Involvement of long non-coding RNA LOXL1-AS1 in the tumourigenesis and development of malignant tumours: a narrative review.

Background and Objective: Long noncoding RNAs (lncRNAs) are involved in a wide variety of physiological and pathological processes in organisms. LncRNAs play a significant role as oncogenic or tumour-suppressing factors in various biological processes associated with malignant tumours and are closely linked to the occurrence and development of malignancies. Lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1) is a recently discovered lncRNA. It is upregulated in various malignant tumours and is associated with pathological characteristics such as tumour size, tumour node metastasis (TNM) staging, lymph node metastasis, and tumour prognosis. LOXL1-AS1 exerts its oncogenic role by competitively binding with multiple microRNAs (miRs), thereby regulating the expression of downstream target genes and controlling relevant signalling pathways. This article aims to explore the structure and the function of LOXL1-AS1, and the relationship between LOXL1-AS1 and the occurrence and development of human malignant tumours to provide a reference for further clinical research. Methods: English literature on LOXL1-AS1 in the occurrence and development of various malignant tumours was searched in PubMed. The main search terms were "LOXL1-AS1", "tumour". Key Content and Findings: This article mainly summarizes the biological processes in which LOXL1-AS1 is involved in various human malignant tumours and the ways in which this lncRNA affects malignant biological behaviours such as proliferation, metastasis, invasion, and apoptosis of tumour cells through different molecular regulatory mechanisms. This article also explores the potential clinical significance and application prospects of LOXL1-AS1, aiming to provide a theoretical basis and reference for the clinical diagnosis, treatment, and screening of prognostic markers for malignant tumours. Conclusions: LOXL1-AS1 acts as a competing endogenous RNA (ceRNA), binding to miRs to regulate downstream target genes and exert its oncogenic effects. LOXL1-AS1 may become a novel molecular biomarker for cancer diagnosis and treatment in humans, and it may also serve as an independent prognostic indicator.

The misunderstanding of the R Classification-a survey amongst medical specialties treating breast cancer.

Frequent discussions in the tumour board about the Residual tumour (R) Classification of the UICC's "TNM Classification of Malignant Tumours", especially in the case of breast surgery specimens, raised the question about differing interpretations amongst different medical specialties. Thus, we designed a survey about the R Classification with a special focus on breast cancer specimens. An online survey was conducted, where a web link to the survey was distributed via email to various medical professional societies dealing with breast cancer in Austria and Germany with the request to distribute the link to their members. The study population consisted of physicians of all educational levels of different medical professions, who deal with breast carcinomas in their daily routine. Two hundred two participants, of which 160 (79.2%) have more than 10 years' professional experience, took part in the survey; 88 (43.6%) were surgeons/gynaecologists, 80 (39.6%) pathologists, 19 (9.4%) radiation oncologists/ therapists, 8 (4.0%) radiologists, and 7 (3.5%) oncologists. We show that the R Classification is not completely mastered by anyone and that there are significant differences in the interpretation of the R Classification between different medical specialties. For better differentiation between the residual tumour (R Classification) of the TNM and a pure resection margin assessment, we suggest the use of a Resection margin (Rm) Classification to avoid further misunderstandings. To assist better multidisciplinary cooperation and to ensure better patient care all medical disciplines should be educated about the actual meaning and correct application of the R Classification.

Non-intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses: an analysis of clinical characteristics and prognosis.

