There is increasing evidence that the behaviour of naevi and melanoma is under significant genetic and/or epigenetic control. Melanoma tumours behaves similarly all over the world. Many genes have ...now been implicated in melanoma risk and naevi number. Embryogenesis has also been important in the discovery of links between several neurological diseases and melanoma susceptibility. Telomere biology, which regulates cell senescence, is increasingly relevant in melanoma. Melanoma is often found in the context of family cancer syndromes and the identification of these families is important as screening for cancer will save lives. Melanoma is also one of the most immunogenic cancer as the behaviour of naevi and melanoma differ in patients with vitiligo or eczema. The search for non-sun related melanoma risk factors should continue as it is likely to lead to important discoveries which will, in turn, have an impact on therapeutic targets for this tumour.
Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumor and causes 90% of skin cancer mortality. A unique collaboration of multidisciplinary experts from the European Dermatology ...Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. The diagnosis of melanoma can be made clinically and shall always be confirmed through dermatoscopy. If a melanoma is suspected, a histopathological examination is required. Sequential digital dermatoscopy and full-body photography can be used in risk persons to detect the development of melanomas at an earlier stage. Where available, confocal reflectance microscopy can improve clinical diagnosis in special cases. Melanoma shall be classified according to the 8th version of the AJCC classification. Thin melanomas up to 0.8 mm tumor thickness does not require further imaging diagnostics. From stage IB onwards, examinations with lymph node sonography are recommended, but no further imaging examinations. From stage IIC whole-body examinations with CT or PET-CT in combination with brain MRI are recommended. From stage III and higher, mutation testing is recommended, particularly for BRAF V600 mutation. It is important to provide a structured follow-up to detect relapses and secondary primary melanomas as early as possible. There is no evidence to support the frequency and extent of examinations. A stage-based follow-up scheme is proposed, which, according to the experience of the guideline group, covers the minimum requirements; further studies may be considered. This guideline is valid until the end of 2021.
Immune-checkpoint inhibitors (ICIs) have revolutionised the therapeutic landscape for multiple malignancies and the health of the gut microbiome (GM) is strongly linked with therapeutic responses to ...ICI. This review explores the implications of diet and medication on the GM for patients receiving ICI. Clinical trials are underway to explore the impact of factors such as faecal microbiota transfer, probiotics, prebiotics, bacteria consortia and a number of dietary interventions on patients receiving ICI. Randomised controlled trials are lacking, and inferences are currently based on short-term clinical and observational studies. Antibiotics should be avoided before ICI initiation, and depending on prospective data, future consideration may be given to temporary delay of initiation of non-urgent ICI if patient has had broad spectrum antibiotics within 1 month of planned treatment initiation. Proton pump inhibitor use should be discontinued when not clearly indicated and potential switch to a histamine H2-receptor antagonist considered. Patients should be advised to minimise animal meat intake and maximise plants, aiming to consume ≥30 plant types weekly. A high fibre intake (>30 g/day) has been seen to be beneficial in increasing the chance of ICI response. Fermented foods may have a beneficial effect on the GM and should be introduced where possible. Ideally, all patients should be referred to a nutritionist or dietician with knowledge of GM before commencing ICI.
•Therapeutic response to immune-checkpoint inhibitor (ICI) is linked to the gut microbiome.•Care needs to be given to protecting the microbiome, both by clinicians and patients.•Patients' diets should focus on diversity, variety, plentiful plants, protein and dietary fibres.•Antibiotics and many other common medications can adversely affect responses to ICI.•Before and during ICI patients should have access to nutritional support.
Summary
Background
Symptoms of SARS‐CoV‐2 infection have differed during the different waves of the pandemic but little is known about how cutaneous manifestations have changed.
Objectives
To ...investigate the diagnostic value, frequency and duration of cutaneous manifestations of SARS‐CoV‐2 infection and to explore their variations between the Delta and Omicron waves of the pandemic.
Methods
In this retrospective study, we used self‐reported data from 348 691 UK users of the ZOE COVID Study app, matched 1 : 1 for age, sex, vaccination status and self‐reported eczema diagnosis between the Delta and Omicron waves, to assess the diagnostic value, frequency and duration of five cutaneous manifestations of SARS‐CoV‐2 infection (acral, burning, erythematopapular and urticarial rash, and unusual hair loss), and how these changed between waves. We also investigated whether vaccination had any effect on symptom frequency.
