Ablative Fractional Laser-assisted Low-irradiance Photodynamic Therapy for Treatment of Actinic Keratoses in Organ Transplant Recipients: A Prospective, Randomized, Intraindividual Controlled Trial.

Pain and inferior efficacy are major limiting factors of conventional photodynamic therapy for the field treatment of actinic keratoses in immunosuppressed organ transplant recipients. This prospective randomized controlled study evaluates the efficacy and tolerability of ablative fractional laser system pretreatment combined with low-irradiance photodynamic therapy (18.5 mW/cm2) compared with conventional photodynamic therapy (61.67 mW/cm2) in the treatment of actinic keratoses on the face and scalp in organ transplant recipients, using a red light-emitting diode lamp at a total light dose of 37 J/cm2. Low-irradiance photodynamic therapy combined with Er:YAG pretreatment achieved a significantly superior lesion response rate (mean ± standard deviation 77.3 ± 23.6%) compared with conventional photodynamic therapy (61.8 ± 21.4%; p = 0.025) in intra-individual fields at 3 months without negatively impacting pain (p = 0.777) or cosmetic outcome (p = 0.157).

Efficacy and safety of endovenous laser ablation with the 1470 nm diode laser using a novel optical probe.

Objectives: Outcome assessment of a novel optical fiber probe for the 1470 nm diode laser under real-world conditions. Methods: Prospective clinical pilot study in 10 patients undergoing endovenous laser ablation with a follow-up period of 1 year. Primary endpoints were efficacy and safety. Secondary endpoints include, inter alia, quality of life and patient satisfaction. Results: After a follow-up period of 1 year all treated vein segments were still occluded. Only mild and short-term side effects (hematoma, ecchymosis and hyperpigmentation) were observed. No intake of pain medication was needed and a quick return to normal activity was documented (0.9 days). Clinical hallmarks of the venous disease (VCSS) improved significantly (p= .003). All patients were very satisfied with the treatment and quality of life (AVVQ) was significantly improved after the procedure (p=.008). Conclusions: The study demonstrates that the endoluminal treatment with the novel fiber probe is highly effective and safe.

Pulse rate and blood pressure changes during low-irradiance PDT compared with conventional PDT in the treatment of facial actinic keratoses: A retrospective study.

BACKGROUND: Conventional photodynamic therapy (c-PDT) is a highly effective treatment for actinic keratoses. Besides pain as the main side effect, blood pressure (BP) increases and hypertensive crises may occur during treatment. Reducing the irradiation intensity while keeping the total dose constant (low-irradiance PDT) can achieve a clinically relevant reduction in pain. This study aimed to evaluate the influence of li-PDT on the BP and pulse (PR) during therapy and the incidence of post-interventional hypertension compared with c-PDT. METHODS: We retrospectively analyzed the treatment data of 79 patients (39 c-PDT and 40 li-PDT). BP and PR measurements were performed in all patients before PDT, at mid-exposure, and immediately after PDT. In addition, the pain was assessed by using the visual analog scale. RESULTS: Patients treated with li-PDT reported significantly lower pain than those receiving c-PDT (p < .0005). Additionally, they showed less systolic (SBP) and diastolic (DBP) BP increase (∆SBP: p < .0005, ∆DBP: p = .015) and overall lower absolute BP values (SBP: p < .0005, DBP: p = .008) compared with c-PDT. They were also significantly less likely to develop post-interventional hypertension (p = .037) or higher stages of arterial hypertension. Regarding PR, there was no difference in absolute values between both groups, but the increase from onset to half irradiation duration was significantly higher in c-PDT (p = .013). CONCLUSIONS: Li-PDT is an excellent option to reduce the elevation of arterial BP and decrease the incidence of post-interventional hypertension and hypertensive crisis. This finding has considerable relevance, especially with the risk profile of many PDT patients in mind (advanced age and cardiovascular history).

Improvement in Quality of Life and Pain in Patients With Hidradenitis Suppurativa After Wide Local Excision: A Prospective Study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects patients' quality of life (QoL). OBJECTIVE: To investigate changes in QoL in patients with HS after wide local excision (WLE) and to examine the level of pain, rate of postoperative complications, recurrences, and the time to complete wound closure. METHODS: Fifty-five patients were enrolled in this prospective study. All patients underwent WLE of HS, followed by secondary wound healing. Dermatologic Life Quality Questionnaire, pain, and wound size were measured 1 day, 3 weeks, 3 months, and 6 months after surgery. RESULTS: Dermatologic Life Quality Questionnaire and pain scores (mean ± SD) improved significantly (both p < .001) from 14.5 ± 7.3 and 3.7 ± 2.8 at baseline to 5.8 ± 6.9 and 0.8 ± 1.7, 6 months postoperatively, respectively. Wounds were closed completely by secondary intention after 4.4 ± 2.8 months. Sixteen patients (29.1%) experienced postoperative complications, local recurrences in the treated sites were observed in 11 patients (20%), and new lesions in untreated sites were observed in 5 cases (9.1%). CONCLUSION: Wide local excision significantly improves patients' QoL and pain, and, given its low rate of recurrence and complications, should be considered as a first-line therapy, especially in patients with higher Hurley stages.

