Basal cell carcinoma treated with combined ablative fractional laser and ingenol mebutate - an exploratory study monitored by optical coherence tomography and reflectance confocal microscopy.

BACKGROUND: Basal cell carcinomas (BCCs) have previously been treated off-label with ingenol mebutate (IM). Ablative fractional laser (AFL) may improve efficacy of IM by increasing drug uptake in the tumour. Optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) detect BCC non-invasively. Our aim was to investigate BCC response and tolerability after combined AFL and IM treatment of low-risk BCCs. METHODS: Twenty patients with histologically verified superficial (n = 7) and nodular (n = 13) BCCs were treated with combined fractional CO2 -laser (10 600 nm) and IM 0.015% or 0.05%, the concentration depending on anatomical location. BCC response was evaluated clinically, by OCT and RCM at day 29 and 90 after first treatment, and histologically at day 90. Treatment was repeated at day 29 if BCC persisted. Local skin reactions (LSRs) were assessed using LSR scale at all visits. RESULTS: At day 29, 18/20 patients received a second treatment due to residual BCC detected clinically, by OCT or RCM. OCT and RCM presented subclinical BCCs in five of 20 cases (25%). At day 90, overall histological cure rate was 70%, corresponding to clinical (65%) and OCT/RCM (60%) cure rates, and agreement between evaluation methods was substantial (kappa ≥ 0.796, P < 0.0001). Clearance rates were similar for sBCCs and nBCCs (P = 0.354) and for lesions treated with IM 0.015% and 0.05% (P = 0.141). LSRs were tolerable, but scarring was observed in the majority of cleared patients. CONCLUSION: Two treatments of combined AFL and IM show potential to treat low-risk BCCs with acceptable tolerability. OCT and RCM show promise to detect subclinical BCCs at short-term follow-up.

Laser treatments in early wound healing improve scar appearance: a randomized split-wound trial with nonablative fractional laser exposures vs. untreated controls.

BACKGROUND: In recent years, various lasers have increasingly been applied during wound healing to minimize scar formation. However, no consensus regarding treatment procedures exists. OBJECTIVES: To assess scar formation clinically after three nonablative fractional laser (NAFL) exposures, targeting the inflammation, proliferation and remodelling wound healing phases in patients vs. untreated controls. METHODS: A randomized controlled trial was performed using a split-wound design to assess excisional wound halves treated with 1540-nm NAFL vs. no laser treatment. Three NAFL exposures were provided: immediately before surgery, at suture removal and 6 weeks after surgery. NAFL exposures were applied using two handpieces, sequentially distributing energy deeply and more superficially in the skin (40-50 mJ per microbeam). Evaluated at 3 months of follow-up, the primary outcome was blinded, on-site evaluation using the Patient Observer Scar Assessment Scale (POSAS total; range from 6, normal skin to 60, worst imaginable scar). Secondary outcomes comprised blinded evaluation on the Vancouver Scar Scale (VSS) and standardized assessment comparing scar sides, carried out by blinded on-site, photo and patient assessments. This trial was registered with ClinicalTrials.gov (NCT03253484). RESULTS: Thirty of 32 patients completed the trial. At the 3-month follow-up, the NAFL-treated scar halves showed improvement compared with the untreated control halves on POSAS total: NAFL treated, median 11, interquartile range (IQR) 9-12 vs. control, median 12, IQR 10-16; P = 0·001. The POSAS subitems showed that the NAFL-treated halves were significantly less red and more pliable, and presented with smoother relief than the untreated controls. VSS total correspondingly revealed enhanced appearance in the NAFL-treated halves: median 2, IQR 1-2·5 vs. control, median 2, IQR 1·75-3, P = 0·007. The standardized assessment comparing appearance of scar halves demonstrated a low degree of correspondence between on-site, photo and patient assessments. NAFL-treated scars were rated as superior to untreated scars by 21 of 29 patients. CONCLUSIONS: NAFL-treated scars showed subtle improvement compared with untreated control scars.

An exploratory, prospective, open-label trial of ingenol mebutate gel 0.05% for the treatment of external anogenital warts.