Results
We show a significant association between any cutaneous manifestations and a positive SARS‐CoV‐2 test result, with a diagnostic value higher in the Delta compared with the Omicron wave (odds ratio 2·29, 95% confidence interval 2·22–2·36, P < 0·001; and odds ratio 1·29, 95% confidence interval 1·26–1·33, P < 0·001, respectively). Cutaneous manifestations were also more common with Delta vs. Omicron (17·6% vs. 11·4%, respectively) and had a longer duration. During both waves, cutaneous symptoms clustered with other frequent symptoms and rarely (in < 2% of the users) as first or only clinical sign of SARS‐CoV‐2 infection. Finally, we observed that vaccinated and unvaccinated users showed similar odds of presenting with a cutaneous manifestation, apart from burning rash, where the odds were lower in vaccinated users.
Conclusions
Cutaneous manifestations are predictive of SARS‐CoV‐2 infection, and their frequency and duration have changed with different variants. Therefore, we advocate for their inclusion in the list of clinically relevant COVID‐19 symptoms and suggest that their monitoring could help identify new variants.
What is already known about this topic?
Several studies during the wildtype COVID‐19 wave reported that patients presented with common skin‐related symptoms.
It has been observed that COVID‐19 symptoms differ among variants.
No study has focused on how skin‐related symptoms have changed across different variants.
What does this study add?
We showed, in a community‐based retrospective study including over 348 000 individuals, that the presence of cutaneous symptoms is predictive of SARS‐CoV‐2 infection during the Delta and Omicron waves and that this diagnostic value, along with symptom frequency and duration, differs between variants.
We showed that infected vaccinated and unvaccinated individuals reported similar skin‐related symptoms during the Delta and Omicron waves, with only burning rashes being less common after vaccination.
Odds ratios in adults testing positive for COVID‐19 of self‐reporting some of the typical COVID‐19 symptoms and skin signs of COVID‐19 infection. Results are based on 198 609 users of the ZOE COVID Study App that self‐reported their symptoms during the Delta wave and 198 609 users matched for age, sex, vaccination status and self‐reported eczema diagnosis that self‐reported their symptoms during the Omicron wave. The OR for anosmia (13·4, 95% confidence interval 13·1–13·8) is not shown for the Delta wave to improve visualization.
Linked Comment: M. Grau‐Pérez and I. Garcia‐Doval. Br J Dermatol 2022; 187:839.
Plain language summary available online
Melanoma of the small intestine Lens, Marko, Dr; Bataille, Veronique, MD; Krivokapic, Zoran, Prof
The lancet oncology,
05/2009, Letnik:
10, Številka:
5
Journal Article
Recenzirano
Summary Intestinal melanomas can be primary tumours or metastases of cutaneous, ocular, or anal melanomas. Primary intestinal melanoma is extremely rare, whereas metastatic melanoma of the small ...bowel is common because of the tendency for cutaneous melanoma to metastasise to the gastrointestinal tract. Because distinguishing between primary and metastatic intestinal melanoma can be difficult, the main features of each are discussed, and the diagnostic images used to detect intestinal melanoma are assessed. Routine barium examinations and CT have limited sensitivity, but PET imaging can improve detection of melanoma metastases to the small bowel. Although various treatment strategies have been tried in patients with intestinal melanoma, surgical removal of intestinal metastases is the treatment of choice in patients with resectable tumours. No systemic therapy improves survival in patients with melanoma metastatic to the intestines; thus, the prognosis for these patients is poor. Patients with primary melanoma of the small intestine have a worse prognosis than do patients with metastases of cutaneous melanoma.
The skin's tendency to sunburn rather than tan is a major risk factor for skin cancer. Here we report a large genome-wide association study of ease of skin tanning in 176,678 subjects of European ...ancestry. We identify significant association with tanning ability at 20 loci. We confirm previously identified associations at six of these loci, and report 14 novel loci, of which ten have never been associated with pigmentation-related phenotypes. Our results also suggest that variants at the AHR/AGR3 locus, previously associated with cutaneous malignant melanoma the underlying mechanism of which is poorly understood, might act on disease risk through modulation of tanning ability.
