Post-Excision Soft X-Ray Radiotherapy for Keloids: Experience in a Tertiary Referral Center.

INTRODUCTION: Keloid is an abnormal proliferation of scar tissue that grows beyond the original margins of the injury. Even after complete resection, recurrences are common and pose a poorly understood challenge in dermatology. There is lack of large prospective clinical trials; thus, treatment recommendations are based on retrospective analyses and small cohort studies. Superficial radiotherapy is recommended in recurrent keloids; however, the successful treatment rates vary greatly. The aim of this study was to evaluate the keloid recurrence rate after post-excision soft X-ray radiotherapy and the associated factors. METHODS: We reviewed retrospective data of all patients, treated with adjuvant post-excision soft X-ray radiotherapy with 12 Gy in 6 sessions at the tertiary referral center, Department of Dermatology, University Hospital Zurich, Switzerland, between 2005 and 2018. We analyzed individual keloids as separate cases. Successful treatment was defined as no sign of recurrence within 2 years. RESULTS: Of the 200 identified patients, 90 met the inclusion criteria and were included in the final analysis. In 90 patients, 104 cases of treated keloids were analyzed. Keloids were mainly located on the trunk (49%) and were mostly caused by previous surgery (52.2%). 50% of the keloids did not relapse within 2 years after therapy. A significant factor leading to recurrence was the presence of previous therapy, with prior topical therapies, such as steroid injections or 5-fluorouracil, leading to most relapses. 69.2% of keloid cases who relapsed were pretreated. Soft X-ray radiotherapy was well tolerated, with posttreatment hyperpigmentation noted in 34% of patients, particularly in patients with non-Caucasian origin (61.3%). CONCLUSION: Treatment of refractory keloids is difficult. Post-excision radiotherapy is an established adjuvant treatment option; nevertheless, recurrence rates are high, especially in pretreated keloids. Prospective studies determining the exact dosage and fraction of post-excisional radiotherapy are needed to determine the optimal radiation parameters.

Impact of Covid-19 on the management of patients with metastatic melanoma.

The Covid-19 pandemic created new uncertainties in the management of metastatic melanoma patients. In particular, the impact of immunotherapy, targeted therapy, or chemotherapy on the risk of Sars-CoV-2 infection and severity was debated. In this study, we analyzed all patients with metastatic melanoma receiving therapy who developed Covid-19 between February 2020 and February 2022. We retrospectively collected demographic data, cancer-specific parameters, melanoma treatment regimen, comorbidities and Covid-19-specific parameters in these patients. Of the 350 patients with metastatic melanoma, 25 had Covid-19. The median age at the time of Covid-19 diagnosis was 66 years (range 36-86), 10 patients were female, and 15 patients were male. The treatment regimen during infection was immunotherapy in 12 cases, followed by targeted therapy (n = 8), chemotherapy (n = 2), and TVEC injections, follow-up and palliative therapy in 1 case each. The severity was mild in 17 patients and 8 had a moderate to critical course. Patients with a severe Covid-19 course were often older and had more comorbidities than patients with a mild infection. Many of the patients had a mild Covid-19 course despite having metastatic melanoma and systemic therapy. We therefore recommend continuing systemic therapy whenever possible, even in such exceptional situations as the Covid-19 pandemic.

HautTief Multidisciplinary Educational Program for Patients with Psoriasis or Atopic Dermatitis: A Randomized Controlled Study.

