The role of regional chemotherapy for advanced limb melanoma in the era of potentially effective systemic therapies

xlomafota13 shared this article with you from Inoreader The role of regional chemotherapy for advanced limb melanoma in the era of potentially effective systemic therapies Via Melanoma Research - Published Ahead-of-Print To review the current role of regional chemotherapy in the management of advanced limb melanoma. Articles reporting the results of isolated limb infusion (ILI) were identified by performing a comprehensive literature search using the PubMed database. Keywords included isolated limb infusion, in-transit me lanoma and melphalan. No publication date restrictions were applied. ILI data were compared with those from current systemic therapy clinical trials and the previously reviewed isolated limb perfusion (ILP) literature. Regional chemotherapy is today required in fewer patients because effective systemic therapies now provide an alternative treatment for those who develop extensive local melanoma recurrence or in-transit metastases (ITMs). However, regional chemotherapy may be a valuable treatment option when the side-effects of systemic therapies are of concern, or after systemic treatment failure. ILP achieves overall response rates (ORRs) of 64–100% and complete response rates (CRRs) of 25–89%. ILI achieves ORRs of 41–91% and CRRs of 6–39%. ILP and ILI can have a low risk of serious morbidity. Early results from treatment with ILP or ILI in conjunction with systemic immune therapies suggest that these modalities can be safely combined, which may be useful in patients with r efractory limb disease. Regional chemotherapy remains important in the armamentarium of clinicians managing patients with unresectable limb melanoma and may be preferable in those who are frail, elderly or who are at high risk from complications of systemic therapies. The efficacy of combining regional chemotherapy with systemic immune therapy is currently being assessed. Received 31 December 2020 Accepted 18 March 2021 Correspondence to John F. Thompson, MD, Melanoma Institute Australia, The University of Sydney, 40 Rocklands Rd, North Sydney, NSW 2060, Australia, Tel: +61 (0)2 9911 7366; fax: +61 (0)2 9954 9290; e-mail: john.thompson@melanoma.org.au Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The role of osteopontin in the development and metastasis of melanoma

xlomafota13 shared this article with you from Inoreader The role of osteopontin in the development and metastasis of melanoma Via Melanoma Research - Published Ahead-of-Print Melanoma is a highly heterogeneous tumor. The incidence of melanoma increases with age and its long-term prognosis is poor. The treatment of melanoma includes surgical removal, chemotherapy and immunotherapy; however, the effect of these treatments is limited on mutated melanoma. Osteopontin is an extrace llular protein which is expressed in numerous kinds of cells; it is related to the proliferation and invasion of cancer cells as well as the development of tumor microenvironment. The relationship between osteopontin and metastasis of melanoma has been clarified in recent years. This review focuses on the expression of osteopontin in patients with melanoma and associated signaling pathways involved in development and metastasis of melanoma; the potential role of osteopontin in immune modulation and prognosis prediction is also discussed here. Received 6 December 2020 Accepted 30 April 2021 Correspondence to Yun Zhao, MD, Department of Dermatology, General Hospital of the Yangtze River Shipping, Wuhan 430015, China, Tel: +86 18207196192; e-mail: 458459025@qq.com Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

ETS1 promoted cell growth, metastasis and epithelial–mesenchymal transition process in melanoma by regulating miR-16-mediated SOX4 expression

xlomafota13 shared this article with you from Inoreader ETS1 promoted cell growth, metastasis and epithelial–mesenchymal transition process in melanoma by regulating miR-16-mediated SOX4 expression Via Melanoma Research - Published Ahead-of-Print Objective Melanoma is a malignant tumor with high metastasis and mortality. Epithelial–mesenchymal transition (EMT) was reported to be involved in the growth and metastasis of melanoma. To investigate these sections further, we showed that E26 transformation specific 1 (ETS1) could regulate growth, metastasis and EMT process of melanoma by regulating microRNA(miR)-16/SRY-related HMG box (SOX) 4 expression. Methods MiR-16, ETS1, SOX4 and nuclear factor κB (NF-κB) expression levels in melanoma cells were examined using qPCR. ETS1, SOX4, EMT-related proteins and NF-κB signaling pathway-related proteins were examined using western blot. Cell counting kit-8 assay, transwell assay were applied to evaluate the cell proliferation, migration and invasion of melanoma cells, respectively. Besides, a dual-luciferase reporter assay was employed to verify the binding relationship between ETS1 and miR-16, miR-16 and SOX4, miR-16 and NF-κB1. Results We showed that ETS1 and SOX4 were upregulated in melanoma cells, while miR-16 was downregulated. MiR-16 overexpression suppressed growth, metastasis and EMT process of melanoma. We found ETS1 could bind to the promoter region of miR-16 and inhibited its transcription. ETS1 silence could inhibit growth, metastasis and EMT process of melanoma, and inhibition of miR-16 could reverse the effects. Besides, miR-16 is directly bound to SOX4 and downregulated its expression. Rescued experiments confirmed that SOX4 overexpression abolished the inhibition effect of miR-16 mimics on growth, metastasis and EMT process of melanoma. Finally, NF-κB1 as the target of miR-16 mediated downstream biological responses. Conclusion ETS1 activated NF-κB signaling pathway through miR-16 via targeting SOX4, thus promoting growth, metastasis and EMT of melanoma. Received 17 September 2020 Accepted 30 March 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 Hu-Bing Guo, MM, The First Department of Orthopaedic Surgery, The First Hospital of Tianshui, No.105, Jianshe Road, Tianshui 741000, Gansu Province, P.R. China, Tel: +86 15809415658; e-mail: hbingu477@163.com Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Surgery of small bowel melanoma metastases in the era of efficient medical therapies: a retrospective cohort study

