Τετάρτη 29 Σεπτεμβρίου 2021

An Endoscopic Endonasal Nasopharyngectomy with Posterolateral Extension

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J Neurol Surg B Skull Base
DOI: 10.1055/s-0041-1735557

Background Invasion depth influences the choice for extirpation of nasopharyngeal malignancies. This study aims to validate the feasibility of endoscopic endonasal resection of lesions with a posterolateral invasion. As a secondary goal, the study intends to propose a classification system of endoscopic endonasal nasopharyngectomy determined by the depth of posterolateral invasion. Methods Eight cadaveric specimens (16 sides) underwent progressive nasopharyngectomy using an endoscopic endonasal approach. Resection of the torus tubarius, Eustachian tube (ET), medial pterygoid plate and muscle, lateral nasal wall, and lateral pterygoid plate and muscle were sequentially performed to expose the fossa of Rosenmüller, petroclival region, parapharyngeal space (PPS), and jugular foramen, respectively. Results Technical feasibility of endonasal nasopharyngectomy toward a posterolateral direction was validated in all 16 sides. Nasopharyngectomy was classified into four types as follows: (1) type 1: resection restricted to the posterior or superior nasopharynx; (2) type 2: resection includes the torus tubarius which is suitable for lesions extended into the petroclival region; (3) type 3: resection includes the distal cartilaginous ET, medial pterygoid plate, and muscle, often required for lesions extending laterally into the PPS; And (4) type 4: resection includes the lateral nasal wall, pterygoid plates and muscles, and all the cartilaginous ET. This extensive resection is required for lesions involving the carotid artery or extending to the jugular foramen region. Conclusion Selected lesions with posterolateral invasion into the PPS or jugular foramen is amenable to a resection via expanded endonasal approach. Classification of nasopharyngectomy based on tumor depth of posterolateral invasion helps to plan a surgical approach.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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Treatment Modality and Second Primary Tumors of the Head and Neck

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Introduction: Second primary tumors (SPTs) in head and neck cancer are thought to occur from premalignant lesions that are present at the time of the primary tumor diagnosis. The association of the modality used to treat the primary lesion with SPT occurrence is not clear. Objective: The aim of the study was to assess the incidence of SPTs in patients with head and neck malignancies, according to treatment modality. Methods: We conducted a retrospective cohort study. All patients who were treated at Soroka Medical Cente r between 2000 and 2013 for a head and neck squamous cell carcinoma were assessed. Data analysis included tumor site of the primary and second primary and treatment modality of the primary tumor. In addition, demographics as well as habits were recorded as well. Results: Of the 184 patients included in the cohort, SPT developed in 31 patients (17%) with a median time to diagnosis of 4.3 years. Smoking was reported in 74% of those with SPT and 78% of those without. The most common site for SPT was the lungs, with 13 cases, 42% of the total SPTs. Among patients who developed an SPT, for 12 of those with an index tumor in the oral cavity or oro-hypopharynx, 8 (67%) developed an SPT in the same location; for 18 of those with an index tumor in the larynx, 11 (61%) developed a SPT in the lungs and bronchi (p = 0.001). On multivariate analysis, the treatment modality used was not found to be associated with the occurrence of SPTs and the radiotherapy showed no protecti ve or harmful effect (HR 0.64 p = 0.24). Conclusion: Treatment modality used for head and neck cancer does not seem to be associated with the occurrence of SPTs.
ORL
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Superior Semicircular Canal Dehiscence Revision Surgery Outcomes: A Single Institution's Experience

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World Neurosurg. 2021 Sep 25:S1878-8750(21)01426-1. doi: 10.1016/j.wneu.2021.09.083. Online ahead of print.

ABSTRACT

BACKGROUND: Superior semicircular canal dehiscence (SSCD) is an abnormality of the otic capsule which normally overlies the superior semicircular canal. Surgical management is indicated in patients with persistent and debilitating symptoms. Given the complexity of the disease, there are patients who experience less favorable surgical outcomes and require revision surgery. The purpose of this study was to report to the rate of postoperative symptomatic improvement in patients who required revision surgery.

