Expression of p16 protein in acral lentiginous melanoma

Background Acral lentiginous melanoma (ALM) is a clinicopathologic subtype of cutaneous malignant melanoma. ALM is the most common type of melanoma amongst Asians, Africans, and patients with mixed ancestry. In Brazil, ALM comprises 10% of cutaneous melanoma. ALM develops on palmar, plantar, and subungual skin, and its biology is different from that of other cutaneous melanomas, where sunlight is the major known environmental determinant. Alterations and inactivation of the p16INK4 gene that encodes a specific inhibitor of cyclin‐dependent kinase have been related to melanoma genesis and progression. Few studies, however, have addressed p16 expression in ALM. Methods In order to verify and compare p16 protein expression, 32 paraffin‐embedded ALM specimens were subjected to a immunohistochemical technique using a monoclonal anti‐p16 antibody. The tumors were classified according to thickness (up to 1.0 mm and thicker than 1.0 mm) and the presence of ulceration. Results Twenty‐five (78%) ALMs displayed positive p16 protein expression: 21 of the 25 (84%) with a thickness of more than 1.0 mm, and four of the seven (57%) with a thickness of 1.0 mm or less. Thirteen of the 17 (76%) nonulcerated lesions and 12 of the 15 (80%) ulcerated lesions displayed positive p16 protein expression. Conclusion The data obtained suggest that p16 protein expression per se may not represent a marker of retinoblastoma protein (pRb) pathway disturbance in ALM tumorigenesis.     

CDKN2A mutations with p14 loss predisposing to multiple nerve sheath tumours,melanoma, dysplastic naevi and internal malignancies: a case series and review of the literature

An inherited germline mutation in CDKN2A is the most common cause of familial atypical multiple mole melanoma (FAMMM) syndrome. Although it is well known that CDKN2A mutations confer an increased risk for melanoma and pancreatic carcinoma, the association with an increased risk for nerve sheath tumours and other tumour types is under‐recognized. We report a family with a missense mutation (c.151–1G>C) at the acceptor splice site of intron 1 of CDKN2A, resulting in loss of function of both tumour suppressor proteins p16^INK4 and p14^ARF. This mutation is associated with a clinical phenotype of FAMMM syndrome in which patients develop numerous benign and malignant mutations, brain tumours, sarcomas and other solid tumours, in addition to melanoma and dysplastic naevi. Our proband initially presented with multiple nerve sheath tumours, leading to diagnostic confusion with Neurofibromatosis type 1. Loss of p14 expression results in increased MDM2‐mediated degradation of the tumour suppressor protein p53, and predisposes mutation carriers to multiple benign and malignant neoplasms. This article highlights the importance of considering CDKN2A mutations in patients with dysplastic naevi, melanoma and multiple nerve sheath tumours, specifically those with histological features of both neurofibromas and schwannomas. We also present a discussion of medical management for patients with this high‐risk cancer susceptibility syndrome.     

On the relationship between VDR,RORα and RORγ receptors expression and HIF1‐α levels in human melanomas

We analysed the correlation between the expression of HIF‐1α (hypoxia‐inducible factor 1 alpha), the nuclear receptors: VDR (vitamin D receptor), RORα (retinoic acid receptor‐related orphan receptor alpha), and RORγ and CYP24A1 (cytochrome P450 family 24 subfamily A member 1) and CYP27B1 (cytochrome P450 family 27 subfamily B member 1), enzymes involved in vitamin D metabolism. In primary and metastatic melanomas, VDR negatively correlated with nuclear HIF‐1α expression (r = ?.2273, P = .0302; r = ?.5081, P = .0011). Furthermore, the highest HIF‐1α expression was observed in pT3‐pT4 VDR‐negative melanomas. A comparative analysis of immunostained HIF‐1α and CYP27B1 and CYP24A1 showed lack of correlation between these parameters both in primary tumors and melanoma metastases. In contrast, RORα expression correlated positively with nuclear HIF‐1α expression in primary and metastatic lesions (r = .2438, P = .0175; r = .3662, P = .0166). Comparable levels of HIF‐1α expression pattern was observed in localized and advanced melanomas. RORγ in primary melanomas correlated also positively with nuclear HIF‐1α expression (r = .2743, P = .0129). HIF‐1α expression was the lowest in localized RORγ‐negative melanomas. In addition, HIF‐1α expression correlated with RORγ‐positive lymphocytes in melanoma metastases. We further found that in metastatic lymph nodes FoxP3 immunostaining correlated positively with HIF‐1α and RORγ expression in melanoma cells (r = .3667; P = .0327; r = .4208, P = .0129). In summary, our study indicates that the expression of VDR, RORα and RORγ in melanomas is related to hypoxia and/or HIF1‐α activity, which also affects FoxP3 expression in metastatic melanoma. Therefore, the hypoxia can affect tumor biology by changing nuclear receptors expression and molecular pathways regulated by nuclear receptors and immune responses.     