BACKGROUND: Non­intestinal adenocarcinoma of the nasal cavity and paranasal sinuses (non­ITAC) is a heterogeneous tumour that has rarely been reported in previous studies. We compared and analysed the symptoms, radiographic and pathological features, treatment methods, and prognosis of patients with low-grade (G1) and high-grade (G3) tumours. METHODS: This was a retrospective study included 22 patients with pathologically confirmed non-ITAC of the nasal cavity and paranasal sinuses who were treated between January 2008 and December 2021 at a single centre. Of these, 11 patients had G1 tumours, and 11 patients had G3 tumours. Clinicopathological features, treatment methods, and survival outcomes were analysed. RESULTS: The median follow-up period was 48.5 months. Nasal congestion was the most common initial symptom, and the nasal cavity was the most frequently involved site. For G1 tumours, the main treatment was simple surgery, 1 and 3­year overall survival (OS) rates were 100 and 88.9%, while the 1 and 3­year local control (LC) rates were 100 and 100%, respectively. For G3 tumours, the main treatments were surgery combined with radiotherapy and/or chemotherapy,1 and 3­year OS rates were 72.7 and 72.7%, while the 1 and 3­year LC rates were 100 and 90.91%, respectively. G3 tumours was associated with significantly shorter overall survival than G1 tumours (P = 0.035). Patients with stage III-IV showed shorter overall survival compared to stage I-II patients (P = 0.035). CONCLUSIONS: Non-ITAC of the nasal cavity and paranasal sinuses may frequently occur in the nasal cavity. The main treatment modality is surgery, supplemented by radiotherapy and chemotherapy. Pathological grade and tumour stage were poor prognostic factors for the disease.

Current status and progress of research on the ADP-dependent glucokinase gene.

ADP-dependent glucokinase (ADPGK) produces glucose-6-phosphate with adenosine diphosphate (ADP) as the phosphate group donor, in contrast to ATP-dependent hexokinases (HKs). Originally found in archaea, ADPGK is involved in glycolysis. However, its biological function in most eukaryotic organisms is still unclear, and the molecular mechanism of action requires further investigation. This paper provides a concise overview of ADPGK's origin, biological function and clinical application. It aims to furnish scientific information for the diagnosis and treatment of human metabolic diseases, neurological disorders, and malignant tumours, and to suggest new strategies for the development of targeted drugs.

Genetics of Cardiac Tumours: A Narrative Review.

Cardiac tumours can occur in association with genetic syndromes. Rhabdomyomas have been reported in association with tuberous sclerosis, myxomas with Carney's complex, cardiac fibromas with Gorlin syndrome, and paragangliomas with multiple endocrine neoplasm syndrome. The presentation and prognosis of cardiac tumours associated with genetic syndromes differ compared with sporadic cases. Knowledge about the associated syndromes' genetic features and extracardiac manifestations is essential for the diagnosis, prognosis, and management of cardiac neoplasms. Moreover, identifying genetic mutations in benign and malignant cardiac tumours is needed to personalise management and improve treatment outcomes. Thus, this review discusses the genetic abnormalities associated with cardiac tumours, the current genetic screening recommendations, and the effect of those genetic mutations on the outcomes.

A 10-year clinicopathological analysis of ovarian lesions in a tertiary hospital in Southern Nigeria.

Background: Ovarian tumours are the most lethal of all gynaecological cancers and they are usually diagnosed in advanced stages when the prognosis is very poor. Objective: To determine the pattern of ovarian lesions, their frequency, presentation, and associated clinical symptoms in Uyo, Nigeria. Methods: A 10-year retrospective study of all ovarian specimens that were surgically removed and histologically diagnosed. Results: The patients were between the ages of 5 and 73 years with median age of 34.1 years. Benign tumours occurred most commonly among the 20-39-year age group (31.3%) while malignant tumours were predominant among those aged 50-69 years (10.0%). Surface epithelial tumours (45.4%) were the most common neoplastic tumours while the mature cystic teratoma (33.2%) was the most common tumour overall. Surface epithelial malignancies accounted for 70.6% of all ovarian malignancies and the serous cyst adenocarcinoma (10.2%) was the most common surface epithelial tumour as well as the most common malignant tumour. Conclusion: There has been an increase in the number of malignant ovarian specimens in our centre. Though surface epithelial tumours were the most common category of ovarian tumours, overall, the mature cystic teratoma was the most common tumour. Serous cyst adenocarcinoma was the most common surface epithelial tumour and the most common malignant tumour.