METHODS: A retrospective analysis of patients undergoing SSCD surgical repair at a single institution was performed. Information on patient demographics, primary and secondary surgical approaches, surgical outcomes, and follow-up length was collected.

RESULTS: 17 patients underwent 20 revision surgeries. There were eleven (65%) females and six (35%) males. Mean age of the cohorts was 50 years (range 30-68 years), and mean follow-up length was 6.8 months (range 0.1-31.1 months). Cerebrospinal fluid (CSF) leak was noted in 67% of cases. The greatest postoperative symptomatic resolution was reported in oscillopsia (100%), headache (100%), and internal sound amplification (71%), while the least postoperative symptomatic resolution was reported in tinnitus (42%), aural fullness (40%), and dizziness (29%).

CONCLUSION: Revision surgery can provide symptomatic improvement in select SSCD patients; however, patients should be cautioned about the possibility of less favorable outcomes than in index surgery. Revision surgeries are associated with a considerably higher rate of perioperative CSF leak.

PMID:34583007 | DOI:10.1016/j.wneu.2021.09.083

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Ultra-high-frequency ultrasound monitoring of melanomas arising in congenital melanocytic nevi: a case series

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The aims of our study were to evaluate with ultra-high-frequency ultrasound (UHFUS) the ultrasound features of congenital melanocytic nevi (CMNs) and malignant melanomas (MMs) arising in CMNs and the correlation between ultrasonographic thickness and histological thickness in MMs. We evaluated 10 patients with small-medi um CMNs and 10 patients with MMs arising in small-medium CMNs. We collected patient's data, clinical and dermoscopic features. The UHFUS was performed using a 70 MHz frequency probe to study the ecostructure, shape and vascularization. Breslow thickness was compared with ultrasonographic thickness. In the MMs group the following dermoscopic features were described: hyperpigmentation (n = 9), regression area (n = 6), whitish-blue veil (n = 5), thickened network (n = 5), irregular globules (n = 3), inverse network (n = 2) and striae (n = 1). Hyperpigmentation (n = n = 9), thickened network (n = 7), irregular globules (n = 5), regression area (n = 5), striae (n = 1) and whitish-blue veil (n = 1) were found in the CMNs group. The multicomponent pattern was present in both MMs (n = 4) and in CMNs (n = 5). Moreover, the parameters indicative of suspected malignancy were variously combined in the two groups, without showing significant differences in the statistical analysis; with the ex ception of the blue veil that correlated with the diagnosis of MM. Ultrasonoghaphic vascularization was an ever-present parameter in MMs (100%), with high intensity of intratumoral signal, as opposed to CMNs. We also found a statistically significant correlation between ultrasound thickness and Breslow thickness. In the future, this technique could implement the diagnostic preoperative phase of MMs arising in CMNs in combination with standard clinical-dermatoscopic evaluation. Received 20 May 2021 Accepted 22 August 2021 Correspondence to Agata Janowska, MD, Department of Dermatology, University of Pisa, Via Roma 67, 56127, Pisa, Italia, Tel: +39 050 992436; fax: +39 050 992556; e-mail: dottoressajanowska@gmail.com Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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The potential of using artificial intelligence to improve skin cancer diagnoses in Hawai‘i’s multiethnic population