Human papillomavirus infection in Bowen disease: Negative p53 expression,not p16INK4a overexpression,is correlated with human papillomavirus‐associated Bowen disease

Genital Bowen disease (BD) has been linked to the high‐risk types of human papillomavirus (HPV) infection. Recently, it has been recognized that HPV also can be associated with extragenital BD. HPV oncoproteins E6 and E7 interfere with the function of p53 and pRb, respectively, leading carcinogenesis. p16^INK4a overexpression induced by inactivation of pRb is recognized as a surrogate marker for HPV‐associated cervical cancer. In this study, we examined the presence of HPV DNA in 142 BD lesions by polymerase chain reaction (PCR), and determined the type of HPV by PCR restriction fragment length polymorphism or direct DNA sequencing. HPV DNA was detected in 66.7% of genital BD and 8.3% of extragenital BD. The types of HPV detected were HPV types 6, 16, 33, 52, 56, 58 and 59. We also investigated the expression of p16^INK4a, pRb and p53 by immunohistochemistry. Positive expression was detected in 88.6% for p16^INK4a, 25.2% for pRb, and 63.8% for p53. There was no significant difference in p16^INK4a and pRb expression between HPV‐positive and ‐negative BD. However, a strong correlation of HPV positivity with p53 negativity was found. A total of 66.7% of HPV‐positive BD showed no p53 expression, whereas the corresponding rate was 32.8% of HPV‐negative BD. This study demonstrated that HPV can participate in the development of BD, not only in the genital lesion, but also in extragenital lesion. p16^INK4a overexpression is not a marker for HPV infection in BD. Instead, negative p53 expression is correlated with HPV‐associated BD.     

Serum Th1/Th2 and macrophage lineage cytokines in leprosy; correlation with circulating CD4+ CD25highFoxP3+ T‐regs cells

Not only macrophages, T‐helper (Th)1 and Th2, but also CD4⁺ CD25^highFoxP3⁺ regulatory T cells (T‐regs) are involved in immune response to Mycobacterium leprae. We aimed to evaluate serum interleukin (IL)‐1β and IL‐12p70 (macrophage cytokines), interferon‐γ (IFN‐γ) (Th1 cytokine), IL‐4 (Th2 cytokine) and circulating CD4⁺ CD25^highFoxP3⁺ T‐regs, in untreated leprosy patients. Forty three patients and 40 controls were assessed for the mentioned cytokines using ELISA. Patients were assessed for circulating T‐regs using flow cytometry. Patients were subgrouped into tuberculoid (TT), pure neural leprosy (PNL), borderline cases, lepromatous (LL), type 1 reactional leprosy (RL1) and erythema nodosum leprosum (ENL). Serum IL‐12p70, IFN‐γ and IL‐4 were significantly higher in patients versus controls (P < 0.05). Serum IL‐4 was highest in LL and lowest in RL1 (P = 0.003). Serum IL‐1β levels was significantly higher in multibacillary versus paucibacillary patients (P = 0.006). Significantly higher T‐regs levels was detected in TT, RL1 and PNL, while the lowest levels in ENL(P < 0.001), with significant differences versus controls (P < 0.05). FoxP3 expression% was significantly lower in PNL than other patients and controls (P < 0.05). T‐regs/T‐effs was lowest in ENL(P < 0.05). IFN‐γ correlated positively with T‐regs but negatively with IL‐1β (P = 0.041&0.046 respectively), which correlated positively with T‐effs%( P = 0.05). IL‐4 correlated positively with T‐regs FoxP3 expression% (P = 0.009). We concluded that: Circulating T‐regs were increased in TT, RL1 and PNL patients, known of relatively high cell‐mediated immunity. This finding was supported by low FoxP3 expression (in PNL) and correlation between T‐regs count and IFN‐γ level. Overproduction of IL‐4 in LL may infer liability to develop ENL, with disease progression and immune hyperactivation, marked by deficient T‐regs and increased T‐regs FoxP3 expression%. IL‐1β probably has a pro‐inflammatory role in multibacillary patients as correlated with T‐effs%.     