Chondrosarcoma of the Proximal Humerus: Does the Margin Affect Survival?

Chondrosarcoma (CS) is the second most common primary malignant bone tumour and, in the absence of reliable chemotherapy and radiotherapy, is effectively a surgical disease. Overall disease specific survival (DSS) is affected by tumour grade, whilst resection margin contributes to local recurrence free survival (LRFS). The aim of this study was to investigate factors that affect the local and systemic prognoses for conventional central CSs arising from the proximal humerus. A multi-centre, retrospective study from three international collaborative sarcoma centres identified 110 patients between 1995 and 2020 undergoing treatment for a conventional central CS of the proximal humerus; 58 patients (53%) had a grade 1 tumour, 36 (33%) had a grade 2 tumour, and 16 patients (13%) had a grade 3 CS. The mean age of patients was 50 years (range 10-85). The incidence of local recurrence (LR) was 9/110 (8.2%), and the disease specific mortality was 6/110 (5.5%). The grade was a statistically significant factor for LRFS (p < 0.001). None of the grade 1 tumours developed LR. The DSS was affected by the grade (p < 0.001) but not by the LR (p = 0.4). Only one patient with a grade 2 tumour died from the disease. The proximal humeral grade 1 CS behaved as a benign tumour, having no cases of LR nor death due to disease. Grade 2 CSs of the proximal humerus behaved in a more indolent way when compared with comparable grade tumours elsewhere in the appendicular skeleton, being locally aggressive with a higher LR rate than grade 1 CSs but still having very low mortality and a high rate of DSS. The LR in grade 2 CSs did not affect the DSS; therefore, surgical management in proximal humeral grade 2 CSs should have a greater emphasis on preserving function whilst maintaining an adequate margin for resection. The proximal humeral grade 3 CS was, as elsewhere in the skeleton, an aggressive, high-grade tumour. Therefore, surgical management should include en bloc resection with clear margins to avoid LR.

PU.1 is a useful nuclear marker to distinguish between histiocytosis and histiocyte-rich tumours.

AIMS: The aim was to test the expression of PU.1 on different types of histiocytoses and to test the utility of PU.1 in confirming or excluding a histiocytic origin in tumour samples with suspicion of histiocytosis. METHODS AND RESULTS: We analysed 66 biopsies of nonmalignant histiocytoses represented by Langerhans-cell histiocytosis (n = 13), Erdheim-Chester disease (ECD) (n = 19), Rosai-Dorfman disease (RDD) (n = 14), mixed ECD-RDD (n = 3), ALK-positive histiocytosis (n = 6), and juvenile xanthogranuloma (n = 11). All cases were positive for PU.1 in reactive and neoplastic histiocytes. In addition, 39 cases of tumours with high-grade cytological atypia were referred to our center as suspicion of malignant histiocytosis/histiocytic sarcoma and only 18 were confirmed. Indeed, more than half of these tumours (21/39) were either undifferentiated malignant tumours with a stroma rich in histiocytes, diffuse large B-cell lymphoma, or high-grade dedifferentiated liposarcoma. PU.1 was useful to distinguish between the negativity of large atypical nuclei and the positivity of stromal reactive histiocytes. CONCLUSION: PU.1 is expressed by all types of histiocytosis. It distinguishes histiocytosis from histiocyte-rich tumours with an easy interpretation due to its sharp nuclear staining. Its negativity in lesional/tumour cells in histiocyte-like lesions is useful to eliminate a histiocytosis.

Increased incidence rates of positive blood cultures shortly after chemotherapy compared to radiotherapy among individuals treated for solid malignant tumours.

