Clinical practice consensus for the diagnosis and management of melanoma in Taiwan.

Melanoma is rare in Taiwan. Asian melanoma is distinct from Western melanoma because acral and mucosal melanoma accounts for the majority of melanoma cases, leading to distinct tumor behaviors and genetic profiling. With consideration of the clinical guidelines in Western countries, Taiwanese experts developed a local clinical practice consensus guideline. This consensus includes diagnosis, staging, and surgical and systemic treatment, based only on clinical evidence, local epidemiology, and available resources evaluated by experts in Taiwan. This consensus emphasizes the importance of surgical management, particularly for sentinel lymph node biopsies. In addition, molecular testing for BRAF is mandatory for patients before systemic treatment. Furthermore, immunotherapy and targeted therapy are prioritized for systemic treatment. This consensus aimed to assist clinicians in Taiwan in diagnosing and treating patients according to available evidence.

Genomic and tumour microenvironmental biomarkers of immune checkpoint inhibitor response in advanced Taiwanese melanoma.

Objective: Genomic biomarkers predicting immune checkpoint inhibitor (ICI) treatment outcomes for Asian metastatic melanoma have been rarely reported. This study presents data on next-generation sequencing (NGS) and tumour microenvironment biomarkers in 33 cases. Methods: Thirty-three patients with advanced melanoma, who underwent ICI treatment at the Chang Gung Memorial Hospital in Taiwan, were recruited. The study evaluated clinical outcomes, including response rate, disease control rate, progression-free survival (PFS) rate and overall survival (OS) rate. Archived tissue samples from 33 cases were subjected to NGS by ACTOnco, and ACTTME was employed in 25 cases. Results: The most prevalent driver mutations were BRAF mutations (24.2%), followed by NRAS (15.2%), KIT (12.1%), KRAS (9.1%) and NF1 (9.1%) mutations. Acral/mucosal melanomas exhibited distinct mutation patterns compared to non-acral melanomas. Tumour mutational burden estimated using ACTOnco was not associated with ICI efficacy. Notably, genetic alterations in the p53 pathway (CDKNA2 loss, MDM2 gain/amplification and TP53 mutation) accounted for 36.4% and were significantly associated with unfavourable PFS (median PFS 2.7 months vs. 3.9 months, P = 0.0394). Moreover, 26 genes were identified as differentially expressed genes that were upregulated in patients with clinical benefits compared to those without benefits. Four genes, GZMH, GZMK, AIM2 and CTLA4, were found to be associated with both PFS and OS. Conclusion: Genetic alterations in the p53 pathway may be critical in Asian patients with melanoma undergoing ICI treatment. Further investigation is required to explore this mechanism and validate these findings.

Immune Checkpoint Inhibitors for Advanced Melanoma: Experience at a Single Institution in Taiwan.

Background: Immune checkpoint inhibitors (ICIs) have significantly changed the current approach to cancer treatment. Although the use of ICIs has become the standard of care for advanced melanoma, reports of ICI use among Asian populations with melanoma are limited. Therefore, we conducted this retrospective study to assess the efficacy and safety of ICI use in Taiwanese patients. Patients: Patients with histologically confirmed melanoma treated with ICIs at Linkou Chang Gung Memorial Hospital from January 2014 to July 2019 were retrospectively reviewed. Univariant and multivariant analyses were performed to identify possible prognostic factors. Results: Among 80 patients, 45 were treatment-naïve (56.3%), and 35 received prior systemic drugs other than ICIs. Regarding treatment regimens, patients were treated with ipilimumab (n = 9), nivolumab (n = 33), pembrolizumab (n = 16), or combination drugs (n = 22). Nine patients achieved either a complete (n = 2) or partial (n = 7) response and 13 patients were stable, with a resulting response rate of 11.3% and disease control rate of 27.5%. As of the last follow-up in January 2020, patients treated with combination drugs had longer median progression-free survival (PFS) of 5.6 (95% confidence interval [CI]: 1.6-9.6) months than nivolumab (2.9 months, 95% CI: 1.9-3.9 months), pembrolizumab (3.2 months, 95% CI: 2.6-3.8 months), and ipilimumab (2.6 months, 95% CI: 2.4-2.8 months; p = 0.011). No significant differences in overall survival (OS) among the four regimens (p = 0.891) were noted. In the multivariate analysis, combination treatment, disease control, and performance ≤ 1 were independent prognostic factors for PFS. Liver metastases and no disease control were independent unfavorable prognostic factors for OS. The most common factor was skin toxicity (45%), followed by endocrine toxicity (18.8%). Patients undergoing combination treatment experienced more frequent and serious adverse events than patients undergoing monotherapy. Conclusion: ICIs demonstrated efficacy and safety in Taiwanese patients with melanoma. Combination treatment showed the greatest efficacy, but this was also accompanied by greater toxicity among the four regimens. In addition, we identified important prognostic factors, such as liver metastases, performance status, and tumor response, for both PFS and OS. These findings could provide physicians with more information to justify clinical outcomes observed in Asian patients with advanced melanoma.