Motor function and survival following radiotherapy alone for metastatic epidural spinal cord compression in melanoma patients

The major goal of this study was the identification of predictors for motor function and survival after irradiation alone for metastatic epidural spinal cord compression (MESCC) from melanoma. Ten variables (age, gender, performance status, number of involved vertebrae, pre‐radiotherapy ambulatory status, further bone metastases, visceral metastases, interval from melanoma diagnosis to MESCC, time developing motor deficits before radiotherapy, fractionation regimen) were investigated for post‐radiotherapy motor function, ambulatory status and survival in 27 patients. On multivariate analysis, motor function was significantly associated with time developing motor deficits (P = 0.006). On univariate analysis, post‐radiotherapy ambulatory rates were associated with pre‐radiotherapy ambulatory status (P < 0.001) and performance status (P = 0.046). Variables having a significant impact on survival in the univariate analysis were performance status (P < 0.001), number of involved vertebrae (P = 0.007), pre‐radiotherapy ambulatory status (P = 0.020), further bone metastases (P = 0.023), visceral metastases (P < 0.001), and time developing motor deficits (P = 0.038). On multivariate analysis of survival, the Eastern Cooperative Oncology Group (ECOG) performance status (risk ratio [RR] = 4.35; 95% confidence interval [CI] = 1.04–16.67; P = 0.044) and visceral metastases (RR = 3.70; 95% CI = 1.10–12.50; P = 0.034) remained significant and were included in a survival score. Scoring points were obtained from 6‐month survival rates divided by 10. Total scores represented the sum scores of both variables and were 3, 9 or 15 points. Six‐month survival rates were 7%, 29% and 100% (P = 0.004). Thus, three predictors for functional outcomes were identified. The newly developed survival score included three prognostic groups. Patients with 3 points may receive 1 × 8 Gy, patients with 9 points 5 × 4 Gy and patients achieving 15 points longer‐course radiotherapy. In the latter two groups, upfront decompressive surgery may be considered.     

Sentinel lymph node biopsy for 102 patients with primary cutaneous melanoma at a single Japanese institute

Sentinel lymph node biopsy (SLNB) is a widely accepted standard procedure for patients with clinically localized melanoma. Melanoma prevalence and Clark's subtype differ between Asians and Caucasians. Here, we evaluated our experience on SLNB for cutaneous melanoma in a Japanese population. SLNB was performed for patients with melanoma between July 2000 and June 2014. We retrospectively analyzed 102 patients regarding association of clinicopathological features with sentinel lymph node (SLN) status, melanoma‐specific survival (MSS) and disease‐free survival (DFS). A positive SLN was significantly associated with primary Breslow thickness. Compared with 43 patients with negative SLN, 59 patients with positive SLN had significantly shorter MSS (5‐year survival rate, 94.3% vs 63.2%; P = 0.0002) and DFS (5‐year survival rate, 92.7% vs 63.4%; P = 0.0004). According to our subgroup analyses, nine patients with positive non‐SLN had significantly shorter MSS compared with 32 patients with negative non‐SLN (5‐year survival rate, 32.4% vs 68.5%; P = 0.0273). The survival of 51 Japanese patients with acral lentiginous melanoma (ALM) was not inferior to the survival of patients with other Clark's subtype. Breslow thickness is an important factor for both MSS and DFS, and the status of SLN is the most predictive prognostic factor in Japanese patients with clinically localized melanomas, as in case of Caucasians. Features of ALM may be different between Asians and Caucasians.     