BACKGROUND: Cancer treatments suppress immune function and are associated with increased risk of infections, but the overall burden of serious infectious diseases in treated patients has not been clearly elucidated. METHODS: All patients treated for solid malignant tumours with radiotherapy (RT) and/or standard first-line chemotherapy (C) at the Department of Oncology at Rigshospitalet between 01/1/2010 and 31/12/2016 were included. Patients were followed from treatment initiation until the first of new cancer treatment, 1 year after treatment initiation, end of follow-up or death. Incidence rates (IR) of positive blood culture (PBC) per 1000 person-years follow-up (PYFU) were calculated. FINDINGS: 12,433 individuals were included, 3582 (29%), 6349 (51%), and 2502 (20%) treated with RT, C, or both RT & C, respectively, contributing 8182 PYFU. 429 (3%) individuals experienced 502 unique episodes of PBC, incidence rate (95% CI) 52.43 (47.7, 57.6) per 1000 PYFU. The 30-day mortality rate after PBC was 24% independent of treatment modality. Adjusted incidence rate ratios in the first 3 months (95% CI) after PBC significantly varied by treatment: 2.89 (1.83, 4.55) and 2.52 (1.53, 4.14) for C and RT & C compared to RT. Escherichia coli (n = 127, 25%) was the top microorganism identified. INTERPRETATION: PBCs are not common, but when they occur, mortality is high.

The management of sacral tumours.

Tumours of the sacrum are difficult to manage. The sacrum provides the structural connection between the torso and lower half of the body and is subject to both axial and rotational forces. Thus, tumours or their treatment can compromise the stability of the spinopelvic junction. Additionally, nerves responsible for lower limb motor groups as well as bowel, bladder, and sexual function traverse or abut the sacrum. Preservation or sacrifice of these nerves in the treatment of sacral tumours has profound implications on the function and quality of life of the patient. This annotation will discuss current treatment protocols for sacral tumours.Cite this article: Bone Joint J 2022;104-B(12):1284-1291.

NECTIN4 expression in sebaceous and sweat gland carcinoma

Background: Sebaceous carcinoma and sweat gland carcinoma (malignant tumours with apocrine and eccrine differentiation) are rare malignant adnexal tumours that differentiate toward sebaceous glands and eccrine and apocrine glands, respectively. Because of the rarity of these malignancies, standard treatments for advanced disease have yet to be established. The outcomes of patients with systemic metastasis remain poor, highlighting the need for novel treatment strategies. Nectin cell adhesion molecule 4 (NECTIN4) and its antibody-drug conjugate, enfortumab vedotin, have attracted attention as potential treatments for solid tumours. Objectives: To examine the potential use of NECTIN4-target therapy for sebaceous and sweat gland carcinoma. Materials & Methods: We immunohistochemically investigated NECTIN4 expression in 14 sebaceous carcinoma samples and 18 sweat gland carcinoma samples, and examined whether NECTIN4-targeted therapy could be applied to these cancers. Results: We found strong and frequent expression of NECTIN4 in both cancers. All tumours exhibited positive staining at least in a part of the lesion, and the mean H-score, a semiquantitative score ranging from 0 to 300, was 259.4 for sebaceous carcinoma and 253.1 for sweat gland carcinoma. Conclusion: Our results suggest that both sebaceous carcinoma and sweat gland carcinoma could be potentially treated with NECTIN4-targeted antibody-drug conjugates, such as enfortumab vedotin.

Elbow hemiarthroplasty with a 3D-printed megaprosthesis for defects of the distal humerus or proximal ulna after tumour resection : a preliminary report.