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Skin cancer remains the most commonly diagnosed cancer in the USA with more than 1 million new cases each year. Melanomas account for about 1% of all skin cancers and most skin cancer deaths. Multiethnic individuals whose skin is pigmented underestimate their risk for skin cancers and melanomas and may delay seeking a diagnosis. The use of artificial intelligence may help improve the diagnostic precision of dermatologists/physicians to identify malignant lesions. To validate our artificial intelligence's efficiency in distinguishing between images, we utilized 50 images obtained from our International Skin Imaging Collaboration dataset (n = 25) and pathologically confirmed lesions (n = 25). We compared the ability of our artificial intelligence to visually diagnose these 50 skin cancer lesions with a panel of three dermatologists. The artificial intelligence model better differentiated between melanoma vs. nonmelanoma with an area under the curve of 0.948. The three-panel member dermatologists correctly diagnosed a similar number of images (n = 35) as the artificial intelligence program (n = 34). Fleiss' kappa (ĸ) score for the raters and artificial intelligence indicated fair (0.247) agreement. However, the combined result of the dermatologists panel with the artificial i ntelligence assessments correctly identified 100% of the images from the test data set. Our artificial intelligence platform was able to utilize visual images to discriminate melanoma from nonmelanoma, using de-identified images. The combined results of the artificial intelligence with those of the dermatologists support the use of artificial intelligence as an efficient lesion assessment strategy to reduce time and expense in diagnoses to reduce delays in treatment. Received 1 March 2021 Accepted 6 August 2021 Correspondence to Mark Lee Willingham Jr., MS, Department of Sociology, Community Health Educator, University of Hawai'i Cancer Center, 701 Ilalo St., Suite #414, Honolulu, HI 96813, Hawai'i, USA, Tel: 1 808 441 8186; fax: 1 808 586 3052; e-mail: Mlw237@hawaii.edu Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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A novel prognostic biomarker for cutaneous malignant melanoma: red cell distribution width (RDW) to lymphocyte ratio

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It is well-known that inflammation plays a significant role in cancer formation and prognosis. Both lymphocyte count and red cell distribution width (RDW) has been used to predict prognosis in various cancers as an indicator of inflammation. Yet, the role of RDW-lymphocyte ratio (RLR) in determining prognosis is still unkn own. We aimed to determine the prognostic role of RLR in cutaneous malignant melanoma (MM). One hundred fifteen patients with MM were included in the study retrospectively. The relationship of the clinical-pathological data with overall survival (OS) and progression-free survival (PFS) was analyzed using Kaplan–Meier curves. The cut-off values of neutrophil to lymphocyte ratio, systemic immune-inflammation index (SII), prognostic nutritional index (PNI) and RLR were determined as 2, 487, 51.5 and 6.52, respectively. OS was significantly longer in the low SII, high PNI, low RLR group, while PFS was longer in groups with high PNI and low RLR. In univariate analysis, it was determined that PFS was significantly correlated with Eastern Cooperative Oncology Group (ECOG) performance, TNM stage, PNI and RLR. Moreover, in univariate analysis, a significant correlation was determined between OS and age, ECOG performance, TNM stage, adjuvant interferon, SII, PNI and RLR. In multivariate ana lysis, ECOG performance, TNM stage and RLR were determined as independent prognostic factors for PFS, while TNM stage and RLR were found to be independent prognostic factors for OS. RLR could be a novel prognostic marker for both PFS and OS in patients with cutaneous MM. Received 15 June 2021 Accepted 4 September 2021 Correspondence to Zekeriya Hannarici, Department Of Medical Oncology, Atatürk University Faculty of Medicine, Yakutiye, Erzurum 25100, Turkey, Tel: +905303768489; e-mail: hannarici@hotmail.com Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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Risk factors in pediatric melanoma: a retrospective study of 39 cases