Low irradiance compared with conventional photodynamic therapy in the treatment of actinic keratoses.

BACKGROUND: Photodynamic therapy (PDT) is an effective therapy treating photodamaged areas with multiple actinic keratoses (AK). Still pain during therapy is one of the most challenging obstacles for patients. This retrospective study compares pain and efficacy intra-individual in patients using conventional PDT (c-PDT) compared to a low irradiance PDT protocol (li-PDT) with a reduced irradiance to 25% of c-PDT. METHODS: Thirty-one patients were enrolled into this retrospective analysis treated with li-PDT and c-PDT on comparable fields of actinic damage on the forehead or the cheek. Pain was scored by the patients using a VAS. Moreover, number and time to therapy interruptions were documented. For effectiveness number and grade of AK were counted before and 4 weeks after PDT. RESULTS: Maintaining a total light dose of 37 J/cm2 , a decrease in irradiation in li-PDT patients resulted in significant less pain (VAS score 2.8 vs 7.6) and fewer therapy interruptions compared to treatment with c- PDT (P < 0.0005). No significant difference in treatment outcome was found (P = 0.068). CONCLUSION: Our data shows that li-PDT can reduce pain with at least comparable clinical outcome compared to c-PDT. Therefore, it is an effective and well-tolerated treatment for patients with multiple AK.

Impact of red versus blue light on tolerability and efficacy of PDT: a randomized controlled trial.

Various light sources may be used for photodynamic therapy of actinic keratosis since photosensitizing agents are activated by different wavelengths. However, the relative impact of red and blue light irradiation on the efficacy and tolerability of therapy is controversial. OBJECTIVE: The aim of this study is to compare the efficacy and tolerability of therapy with red versus blue light sources, as well as the patients' evaluation of cosmetic results, clinical response, painfulness and preferred light source for future photodynamic treatments. METHODS: This is a prospective, single-center, randomized, controlled, open-label study with 28 patients undergoing elective photodynamic therapy. RESULTS: Red and blue light sources both showed very good results with a complete response rate of 84 % and 85 % respectively. Pain during photodynamic therapy was 6.1 vs. 5.4 (and 2.1 vs. 1.5 eight hours after therapy) on the visual analogue scale. Although these differences were statistically significant, the clinical relevance is low, since the number of therapy interruptions were equally distributed in both groups, and patients' subjective evaluation of the treatment showed no personal preference towards the light sources. CONCLUSION: Both light sources showed very good clinical results and satisfactory tolerability in this study.

Photodynamic therapy--aspects of pain management.

Topical photodynamic therapy (PDT) is a highly effective and safe treatment method for actinic keratoses with an excellent cosmetic outcome and is commonly used for the therapy of large areas of photodamaged skin with multiple clinically manifest and subclinical lesions. However, the major drawback of photodynamic therapy is the pain experienced during the treatment that can be intense and sometimes even intolerable for patients, requiring interruption or termination of the process. Several strategies for controlling pain during photodynamic therapy have been studied but few effective methods are currently available. Therefore, this review puts the spotlight on predictors on pain intensity and aspects of pain management during photodynamic therapy.

Dermatology life quality index and side effects after topical photodynamic therapy of actinic keratosis.

BACKGROUND: Photodynamic therapy (PDT) is an excellent treatment option for actinic keratosis. However the side effects lead to an impairment of the patients' quality of life. OBJECTIVES: To evaluate the impact of PDT on patients' quality of life and to determine the frequency and intensity of side effects over the course of 4 weeks post PDT. PATIENTS AND METHODS: 22 patients with actinic keratosis in the face were included into this prospective study. Pain was measured using a visual analog scale immediately and 8 h after PDT. The Dermatology Life Quality Index (DLQI) was assessed at screening, after treatment as well as 2 and 4 weeks after PDT. The physician and patient evaluated the intensity of side effects during the treatment, 2 and 4 weeks post PDT. Additionally, the patient documented side effects daily from the 1st to the 14th day after PDT and on day 28 post PDT, using a diary. RESULTS: We observed a significant (p < 0.001) increase in the DLQI from 1.6 ± 1.7 prior to PDT to 7.3 ± 4.9 post PDT. The DLQI normalized in the following 4 weeks. Immediately and 8 h after PDT mean pain was 4.3 ± 2.5 and 2.3 ± 2.1. Side effects documented by the patients were erythema (100%), pain, burning, edema (90.9%), itching (86.4%), scaling (81.8%) and pustules (59.1%). No scar formation, hyper-/hypopigmentation or infections were observed. CONCLUSION: PDT has a significant temporary impact on patients' DLQI. Transitory side effects are common and show typical kinetics.