Inverse correlation between microtubule‐associated protein 1A/1B‐light chain 3 and p62/sequestosome‐1 expression in the progression of cutaneous squamous cell carcinoma

The expression of autophagy‐related markers has occasionally been reported to correlate with the clinical stage of disease in patients with solid cancer, indicating autophagy activation. However, there have been no such reports for cutaneous squamous cell carcinoma. In this study, we investigated the expression levels of two autophagy‐related markers, microtubule‐associated protein IA/IB light chain 3 (LC3) and p62/sequestosome‐1 (p62), in cutaneous squamous cell carcinoma specimens and assessed their correlation to clinicopathological factors in patients with this type of cancer. As a marker of the autophagosome, LC3 expression increases with autophagosome formation/accumulation, whereas p62 expression decreases due to selective degradation via autophagy. We performed immunostaining for LC3 and p62 in 50 cutaneous squamous cell carcinoma specimens obtained from patients treated by surgical resection, counted the number of cells that showed positive staining, and calculated the percentage of positive cells per low‐power microscopic field. We next investigated the correlations between the expression levels of these markers and various clinicopathological factors. The results indicated that LC3 expression increased significantly with advanced clinical stage (P < 0.001) and increased tumor diameter (P = 0.046). By contrast, the expression of p62 decreased significantly with advanced clinical stage (P < 0.001) and increased tumor diameter (P = 0.001). These results suggest that autophagy becomes activated during disease progression in patients with cutaneous squamous cell carcinoma.     

Association of human leukocyte antigen class I antigens in Iranian patients with pemphigus vulgaris

There are a limited number of reports indicating the role of human leukocyte antigen (HLA) class I alleles in pemphigus vulgaris. This study was designed to highlight the association of HLA class I alleles with pemphigus vulgaris in Iran. Fifty patients with pemphigus vulgaris, diagnosed based on clinical, histological and direct immunofluorescence findings were enrolled into this study. The control group consisted of 50 healthy, age‐ and sex‐matched individuals. HLA typing of class I (A, B and C alleles) was carried out using polymerase chain reaction based on the sequence‐specific primer method. This study showed the higher frequency of HLA‐B*44:02 (P = 0.007), ‐C*04:01 (P < 0.001), ‐C*15:02 (P < 0.001) and ‐C*16:01 (P = 0.027) in the patient group, compared to the controls, while the frequency of HLA‐C*06:02 (P < 0.001) and ‐C*18:01 (P = 0.008) in the patients with pemphigus vulgaris was significantly lower than the controls. Regarding the linkage disequilibrium between HLA class I alleles, the HLA‐A*03:01, ‐B*51:01, ‐C*16:02 haplotype (4% vs 0%, P = 0.04) is suggested to be a predisposing factor, whereas HLA‐A*26:01, ‐B*38, ‐C*12:03 haplotype (0% vs 6%, P = 0.01) is suggested to be a protective factor. In conclusion, it is suggested that HLA‐B*44:02, ‐C*04:01, ‐C*15:02 alleles and HLA‐A*03:01, ‐B*51:01, ‐C*16:02 haplotype are susceptibility factors for development of pemphigus vulgaris in the Iranian population, while HLA‐C*06:02, ‐C*18:01 alleles and HLA‐A*26:01, ‐B*38, ‐C*12:03 haplotype may be considered as protective alleles.     

Adjuvant therapy with nivolumab versus ipilimumab after complete resection of stage III/IV melanoma: Japanese subgroup analysis from the phase 3 CheckMate 238 study

The multinational phase 3 CheckMate 238 trial compared adjuvant therapy with nivolumab versus ipilimumab among patients with resected stage III or IV melanoma (N = 906). In this Japanese subgroup analysis of CheckMate 238 (n = 28; nivolumab, n = 18; ipilimumab, n = 10), both the 12‐ and 18‐month recurrence‐free survival rates were 56% for nivolumab and 30% for ipilimumab (hazard ratio, 0.66; 97.56% confidence interval, 0.19–2.24; P = 0.4390). No new safety signals were reported for Japanese patients. Results were consistent with those from the CheckMate 238 global population, indicating that nivolumab has the potential to be a treatment option for Japanese patients with resected melanoma who are at high risk of recurrence.     

