Prognostic Role Of Microsatellites In Melanoma and Implications In The American Joint Committee On Cancer Classification System
Microsatellites were associated with other adverse melanoma prognostic factors. A multivariate Cox regression analysis showed that they are an independent risk factor for worse OS, MSS, and disease-free survival.
KEY FINDINGS: Microsatellites were associated with other adverse melanoma prognostic factors. A multivariate Cox regression analysis showed that they are an independent risk factor for worse OS, MSS, and disease-free survival. Patients with stage IIIB melanoma with microsatellites had worse OS and MSS, whereas patients with stage IIIC melanoma had worse OS but not MSS.
BACKGROUND: There is limited information on microsatellite survival outcomes in patients with melanoma. Purpose of this study is to evaluate survival outcomes in patients with microsatellites, assess their role within stage III stratification of the American Joint Committee on Cancer classification, and assess the results of sentinel lymph node biopsies in patients with microsatellites.
DETAILS: A retrospective bicenter cohort study from 1998 to 2019 included patients with a diagnosis of invasive cutaneous melanoma. Of a total of 5216 patients, 108 (2.1%) had microsatellites at initial staging. Survival analysis showed that microsatellites were an independent risk factor with decreased overall survival (OS), melanoma-specific survival (MSS), and disease-free survival, with hazard ratios of 1.57, 1.76, and 1.76, respectively. Stratified analysis in patients with stage III melanoma showed a 5-year OS of 35% (95% CI, 17.3%-73.4%) and a MSS of 45% (95% CI, 23.1-87.5) for patients with stage IIIB melanoma with microsatellites.
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Source: Riquelme-Mc Loughlin, C., Sandoval-Clavijo, A., Blnco de Tord, M., et al. (2023). Prognostic Role Of Microsatellites In Melanoma and Implications In The American Joint Committee On Cancer Classification System: A Cohort Study. Journal of the American Academy of Dermatology. 2023; 88(2): 338-347. Published: February, 2023. DOI: 10.1016/j.jaad.2022.10.027.
Postoperative Time and Anatomic Location Influence Skin Graft Reperfusion Assessed With Laser Speckle Contrast Imaging
Skin graft reperfusion is a protracted process that evolves differently in the graft centre and periphery, influenced by postoperative time and anatomic location. A better knowledge of this process can potentially enhance the development of strategies to induce vessel ingrowth into tissue-engineered skin substitutes.
KEY FINDINGS: Skin graft reperfusion is a protracted process that evolves differently in the graft centre and periphery, influenced by postoperative time and anatomic location. A better knowledge of this process can potentially enhance the development of strategies to induce vessel ingrowth into tissue-engineered skin substitutes.
BACKGROUND: Under optimal conditions, afferent and efferent human skin graft microcirculation can be restored 8-12 days postgrafting. Still, the evidence about the reperfusion dynamics beyond this period in a dermato-oncologic setting is scant. Authors aimed to characterise the reperfusion of human skin grafts over 4 weeks according to the necrosis extension (less than 20%, or 20%-50%) and anatomic location using laser speckle contrast imaging (LSCI).
DETAILS: Over 16 months, all eligible adults undergoing skin grafts following skin cancer removal on the scalp, face and lower limb were enroled. Perfusion was assessed with LSCI on the wound margin (control skin) on day 0 and on the graft surface on days 7, 14, 21 and 28. Graft necrosis extension was determined on day 28. Forty-seven grafts of 47 participants were analysed. Regardless of necrosis extension, graft perfusion equalled the control skin by day 7, surpassed it by day 21, and stabilised onwards. Grafts with less than 20% necrosis on the scalp and lower limb shared this reperfusion pattern and had a consistently better-perfused centre than the periphery for the first 21 days. On the face, the graft perfusion did not differ from the control skin from day 7 onwards, and there were no differences in reperfusion within the graft during the study.
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Source: Pinho, A., Brinca, A., Xara, J., et al. (2024). Postoperative Time and Anatomic Location Influence Skin Graft Reperfusion Assessed With Laser Speckle Contrast Imaging. Lasers in Surgery and Medicine. 2024; 56(6): 564-573. Published: August, 2024. DOI: 10.1002/lsm.23815.
Drug Survival of Methotrexate and Predictor Factors for Discontinuation in Psoriasis
MTX is a valuable, cost-effective option for long-term treatment of psoriasis although drug survival is not comparable with that of biological treatments.