BACKGROUND: Anogenital warts (AGW) can cause physical discomfort and decreased quality of life. Recent case reports suggest that ingenol mebutate gel might be an effective treatment of AGW. OBJECTIVE: To explore primarily the safety, and secondarily the efficacy of ingenol mebutate gel 0.05% in patients with AGW. METHODS: This was an exploratory, open-label, 1-arm trial of ingenol mebutate gel 0.05% administered up to three times to patients with AGW. Safety was assessed by occurrence and severity of local skin reactions (LSRs) and treatment-related adverse events (AEs). Efficacy was assessed by complete clearance and reduction in AGW count 14 days after last treatment, and recurrence 12 weeks after clearance. RESULTS: Of 41 patients enrolled, 40 received treatment and 26 completed the trial. Patients had a median AGW count of 11.0 and AGW duration of 3.0 years at baseline. All patients experienced transient LSRs following treatment with a maximum composite LSR score of 7.5 (on a scale from 0 to 18). A total of 93% of patients reported treatment-related AEs, most frequently pain (85%) and procedural complications (35%) due to smearing of the gel. 78% of patients took mild analgesics for the pain, typically for 1-2 days following treatment. The majority of AEs were of moderate-to-severe intensity. Seventeen of 39 patients (43.6%) had complete clearance 14 days after last treatment, and AGW count was reduced by 90.9%. There was a tendency towards lower clearance rate in patients with longer duration of AGW. Eight of 14 patients (57.1%) had AGW recurrence 12 weeks after clearance. CONCLUSION: Ingenol mebutate gel was associated with a high number of AEs and withdrawals due to painful local and adjacent skin reactions. Furthermore, it showed promising efficacy in reducing AGW despite a difficult-to-treat population. Optimization of the formulation is warranted to improve the safety profile of the treatment.

Neural alterations of fronto-striatal circuitry during reward anticipation in euthymic bipolar disorder.

BACKGROUND: Bipolar disorder (BD), with the hallmark symptoms of elevated and depressed mood, is thought to be characterized by underlying alterations in reward-processing networks. However, to date the neural circuitry underlying abnormal responses during reward processing in BD remains largely unexplored. The aim of this study was to investigate whether euthymic BD is characterized by aberrant ventral striatal (VS) activation patterns and altered connectivity with the prefrontal cortex in response to monetary gains and losses. METHOD: During functional magnetic resonance imaging 20 euthymic BD patients and 20 age-, gender- and intelligence quotient-matched healthy controls completed a monetary incentive delay paradigm, to examine neural processing of reward and loss anticipation. A priori defined regions of interest (ROIs) included the VS and the anterior prefrontal cortex (aPFC). Psychophysiological interactions (PPIs) between these ROIs were estimated and tested for group differences for reward and loss anticipation separately. RESULTS: BD participants, relative to healthy controls, displayed decreased activation selectively in the left and right VS during anticipation of reward, but not during loss anticipation. PPI analyses showed decreased functional connectivity between the left VS and aPFC in BD patients compared with healthy controls during reward anticipation. CONCLUSIONS: This is the first study showing decreased VS activity and aberrant connectivity in the reward-processing circuitry in euthymic, medicated BD patients during reward anticipation. Our findings contrast with research supporting a reward hypersensitivity model of BD, and add to the body of literature suggesting that blunted activation of reward processing circuits may be a vulnerability factor for mood disorders.

A case report of differentiating staphylococcal scalded skin syndrome and toxic epidermal necrolysis by optical coherence tomography.

BACKGROUND: Staphylococcal scalded skin syndrome (SSSS) and toxic epidermal necrolysis (TEN) both present with acute onset, high morbidity and significant mortality. Rapid diagnosis is therefore of importance. The aim of this study was to investigate and compare the presentation of these diseases using optical coherence tomography (OCT). METHODS: Two male patients with bullous diseases, SSSS and TEN, respectively, were photographed digitally, examined using dermoscopy, OCT scanned and subsequently biopsied in the said order. RESULTS: The bullous skin was visualized by OCT showing two distinct images: the SSSS-patient displayed superficial hyporefletive flaccid structures with a split high in the thickened (0.51 mm vs. 0.12 mm) epidermis while the TEN-patient demonstrated a larger hyporeflective ovoid structure with a split right below the thickened epidermis (0.18 mm vs. 0.06 mm). CONCLUSION: These findings suggest that there is a potential for the application of OCT scanning in the acute phase of SSSS and TEN in order to distinguish them for a faster diagnosis and better management and treatment.

Imaging of collagen deposition disorders using optical coherence tomography.