xlomafota13 shared this article with you from Inoreader Surgery of small bowel melanoma metastases in the era of efficient medical therapies: a retrospective cohort study Via Melanoma Research - Published Ahead-of-Print Surgery of small bowel melanoma metastases has to be reconsidered in the era of targeted treatments and immunotherapy. To retrospectively assess context and outcomes of small bowel melanoma metastases resections. All consecutive melanoma patients who underwent resection of small bowel metastases betwee n 2011 and 2017, in a single referral center, were retrospectively analyzed through melanoma-specific survival (MSS). A total of 20 patients were included with a 47.8 months median follow-up. Before small bowel surgery, eight patients (40%) were asymptomatic while seven had anemia and five patients had abdominal pain. All resections were decided on tumor boards except for three surgeries performed in the emergency setting. In the whole cohort, MSS was 89.5 months with 50% of patients alive at the study endpoint. We classified surgical indications in three groups: (1) surgery as a pivotal treatment for mono- or oligo-metastases limited to the small bowel (n = 6); (2) salvage surgery for symptomatic patients in order to preserve their chances to switch to an active line of medical treatment (n = 8); and (3) surgery of small bowel dissociated metastatic progression for patients otherwise controlled (n = 6), aiming at keeping patients with the same treatment or active fo llow-up. In these three situations, the objective of surgery was usually met, and most patients had a long median MSS after surgery: 70.3 months, 89.5 months and 72.4 months, respectively. Although medical treatments have dramatically improved survival in metastatic melanoma, surgical control of life-threatening localization like small bowel metastases is often a condition for long survival. * Nausicaa Malissen and Georges Farvacque contributed equally to the writing of this article. Received 13 October 2020 Accepted 17 March 2021 Correspondence to Nausicaa Malissen, MD, PhD, Dermatology and Skin Cancer Department, Hôpital La Timone, 278 rue Saint-Pierre, 13005 Marseille, France, Tel: +33 4 91 38 75 98; fax +33 4 91 38 79 89; e-mail: nausicaa.malissen@ap-hm.fr Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

AfHNS fellowship: A model to improve access to head and neck cancer care in Africa and developing countries

xlomafota13 shared this article with you from Inoreader AfHNS fellowship: A model to improve access to head and neck cancer care in Africa and developing countries Via Head & Neck Abstract Background Head and neck cancers occur predominantly in developing countries where access to care is poor. Sub-Saharan Africa has <20 head and neck surgeons for >1 billion people and has only two fellowship training programs. Methods and results The AfHNS Head and Neck Fellowship is being introduced to accelerate training of African surgeons to improve access to resource appropriate cancer care. By avoiding fixed time-in-training and single training sites, training can be offered at multiple centers in Africa, even with lower patient volumes. It also creates opportunities for accredited international surgical outreach programs to contribute to training. Conclusions Having prescribed reading and appropriate Entrustable Professional Activities that are assessed through Workplace Based Assessment, and having a summative virtual oral examination ensures that fellows are fit-for-purpose to practice in an African resource-constrained setting. Other developing countries are encouraged to adopt a similar approach to expanding head and neck cancer services. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A matched pair analysis of oncological outcomes in human papillomavirus‐negative oropharyngeal squamous cell carcinoma: Transoral surgery versus radiotherapy or concurrent chemoradiation