As for all types of cancer, the incidence of melanoma increases with age. However, naevus counts (the principal risk factor for melanoma) decrease with age; hence the relationship between ageing and ...melanoma is complex. Subjects who maintain a high naevus count after the age of 50 years are more likely to be affected by melanoma, as their lesions do not senesce. Longer telomere length, which is strongly related to age, is linked to high naevus counts/melanoma risk; thus melanoma biology is influenced by factors that slow down ageing. Age is also an important prognostic factor in melanoma. Increasing age leads to worse survival in stages I, II and III. Sentinel lymph node (SLN) status, which is a strong predictor of melanoma survival, is also affected by age, as SLN positivity decreases with age. However, the prognostic predictive value of SLN status on survival increases with age, so, again, these relationships are complex. In patients with stage IV melanoma, age impacts on survival because it affects responses to treatment. This review examines the effects of age on melanoma risk, prognostic factors and responses to treatment.
In order to update recommendations on treatment, supportive care, education, and follow-up of patients with invasive cutaneous squamous cell carcinoma (cSCC), a multidisciplinary panel of experts ...from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), the European Society for Radiotherapy and Oncology (ESTRO), the European Union of Medical Specialists (UEMS), the European Academy of Dermatology and Venereology (EADV), and the European Organisation of Research and Treatment of Cancer (EORTC) was formed. Recommendations wereḥ based on an evidence-based literature review, guidelines, and expert consensus. Treatment recommendations are presented for common primary cSCC (low risk, high risk), locally advanced cSCC, regional metastatic cSCC (operable or inoperable), and distant metastatic cSCC. For common primary cSCC, the first-line treatment is surgical excision with postoperative margin assessment or micrographically controlled surgery. Achieving clear surgical margins is the most important treatment consideration for patients with cSCCs amenable to surgery. Regarding adjuvant radiotherapy for patients with high-risk localised cSCC with clear surgical margins, current evidence has not shown significant benefit for those with at least one high-risk factor. Radiotherapy should be considered as the primary treatment for non-surgical candidates/tumours. For cSCC with cytologically or histologically confirmed regional nodal metastasis, lymph node dissection is recommended. For patients with metastatic or locally advanced cSCC who are not candidates for curative surgery or radiotherapy, anti-PD-1 agents are the first-line systemic treatment, with cemiplimab being the first approved systemic agent for advanced cSCC by the Food and Drugs Administration/European Medicines Agency. Second-line systemic treatments for advanced cSCC, include epidermal growth factor receptor inhibitors (cetuximab) combined with chemotherapy or radiotherapy. Multidisciplinary board decisions are mandatory for all patients with advanced cSCC, considering the risks of toxicity, the age and frailty of patients, and co-morbidities, including immunosuppression. Patients should be engaged in informed, shared decision-making on management and be provided with the best supportive care to improve symptom management and quality of life. The frequency of follow-up visits and investigations for subsequent new cSCC depends on underlying risk characteristics.
•Treatment depends on the characteristics of the patient, e.g. frailty, co-morbidities, preferences, and of cSCC, e.g. primary low-risk or high-risk, locally advanced, regional metastatic (operable or inoperable), or distant metastatic.•Achieving clear surgical margins is the most important treatment consideration for patients with cSCC amenable to surgery.•Multidisciplinary board decisions are mandatory for all patients with advanced cSCC.•Anti-PD-1 agents (cemiplimab) are the first-line systemic treatment for patients with metastatic or locally advanced cSCC who are not candidates for curative surgery or radiotherapy.
Naevus count is the strongest risk factor for melanoma. Body Mass Index (BMI) has been linked to melanoma risk. In this study, we investigate the link between naevus count and height, weight and bone ...mineral density (BMD) in the TwinsUK cohort (N = 2119). In addition we adjusted for leucocyte telomere length (LTL) as LTL is linked to both BMD and naevus count. Naevus count was positively associated with height (p = 0.001) but not with weight (p = 0.187) despite adjusting for age and twin relatedness. This suggests that the previously reported melanoma association with BMI may be explained by height alone. Further adjustment for LTL did not affect the significance of the association between height and naevus count so LTL does not fully explain these results. BMD was associated with naevus count at the spine (coeff 18.9, p = 0.01), hip (coeff = 18.9, p = 0.03) and forearm (coeff = 32.7, p = 0.06) despite adjusting for age, twin relatedness, weight, height and LTL. This large study in healthy individuals shows that growth via height, probably in early life, and bone mass are risk factors for melanoma via increased naevus count. The link between these two phenotypes may possibly be explained by telomere biology, differentiation genes from the neural crests but also other yet unknown factors which may influence both bones and melanocytes biology.
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