Phase I/II study of vemurafenib in patients with unresectable or recurrent melanoma with BRAFV600 mutations

We investigated the efficacy and safety of vemurafenib in Japanese patients with unresectable or recurrent melanoma with BRAF^V600 mutations. This was a two‐step open‐label multicenter phase I/II study. Step 1 evaluated the initial safety of vemurafenib 960 mg administrated p.o. twice daily in three patients. In step 2, eight patients received vemurafenib 960 mg administrated p.o. twice daily for 28‐day treatment cycles; the primary outcome measure was response rate, as determined by independent review committee using Response Evaluation Criteria in Solid Tumors version 1.1. Adverse events (AE) experienced by five or more patients were arthralgia (n = 10), myalgia (n = 8), alopecia (n = 7), and rash, maculopapular rash and decreased appetite (n = 5 each). Three patients had grade 3 AE. One serious AE occurred in one patient (abnormal hepatic function). Six patients required dose reduction because of AE. One patient died within 28 days after the last dose, but death was caused by disease progression and not associated with the study drug. In the eight patients in step 2, overall response rate was 75.0%, none had a complete response and six had a partial response (75.0%). Median response duration was 240.0 days, disease control rate 87.5%, median progression‐free survival 416.0 days and median overall survival 443.0 days. In conclusion, vemurafenib treatment resulted in an overall response rate of 75% in Japanese patients with metastatic melanoma with BRAF^V600 mutations. All toxicities were manageable.     

Secukinumab demonstrates superior efficacy and a faster response in clearing skin in Asian subjects with moderate to severe plaque psoriasis compared with ustekinumab: Subgroup analysis from the CLEAR study

The 52‐week results from the CLEAR (NCT02074982) study showed high and superior efficacy of secukinumab versus ustekinumab in clearing skin and improving patient‐reported outcomes, with comparable safety profile in subjects with moderate to severe psoriasis. Here, we analyzed the efficacy and safety of secukinumab in Asian subjects from the CLEAR study. In this double‐blind, phase IIIb study, eligible subjects with moderate to severe plaque psoriasis were randomized (1:1) to receive s.c. injection of secukinumab 300 mg or ustekinumab as per label. Of 62 subjects included in Asian subanalyses, 23 were randomized to secukinumab and 39 to ustekinumab. A significantly higher proportion of subjects achieved 90% or more improvement in Psoriasis Area and Severity Index (PASI 90) with secukinumab versus ustekinumab at week 16 (78.3% vs 35.9%, P = 0.0010) and at week 52 (60.9% vs 33.3%, P = 0.0196). Similarly, a higher proportion of subjects achieved PASI 100 with secukinumab versus ustekinumab at week 16 (43.5% vs 10.3%, P = 0.0029) and at week 52 (30.4% vs 12.8%, P = 0.0704). The median time to achieve 50% improvement in baseline PASI was 2.8 weeks in the secukinumab group versus 6.3 weeks in the ustekinumab group. The safety profile of secukinumab was in line with the known profile and no deaths occurred. Overall, 95.7% and 84.6% of subjects remained on secukinumab and ustekinumab, respectively. Similar to the core study, secukinumab showed sustained and superior efficacy with faster response versus ustekinumab, and no new or unexpected safety concerns were identified, in Asian subjects with moderate to severe plaque psoriasis.     

Balance of Treg versus T‐effector cells during systemic treatment with adalimumab and topical treatment with calcipotriol–betamethasone dipropionate ointment

Diminished suppressive capacity of regulatory T cells (Treg) has been demonstrated in blood and in lesional skin of psoriatic patients. Treatment with anti‐TNFα restored the number and function of circulating Treg in psoriasis. We aimed to study Treg in the skin of psoriatic patients undergoing topical treatment with calcipotriol–betamethasone dipropionate (CBD) ointment (n = 12) or systemic treatment with anti‐TNFα agent adalimumab (n = 10). Skin biopsies were collected from patients with chronic plaque psoriasis who responded to the above‐mentioned treatments with a SUM‐score improvement of at least 50% (at the end of treatment). Biopsies were processed for immunohistochemistry. As Treg function is associated with a numerical balance between Treg and effector T cells, Foxp3/CD4 ratios were calculated. It appeared that both treatments cause a significant decrease in the presence of Foxp3+ cells. However, in patients that were treated with CBD ointment, we observed lower Foxp3/CD4 ratios after 8 weeks of treatment compared to baseline (t = 0: 0.41 ± 0.08; t = 8: 0.22 ± 0.04, P = 0.033), whereas in patients who were treated with adalimumab we observed an increase of the Foxp3/CD4 ratios after 1.5 and 16 weeks of treatment compared to baseline (t = 0: 0.25 ± 0.04; t = 1.5: 0.32 ± 0.06; t = 16: 0.49 ± 0.10, P = 0.15). Based on Foxp3/CD4 ratios, we can conclude that adalimumab treated skin differs from CBD treated skin with regard to the anti‐inflammatory/inflammatory balance. We suggest that, in contrast to CBD ointment, adalimumab favours local Treg function in the skin.     

