Clinical Outcomes and Risk Stratification of Early-Stage Melanoma Micrometastases From an International Multicenter Study: Implications for the Management of American Joint Committee on Cancer IIIA Disease.

PURPOSE: Indications for offering adjuvant systemic therapy for patients with early-stage melanomas with low disease burden sentinel node (SN) micrometastases, namely, American Joint Committee on Cancer (AJCC; eighth edition) stage IIIA disease, are presently controversial. The current study sought to identify high-risk SN-positive AJCC stage IIIA patients who are more likely to derive benefit from adjuvant systemic therapy. METHODS: Patients were recruited from an intercontinental (Australia/Europe/North America) consortium of nine high-volume cancer centers. All were adult patients with pathologic stage pT1b/pT2a primary cutaneous melanomas who underwent SN biopsy between 2005 and 2020. Patient data, primary tumor and SN characteristics, and survival outcomes were analyzed. RESULTS: Three thousand six hundred seven patients were included. The median follow-up was 34 months. Pairwise disease comparison demonstrated no significant survival difference between N1a and N2a subgroups. Survival analysis identified a SN tumor deposit maximum dimension of 0.3 mm as the optimal cut point for stratifying survival. Five-year disease-specific survival rates were 80.3% and 94.1% for patients with SN metastatic tumor deposits ≥ 0.3 mm and < 0.3 mm, respectively (hazard ratio, 1.26 [1.11 to 1.44]; P < .0001). Similar findings were seen for overall disease-free and distant metastasis-free survival. There were no survival differences between the AJCC IB patients and low-risk (< 0.3 mm) AJCC IIIA patients. The newly identified high-risk (≥ 0.3 mm) subgroup comprised 271 (66.4%) of the AJCC IIIA cohort, whereas only 142 (34.8%) patients had SN tumor deposits > 1 mm in maximum dimension. CONCLUSION: Patients with AJCC IIIA melanoma with SN tumor deposits ≥ 0.3 mm in maximum dimension are at higher risk of disease progression and may benefit from adjuvant systemic therapy or enrollment into a clinical trial. Patients with SN deposits < 0.3 mm in maximum dimension can be managed similar to their SN-negative, AJCC IB counterparts, thereby avoiding regular radiological surveillance and more intensive follow-up.

Evaluation of the Indications for Sentinel Node Biopsy in Early-Stage Melanoma with the Advent of Adjuvant Systemic Therapy: An International, Multicenter Study.

BACKGROUND: Patients presenting with early-stage melanoma (AJCC pT1b-pT2a) reportedly have a relatively low risk of a positive SNB (~5-10%). Those patients are usually found to have low-volume metastatic disease after SNB, typically reclassified to AJCC stage IIIA, with an excellent prognosis of ~90% 5-year survival. Currently, adjuvant systemic therapy is not routinely recommended for most patients with AJCC stage IIIA melanoma. The purpose was to assess the SN-positivity rate in early-stage melanoma and to identify primary tumor characteristics associated with high-risk nodal disease eligible for adjuvant systemic therapy METHODS: An international, multicenter retrospective cohort study from 7 large-volume cancer centers identified 3,610 patients with early primary cutaneous melanomas 0.8-2.0 mm in Breslow thickness (pT1b-pT2a; AJCC 8th edition). Patient demographics, primary tumor characteristics, and SNB status/details were analyzed. RESULTS: The overall SNB-positivity rate was 11.4% (412/3610). Virtually all SNB-positive patients (409/412; 99.3%) were reclassified to AJCC stage IIIA. Multivariate analysis identified age, T-stage, mitotic rate, primary site and subtype, and lymphovascular invasion as independent predictors of sentinel node status. A mitotic rate of >1/mm2 was associated with a significantly increased SN-positivity rate and was the only significant independent predictor of high-risk SNB metastases (>1 mm maximum diameter). CONCLUSIONS: The new treatment paradigm brings into question the role of SNB for patients with early-stage melanoma. The results of this large international cohort study suggest that a reevaluation of the indications for SNB for some patients with early-stage melanoma is required.

Managing infected seroma post-lymphadenectomy; A retrospective cohort study and cost analysis in melanoma patients.

BACKGROUND AND PURPOSE: Seromas are a common and unavoidable complication following lymphadenectomy, and often become clinically significant with superseded infection requiring re-admission for prompt intervention. However, there is no consensus as to whether a formal surgical incision and drainage (I&D), ultrasound (US)-guided aspiration or intravenous (IV) antibiotics alone is the most efficacious method of managing an infected seroma, the investigation of which formed the rationale for this study. SUBJECTS AND METHODS: This retrospective cohort study included a consecutive series of patients readmitted for infected seroma following a lymphadenectomy for melanoma at Leeds Teaching Hospitals Trust (LTHT) from 2006 to 2017. Details on management, length of hospital stay, length of follow-up and number of clinical appointments required were examined. FINDINGS: Seventy-one cases of infected seroma were identified from the cohort of 1691 lymphadenectomies. Initially, 21 patients (29.5%) were managed by IV antibiotics alone (failure rate of 52.4%); 18 (25.4%) with US-guided aspiration (failure rate 27.8%) and 32 (45.1%) with surgical I&D, which was 100% effective. Ultimately, 62.5% of the cohort required surgical management. Patients who underwent surgical I&D were discharged significantly faster following the procedure (3 versus 5 days for US-guided aspiration, p = 0.002) and spent fewer days in hospital overall (p = 0.022). The overall average cost was comparable across the three treatment groups. CONCLUSIONS: Surgical management seemed preferential to conservative approaches in terms of efficacy and was not significantly more expensive overall; but carries anaesthetic risk. There may be a clinically significant difference in outcome depending on management; however, more evidence is required to investigate this.