BACKGROUND: Improving health-related quality of life (HRQoL), disease severity, and treatment adherence through patient education is an increasingly important, yet relatively new area in dermatology. This randomized controlled trial aims to contribute to this growing area of research by exploring the effects of a 9-week educational program for patients with chronic skin diseases. OBJECTIVE: The aim of the study was to evaluate the effect of a multidisciplinary educational program on HRQoL and disease severity in patients with psoriasis or atopic dermatitis (AD). METHODS: Sixty-four patients with diagnosed psoriasis or AD were recruited from University Hospital Zurich and randomized (1:1) to the intervention or control group. To assess HRQoL, the following self-reported questionnaires were used: Dermatology Life Quality Index (DLQI), Skindex-29, EuroQol-5D (EQ-5D), RAND 36-Item Short Form Survey (SF-36), and Beck Depression Inventory (BDI) to measure depression symptoms. Psoriasis Area and Severity Index (PASI) and the Eczema Area and Severity Index (EASI) were used to capture disease extent. These scores were assessed at four study visits, which were performed at baseline and 3, 6, and 9 months after the start of the program. RESULTS: At month 6, an improvement of at least 25% in BDI was recorded in 15 (68.2%) of 22 patients in the intervention group and 6 (27.3%) of 22 patients in the control group (difference 40.9%, p = 0.016). 53.3% (16 of 30) of patients achieved an improvement in one subdomain of the SF-36 score (role limitations due to emotional problems) at 6-month follow-up, compared with 23.1% (6 of 26) of those not attending the educational program (difference 30.2%; p = 0.042). No significant differences in DLQI, Skindex-29, EQ-5D, PASI, and EASI between both groups at the three time points were found. CONCLUSION: An educational program may improve HRQoL and depression status of patients with psoriasis or AD.

Radiotherapy as a Treatment Option for Local Disease Control in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type.

BACKGROUND: Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT) is an aggressive lymphoma variant. Anthracycline-based chemotherapy with rituximab is recommended as first-line treatment. Radiotherapy (RT) has been considered as a therapeutic option for local disease control in patients with solitary or localized lesions. METHODS: We report the results of a retrospective analysis of PCDLBC, LT patients treated either with RT alone or with physician's decision as first-line treatment, aiming to assess disease progression and/or first recurrence in these treatment groups. RESULTS: We retrospectively analyzed 20 patients treated either with RT alone (n = 8) or with investigator's choice treatment (n = 12), which included chemotherapy alone or combined with local therapy (RT and wide local excision). Complete response (CR) was achieved in 8 patients from the first group and 9 patients from the second group, with 1 treatment failure. Six patients treated with RT alone progressed with a median time to progression (TTP) of 12.5 months. In the second group, 5 patients progressed with a median TTP of 5.2 months. RT showed good local disease control in both groups without any skin relapses during the follow-up period. CONCLUSION: RT as first-line monotherapy followed by watchful waiting did not significantly improve the overall risk of disease progression but resulted in good local disease control. After progression, RT could still easily be combined with systemic treatment. The strength of this analysis needs to be evaluated in a larger patient cohort.

Results of a 10-year web-based health promotion campaign against skin cancer in Switzerland.

Skin cancer is the most common malignancy with rising incidence. Although early detection can be lifesaving, prevention programmes are under-utilized. In 2008, a group of board-certified dermatologists in Switzerland established a website aimed at educating about skin cancer risk factors and providing guidance on self-assessment. To present the data of this programme over the last 10 years with regards to representation of the targeted groups and sustained impact on primary skin cancer prevention. A comprehensive web-based health promotion campaign was established for education and guidance on self-assessment. Teledermatological evaluation was offered and participants were then interviewed. In total, 11,171 digital photos were evaluated during 2008-2018; 54.3% (n = 6,067) from females and 45.7% (n = 5,104) from males. In 26.7% (n = 2,983), clinical examination was recommended. Of the participants, 1,874 replied revealing 103 malignancies (9.2% of the lesions were presented to a physician): 34 melanomas in situ, six squamous cell carcinomas, 53 basal cell carcinomas and 10 malignant lesions (not further specified). Of the participants, 40.5% (n = 683) changed their attitude towards sun exposure, 48.7% (n = 820) used more sunscreen, and 57.5% (n = 966) improved sunscreen measures. Web-based educational programmes raise public awareness, enhance prevention, and support early diagnosis of skin cancer. Teledermatology might contribute to reducing skin cancer mortality rates.

Fractional CO2 laser to improve noticeable scars after skin cancer surgery: An appraisal by the patients, laypersons, and experts.

Ablative fractionated carbon dioxide (fCO2 ) laser may be a useful tool to improve noticeable scars after skin cancer surgery. Therefore we evaluated 40 patients who have been treated with fCO2 laser for facial scars after skin cancer surgery. This retrospective study is based on blinded evaluation of pre- and postoperative photographs. Patients (n = 40), laypersons (n = 5) and experts (n = 5) evaluated the esthetics and the Vancouver scar scale as primary endpoints. Secondary endpoints included patient satisfaction and treatment safety. Patients, laypersons and experts consistently assessed a significant improvement of scar quality and appearance after fCO2 laser treatment, which was paralleled by high patient satisfaction. In conclusion, ablative fCO2 laser is effective in improving noticeable postsurgical scars. Patients are highly satisfied with post-laser results.