Risk of subsequent cutaneous malignancy in patients with prior melanoma: a systematic review and meta‐analysis

Melanoma patients are known to be at risk of developing multiple cutaneous (pre‐) malignancies, however, the exact dimensions of these risks are unknown. In this meta‐analysis, risks of developing a melanoma, basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) after a melanoma were investigated. An extensive systematic literature search was conducted (last performed on 18 January 2012). Studies reporting risks, i.e. proportions, standardized incidence ratios (SIR) and cumulative risks (CRs) were included. Fifty, of 233 fully read articles, met selection criteria. Two independent reviewers extracted data on study characteristics and risks measurements. Random‐effects meta‐analyses were used to pool the risk estimates for the three tumour combinations. In melanoma patients, pooled proportions for a subsequent melanoma, BCC or SCC were respectively 3.8% (n = 47), 2.8% (n = 5) and 1.0% (n = 6). The pooled SIRs for a subsequent melanoma, BCC or SCC in melanoma patients were respectively 10.4 (n = 12), 4.6 (n = 2) and 2.8 (n = 2). Mean 20‐year CRs of a subsequent melanoma, BCC or SCC in melanoma patients were respectively 5.4% (n = 3), 14.0% (n = 1) and 4.0% (n = 1). Subgroup analyses showed substantial differences in reported risks between continents and study design. In conclusion, a history of a prior melanoma is a strong predictor for development of a subsequent melanoma (approximately 10‐fold increased risk) and to a lesser extent BCC or SCC. This information could serve as information for health care systems. Further, secondary prevention seems pivotal in this patient group.     

Novel CDKN2A mutation detected in Spanish melanoma pedigree

Please cite this paper as: Novel CDKN2A mutation detected in Spanish melanoma pedigree. Experimental Dermatology 2010; 19 : e333–e335. Abstract: We have examined alterations in the cyclin‐dependent kinase inhibitor 2A (CDKN2A) and cyclin‐dependent kinase 4 (CDK4), major melanoma predisposing genes, in a Spanish melanoma‐prone population comprising 61 patients from 45 families. Using an extensive genetic analysis of these genes, including sequence analysis and multiplex ligation‐dependent probe amplification, we have found four different CDKN2A alterations in cases from seven melanoma kindred. Three of them are CDKN2A mutations previously described in the Mediterranean population (p.G101W, p.V59G and c.358delG) in addition to an undescribed deletion (p. M54del) which has been detected in a melanoma kindred. This codon deletion affects an essential residue in the interaction of p16INK4A with cdk6 and has not been reported in melanoma patients and other cancers.     

Aberrant hypermethylation in primary tumours and sentinel lymph node metastases in paediatric patients with cutaneous melanoma