xlomafota13 shared this article with you from Inoreader A matched pair analysis of oncological outcomes in human papillomavirus‐negative oropharyngeal squamous cell carcinoma: Transoral surgery versus radiotherapy or concurrent chemoradiation Via Head & Neck Abstract Background With the termination of RTOG 1221, there remains a lacuna regarding the optimal treatment for human papillomavirus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC). Methods Matched pair analysis with propensity score matching (PSM) between Arm I (transoral surgery [TOS] + risk-stratified adjuvant treatment) and Arm II (nonsurgical treatment − radiation/chemoradiation) in HPV(−) OPSCC. Results Unmatched comparison of Arm I (n = 57) and Arm II (n = 89) indicated significantly better overall survival (OS) and disease-free survival (DFS) for Arm I. PSM by matched pairs (n = 48, 24 each arm) indicated 5-year OS at 80% and 72.1%, respectively, for Arm I and II (p > 0.05) and corresponding DFS at 65.3% and 33.4% (p > 0.05). Subgroup analysis did not demonstrate statistical difference in outcomes in stage II and III, but stage IV tumors had significantly better outcomes in Arm I than Arm II (4-year OS: 100% vs. 21%, p = 0.04; DFS: 75% vs. 14.3%, p = 0.04). Conclusions TOS +/− adjuvant was found to have oncological outcomes at par with nonsurgical modalities in stage I–III OPSCC, whereas a distinct survival advantage was noted in case of stage IV tumors. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The jaw‐dropping costs of oral cavity cancer malpractice

xlomafota13 shared this article with you from Inoreader The jaw‐dropping costs of oral cavity cancer malpractice Via Head & Neck Abstract Background Medical litigation is different than it was 20 years ago due to changes in health care. This study provides an updated analysis of oral cavity malpractice litigation from the past two decades (2000–2010 and 2011–2019). Methods Verdict reviews from the Westlaw database were analyzed from January 2000 to August 2019. Data were collected and analyzed with the Statistical Package for the Social Sciences. Results Sixty-five lawsuits were evaluated across 24 states. Failure to diagnose was the most common allegation in both decades. Adjusting for inflation, the average amount awarded from 2000 to 2010 was $1 721 068 and $3 925 504 from 2011 to 2019. Conclusions There has been a significant rise in allegations of failure to biopsy and failure to refer (p < 0.05). In addition, while award amounts appear different between decades, the difference is not statistically significant (p = 0.248). Education should focus on early diagnosis, biopsy, and referral to physicians who routinely care for this patient population. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Relationships between intraoral ultrasonographic and histopathological findings in patients with tongue cancer

xlomafota13 shared this article with you from Inoreader Relationships between intraoral ultrasonographic and histopathological findings in patients with tongue cancer Via Head & Neck Abstract Background In this study, we aimed to investigate the relationships between histopathological and intraoral ultrasonographic (IUS) findings in patients with tongue cancer. Methods IUS and histopathological findings in 46 patients with tongue cancer were considered for this study. We assessed the relationships between IUS findings regarding tumor thickness, margin type, border type, and internal echo intensity; internal/peripheral Doppler findings; and muscle invasion and histopathological findings regarding tumor thickness, differentiation, Yamamoto–Kohama (YK)-classification grade, blood vessel invasion, lymphatic invasion, perineural invasion, and muscle invasion. Results Statistical associations were found between the following findings: between thickness determined through IUS measurement and that determined through histopathological measurement, between the IUS findings regarding tumor margin and border types and the histopathologically determined YK-classifications grades, and between a Doppler image of the internal area of tongue lesions and lymphatic invasion. Conclusions IUS findings may be used to predict histopathological findings about tumor thickness and YK-classification grades. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Long‐Term Facial Nerve Outcome in Primary Parotid Cancer Surgery: A Population‐Based Analysis

