Κυριακή 30 Μαΐου 2021

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

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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.
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The role of osteopontin in the development and metastasis of melanoma

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

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

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

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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.

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

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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.

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The jaw‐dropping costs of oral cavity cancer malpractice

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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.

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