AIMS: The aim of this study was to investigate the feasibility of application of a 3D-printed megaprosthesis with hemiarthroplasty design for defects of the distal humerus or proximal ulna following tumour resection. METHODS: From June 2018 to January 2020, 13 patients with aggressive or malignant tumours involving the distal humerus (n = 8) or proximal ulna (n = 5) were treated by en bloc resection and reconstruction with a 3D-printed megaprosthesis with hemiarthroplasty, designed in our centre. In this paper, we summarize the baseline and operative data, oncological outcome, complication profiles, and functional status of these patients. RESULTS: Preparation of the prosthesis was a mean of 8.0 days (SD 1.5), during which time no patients experienced tumour progression. The mean operating time and intraoperative blood loss were 158.1 minutes (SD 67.6) and 176.9 ml (SD 187.8), respectively. All of the prostheses were implanted successfully. During a mean follow-up of 25.7 months (SD 7.8), no patients died, but four had complications (two superficial wound problems, one temporary palsy of radial nerve, and one dislocation). No aseptic loosening, structural failure, infection, heterotopic ossification, or degenerative arthritis was seen in this study. The mean flexion of the elbow was 119.6° (SD 15.9°) and the mean extension lag was 11.9° (SD 13.8°). The mean Musculoskeletal Tumor Society 93 score and Mayo Elbow Performance Score were 28.4 (SD 0.9) and 97.7 (SD 4.4), respectively. CONCLUSION: The custom-made, 3D-printed megaprosthesis with hemiarthroplasty is a feasible option for functional reconstruction after resection of a tumour in the distal humerus or proximal ulna. Cite this article: Bone Joint J 2022;104-B(6):747-757.

Successful treatment of a case with synchronous follicular lymphoma and gastric adenocarcinoma with CD19 CAR T cells and literature review.

WHAT IS KNOWN AND OBJECTIVE: Anti-CD19 CAR-T cell therapy is effective in B-cell lymphoma. However, it is rarely used in lymphoma combined with other malignant tumours. CASE DESCRIPTION: A relapsed/refractory follicular lymphoma (r/r FL) patient underwent anti-CD19 CAR-T cell therapy and achieved complete response to lymphoma. However, gastric adenocarcinoma (GAC) was diagnosed during the cellular therapy. After infusion of CAR-T cells, he received curative treatment for GAC, and maitained complete response in both r/r FL and GAC after the treatment. WHAT IS NEW AND CONCLUSION: Anti-CD19 CAR-T therapy is an effective treatment for r/r FL, also provided opportunity for the sequential therapy of GAC, and remained significant quality of life afterwards.

The Selective Role of Open and Endoscopic Approaches for Sinonasal Malignant Tumours.

Endoscopic endonasal surgery has been demonstrated to be effective in the treatment of selected cases of sinonasal cancers. However, in cases of locally advanced neoplasms, as well as recurrences, the most appropriate approach is still debated. The present review aims to summarize the current state of knowledge on the utility of open approaches to resect sinonasal malignant tumours. Published comparative studies and meta-analyses suggest comparable oncological results with lower morbidity for the endoscopic approaches, but selection biases cannot be excluded. After a critical analysis of the available literature, it can be concluded that endoscopic surgery for selected lesions allows for oncologically safe resections with decreased morbidity. However, when endoscopic endonasal surgery is contraindicated and definitive chemoradiotherapy is not appropriate, craniofacial and transfacial approaches remain the best therapeutic option.

Moxibustion for alleviating chemotherapy-induced gastrointestinal adverse effects: A systematic review of randomized controlled trials.