Topical Over-the-Counter Antiaging Agents: An Update and Systematic Review.

Over-the-counter antiaging formulations aim to prevent or minimize the signs of aging skin, and to maintain the benefits obtained from different cosmetic procedures. Even though a huge selection of such products is available on the market, evidence and good clinical practice of the data supporting their use are oftentimes lacking. In this systematic review, the authors reviewed scientific data available in the published literature on the most common ingredients used in antiaging cosmetics, with a particular focus on in vivo studies.

Canakinumab Lacks Efficacy in Treating Adult Patients with Moderate to Severe Chronic Spontaneous Urticaria in a Phase II Randomized Double-Blind Placebo-Controlled Single-Center Study.

BACKGROUND: Chronic idiopathic/spontaneous urticaria (CSU) is a common disease with a significant proportion of patients who do not respond to standard therapy with antihistamines and optionally corticosteroids/immunosuppressants. OBJECTIVE: The IL-1ß antagonist canakinumab is effective in cryopyrin-associated periodic syndromes associated with urticarial symptoms and urticarial vasculitis, and so it was suspected that it could also be effective in patients with CSU. METHODS: The effect of canakinumab was investigated in 20 patients with moderate to severe CSU in a 1:1 randomization to either canakinumab or placebo in a double-blind single-dose crossover design. The verum group received 150 mg canakinumab subcutaneously once at baseline. Patients who had received placebo were able to switch to canakinumab at week 4 if they did not improve. The primary end point was clinical improvement at week 4 compared with baseline in sum of urticaria activity scores over 7 consecutive days. Secondary end points were the clinical improvement at week 8 compared with baseline in sum of urticaria activity scores over 7 consecutive days and the clinical improvement measured by the Physician Score and Dermatology Life Quality Index at week 1, 2, 4, and 8. RESULTS: At week 4, 2 patients with canakinumab and 3 with placebo met the primary end point, and so canakinumab failed the significant superiority to the placebo (P = 1.0). An inclusion of the patients who switched to canakinumab after 4 weeks did not alter the result. There was also no significant difference between the verum and placebo groups for all secondary end points. The therapy was well tolerated, and mild adverse events were equally distributed between verum and placebo groups. CONCLUSIONS: Because of this clinical trial with 20 patients, it must be assumed that canakinumab has no effect on lesions of CSU. This suggests that IL-1ß may not play a crucial role in pathology of patients with CSU, unlike, for example, in hereditary fevers or urticarial vasculitis, where targeting IL-1 is a main treatment option. However, the good tolerability of canakinumab could be confirmed.

Serum CD73 is a prognostic factor in patients with metastatic melanoma and is associated with response to anti-PD-1 therapy.

BACKGROUND: Inhibitors of immune checkpoint programmed cell death protein 1 (PD-1) receptor on T cells have shown remarkable clinical outcomes in metastatic melanoma. However, most patients are resistant to therapy. Production of extracellular adenosine, via CD73-mediated catabolism of AMP, contributes to suppress T-cell-mediated responses against cancer. In this study, we analyzed the expression and activity of soluble CD73 in sera of patients with melanoma undergoing anti-PD-1± cytotoxic T-lymphocyte-associated antigen 4 therapy. METHODS: Soluble CD73 expression and activity were retrospectively analyzed in serum of a total of 546 patients with melanoma from different centers before starting treatment (baseline) with anti-PD-1 agents, nivolumab or pembrolizumab, and compared with those of 96 healthy subjects. The CD73 activity was correlated with therapy response and survival of patients. RESULTS: Patients with melanoma show significantly higher CD73 activity and expression than those observed in healthy donors (p<0.0001). Elevated pretreatment levels of CD73 activity were associated with non-response to therapy with nivolumab or pembrolizumab. During treatment, levels of soluble CD73 activity remain unchanged from baseline and still stratify clinical responders from non-responders. High levels of serum CD73 enzymatic activity associate with reduced overall survival (OS; HR=1.36, 95% CI 1.03 to 1.78; p=0.03) as well as progression-free survival (PFS; HR=1.42, 95% CI 1.13 to 1.79, p=0.003). Further, the multivariate Cox regression analysis indicates that serum CD73 activity is an independent prognostic factor besides serum lactate dehydrogenase levels and the presence of brain metastases for both OS (p=0.009) and PFS (p=0.001). CONCLUSION: Our data indicate the relevance of serum CD73 in patients with advanced melanoma receiving anti-PD-1 therapy and support further investigation on targeting CD73 in combination with anti-PD-1 antibodies.