Sentinel Lymph Node Biopsy Was Associated With Favorable Survival Outcomes For Patients With Clinically Node-Negative Asian Melanoma.

PURPOSE: Sentinel lymph node biopsy (SLNB) is the standard management for clinically node-negative cutaneous melanoma patients. This study aimed to evaluate the role of SLNB in Taiwanese melanoma patients and in particular, patients with acral lentiginous melanoma (ALM). PATIENTS AND METHODS: We retrospectively analyzed the clinicopathological characteristics and survival outcomes of the patients who underwent primary surgery followed by either SLNB or nodal observation at the Linkou Chang Gung Memorial Hospital from January 2000 to December 2011. RESULTS: Among the total of 209 patients, 127 underwent SLNB and 51 underwent nodal observation only after primary surgery. There were no significant differences in clinicopathological features between the two groups except that patients who underwent SLNB were older and had a higher rate of ALM than those under nodal observation. The median follow-up time was 43.5 months until July 2013. The patients who underwent SLNB had significantly better disease-free survival (DFS) (57.1 vs 18.7 months, p < 0.01) and melanoma-specific survival (MSS) (112.4 vs 45.2 months, p < 0.01) than those under observation. Improvement in DFS (HR: 0.51, p < 0.01) and MSS (HR: 0.60, p = 0.03) was observed even after adjusting for age and disease pathology by multivariate analysis. This benefit of clinical outcomes persisted in patients with ALM, Breslow thickness ≤2 mm, or no ulceration, but not in patients with non-ALM, Breslow thickness >2 mm, or ulceration. CONCLUSION: SLNB was associated with favorable outcomes in patients with clinically node-negative cutaneous melanoma, particularly in Taiwanese patients with ALM, Breslow thickness ≤2 mm, and nonulcerated melanoma.

Psoriasiform drug eruption secondary to sorafenib: case series and review of the literature.

The expanding use of novel targeted anticancer agents such as sorafenib has led to an increasing number of dermatologic adverse events. Although cutaneous adverse events are commonly described in patients taking sorafenib, there are few reports describing psoriasis secondary to this medication. In this report, we describe 3 patients with sorafenib-induced psoriasiform drug eruption and review the available literature of similar patient cases. Our findings highlight shared characteristics among affected patients and potential treatment options for patients in whom sorafenib cannot be discontinued. Increased awareness of such drug eruptions and management options is critical to prevent suboptimal dosing and decreased quality of life.

Merkel cell carcinoma in Taiwan: A series of 24 cases and literature review.

