artery (ICA) walls documented a significantly decreased thickness of the tunica media and adventitia on the side of the anomalous ophthalmic artery, with a significantly different content of collagen types I and III. The literature review documented an association of aneurysms and anomalous ophthalmic arteries. To the best of our knowledge, this is the first anatomical report that includes a radiological and arterial wall analysis of a persistent ventral ophthalmic artery. The latter provides histological data that support the clinical evidence of a higher association of aneurysms with anomalous origins of the ophthalmic artery.

Nicotine-induced morphological changes in rat aorta: the protective role of melatonin.

We analyzed the morphological changes in rat aortas during nicotine administration in order to investigate the involvement of vascular smooth muscle cells (VSMCs) in the regulation of vascular wall homeostasis. We also considered the possibility of restoring VSMC changes using melatonin as an antioxidant. We studied 4 groups of animals over 56 days. Three groups of rats were used as controls (the first without treatment, the second with melatonin alone and the third with nicotine alone). The last group of rats was orally treated with nicotine for the first 28 days and with melatonin for the last 28 days. Morphological changes in vessels were evaluated by histological procedures and immunohistochemical analysis using thrombospondin-1 (TSP-1), transforming growth factor-ß1 (TGF-ß1), plasminogen activator inhibitor-1 (PAI-1) and CD31 antibodies. We demonstrated that TSP-1, TGF-ß1 and PAI-1 increased after nicotine administration. We believe that TSP-1 is responsible for neointima formation and that it is able to influence TGF-ß1 and PAI-1 expression. Histological and immunohistochemical analysis by CD31 antibody showed that only a few endothelial cells were present in the aorta after nicotine administration compared to controls and rats treated with melatonin after nicotine administration. Moreover, histological analysis showed that neointima formation was present after nicotine treatment. Furthermore, melatonin inhibited neointima formation increasing TSP-1 expression. The ability of melatonin to inhibit neointima formation suggests that it could be a useful treatment for homeostasis of vascular walls.

The Juxtaoral Organ: From Anatomy to Clinical Relevance.

The juxtaoral organ was first described 1885 as a rudimentary structure that developed and disappeared in the embryonic period. Since then, it has been studied further and is now known to be a permanent anatomical structure of considerable importance in clinical, surgical and pathological fields. However, there are no precise and uniform descriptions about its anatomical localization and functional significance. Precise and in-depth anatomical knowledge is crucial to reducing the risk of incorrect identification of the juxtaoral organ, due to fact that this anatomical structure can be misinterpreted as a carcinoma, leading to unnecessary treatments. Therefore, the purpose of this review is to summarize the actual knowledge on the gross and microscopic anatomy of the juxtaoral organ and outline its clinical relevance in order to prevent unnecessary investigations/treatments of this anatomical pitfall. We believe that further studies are still needed to add new perspectives in relation to the juxtaoral organ.

Concentrated Growth Factors (CGF) Combined with Melatonin in Guided Bone Regeneration (GBR): A Case Report.

During implant restorative dentistry, common and crippling postoperative complications are pain and swelling of perioral soft tissues which engraving on patient quality of life. Concentrated growth factors (CGF), a novel generation of autologous platelet concentrate, and melatonin, endogenous indoleamine with also bone regenerative properties, may be useful for reconstruction of bony defects as well as in prosthetic and esthetic rehabilitation. We report a clinical case in which guided bone regeneration was performed combining CGF, melatonin and heterologous biomaterial. Great postoperative recovery without any complications was reported. In conclusion, in restorative dentistry the combined use of CGF and melatonin may have important roles in restoring bone defect, in improving implant osteointegration and, not less important, in preventing postoperative complications.

Peripheral Purinergic Modulation in Pediatric Orofacial Inflammatory Pain Affects Brainstem Nitroxidergic System: A Translational Research.

Physiology of orofacial pain pathways embraces primary afferent neurons, pathologic changes in the trigeminal ganglion, brainstem nociceptive neurons, and higher brain function regulating orofacial nociception. The goal of this study was to investigate the nitroxidergic system alteration at brainstem level (spinal trigeminal nucleus), and the role of peripheral P2 purinergic receptors in an experimental mouse model of pediatric inflammatory orofacial pain, to increase knowledge and supply information concerning orofacial pain in children and adolescents, like pediatric dentists and pathologists, as well as oro-maxillo-facial surgeons, may be asked to participate in the treatment of these patients. The experimental animals were treated subcutaneously in the perioral region with pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), a P2 receptor antagonist, 30 minutes before formalin injection. The pain-related behavior and the nitroxidergic system alterations in the spinal trigeminal nucleus using immunohistochemistry and western blotting analysis have been evaluated. The local administration of PPADS decreased the face-rubbing activity and the expression of both neuronal and inducible nitric oxide (NO) synthase isoforms in the spinal trigeminal nucleus. These results underline a relationship between orofacial inflammatory pain and nitroxidergic system in the spinal trigeminal nucleus and suggest a role of peripheral P2 receptors in trigeminal pain transmission influencing NO production at central level. In this way, orofacial pain physiology should be elucidated and applied to clinical practice in the future.

