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Αλέξανδρος Γ. Σφακιανάκης

Thursday, December 2, 2021

Clinical features, molecular characteristics and surgical management of primary penile mucosal melanoma based on the European Association of Urology Penile Cancer Guidelines

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Penile mucosal melanoma is an aggressive and rare genital malignancy. The aim of the present study was to review the management and outcomes of a homogenous cohort of patients with histologically confirmed penile mucosal melanoma, at a single specialist centre. A retrospective review of an institutional database ident ified patients with penile mucosal melanoma over a 10-year period. Patient demographics, histopathological characteristics, type of primary surgery, recurrence, presence of metastatic disease and molecular markers were evaluated. The management of the patients was initially based on the European Association of Urology (EAU) penile cancer guidelines which are primarily for squamous cell carcinoma with inputs from a melanoma multidisciplinary team. Twelve patients with penile mucosal melanoma were analysed. Median [interquartile range (IQR)] age was 69.5 (67.25−81) years. The overall median follow-up (IQR) was 69.5 (20−114) months, while median follow-up for cancer-specific survival (CSS) was 11.5 (8−37) months. Location of primary tumour was glans penis (n = 7), urethra (n = 2) and inner prepuce (n = 3). The CSS at 1, 2 and 5 years after primary surgery was 33%, 16.7% and 0%, respectively. The recurrence-free survival at 1, 3 and 5 months after the primary surge ry was 90%, 67% and 56%, respectively. All patients with metastatic disease or with inguinal lymph node invasion at presentation, died within 25 months of the primary diagnosis. Management based on the modified EAU penile cancer guidelines still led to poor outcomes. We present a management diagram based on our experience. Received 6 June 2021 Accepted 18 September 2021 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.melanomaresearch.com. Correspondence to Asif Muneer, MD, FRCS (Urol), Division of Surgery and Interventional Science, NIHR Biomedical Research Centre, University College London Hospital, University College London, 235 Euston Rd, London NW1 2BU, UK, Tel: +44 0203 447 9280; e-mail: asif.muneer@nhs.net Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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Evaluation of human acellular amniotic membrane for promoting anterior auricle reconstruction

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Long‐term hearing performance and soft tissue outcomes of the Baha® Attract system in patients with bilateral congenital microtia in a single centre

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Abstract

The Baha® Attract system can provide effective and stable hearing amplification for patients with microtia.

Concurrent surgeries of auricle reconstruction and Baha® Attract implantation do not result in more soft tissue complications.

The number of adverse events increased with the duration of implantation, even one year postoperatively.

Benign skin evolutions, including skin thinning and erythema at the implant side, are commonly seen in Baha® Attract users.

Implants are not necessarily removed when skin necrosis occurs in Baha® Attract users.

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The Liverpool Experience: The Role of Immunosuppression in treating Vasculitic Subglottic Stenosis

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Abstract

Subglottic stenosis (SGS) is the commonest tracheobronchial manifestation of granulomatosis with polyangiitis (GPA), with early recognition and treatment key to preventing its vasculitic progression and fibrosis.

Previous studies have shown SGS to be the first feature of GPA in 4% of cases. It is not uncommon to see negative immunological (10% ANCA negative) and non-specific histological biopsies (77% of head and neck specimens).

Our management strategy emphasized rapid SGS-GPA treatment with limited surgical manipulation of the airway and systemic immunosuppression (IS) to prevent evolution of SGS & concurrent systemic vasculitic relapse.

In our study early multi-disciplinary team involvement to deliver induction IS in the presence of active SGS-GPA led to a procedure free interval (PFI) of 33.3 months. This is a significant increase compared to other published studies.

20% (4/20) of the cohort did not require any surgical input following induction IS during the study's timeframe.

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The effect of radioiodine treatment on the characteristics of TRAb in Graves' disease

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BMC Endocr Disord. 2021 Nov 30;21(1):238. doi: 10.1186/s12902-021-00905-4.

ABSTRACT

BACKGROUND: Graves' disease (GD) is one of the most common autoimmune thyroid diseases (AITDs) in humans, and thyrotropin receptor antibody (TRAb) is a characterized autoantibody in GD. The use of radioactive iodine therapy (RAI) for GD treatment is increasing.

OBJECTIVES: We studied the biological properties of TRAb and evaluated the effect of RAI therapy on TRAb in GD patients.

METHODS : In total, 225 patients (22 onset GD patients without 131I therapy, 203 GD patients treated with 131I therapy) and 20 healthy individuals as normal controls were included in this study. Clinical assessments were performed, and we examined in vitro the biological properties of TRAb in the 22 onset GD patients and 20 controls as well as 84 GD patients with 131I therapy.