Helicopter-borne NMR for detection of oil under sea-ice.

Mobile nuclear magnetic resonance (NMR) operating in Earth's magnetic field is adapted to detect leaked or spilled oil trapped in or under sea ice without the need to place any personnel on the ice. A helicopter placed a 6-meter diameter NMR coil system weighing approximately 1000 kg on 92 cm-thick ice surrogate and detected the equivalent of 1 cm thick oil under the ice surrogate in 3-1/2 min.

Spontaneous regression of metastatic melanoma - clinical evidence of the abscopal effect.

INTRODUCTION: Metastatic melanoma is poorly understood. Regression of primary lesions has been associated with poor prognosis, but spontaneous regression of all metastatic disease is clearly beneficial. A patient's own immune responses occasionally appear to stimulate spontaneous regression of metastatic disease in melanoma. PATIENTS AND METHODS: We present six interesting cases of complete or nearly complete spontaneous regression of metastatic melanoma, suggest possible causes and review the literature. RESULTS AND CONCLUSIONS: These cases show clear radiological, pathological or clinical evidence of spontaneous regression of metastatic melanoma. This remains a poorly understood phenomena warranting further investigation and may prove useful in the development of immune mediated solutions.

Merkel cell polyomavirus small T antigen targets the NEMO adaptor protein to disrupt inflammatory signaling.

Merkel cell carcinoma (MCC) is a highly aggressive nonmelanoma skin cancer arising from epidermal mechanoreceptor Merkel cells. In 2008, a novel human polyomavirus, Merkel cell polyomavirus (MCPyV), was identified and is strongly implicated in MCC pathogenesis. Currently, little is known regarding the virus-host cell interactions which support virus replication and virus-induced mechanisms in cellular transformation and metastasis. Here we identify a new function of MCPyV small T antigen (ST) as an inhibitor of NF-κB-mediated transcription. This effect is due to an interaction between MCPyV ST and the NF-κB essential modulator (NEMO) adaptor protein. MCPyV ST expression inhibits IκB kinase α (IKKα)/IKKß-mediated IκB phosphorylation, which limits translocation of the NF-κB heterodimer to the nucleus. Regulation of this process involves a previously undescribed interaction between MCPyV ST and the cellular phosphatase subunits, protein phosphatase 4C (PP4C) and/or protein phosphatase 2A (PP2A) Aß, but not PP2A Aα. Together, these results highlight a novel function of MCPyV ST to subvert the innate immune response, allowing establishment of early or persistent infection within the host cell.

Ischemic skin ulceration complicating glue embolization of type II endoleak after endovascular aneurysm repair.

The optimal treatment for type II endoleaks remains unclear. The present report describes a case of ischemic skin ulceration after glue embolization of a type II endoleak with challenging access in a multiply comorbid 82-year-old woman with an expanding aneurysm sac 3 years after endovascular aneurysm repair. Embolization was performed from a proximal position with an n-butyl cyanoacrylate/Ethiodol mixture to allow flow into the endoleak because direct sac puncture was hazardous. One week after intervention, an eschar, which progressed to superficial necrosis as a result of partial nontarget delivery of sclerosant, developed over the left iliac crest. The eschar was self-limiting, with complete resolution by 6 months.

IMBA Professional Plus: a flexible approach to internal dosimetry.

IMBA (Integrated Modules for Bioassay Analysis) is a suite of software modules that implement the current ICRP biokinetic and dosimetric models for estimation of intakes and doses. The IMBA modules have gone through extensive quality assurance, and are now used for routine formal dose assessment by Approved Dosimetry Services throughout the UK. HPA has continued to develop the IMBA modules. In addition, several projects, sponsored by organisations both in the USA and in Canada, have resulted in the development of customised user-friendly interfaces (IMBA Expert 'editions'). These enable users not only to use the standard ICRP models, but also to change many of the parameter values from ICRP defaults, and to apply sophisticated data handling techniques to internal dose calculations. These include: fitting measurement data with the maximum likelihood method; using multiple chronic and acute intakes; and dealing with different data types, such as urine, faces and whole body simultaneously. These interfaces were improved further as a result of user-feedback, and a general 'off-the-shelf' product, IMBA Professional, was developed and made available in January 2004. A new version, IMBA Professional Plus, was released in April 2005, which is both faster and more powerful than previous software. The aim of this paper is to describe the capabilities of IMBA Professional Plus, and the mathematical methods used.

Colour shift following tattoo removal with Q-switched Nd-YAG laser (1064/532).

Colour shift in tattoo pigment is a recognised complication of laser tattoo treatment. We report our experience over the past 4 years in treating 275 patients, with a total of 323 professional tattoos. Of these, 184 tattoos contained a pigment other than black with 33 displaying a colour shift as a consequence of laser treatment. This adverse effect was recorded with red, yellow, crimson and brown pigments but most frequently with white/flesh pigments. We found brown and white/flesh coloured pigments to be significantly more likely to change colour compared to red and that the chance of certain colours shifting related to the age of the tattoo. We outline our management of this problem and discuss the results of continued treatment.

Nurses' attitudes toward patient and family education: implications for clinical nurse specialists.

This study had two purposes: (1) to examine nurses' attitudes toward patient and family education; and (2) to identify issues, barriers, and concerns related to patient and family education. A three-part survey was distributed to licensed nurses employed in a large healthcare system in Central Florida. Analysis of variance with posthoc multiple comparisons found differences in responses between different demographic groups. A model for meeting the patients' and families' education needs is proposed, using the various roles of the clinical nurse specialist to facilitate the process.