OBJECTIVE: This systematic review aims to assess whether moxibustion is effective and safe for gastrointestinal adverse effects, a common and thorny issue arising from chemotherapy. METHODS: Seven electronic databases were searched up to August 28, 2021, to identify randomized controlled trials (RCTs) comparing moxibustion versus non-moxibustion treatments for various gastrointestinal adverse effects after chemotherapy. The Karnofsky performance status (KPS) and quality of life scores and the incidence of moxibustion-related adverse events were also investigated. Effects in meta-analyses were measured by risk ratios (RRs) or mean differences (MDs). RESULTS: Thirty-two RCTs (n = 2990) were included. Compared to the controls, moxibustion significantly reduced the incidences of nausea/vomiting (RR 0.70, 95% CI 0.61-0.79), severe nausea/vomiting (RR 0.39, 95% CI 0.29-0.51), diarrhoea (RR 0.56, 95% CI 0.38-0.82), constipation (RR 0.59, 95% CI 0.44-0.78), and abdominal distension (RR 0.60, 95% CI 0.46-0.78). The KPS (MD 7.53, 95% CI 3.42-11.64) and quality of life (MD 8.88, 95% CI 0.96-16.80) scores were also significantly improved after moxibustion. The results did not support a benefit of moxibustion on inappetence (RR 0.69, 95% CI 0.40-1.22) or abdominal pain (RR 0.60, 95% CI 0.28-1.30). All adverse events related to moxibustion were mild. CONCLUSIONS: Moderate-to very-low-quality evidence suggests that moxibustion may be safely used as an adjuvant treatment after chemotherapy to reduce the incidences of nausea and vomiting, diarrhoea, constipation, and abdominal distension and improve the performance status and quality of life in patients with malignant tumours. Its effects on abdominal pain and inappetence are uncertain.

The role of multidetector computed tomography enterography in the evaluation of localized malignant small intestinal lesions: retrospective radiological and pathological experience.

PURPOSE: Our purpose is to present our experience in using multidetector computed tomography (MDCT) enterography in the evaluation of localized malignant small intestinal lesions with pathological correlation. MATERIAL AND METHODS: We retrospectively evaluated 53 patients of pathologically proven malignant localized small intestinal tumours, who underwent multidetector CT enterography. RESULTS: In this study, the mean age was 51.39 ± 17.4 years. The most commonly affected age group was from 50 to 59 years. The commonest clinical complaint was abdominal pain. The ileum was the most commonly affected anatomical region, showing 25 lesions (47.16%). Radiologically irregular/asymmetric wall thickening was detected in 42 cases(79.24%). Pathologically the most common malignancy was small intestinal adenocarcinoma, followed by carcinoid tumour, lymphoma, and gastrointestinal stromal tumours (GIST). We found that there was a statistically significant association between the pathological lymphadenopathy (p = 0.005) and absent proximal intestinal dilatation (p = 0.01) with intestinal lymphoma. Also, there was a statistically significant association between the extra-intestinal mesenteric fat changes with carcinoid tumours (p = 0.001). Irregular/asymmetric wall thickening was detected in 14 cases of small intestinal adenocarcinoma with a statistically significant association (p = 0.001) while exophytic pathological mass formation was statistically significant associated (p ≤ 0.001) with small intestinal GIST. CONCLUSIONS: Multidetector CT enterography is a non-invasive and accurate method in the evaluation of focal and localized small intestinal malignant lesions. The accurate detection of these lesions depends to some degree on the experience of the radiologist, lesional size, site and pattern of enhancement, as well as adequate intestinal distension.

Advances in the DNA methylation hydroxylase TET1.

BACKGROUND: The ten-eleven translocation 1 (TET1) protein is a 5-methylcytosine hydroxylase that belongs to the TET protein family of human α-ketoglutarate oxygenases. TET1 recognizes and binds to regions of high genomic 5'-CpG-3' dinucleotide density, such as CpG islands, initiates the DNA demethylation program, and maintains DNA methylation and demethylation balance to maintain genomic methylation homeostasis and achieve epigenetic regulation. This article reviews the recent research progress of TET1 in the mechanism of demethylation, stem cells and immunity, various malignant tumours and other clinical diseases. CONCLUSION: TET1 acts as a key factor mediating demethylation, the mechanism of which still remains to be investigated in detail. TET1 is also critical in maintaining the differentiation pluripotency of embryonic stem cells and plays anti- or oncogenic roles in combination with different signalling pathways in different tumours. In certain tumours, its role is still controversial. In addition, the noncatalytic activity of TET1 has gradually attracted attention and has become a new direction of research in recent years.

Regional variation in the survival of patients with a soft-tissue sarcoma of the extremity and trunk wall under a centralized care system : what has been the impact of national policies in the UK?