Photodynamic therapy improves skin antisepsis as a prevention strategy in arthroplasty procedures: A pilot study.

BACKGROUND: Current standard skin antisepsis to prevent surgical site infections are ineffective to eradicate all skin-colonizing bacteria. Photodynamic therapy (PDT) has shown bactericidal effects in vitro, but no clinical study with improvements in skin antisepsis has been documented. METHODS: We investigated the effect of methyl aminolevulinate (MAL)-PDT versus no PDT for skin antisepsis treatment (povidone-iodine/alcohol) in the groin of 10 healthy participants. Skin swabs were taken at baseline, immediately after PDT, and after skin antisepsis treatment to cultivate bacteria. At day 7 and 21, bacterial cultures were repeated before and after antisepsis treatment without PDT. Skin biopsies were performed to examine the grade of inflammation. RESULTS: Skin-colonizing bacteria were found in all 20 participants at baseline sampling. Immediately after MAL-PDT, skin was sterile in 7 (70%) participants before and in all 10 (100%) participants after skin antisepsis treatment. In contrast, we found skin-colonizing bacteria in 5 (50%) participants of the control group receiving only skin antisepsis. After 7 and 21 days, skin sterility was similar to the baseline. We observed slight perivascular inflammation with lymphocytes and eosinophils without changes in the histomorphology of eccrine or sebaceous glands in skin biopsies. PDT was generally well tolerated except for localized redness. CONCLUSION: MAL-PDT with skin antisepsis treatment sterilized skin immediately after its use but did not maintain sterility 7-21 days post-treatment. Due to local side effects, further clinical studies with less intensive PDT conditions or other photosensitizers are needed before PDT is integrated into clinical practice.

Donor site aesthetics and morbidity after DIEP flap breast reconstruction-A retrospective multicenter study.

The deep inferior epigastric artery perforator flap (DIEP) has gained widespread popularity in autologous breast reconstruction due to its natural aesthetic results and muscle-sparing design. However, donor site results regarding aesthetic outcome are often less favorable. We therefore aimed to identify crucial factors that might increase the risk for abdominal bulging and an impaired aesthetic appearance. We conducted a multicenter study evaluating all patients receiving autologous breast reconstruction using a DIEP flap between 2013 and 2017. Medical records were analyzed with special attention to flap technique, number of perforators, localization of perforator, and donor site complications. In addition, the aesthetic appearance of the abdominal donor site was evaluated by blinded clinicians at one-year follow-up. A total of 242 patients underwent DIEP flap breast reconstruction. Abdominal bulging occurred in 7%. Further subgroup analysis revealed a significant correlation between abdominal bulging and two or more perforators (P = .003), the use of lateral row perforators (P = .009), and a higher BMI (P = .002). Obesity (P = .003) and higher patient's age (P = .003) could be identified as risk factors for an undesirable appearance of the donor site. We recommend the use of a medial-row single perforator whenever possible in order to optimize donor site morbidity and decrease the risk of abdominal bulging. Proper patient selection and careful donor site closure following a standardized approach should be performed to limit the risk of aesthetically undesirable results.

Toxicity of combined targeted therapy and concurrent radiotherapy in metastatic melanoma patients: a single-center retrospective analysis.