KEY FINDINGS: MTX is a valuable, cost-effective option for long-term treatment of psoriasis although drug survival is not comparable with that of biological treatments. Studies are needed to better understand the best dosing regimen to use, with the aim of achieving the best clinical outcomes and the lowest rate of side effects with this drug.
BACKGROUND: Methotrexate (MTX) is a systemic therapy largely used for moderate-severe psoriasis. There is a lack of data on its use in daily practice and particularly on its long-term effectiveness and survival in psoriasis.
DETAILS: Authors performed a single-centered, retrospective, observational study to evaluate the drug survival of MTX in patients with psoriasis, treated in monotherapy with MTX between March 2015 and March 2022. Clinical and demographic characteristics were extracted from files of the patients. The drug survival was analyzed using Kaplan-Meier survival curves, considering separately overall discontinuation, discontinuation due to MTX ineffectiveness, and discontinuation due to adverse events. Multivariable Cox regression analyses were carried out including clinically meaningful variables. A total of 199 patients were included; 148 (74.4%) suspended MTX during the observation period. The reasons for discontinuation were adverse events (39.2%), ineffectiveness (38.5%), remission of psoriasis (12.2%), and other reasons (10.1%). Average duration of therapy was 10.1 months. Patients who remained on therapy after 1, 2, and 5 years of treatment were respectively 46.9, 35.6, and 29.3%. Positive predictive factors for therapy continuation were increasing age and the use of > 15 mg of MTX for a period > 3 months; the only negative predictive factor was the clinical variant of palmoplantar pustular.
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Source: Caldarola, G., De Luca, E., Mariani, M., et al. (2024). Drug Survival of Methotrexate and Predictor Factors for Discontinuation in Psoriasis. Int J Dermatol. 2024; 62(5): 649-656. Published: May, 2024. DOI: 10.1111/ijd.16652.
Metastasis Of Skin Squamous Cell Carcinoma In Kidney Transplant Recipients
Both groups, KTRs and ICs, exhibited similar primary tumor grades and metastasis evolution, but KTRs had a higher prevalence of lymphovascular invasion. Metastasis of cSCC was more common in males with low skin phototype, in KTRs, particularly on the head and neck. The study suggests a possible link between lymphovascular invasion and metastasis development in KTRs.
KEY FINDINGS: Both groups, KTRs and ICs, exhibited similar primary tumor grades and metastasis evolution, but KTRs had a higher prevalence of lymphovascular invasion. Metastasis of cSCC was more common in males with low skin phototype, in KTRs, particularly on the head and neck. The study suggests a possible link between lymphovascular invasion and metastasis development in KTRs.
BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the most common skin malignancy in kidney transplant recipients (KTRs) as a result of immunosuppression.
DETAILS: A worldwide increase in kidney transplantation justifies the determination of prognostic biomarkers by collecting detailed patient data on metastasis development. This study aims to characterize the clinical, epidemiological, and histopathological profiles of KTRs who developed metastasis of cSCC. Authors conducted a retrospective single-center study on 18 KTRs and 21 immunocompetent patients (ICs) with metastatic cSCC, using data from 2004 to 2021. ICs were older (median age 70.5 years) than KTRs (median age: 59.5 years). Both groups were predominantly male with Fitzpatrick skin phototype I/II. The primary tumor appeared around 83.5 ; months post-transplant, usually in sun-exposed areas (61.1%), though some non-exposed areas in ICs (23.8%) contradicted literature findings. KTRs took longer to develop metastasis (median: 11.0 months) compared to ICs (median: 5.5 months). The mean size of the primary tumor was smaller in KTRs (2.50 cm2) compared to ICs (4.55 cm2). The main lymph node chain affected by metastasis was parotid lymph nodes in KTRs (27.8%) and cervical/axillar lymph nodes in ICs (both 19.0%).
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Source: Alves, F. F. C., de Jesus, L. C. B., Cristelli, M. P., et al. (2024). Metastasis Of Skin Squamous Cell Carcinoma In Kidney Transplant Recipients. Int J Dermatol. 2024; 63(5): 560-564. Published: March, 2024. DOI: 10.1111/ijd.17029.