Critical Role of NFκB in the Pathogenesis of Non-alcoholic Fatty Liver Disease: A Widespread Key Regulator.

Non-alcoholic fatty liver disease is a chronic metabolic disorder representing the most common cause of chronic liver disease in western civilization and one of the main causes of cirrhosis with a significant impact on all-cause mortality in the most advanced phases. It is characterized by hepatic fat accumulation in the absence of significant ethanol consumption, virus infection or other specific causes of liver disease. Accumulation of fat in liver tissue occurs as a consequence of the imbalance between overconsumption of high-fat diet and increased de novo lipogenesis and decreased lipid disposal. Novel dietary and pharmacological therapies for the prevention of fatty liver disease and the progression to cirrhosis are an actual field of study but still poorly understood. In this perspective, the current review aims to summarise and clarify the transcription factor NFκB effects, which may exert among non-alcoholic fatty liver diseases and their progression. Through extensive previous research, it has become clear that several signaling pathways are involved: metabolic dysregulation (such as free fatty acids increase, adipokine alteration, insulin resistance), oxidative stress and inflammation contribute together in a "vicious circle" to the pathogenesis of non-alcoholic fatty liver diseases. Within this, NFκB signaling is a primary factor in inflammatory reactions and diseases, with important molecular connections between metabolic, oxidative, immune and inflammation systems.

A new landmark for lingual artery identification during transoral surgery: Anatomic-radiologic study.

BACKGROUND: A landmark for the identification of the lingual artery (LA) through a transoral perspective can provide surgeons with an easy method to prevent and manage intraoperative bleeding during transoral approach to the base of tongue (BOT). METHODS: Thirteen tongue and five head and neck specimens were dissected to identify and assess the reliability of the lingual point (LP) as a new landmark for the LA at BOT. The pathway of 42 LAs was radiologically evaluated; axial depth and vertical offset were measured for each LA. RESULTS: Dissection study: a description of LP is provided; the LA was easily identified in all specimens (36/36 sides) using LP as a landmark. Radiologic study: the mean depth of the LA was 4.2 mm, the mean vertical offset was 1.3 mm. CONCLUSIONS: LP is a simple and reliable landmark for identification of the LA, potentially helping surgeons to prevent and manage intraoperative bleeding.

Step-by-Step Cadaver Dissection and Surgical Technique for Compartmental Tongue and Floor of Mouth Resection.

BACKGROUND: The aim of oral cancer surgery is tumor removal within clear margins of healthy tissue: the latter definition in the literature, however, may vary between 1 and 2 cm, and should be intended in the three dimensions, which further complicates its precise measurement. Moreover, the biological behavior of tongue and floor of mouth cancer can be unpredictable and often eludes the previously mentioned safe surgical margins concept due to the complexity of tongue anatomy, the intricated arrangements of its intrinsic and extrinsic muscle fibers, and the presence of rich neurovascular and lymphatic networks within it. These structures may act as specific pathways of loco-regional tumor spread, allowing the neoplasm to escape beyond its visible macroscopic boundaries. Based on this concept, in the past two decades, compartmental surgery (CS) for treatment of oral tongue and floor of mouth cancer was proposed as an alternative to more traditional transoral resections. METHODS: The authors performed three anatomical dissections on fresh-frozen cadaver heads that were injected with red and blue-stained silicon. All procedures were documented by photographs taken with a professional reflex digital camera. RESULTS: One of these step-by-step cadaver dissections is herein reported, detailing the pivotal points of CS with the aim to share this procedure at benefit of the youngest surgeons. CONCLUSIONS: We herein present the CS step-by-step technique to highlight its potential in improving loco-regional control by checking all possible routes of tumor spread. Correct identification of the anatomical space between tumor and nodes (T-N tract), spatial relationships of extrinsic tongue muscles, as well as neurovascular bundles of the floor of mouth, are depicted to improve knowledge of this complex anatomical area.