AIMS: While a centralized system for the care of patients with a sarcoma has been advocated for decades, regional variations in survival remain unclear. The aim of this study was to investigate regional variations in survival and the impact of national policies in patients with a soft-tissue sarcoma (STS) in the UK. METHODS: The study included 1,775 patients with a STS who were referred to a tertiary sarcoma centre. The geographical variations in survival were evaluated according to the periods before and after the issue of guidance by the National Institute for Health and Care Excellence (NICE) in 2006 and the relevant evolution of regional management. RESULTS: There had been a significant difference in survival between patients referred from the North East, North West, East Midlands, West Midlands, South West, and Wales in the pre-NICE era (five-year disease-specific survival (DSS); South West, 74% vs North East, 47% (p = 0.045) or West Midlands, 54% (p = 0.049)), which was most evident for patients with a high-grade STS. However, this variation disappeared in the post-NICE era, in which the overall DSS for high-grade STS improved from 47% to 68% at five years (p < 0.001). Variation in the size of the tumour closely correlated with the variation in DSS, and the overall size of the tumour and incidence of metastasis at the time of diagnosis also decreased after the national policies were issued. CONCLUSION: The survival of patients with a STS improved and regional variation corrected after the introduction of national policies, as a result of a decreasing size of tumour and incidence of metastasis at the time of diagnosis, particularly in patients with a high-grade STS. This highlights the positive impact of national guidelines on regional variation in the presentation, management, and outcome in patients with a STS. Cite this article: Bone Joint J 2021;103-B(9):1541-1549.

New Targeted Therapies and Immunotherapies for Locally Advanced Periocular Malignant Tumours: Towards a New 'Eye-Sparing' Paradigm?

The management of periocular skin malignant tumours is challenging. Surgery remains the mainstay of treatment for localised eyelid cancers. For more locally advanced cancers, especially those invading the orbit, orbital exenteration has long been considered the gold standard; however, it is a highly disfiguring and traumatic surgery. The last two decades have been marked by the emergence of a new paradigm shift towards the use of 'eye-sparing' strategies. In the early 2000s, the first step consisted of performing wide conservative eyelid and orbital excisions. Multiple flaps and grafts were needed, as well as adjuvant radiotherapy in selected cases. Although being incredibly attractive, several limitations such as the inability to treat the more posteriorly located orbital lesions, as well as unbearable diplopia, eye pain and even secondary eye loss were identified. Therefore, surgeons should distinguish 'eye-sparing' from 'sight-sparing' strategies. The second step emerged over the last decade and was based on the development of targeted therapies and immunotherapies. Their advantages include their potential ability to treat almost all tumours, regardless of their locations, without performing complex surgeries. However, several limitations have been reported, including their side effects, the appearance of primary or secondary resistances, their price and the lack of consensus on treatment regimen and exact duration. The aim of this article was to review the evolution of the management of locally advanced periocular malignant tumours over the last three decades and highlight the new paradigm shift towards the use of 'eye-sparing' strategies.

Effects and mechanisms of Eps8 on the biological behaviour of malignant tumours (Review).

Epidermal growth factor receptor pathway substrate 8 (Eps8) was initially identified as the substrate for the kinase activity of EGFR, improving the responsiveness of EGF, which is involved in cell mitosis, differentiation and other physiological functions. Numerous studies over the last decade have demonstrated that Eps8 is overexpressed in most ubiquitous malignant tumours and subsequently binds with its receptor to activate multiple signalling pathways. Eps8 not only participates in the regulation of malignant phenotypes, such as tumour proliferation, invasion, metastasis and drug resistance, but is also related to the clinicopathological characteristics and prognosis of patients. Therefore, Eps8 is a potential tumour diagnosis and prognostic biomarker and even a therapeutic target. This review aimed to describe the structural characteristics, role and related molecular mechanism of Eps8 in malignant tumours. In addition, the prospect of Eps8 as a target for cancer therapy is examined.