The Eastern Cooperative Oncology Group consensus guidelines from 2016 recommend interruption of targeted therapy with BRAF- and MEK-inhibitors during radiotherapy with data being based mostly on BRAF monotherapy. The aim of this study is to provide data on the safety of concurrent radiotherapy and combination targeted therapy with BRAF- and MEK-inhibitors. A total of 32 patients with 51 sessions of radiotherapy from one center receiving concurrent radiotherapy and BRAF- and MEK- inhibitors were included. Radiotherapy-associated toxicities were retrospectively collected. Incidence was compared between three groups: (A) targeted therapy during radiotherapy with and, (B) without interruption, and (C) radiotherapy before the start of targeted therapy. Survival and local disease control were examined. Targeted therapy was interrupted during radiotherapy in 16, not interrupted in 14, and only started after radiotherapy in 21 sessions. Stereotactic radiotherapy was applied in 28 sessions, conventionally fractionated radiotherapy in 23. The brain was the most common site of irradiation (n = 36). Radiotherapy-associated toxicities occurred in 41.2% (n = 21) of sessions and did not differ significantly among the groups. Overall survival was 11.7 months and progression-free survival was 8.4 months. No increase in radiotherapy-associated toxicity was seen where combination targeted therapy was not interrupted during radiotherapy. Prospective clinical trials are warranted to support our findings.

Laser Treatment of Accidental Tattoos: Experience at a Tertiary Referral Center.

BACKGROUND: To date, information on laser treatment of accidental tattoos is limited. OBJECTIVES: This study analyzes the efficacy and safety of quality-switched ruby, quality-switched Nd:YAG and picosecond lasers in the treatment of accidental hyperpigmentation in a larger patient cohort. To date, there is limited information on laser therapy of accidental hyperpigmentation. METHODS: We conducted a retrospective systematic single-center analysis on 70 patients, which presented with accidental hyperpigmentation at the Dermatology Department of the University Hospital of Zurich between 2008 and 2017. Patients with accidental tattoos due to road injuries, explosives or other traumas and iatrogenic measures were included. We analyzed the data including laser parameters such as wavelength, energy density, spot size and intervals between the sessions. Also, the number of sessions performed and the overall success were registered. RESULTS: We treated 38 patients by quality-switched nano- and/or picosecond laser therapy and completed the treatment in 28 cases within a mean number of 3-5 laser sessions. No complications occurred. CONCLUSION: We demonstrate the validity and safety of quality-switched and picosecond lasers in the treatment of accidental hyperpigmentation. Using a combination of different wavelengths and pulse lengths on the same lesion and gradually increasing the fluence in the course of the laser treatment is recommendable to increase efficacy. We observed a tendency towards faster elimination of facial accidental tattoos and/or originating from road injuries compared to tattoos located on the extremities and those caused by explosions, piercings or iatrogenic measures or consisting of metal pigment particles.

Evaluation of the minimal erythema dose for UVB and UVA in context of skin phototype and nature of photodermatosis.

BACKGROUND: Phototesting is part of the standard procedure for the evaluation of patients with photosensitivity disorders. The response of patients to targeted UVB or UVA radiation helps to find out more about the nature of photodermatosis. Nevertheless, there are no default values of the minimal erythema dose (MED). METHODS: This study evaluated data of 203 patients (131 female, 72 male, mean age 52 years) who were referred for phototesting to the University Hospital Zurich between 2012 and 2017. We retrospectively analyzed the demographic data, medical history, skin phototype, reaction to UVB and UVA radiation, and, if present, the diagnosis of photodermatosis. In patients who did not develop erythema at the highest tested UV doses, the next logical increment was taken for analysis. In case of UVA, the two periphery doses could not be evaluated due to technical issues, so the closest reliable UVA doses were used. RESULTS: The MED-UVB correlated with the skin type and increased with a higher phototype. No such correlation could be seen for MED-UVA. However, the MED-UVA was significantly reduced in patients with photodermatosis without significant differences between the subgroups of photodermatosis. More than half of the patients did not show a reduced MED despite a diagnosed photodermatosis. CONCLUSION: We showed, how different skin types with and without photodermatosis react to UV radiation. Based on the results, we suggested threshold doses that can be chosen for phototesting, presented which doses can be considered pathologic and showed the probability of a pathologic MED in correlation with a diagnosed photodermatosis.

Buffered lidocaine 1%/epinephrine 1:100,000 with sodium bicarbonate (sodium hydrogen carbonate) in a 3:1 ratio is less painful than a 9:1 ratio: A double-blind, randomized, placebo-controlled, crossover trial.