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine carcinoma of the skin. The available reports of MCC in Asia are limited; in this study, we report the largest series of MCC in Taiwan to date.The series is composed by 24 pathologically proven MCC cases, which were retrospectively reviewed in Chang Gung Memorial Hospital in Taiwan between 2000 and 2018.The tumor occurred predominantly in men (80%) and in the elderly (median 74.8 years). Twenty-one patients had locoregional MCC and 3 had metastatic MCC at the time of diagnosis. Patients with pathologically proven negative nodes by sentinel lymph node biopsy (SLNB) showed better survival time than those without SLNB in 16 clinically node-negative MCC cases undergoing primary surgery. Salvage surgery for loco-regional recurrence lengthened the survival time and possibly cured recurrent MCC. Palliative chemotherapy with cisplatin and etoposide showed a response rate of 25%, progression-free survival of 3.6 months, and overall survival of 14.8 months in 4 metastatic/recurrent MCC. Avelumab treatment was effective in 1 patient, who achieved a durable disease control.This observational cohort of MCC patients in Taiwan suggests aggressive surgical intervention including wide excision and lymph node management, salvage operation is critical for early MCC patients, and palliative chemotherapy and immunotherapy showed their efficacy for advanced MCC patients.

Scleromyxedema and lichen myxedematosus: Is it associated with viral hepatitis?

Scleromyxedema (SM) was previously known to be associated with monoclonal gammopathy. The association of SM and its counterpart lichen myxedematosus (LM) with chronic hepatitis has rarely been reported. We retrospectively reviewed medical records and histopathological reports of consecutive patients who presented at our department with the diagnosis of SM or LM from January 2001 to September 2017. The patients' demographic details, cutaneous presentation, associated underlying diseases and hepatitic profile were studied and compared with previous published cases. In all, 28 patients were enrolled, including one SM, 19 LM and eight atypical LM. Of the patients, 50% (n = 14/28) had hepatitis. Of these, 21.4% (n = 6/28) had hepatitis C, 10.7% (n = 3/28) hepatitis B, 7.1% (n = 2/28) concurrent hepatitis B and C, whereas 10.7% (n = 3/28) had alcoholic liver disease. The prevalence of hepatitis C in our patients was 6.5-times higher than that of the general population (28.6% vs 4.4%) and the prevalence of hepatitis B was similar (17.9% vs 17.3%). Polyclonal gammopathy was found in 28.6% (n = 8/28) of the patients and monoclonal gammopathy was found in 7.1% (n = 2/28). The extent of clonality did not correlate with disease severity. Our study did not notice a significant association with monoclonal gammopathy but the prevalence of hepatitis C was found to increase 6.5-times in these patients compared with the general population. We recommend dermatologists to be aware of hepatitis investigations in such patients and future studies are warranted to understand the mechanism behind such association.

Smartphone wallpapers for dermoscopy training in medical students and residents.

BACKGROUND: Several dermoscopy training programs have found the accuracy of dermoscopy examination depends on adequate training of practitioners. Smartphones are readily available and time-efficient tools for dermoscopy training. AIM: To evaluate the learning efficacy of utilizing dermoscopy smartphone wallpapers to train medical students, PGY (postgraduate year)-1 trainees, and junior dermatological residents without prior dermoscopy training. METHODS: We designed smartphone wallpapers with dermoscopy pictures and features of several common melanocytic and nonmelanocytic conditions. Pretests and posttests were performed before and after a 10-day-long smartphone wallpaper training program to evaluate their diagnostic accuracy using dermoscopy images. RESULTS: Significant progressions were noted between the pretest and posttest scores both in the nonmelanocytic (P < 0.001) and the melanocytic (P = 0.003) sections. Medical students and PGY-1 trainees demonstrated more significant improvement in nonmelanocytic lesions, compared to dermatology residents. Residents of dermatology showed more progression in the melanocytic section than nonresidents. LIMITATIONS: There were limited participants. The frequency and time allotted by each participant in perusing the wallpapers were variable. Further study of the application on clinical practice is still needed. CONCLUSION: Smartphone wallpapers training improves dermoscopic interpretation significantly in medical students, PGY-1 trainees, and dermatological residents. The background knowledge of dermatology has an effect on the degree of improvement in the training course.

Acquired perforating calcific collagenosis in a drug addict with rhabdomyolysis and transient hypercalcemia.