RESULTS: Serum TRAb and thyroid peroxidase antibody (TPOAb) levels increased in the initial year of RAI treatment, and both antibodies decreased gradually after one year. After 5 years from radioiodine treatment, TRAb and TPOAb levels decreased in 88% and 65% of GD patients, respectively. The proportion of patients positive for thyroid-stimulatory antibody (TSAb) was significantly higher in the 7-12-month group, and thyroid-blocking antibody (TBAb) levels were elevated after one year in half of the patients who received 131I treatment.

CONCLUSIONS: Treatment of G D patients with radioiodine increased TPOAb and TRAb (their main biological properties were TSAbs) within the first year after therapy, and the main biological properties of elevated TRAb were TBAbs after 1 year.

PMID:34847904 | DOI:10.1186/s12902-021-00905-4

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Spheroids to organoids: Solid cancer models for anticancer drug discovery

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Bull Cancer. 2021 Nov 27:S0007-4551(21)00443-4. doi: 10.1016/j.bulcan.2021.09.019. Online ahead of print.

ABSTRACT

Cell culture is an important and necessary technology in oncology research. Currently, two-dimensional (2D) cell culture models are the most widely used, but they cannot reproduce the complexity and pathophysiology of tumors in vivo. This may be a major cause of the high rate of attrition of anticancer drugs entering clinical trials, the rate of new anticancer drugs entering the market being less than 5 %. One way to improve the success of new cancer drugs in the clinic is based on the use of three-dimensional (3D) cell culture models, more able to represent the complex environment and architecture of tumors. These 3D culture systems are also a powerful research tool for modeling the evolution of cancer from early stages to metastasis. Spheroids and organoids, the most adaptable models among 3D culture systems, are beginni ng to be used in pharmaceutical research and personalized medicine. In this article, we review the use of spheroids and organoids by highlighting their differences, discussing their impact on drug development, and looking at future challenges.

PMID:34848046 | DOI:10.1016/j.bulcan.2021.09.019

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The management of multimorphic cancer pain, from diagnosis to treatment

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Bull Cancer. 2021 Nov 27:S0007-4551(21)00395-7. doi: 10.1016/j.bulcan.2021.08.013. Online ahead of print.

ABSTRACT

Cancer pain remains a major public health issue. Despite progress in pain medicine thanks to the interest shown in early and timely supportive care, more than half the patients managed for cancer are in pain. One of the key factors in high quality multidisciplinary management throughout the care pathway is to assess more than just pain: it is necessary to assess the patient as a whole. Understanding the complexity of cancer pain - or the various types of pain - through the innovative multimorphic cancer pain model, effectively opens up new perspectives for a targeted, personalised, and multimodal approach. The subsequent treatment strategies, whether drug-based with opioids, or interventional, are codified by guidelines based on scientific evidence for the healthcare professionals and, ultimately, patients.

PMID:34848047 | DOI:10.1016/j.bulcan.2021.08.013

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New MAA: First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma

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Bull Cancer. 2021 Nov 27:S0007-4551(21)00437-9. doi: 10.1016/j.bulcan.2021.09.013. Online ahead of print.

NO ABSTRACT

PMID:34848048 | DOI:10.1016/j.bulcan.2021.09.013

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Evaluation of burned hand function after enzymatic debridement

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J Plast Reconstr Aesthet Surg. 2021 Oct 22:S1748-6815(21)00517-9. doi: 10.1016/j.bjps.2021.09.074. Online ahead of print.

ABSTRACT

Hand burns are common injuries that can result in long-term impairment of hand function. Enzymatic debridement (ED) prevents damage to the viable dermis due to the procedure's selectivity and has become an option for obtaining an accurate depth assessment and enabling wound re-epithelialization with less skin graft use. We conducted a prospective study from July 2015 to July 2018, which enrolled patients with deep partial-thickness hand burns and treated them with ED using bromelain. After a specified period, we assessed the patients' hand function, using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and the Michigan Hand Outcomes Questionnaire (MHOQ) to assess their disabilities and activities of daily life, respectively. We assessed the hand joint range of motion using a goniometer a nd assessed scar quality with the Vancouver Scar Scale (VSS). We analyzed 72 patients with 90 burned hands at 3 months and, at the final assessment, 69 patients with 86 burned hands. Fire was the most common cause of the burns. Bromelain allowed for early debridement (73.6% during the first 24 h). At the 3-month evaluation, the mean DASH and MHOQ scores were 2.35 and 97.9%, respectively, with a high inverse correlation between the 2 types of scores (Spearman's rho, -0.78; p < .001). The mean wrist flexion and extension were 85.7 and 80°, respectively, the mean metacarpophalangeal flexion was 88.3°, the proximal interphalangeal (PIP) flexion was 112.9°, and the thumb opposition was 77°. The mean VSS score was 2.87. At the final evaluation, with a minimum follow-up of 391 days, the mean DASH and MHOQ scores were 0.18 and 99.71%, respectively. ED with bromelain in deep partial-thickness hand burns resulted in normal values at 3 months and at over 1 year of follow-up, with comple te restoration of function and quality of life and good scar results.