Background Debate on how to manage paediatric patients with cutaneous melanoma continues, particularly in those with sentinel lymph node (SLN) metastases who are at higher risk of poor outcomes. Management is often based on adult algorithms, although differences in clinical outcomes between paediatric and adult patients suggest that melanoma in paediatric patients differs biologically. Yet, there are no molecular prognostic studies identifying these differences. Objectives We investigated the epigenetic (methylation) regulation of several tumour‐related genes (TRGs) known to be significant in adult melanoma progression in histopathology(+) SLN metastases (n = 17) and primary tumours (n = 20) of paediatric patients with melanoma to determine their clinical relevance. Methods Paediatric patients (n = 37; ≤ 21 years at diagnosis) with American Joint Committee on Cancer stage I–III cutaneous melanoma were analysed. Gene promoter methylation of the TRGs RASSF1A, RARβ2, WIF1 and APC was evaluated. Results Hypermethylation of RASSF1A, RARβ2, WIF1 and APC was found in 29% (5/17), 25% (4/16), 25% (4/16) and 19% (3/16) of histopathology(+) SLNs, respectively. When matched to adult cutaneous melanomas by Breslow thickness and ulceration, hypermethylation of all four TRGs in SLN(+) paediatric patients with melanoma was equivalent to or less than in adults. With a median follow‐up of 55 months, SLN(+) paediatric patients with melanoma with hypermethylation of > 1 TRG vs. ≤ 1 TRG had worse disease‐free (P = 0·02) and overall survival (P = 0·02). Conclusions Differences in the methylation status of these TRGs in SLN(+) paediatric and adult patients with melanoma may account for why SLN(+) paediatric patients have different clinical outcomes. SLN biopsy should continue to be performed; within SLN(+) paediatric patients with melanoma, hypermethylation of TRGs can be used to identify a subpopulation at highest risk for poor outcomes who warrant vigilant clinical follow‐up.     

A prospective randomized controlled trial assessing the efficacy of adjunctive hyperbaric oxygen therapy in the treatment of hidradenitis suppurativa

Hyperbaric oxygen therapy (HBOT) appears to enhance wound healing, increase bactericidal activity, and act synergistically with a number of antibiotics. The aim of this study was to evaluate the efficacy of HBOT as an adjunctive therapy in patients with hidradenitis suppurativa (HS) treated with a combination of systemic rifampicin and clindamycin. The study was a prospective, single‐center, single‐dose, open‐label, randomized controlled clinical study of HBOT in patients with moderate to severe HS. Efficacy was measured by modified Sartorius score (SS), HS Severity Index (HSSI), Dermatology Life Quality Index (DLQI), and a visual analog scale (VAS) before treatment and after the completion of 4 and 10 weeks of treatment. Erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP) levels were also measured. Forty‐three patients were enrolled in the study. More patients in the HBOT than in the control group showed a decrease of ≥50% from baseline parameters at week 10 for SS (100%), HSSI (100%), DLQI (95.5%), VAS (100%), ESR (100%), and CRP (72.7%). Clinically and statistically significant improvements from baseline were observed at 4 and 10 weeks in HSSI (P = 0.009 at both), SS (P = 0.021 at both), and DLQI (P = 0.044 at week 4, P = 0.009 at week 10). Adjunctive HBOT was considered to be effective in significantly improving antibiotic treatment of HS. The treatment was well tolerated, and no unexpected safety issues were identified.     

Metabolic syndrome and psoriasis severity in South‐East Asian patients: An investigation of potential association using current and chronological assessments

Although studies regarding prevalence of metabolic syndrome (MS) in Asian psoriatic patients are limited and show varying results, a previous report describes a significant increase in prevalence of MS in Thai psoriatic patients, as compared with rates in the general population. However, no significant association between MS and psoriasis severity using the Psoriasis Area and Severity Index (PASI) was found, which differs from the findings of Korean and Japanese studies. This study aimed at re‐evaluating the association between MS and psoriasis severity in Thai patients using current assessment (PASI) and chronological assessment (historical course and interventions). A total of 273 psoriatic patients were recruited. After controlling for age and sex, 96 patients were assigned to the MS group and 96 patients to the non‐MS group. Similar to the previous study, no significant differences were identified between metabolic and non‐metabolic patients regarding PASI, age of onset, disease duration and family history of psoriasis. However, the numbers of hospitalizations (P = 0.018) and interventions (P = 0.028) were significantly higher in metabolic patients than in non‐metabolic patients. Further, a greater number of metabolic components was significantly associated with a higher number of hospitalizations (P = 0.012), pustular or erythrodermic psoriasis episodes (P = 0.049), and interventions (P = 0.005). Body mass index of 23 kg/m² or more, abdominal obesity and high blood pressure were associated with an increased risk of treatment failure. Using chronological assessment, our study supported that MS negatively affects psoriasis severity and treatment outcomes. Screening for MS is highly recommended for psoriatic patients.