Acquired perforating calcific collagenosis (APCC), which is characterized by the calcification of dermal collagen fibers with subsequent transepidermal elimination and perforation, is an extremely rare entity. Thus far, it has only been reported in a patient with direct contact exposure to calcium chloride. Here, we report a unique case of APCC occurring in a drug addict admitted for rhabdomyolysis. The present case is a 20-year-old male patient hospitalized for drug-related rhabdomyolysis and multiple organ damage. During hospitalization, he gradually developed unusual skin rashes. There were multiple confluent umbilicated and keratotic erythematous to brownish papules and plaques with scratch-like linear plaques on his lower abdomen, inguinal areas and gluteal sulci. Also, multiple well-demarcated flesh-colored rough, hard and thin plaques with a "crepe paper"-like texture were found on the bilateral popliteal fossae, olecranon fossae and axillae. The histopathology of two biopsied lesions demonstrated acquired perforating calcific collagenosis. The lesions appeared during the rhabdomyolysis-related hypercalcemia phase and resolved spontaneously after the calcium level returned to normal. This is the first reported case of disseminated APCC occurring during transient hypercalcemia due to rhabdomyolysis.

In vivo detection of UV-induced acute skin effects using optical coherence tomography.

Ultraviolet (UV) rays have been identified as a carcinogen with long-term irradiation and are an important risk factor for skin cancer. Here, we report the use of optical coherence tomography/optical coherence tomography angiography (OCT/OCTA) to study acute UV-induced effects on skin in vivo. To understand the relationship between the acute effects and irradiated UV power density, three groups were irradiated with different power densities in our experiments. Furthermore, the same skin area was repeatedly scanned with OCT during UV irradiation to investigate the progress of the induced acute effects and after irradiation for observation of skin recovery. Subsequently, the OCT/OCTA results were quantitatively analyzed to acquire skin thickness and blood-vessel density for comparison. UV-induced acute effects on morphology and microcirculation can be identified from OCT/OCTA results, which showed the increases in the skin thickness and blood-vessel density and even severe damage types such as blisters. The results of quantitative analyses also illustrated that the severity of damage induced by UV irradiation can be distinguished and the skin recovery can be monitored with OCT. Our results indicate that OCT can be a promising tool for early detection of UV-induced acute skin damage.

Novel Patched 1 Mutations in Patients with Gorlin-Goltz Syndrome Strategic Treated by Smoothened Inhibitor.

We studied a family with Gorlin-Goltz syndrome. The novel mutations of our cases were located on the 21st exon of the PTCH1 gene (c.3450C>G). The father, who received a strategic 56-day vismodegib treatment for disease control, was the first patient with Gorlin syndrome treated with the hedgehog inhibitor in Taiwan. The lesions regressed gradually, with scar formation, and were subsequently removed via a wide excision. Further details are provided below.

Non-Tuberculous Mycobacteria Infection Following Autologous Fat Grafting on the Face.

LEVEL OF EVIDENCE: 5.

Interfacial properties of Pluronics and the interactions between Pluronics and cholesterol/DPPC mixed monolayers.

Pluronics are triblock copolymers of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) with wide range of hydrophilic-lipophilic balance. In order to investigate the relationship between the chemical structures of Pluronics and the interfacial properties at the air-water interface by monolayer techniques, Pluronics L61, P65, F68, P84, P123, L35, and P105 were selected. Since cholesterol influenced substantially the molecular packing stage and the characteristics of cell membranes, the interactions between Pluronics and model cell membranes in the absence and presence of cholesterol were compared. The results of pi-A isotherms and surface elasticities of Pluronic monolayers indicated that the first and second transition like stage were mainly affected by the numbers of EO and PO monomers, respectively. Pluronics with higher hydrophobicities demonstrated larger surface activities and penetration abilities to dipalmitoylphosphatidylcholine (DPPC) monolayers, which might be due to hydrophobic interactions and van der Waals forces. In the presence of cholesterol, hydrogen bonding effects was supposed to exist between the 3beta-hydroxy group of cholesterol and ether oxygen of PEO chains, which led Pluronic F68, with the longest PEO chain herein, to exhibit significantly higher penetration ability. Our findings proposed a theoretical basis for selection of optimized drug carriers and the starting point for further investigations.