BACKGROUND: Neutralizing (buffering) lidocaine 1%/epinephrine 1:100,000 solution (Lido/Epi) with sodium hydrogen carbonate (NaHCO3) (also called sodium bicarbonate) is widely used to reduce burning sensations during infiltration of Lido/Epi. Optimal mixing ratios have not been systematically investigated. OBJECTIVES: To determine whether a Lido/Epi:NaHCO3 mixing ratio of 3:1 (investigational medicinal product 1) causes less pain during infiltration than a mixing ratio of 9:1 (IMP2) or unbuffered Lido/Epi (IMP3). METHODS: Double-blind, randomized, placebo-controlled, crossover trial (n = 2 × 24) with 4 investigational medicinal products (IMP1-4). RESULTS: The 3:1 mixing ratio was significantly less painful than the 9:1 ratio (P = .044). Unbuffered Lido/Epi was more painful than the buffered Lido/Epi (P = .001 vs IMP1; P = .033 vs IMP2). IMP4 (NaCl 0.9% [placebo]) was more painful than any of the anesthetic solutions (P = .001 vs IMP1; P = .001 vs IMP2; P = .016 vs IMP3). In all cases, the anesthesia was effective for at least 3 hours. LIMITATIONS: Results of this trial cannot be generalized to other local anesthetics such as prilocaine, bupivacaine, or ropivacaine, which precipitate with NaHCO3 admixtures. CONCLUSIONS: Lido/Epi-NaHCO3 mixtures effectively reduce burning pain during infiltration. The 3:1 mixing ratio is significantly less painful than the 9:1 ratio. Reported findings are of high practical relevance, given the extensive use of local anesthesia today.

Use of Lasers for Iron-Induced Accidental Tattoos: Experience at a Tertiary Referral Center.

BACKGROUND: Awareness of accidental tattoos after iron injections with paravenous leakage is low. No larger patient cohorts have been analyzed. The lesions are a burden to the patients. The only known treatment is laser therapy. OBJECTIVE: To characterize the clinical appearance and development of iron-induced tattoos and to demonstrate safe and efficient removal with quality-switched (QS) and picosecond lasers. MATERIALS AND METHODS: The authors conducted a retrospective systematic analysis on patients who presented at the Dermatology Department of the University Hospital of Zurich between Year 2008 and 2017 with accidental hyperpigmentations after iron injections. From 29 collected patients, 13 received laser treatment and were analyzed with reference to the lasers used, including wavelength, fluence, spot size, intervals, number of sessions, and overall success. The authors defined the latter as a complete removal or as patients' satisfaction. RESULTS: The authors treated 13 patients and completed the treatment in 8 patients, with an average of 5.6 sessions. No complications occurred. CONCLUSION: Spontaneous regression of iron-induced tattoos is possible within 1 to 2 years, but not guaranteed. Removal with QS ruby, Nd:YAG, and picosecond lasers can be achieved within a mean number of 5.6 sessions. Assuring a valid indication before intravenous iron administration is important.

Radiotherapy in Periocular Cutaneous Malignancies: A Retrospective Study.

BACKGROUND: Due to the importance of function and cosmetics, periocular skin malignancies represent a therapeutic challenge. OBJECTIVE: To evaluate the safety and efficacy of radiotherapy (RT) treating periocular skin tumors. METHODS: Data of patients with periocular tumors treated with grenz or soft X-rays at the University Hospital Zurich, Switzerland, between 2009 and 2014 were reviewed. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with associated in situ lesions, cutaneous melanoma, lentigo maligna (LM), cutaneous lymphoma and Kaposi's sarcoma were included in the analysis. RESULTS: We found 159 periocular lesions in 145 patients. Overall recurrence was highest for actinic keratosis and Bowen's disease (27%), melanoma (17%) and LM (15%), whereas SCC and BCC showed recurrence in 11 and 10%, respectively. 45% of all recurrences occurred within 12 months after treatment, with a median time to recurrence of 13 months (range 3-73). CONCLUSION: RT, which provides a good therapeutic response with minimal adverse events, is a therapy option for periocular cutaneous malignancies.