xlomafota13 shared this article with you from Inoreader Long‐Term Facial Nerve Outcome in Primary Parotid Cancer Surgery: A Population‐Based Analysis Via The Laryngoscope Objectives/Hypothesis To determine immediate postoperative and long-term facial nerve dysfunction after parotid cancer surgery, risk factors, and the role of facial reanimation surgery. Study Design Population-based long-term analysis for all new primary parotid carcinoma cases in Thuringia from 1996 to 2019. Methods Data of the cancer registries of Thuringia, a federal state in Germany, were analyzed in combination with hospital-based data on facial function. Results About 477 patients (42.3% women; median age: 68 years) were included. It was observed that 6.7% had a preoperative facial nerve dysfunction, 11.7% received a radical parotidectomy, that is, that 5% had a normal preoperative facial function but needed radical surgery because of intraoperative detection of tumor infiltration into the facial nerve. About 10.2% received facial nerve reconstruction surgery. Immediate postoperative facial nerve dysfunction in the other patients was observed in 34.4% of the patients. Advanced T classification (odds ratio [OR] = 2.140; confidence interval [CI] = 1.268–3.611; P = .004) and neck dissection (OR = 2.012; CI = 1.027–3.940; P = .041) were independent risk factors for immediate postoperative facial nerve dysfunction. In addition, 22.0% showed no recovery during follow-up. Advanced T classification (OR = 2.177; CI = 1.147–4.133; P = .017) and postoperative radiotherapy (OR = 2.695; CI = 1.244–5.841; P = .012) were independent risk factors for permanent postoperative facial nerve dysfunction. Conclusion Patients with primary parotid cancer are at high risk for long-term facial nerve dysfunction. It seems that the possibilities of facial reanimation surgery needs to be utilized even more effectively. Level of Evidence 3 Laryngoscope, 2021 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Sarcoidosis of the Ear, Nose and Throat: a review of the literature

xlomafota13 shared this article with you from Inoreader Sarcoidosis of the Ear, Nose and Throat: a review of the literature Via Clinical Otolaryngology Abstract Objectives Sarcoidosis is a multisystemic inflammatory disease with extrathoracic manifestations, most commonly affecting the young and middle-aged, female and black populations. Diagnosis usually requires evidence of non-caseating granulomata and, when treated, prognosis is usually favourable. We aim to establish the incidence, clinical features and optimal treatment of ENT manifestations of this disease. Design We performed a PubMed literature review to determine the evidence-base supporting this. Results ENT manifestations are present in 5-15% of patients with sarcoidosis, often as a presenting feature, and require vigilance for swift recognition and coordinated additional treatment specific to the organ. Laryngeal sarcoidosis presents with difficulty in breathing, dysphonia and cough, and may be treated by Speech and Language Therapy (SLT) or intralesional injection, dilatation or tissue reduction. Nasal disease presents with crusting, rhinitis, nasal obstruction and anosmia, usually without sinus involvement. It is treated by topical nasal or intralesional treatments but may also require endoscopic sinus surgery, laser treatment or even nasal reconstruction. Otological disease is uncommon but includes audiovestibular symptoms, both sensorineural and conductive hearing loss, and skin lesions. Conclusions The consequences of ENT manifestations of sarcoidosis can be uncomfortable, disabling and even life threatening. Effective management strategies require good diagnostic skills and use of specific therapies combined with established treatments such as corticosteroids. Comparisons of treatment outcomes are needed to establish best practice in this area. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The immunotherapeutic role of indoleamine 2,3‐dioxygenase in head and neck squamous cell carcinoma: A systematic review

xlomafota13 shared this article with you from Inoreader The immunotherapeutic role of indoleamine 2,3‐dioxygenase in head and neck squamous cell carcinoma: A systematic review Via Clinical Otolaryngology Abstract Background Novel cancer immunotherapy seeks to harness the body's own immune system and tip the balance in favour of antitumour activity. The intracellular enzyme indoleamine 2,3-dioxygenase (IDO) is a critical regulator of the tumour microenvironment (TME) via tryptophan metabolism. The potential immunotherapeutic role of IDO in head and neck squamous cell carcinoma (HNSCC) requires further exploration. We aim to assess the evidence on IDO in HNSCC. Methods A systematic review of literature and clinical trials databases. Results We included 40 studies: seven involved cell lines: eight assessed tumour immunohistochemistry: ten measured IDO gene transcription: 15 reported on clinical trials. Increased cell line IDO expression was postulated to adversely affect tumour metabolism and apoptosis. Immunohistochemical IDO expression correlated with worse survival. Gene transcription studies associated IDO with positive PD-L1 and human papillomavirus (HPV) status. Phase I/II clinical trials showed (a) overall response (34%-55%) and disease control rates (62%-70%) for IDO1 inhibitor in combination with a PD-1 inhibitor, (b) similar safety profiles when both are used in combination therapy compared to each as monotherapies and (c) IDO gene expression as a predictive biomarker for response to PD-L1 therapy. Conclusions IDO expression is increased in the TME of HNSCC, which correlates with poor prognosis. However, the exact mechanism of IDO-driven immune modulation in the TME is an enigma. Future translational studies should map IDO activity during HNSCC treatment and elucidate its precise role in the TME, such research will underpin the development of clinical trials establishing the efficacy of IDO inhibitors in HNSCC. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.