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Pediatric melanoma is a rare form of the tumor whose epidemiology is widely increasing thanks to the improvement of dermoscopic and anatomopathologic diagnostic techniques. Although it is a tumor of considerable interest in adults, little has been described about the pediatric field. The objective of our study was then to ident ify the possible risk factors for the development of melanoma in the pediatric population. We performed a retrospective study conducted in the Melanoma and Skin Cancer Unit and Unit of Dermatology (Livorno, Italy). We analyzed a population of 38 children under 21 years with a diagnosis of melanoma. This population was compared with a control population of 114 children followed up in our dermatologic clinic. From our combined univariate-multivariate statistics analysis, the number of nevi [regression coefficient (RC) of 1.04 and odds ratio (OR) of 2.8 confidence interval (Cl, 1.2–6.6)], and family history of melanoma [RC of 1.99 and OR of 7.3 (Cl, 2.3–22.7)] emerged as possible risk factors for the development of melanoma. The identification of these elements would allow the physician to carry out a more targeted preliminary assessment of the patient, potentially decisive in cases of diagnostic doubt of the lesion. Our study also lays the foundations for identifying those child ren who, despite not having received a diagnosis of melanoma on histologic examination, should be considered as patients susceptible to a focused follow-up, because of the presence of the risk factors that emerged from our research. Received 16 June 2021 Accepted 3 August 2021 Correspondence to Giovanni Bagnoni, MD, Melanoma and Skin Cancer Unit AVNO (Area Vasta Nord Ovest) and Unit of Dermatology, Specialist Surgery Area, Department Of General Surgery, Livorno Hospital, Viale Vittorio Alfieri 36, Livorno, LI 57124, Italy, Tel: +39 0586 223243; e-mail: giovanni.bagnoni@uslnordovest.toscana.it Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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AREL1 E3 ubiquitin ligase inhibits TNF-induced necroptosis via the ubiquitination of MTX2

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Exp Ther Med. 2021 Nov;22(5):1195. doi: 10.3892/etm.2021.10629. Epub 2021 Aug 20.

ABSTRACT

Previously, we reported on a novel anti-apoptotic E3 ubiquitin ligase, apoptosis-resistant E3 ubiquitin protein ligase 1 (AREL1), that ubiquitinates inhibitors of apoptosis proteins antagonists. The present study demonstrated that AREL1 ubiquitinated Metaxin 2 (MTX2), which was involved in TNF-induced necroptosis. MTX2 has been identified as a protein that belongs to the Metaxin family. It interacts with another Metaxin protein, Metaxin 1 (MTX1), which is localized in the outer membrane of mitochondria, and is involved in TNF-induced necroptosis. This study found that AREL1 interacted with MTX2, but not MTX1, while the amino-terminal domain of MTX2 interacted with MTX1, AREL1 interacted with the carboxyl-terminal domain of MTX2. Furthermore, AREL1 expression led to a decrease in the protein expression of MTX2, but not MTX1. However, a mutant form of AREL1, AREL1C790A, which is deficient for E3 activity, did not cause MTX2 degradation. Moreover, the protein levels of MTX2 were increased by AREL1 knockdown. Therefore, these results implied that AREL1 ubiquitinates and promotes the degradation of MTX2. The expression of MTX2, together with MTX1, enhanced TNF-induced necroptosis. However, AREL1 inhibited necroptosis even in cells expressing Metaxin proteins. Therefore, these results suggested that the inhibition of AREL1-dependent ubiquitination of MTX2 could be beneficial to sensitize tumor cells to TNF-induced necroptosis.

PMID:34584540 | PMC:PMC8422393 | DOI:10.3892/etm.2021.10629

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hsa-miR-15b-5p regulates the proliferation and apoptosis of human vascular smooth muscle cells by targeting the ACSS2/PTGS2 axis

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Exp Ther Med. 2021 Nov;22(5):1208. doi: 10.3892/etm.2021.10642. Epub 2021 Aug 24.