Rapidly Evolving Pre- and Post-surgical Systemic Treatment of Melanoma
Melanoma therapeutics continues to advance with combination adjuvant approaches now investigating anti-PD1 with lymphocyte activation gene 3 (LAG3), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), and individualized neoantigen therapies. How this progress will be integrated into the management of a unique patient to reduce recurrence, limit toxicity, and avoid over-treatment will dominate clinical research and patient care over the next decade.
KEY FINDINGS: Melanoma therapeutics continues to advance with combination adjuvant approaches now investigating anti-PD1 with lymphocyte activation gene 3 (LAG3), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), and individualized neoantigen therapies. How this progress will be integrated into the management of a unique patient to reduce recurrence, limit toxicity, and avoid over-treatment will dominate clinical research and patient care over the next decade.
BACKGROUND: With the development of effective BRAF-targeted and immune-checkpoint immunotherapies for metastatic melanoma, clinical trials are moving these treatments into earlier adjuvant and perioperative settings. BRAF-targeted therapy is a standard of care in resected stage III-IV melanoma, while anti-programmed death-1 (PD1) immunotherapy is now a standard of care option in resected stage IIB through IV disease.
DETAILS: With both modalities, recurrence-free survival and distant-metastasis-free survival are improved by a relative 35-50%, yet no improvement in overall survival has been demonstrated. Neoadjuvant anti-PD1 therapy improves event-free survival by approximately an absolute 23%, although improvements in overall survival have yet to be demonstrated. Understanding which patients are most likely to recur and which are most likely to benefit from treatment is now the highest priority question in the field. Biomarker analyses, such as gene expression profiling of the primary lesion and circulating DNA, are preliminarily exciting as potential biomarkers, though each has drawbacks. As in the setting of metastatic disease, markers that inform positive outcomes include interferon-γ gene expression, PD-L1, and high tumor mutational burden, while negative predictors of outcome include circulating factors such as lactate dehydrogenase, interleukin-8, and C-reactive protein. Integrating and validating these markers into clinically relevant models is thus a high priority.
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Source: Augustin, R. C. and Luke, J. J. (2024). Rapidly Evolving Pre- and Post-surgical Systemic Treatment of Melanoma. American Journal of Clinical Dermatology. Published: March, 2024. DOI: 10.1007/s40257-024-00852-5.
Human Hair Graying Revisited
The temporary reversibility of graying is highlighted by several drugs and hormones that induce repigmentation, indicating potential target pathways. Authors advise caution in directly applying mouse model concepts, define major open questions, and discuss future human antigraying strategies.
Summary
Principles, Misconceptions, and Key Research Frontiers
[Posted 6/Mar/2024]
AUDIENCE: Dermatology, Family Medicine
KEY FINDINGS: The temporary reversibility of graying is highlighted by several drugs and hormones that induce repigmentation, indicating potential target pathways. Authors advise caution in directly applying mouse model concepts, define major open questions, and discuss future human antigraying strategies.
BACKGROUND: Hair graying holds psychosocial importance and serves as an excellent model for studying human pigmentation and aging in an accessible miniorgan.
DETAILS: Current evidence suggests that graying results from an interindividually varying mixture of cumulative oxidative and DNA damage, excessive mTORC1 activity, melanocyte senescence, and inadequate production of pigmentation-promoting factors in the hair matrix. Various regulators modulate this process, including genetic factors (DNA repair defects and IRF4 sequence variation, peripheral clock genes, P-cadherin signaling, neuromediators, HGF, KIT ligand secretion, and autophagic flux. This leads to reduced MITF- and tyrosinase-controlled melanogenesis, defective melanosome transfer to precortical matrix keratinocytes, and eventual depletion of hair follicle (HF) pigmentary unit (HFPU) melanocytes and their local progenitors. Graying becomes irreversible only when bulge melanocyte stem cells are also depleted, occurring later in this process. Distinct pigmentary microenvironments are created as the HF cycles: early anagen is the most conducive phase for melanocytic reintegration and activation, and only during anagen can the phenotype of hair graying and repigmentation manifest, whereas the HFPU disassembles during catagen.
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Source: Paus, R., Sevilla, A., and Grichnik, J. M. (2024). Human Hair Graying Revisited: Principles, Misconceptions, and Key Research Frontiers. Journal of Investigative Dermatology. 2024; 144(3): 474-491. Published: March, 2024. DOI: 10.1016/j.jid.2023.09.276.
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