BACKGROUND: Collagen deposition disorders such as hypertrophic scars, keloids and scleroderma can be associated with significant stigma and embarrassment. These disorders often constitute considerable impairment to quality of life, with treatment posing to be a substantial challenge. Optical coherence tomography (OCT) provides a non-invasive, easily applicable bedside optical imaging method for assessment of the skin. It is hypothesized that OCT imaging may be useful in assessing fibrosis to avoid additional biopsies that could potentially worsen the scarring. METHOD: Thirty-three patients with ordinary scars, hypertrophic scars, keloid scarring, lichen sclerosus et atrophicus and localized or systemic scleroderma were recruited for this pilot study. Affected tissue and adjacent healthy skin were scanned using OCT and digitally photographed. Density measurements were performed in ImageJ on OCT images from scleroderma patients, both systemic and morphea (10 patients), keloid patients (10 patients) and healthy skin adjacent to keloids (10 patients). RESULTS: OCT images of scarring diseases showed varying degrees of disruption to the skin architecture. OCT characteristics were identified for each lesion type. Hypertrophic scars displayed an increased vascularity and signal-rich bands correlating to excessive collagen deposition. Keloids depicted a disarray of hyper-reflective areas primarily located in the upper dermis. Additionally, the dermis displayed a heterogeneous morphology without indications of any vascular supply or lymphatic network. In contrast to keloids, scleroderma displayed a more cohesive backscattering indicating a difference in density of collagen or other dermal structures. OCT images demonstrated no significant differences between mean density measurements in OCT images of scleroderma, keloid and healthy skin (P = 0.07). CONCLUSION: The OCT imaging appears to identify different scarring mechanisms, and therefore be of potential use in the assessment of outcomes following non-invasive therapy of e.g. early or progressive lesions.

Optical coherence tomography imaging of non-melanoma skin cancer undergoing imiquimod therapy.

PURPOSE: To explore the application of optical coherence tomography (OCT) imaging of basal cell carcinomas (BCC) and actinic keratosis (AK) before, during and after imiquimod treatment and the ability of OCT to predict treatment outcome. METHODS: The study subjects were 20 patients with biopsy-verified BCC (9) or AK (11). Patients were OCT-scanned before, after 1 and 4 weeks of imiquimod treatment and after 3 months. Lesions were identified clinically and with OCT. Thickness and morphology of the lesions were recorded at each visit. Any remaining lesions were biopsied at follow-up. RESULTS: Complete data sets were available for 16 patients (8 women and 8 men aged 52-82 years), four in-compliant patients were excluded. OCT identified all lesions. Previously suggested OCT-criteria identified 5/8 BCCs. Crusting, ulceration and active treatment significantly reduced image quality. All BCCs cleared, but at follow-up residual structures were seen clinically in 4 cases. OCT and histology both ruled out residual BCC. For AKs significant thinning occurred after 1 week of treatment (P = 0.04). Imiquimod cleared 2/8 AKs, and significantly decreased the thickness of all lesions (P = 0.02). CONCLUSIONS: OCT could identify superficial BCC and AK before treatment. Monitoring during imiquimod treatment revealed impaired image quality most likely caused by inflammation, crusting and ulceration. On follow-up, OCT showed thinning of AKs indicating effect of treatment. All treated BCCs cleared, but where residual tissue was suspected clinically this could be ruled out by OCT.

Optical coherence tomography imaging of non-melanoma skin cancer undergoing photodynamic therapy reveals subclinical residual lesions.

BACKGROUND: Photodynamic therapy with methyl aminolaevulinate (MAL-PDT) is a widely used non-invasive treatment modality for non-melanoma skin cancer (NMSC). The outcome of MAL-PDT is usually primarily evaluated clinically. Optical coherence tomography (OCT) is a non-invasive imaging technology based on interferiometry. OCT has been proven to provide high accuracy in identifying NMSC lesions and performing thickness measurements of thin tumours. OBJECTIVES: To describe the OCT morphology in in-vivo NMSC lesions during MAL-PDT treatment and to investigate the use of OCT in evaluating the response of MAL-PDT treated NMSC lesions. METHODS: A total of 18 biopsy-proven basal cell carcinomas and actinic keratoses were monitored by OCT during 2 sessions of MAL-PDT treatment. At 3-months follow-up the patients were assessed both by OCT and clinically. If the clinical and OCT evaluation came to different conclusions on recurrence of the lesion, patients were followed more closely at clinical appointments for up to one year after the PDT treatment. RESULTS: All lesions displayed at least one OCT characteristic before MAL-PDT treatment. At 3 months follow-up, recurrence was suspected clinically in 5/18 cases, with OCT in 7/18 cases. OCT correctly identified all of the partial responses also found by the clinical examinations. In both cases where recurrence was only found in OCT, this was subsequently confirmed by histology. CONCLUSIONS: Our study suggests that OCT identified 29% more recurrences than clinical examination alone. OCT can detect subclinical residual NMSC lesions after MAL-PDT treatment and may therefore be an accurate tool for early detection of residual lesional tissue.