ABSTRACT

A previous bioinformatic analysis from our group predicted that the interaction of microRNA (miRNA/miR)-15b with the acyl-CoA synthetase short chain family member 2 (ACSS2) gene was important for the development of abdominal aortic aneurysm (AAA). Apoptosis of aortic vascular smooth muscle cells (VSMCs) is a pathological feature of AAA. The present study aimed to explain the roles of miR-15b/ACSS2 in AAA by exploring their effects on the proliferation and apoptosis of aortic VSMCs. Human aortic VSMCs (T/G HA-VSMC cell line) were divided into six groups and were transfected with miR-15b-5p mimics, mimic negative control (NC), miR-15b-5p inhibitors, inhibitor NC, miR-15b-5p mimics+pcDNA3.1 and miR-15b-5p mimics+ACSS2-overexpessing vector. CCK-8 assay was used to determine cell proliferation. Annexin V-FITC/PI staining and flow cytometry assays were used to measure cell apoptosis. Dual-luciferase reporter assays were used to confirm the targeted relationship between miR-15b-5p and ACSS2. Reverse transcription-quantitative PCR and/or western blotting were used to examine the expression levels of miR-15b-5p, ACSS2 and prostaglandin-endoperoxide synthase 2 (PTGS2). Following transfection of T/G HA-VSMCs with mimics and inhibitors to respectively upregulate and downregulate miR-15b-5p, the results demonstrated that overexpression of miR-15b-5p inhibited cell proliferation and promoted cell apoptosis; silencing of miR-15b-5p obtained the opposite results. ACSS2 may be a direct target of miR-15b-5p, since the luciferase activity of a ACSS2 wild-type vector, but not that of a ACSS2 mutant reporter, was significantly inhibited by miR-15b-5p mimics compared with controls. Additionally, the expression levels of ACSS2 and its downstream gene PTGS2 were significantly reduced or increased following transfection with miR-15b-5p mimics or in hibitors, respectively. Furthermore, overexpression of ACSS2 reversed the antiproliferative and proapoptotic effects of miR-15b-5p mimics by blocking the production of PTGS2 protein. In conclusion, miR-15b-5p may promote the apoptosis and inhibit the proliferation of aortic VSMCs via targeting the ACSS2/PTGS2 axis. The present study provided preliminary evidence indicating that the miR-15b-5p/ACSS2/PTGS2 axis may be a potential target for the treatment of AAA.

PMID:34584553 | PMC:PMC8422401 | DOI:10.3892/etm.2021.10642

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HBxAg promotes HBV replication and EGFR activation in human placental trophoblasts

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Exp Ther Med. 2021 Nov;22(5):1211. doi: 10.3892/etm.2021.10645. Epub 2021 Aug 24.

ABSTRACT

Hepatitis B virus (HBV) infection is a global epidemic. The main transmission route of chronic HBV infection is from mother to child, yet the mechanisms underlying HBV intrauterine infection remain unclear. In the present study, the effect and the mechanism underlying hepatitis B virus X antigen (HBxAg) on HBV replication and EGFR activation in trophoblasts was investigated. Serum samples from pregnant women with HBV infection were used to infect trophoblasts and HBxAg expression was detected using ELISA. HBV plasmids carrying either full length hepatitis B virus X (HBx) or HBx with a deletion mutation (ΔHBx) were transfected into trophoblasts and expression levels of HBV DNA, hepatitis B e-antigen and pregenomic (pg)RNA, and structural maintenance of chromosomes (Smc) 5/6 were assessed. The association between HBx and EGFR promoters was charact erized using a luciferase reporter assay and EGFR/PI3K/phosphorylated (p)-AKT expression and apoptosis rate were also monitored. The results of the present study indicated that HBxAg expression increased with the increasing titre of HBV DNA (P<0.05). Compared with the wild-type group, the amount of HBV DNA in the supernatant and cells was significantly reduced (P<0.05) in the ΔHBx group and the intracellular HBeAg and pgRNA levels were also significantly decreased (P<0.05). In addition, Smc5/6 expression was also significantly decreased (P<0.05) when the intracellular HBx protein was expressed compared with mock-transfected cells. Co-transfection of HBx and EGFR promoter plasmids in JEG-3 and HTR-8 cells significantly elevated EGFR promoter driven luciferase expression relative to the control group (P<0.01). In EGFR overexpressing cells, the expression of PI3K/p-AKT was significantly increased, whereas the apoptosis rate was significantly decreased (P<0.05). These results were reversed in the EGFR-knockdown group. In conclusion, the present study demonstrated that HBx promotes HBV replication in trophoblasts via downregulation of Smc5/6, activates the EGFR promoter and inhibits trophoblast apoptosis via the PI3K/p-AKT downstream signalling pathway, thereby increasing the risk of HBV intrauterine infection.

PMID:34584556 | PMC:PMC8422389 | DOI:10.3892/etm.2021.10645

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