PMID:34848129 | DOI:10.1016/j.bjps.2021.09.074

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Six-dimensional dynamic tractography atlas of language connectivity in the developing brain

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Brain. 2021 Nov 29:awab225. doi: 10.1093/brain/awab225. Online ahead of print.

ABSTRACT

During a verbal conversation, our brain moves through a series of complex linguistic processing stages: sound decoding, semantic comprehension, retrieval of semantically coherent words, and overt production of speech outputs. Each process is thought to be supported by a network consisting of local and long-range connections bridging between major cortical areas. Both temporal and extratemporal lobe regions have functional compartments responsible for distinct language domains, including the perception and production of phonological and semantic components. This study provides quantitative evidence of how directly connected inter-lobar neocortical networks support distinct stages of linguistic processing across brain development. Novel six-dimensional tractography was used to intuitively visualize the strength and temporal dynamics of direct inter-lobar eff ective connectivity between cortical areas activated during each linguistic processing stage. We analysed 3401 non-epileptic intracranial electrode sites from 37 children with focal epilepsy (aged 5-20 years) who underwent extra-operative electrocorticography recording. Principal component analysis of auditory naming-related high-gamma modulations determined the relative involvement of each cortical area during each linguistic processing stage. To quantify direct effective connectivity, we delivered single-pulse electrical stimulation to 488 temporal and 1581 extratemporal lobe sites and measured the early cortico-cortical spectral responses at distant electrodes. Mixed model analyses determined the effects of naming-related high-gamma co-augmentation between connecting regions, age, and cerebral hemisphere on the strength of effective connectivity independent of epilepsy-related factors. Direct effective connectivity was strongest between extratemporal and temporal lobe site pairs, which were simultaneously activated between sentence offset and verbal response onset (i.e. response preparation period); this connectivity was approximately twice more robust than that with temporal lobe sites activated during stimulus listening or overt response. Conversely, extratemporal lobe sites activated during overt response were equally connected with temporal lobe language sites. Older age was associated with increased strength of inter-lobar effective connectivity especially between those activated during response preparation. The arcuate fasciculus supported approximately two-thirds of the direct effective connectivity pathways from temporal to extratemporal auditory language-related areas but only up to half of those in the opposite direction. The uncinate fasciculus consisted of <2% of those in the temporal-to-extratemporal direction and up to 6% of those in the opposite direction. We, for the first time, provided an atlas which quantifies and animates the strength , dynamics, and direction specificity of inter-lobar neural communications between language areas via the white matter pathways. Language-related effective connectivity may be strengthened in an age-dependent manner even after the age of 5.

PMID:34849596 | DOI:10.1093/brain/awab225

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CircAKT3 promotes cell proliferation, survival and glutamine metabolism of gastric cancer by activating SLC1A5 expression via targeting miR-515-5p

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Histol Histopathol. 2021 Dec 1:18401. doi: 10.14670/HH-18-401. Online ahead of print.

ABSTRACT

BACKGROUND: Gastric cancer (GC) is a common disorder in the population. Numerous studies have reported that the pathogenesis of GC is implicated in the dysregulation of circular RNAs (circRNAs). The aim of this study was to investigate the role and functional mechanism of circ_0000199 (circAKT3) in GC.

METHODS: The expression of circAKT3, miR-515-5p and solute carrier family 1 member 5 (SLC1A5) mRNA was measured by quantitative real-time PCR (qPCR). Cell proliferation was assessed by cell counting kit-8 (CCK-8) assay, colony formation assay and 5-ethynyl-2'-deoxyuridine (EdU) assay. Cell apoptosis was determined by flow cytometry assay and caspase 3/7 activity. The protein levels of glutaminase (GLS), proliferating cell nuclear antigen (PCNA) and cleaved-caspase3 were detected by western blot. The binding relationship between miR-515-5p and circAKT3 or SLC1A5 was verified by dual-luciferase reporter assay or RIP assay. The role of circAKT3 in vivo was investigated by establishing animal models. The abundance of Ki-67 and PCNA was detected by IHC assay.

RESULTS: The expression of circAKT3 in GC tissues and cells was enhanced. The knockdown of circAKT3 inhibited GC cell proliferation, survival and glutamine metabolism, as well as tumor growth in animal models. MiR-515-5p was a target of circAKT3, and miR-515-5p suppressed the expression of SLC1A5 by binding to SLC1A5 3'UTR. CircAKT3 relieved the inhibition of miR-515-5p on SLC1A5 expression by targeting miR-515-5p. The effects of circAKT3 knockdown were reversed by miR-515-5p depletion, and the effects of miR-515-5p restoration were abolished by SLC1A5 overexpression.

CONCLUSION: CircAKT3 promotes the malignant development of GC by activating SLC1A5 expression via targeting miR-515-5p.

PMID:34850965 | DOI:10.14670/HH-18-401

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