Deep Learning on Basal Cell Carcinoma In Vivo Reflectance Confocal Microscopy Data.

BACKGROUND: Extended skin malignancies of the head and neck region are among the most common cancer types and are associated with numerous diagnostic and therapeutical problems. The radical resection of skin cancer in the facial area often leads to severe functional and aesthetic impairment, and precise margin assessments can avoid the extensive safety margins. On the other hand, the complete removal of the cancer is essential to minimize the risk of recurrence. Reliable intraoperative assessments of the wound margins could overcome this discrepancy between minimal invasiveness and safety distance in the head and neck region. With the help of reflectance confocal laser microscopy (RCM), cells can be visualized in high resolution intraoperatively. The combination with deep learning and automated algorithms allows an investigator independent and objective interpretation of specific confocal imaging data. Therefore, we aimed to apply a deep learning algorithm to detect malignant areas in images obtained via in vivo confocal microscopy. We investigated basal cell carcinoma (BCC), as one of the most common entities with well-described in vivo RCM diagnostic criteria, within a preliminary feasibility study. PATIENTS AND METHODS: We included 62 patients with histologically confirmed BCC in the head and neck region. All patients underwent in vivo confocal laser microscope scanning. Approximately 382 images with BCC structures could be obtained, annotated, and proceeded for further deep learning model training. RESULTS: A sensitivity of 46% and a specificity of 85% in detecting BCC regions could be achieved using a convolutional neural network model ("MobileNet"). CONCLUSION: The preliminary results reveal the potential and limitations of the automated detection of BCC with in vivo RCM. Further studies with a larger number of cases are required to obtain better predictability.

Treatment with 5-aminolaevulinic acid methylester is less painful than treatment with 5-aminolaevulinic acid nanoemulsion in topical photodynamic therapy for actinic keratosis.

BACKGROUND: Topical photodynamic therapy (PDT) is an excellent treatment option for actinic keratosis (AK). Pain is one of the major adverse effects. OBJECTIVE: To compare the pain intensity during the extensive treatment of cosmetic units using 5-aminolaevulinic acid methylester (MAL) or 5-aminolaevulinic acid nanoemulsion (BF-200-ALA). METHODS: 173 patients with 965 treated areas were enrolled in this retrospective monocentric study. All patients had multiple AKs and received an extensive treatment of the photodamaged area. 424 areas were treated with MAL and 541 with BF-200-ALA. Pain was rated using a standardized visual analogue scale (VAS). The number of PDT treatment interruptions was documented. RESULTS: PDT with MAL led to a lower mean VAS score (5.0 vs. 5.8), a lower number of treatment interruptions (13.2 vs. 19.9%) and a lower amount of patients experiencing severe pain (25.0 vs. 36.0%) compared to PDT with BF-200-ALA. CONCLUSION: Our data shows that PDT using MAL is less painful than PDT using BF-200-ALA resulting in a significantly lower mean VAS score (p < 0.001), significantly fewer patients experiencing severe pain (p < 0.001) and a significantly (p < 0.05) lower number of treatment interruptions. Differences in selectivity for tumour cells and transport of ALA in peripheral neurons may play a role.

In vivo reflectance confocal microscopy of wounds: feasibility of intraoperative basal cell carcinoma margin assessment.

BACKGROUND: In vivo reflectance confocal microscopy (RCM) is well established in non-melanoma skin cancer detection and screening. However, there is no sufficient validation regarding intraoperatively obtained images of wound margins. A reliable and fast resection margin detection is of high clinical relevance. Hence, we aimed to investigate feasibility and validity of in vivo RCM imaging for wound margins assessment compared with standard skin surface imaging and the gold standard histopathology. METHODS: A surgical incision through the center of a large basal cell carcinoma (BCC) affected area in the head and face region was performed. After removing half of the tumor, the wound margins of the remaining half as well as the corresponding skin surface were scanned with an in vivo RCM. A total of 50 wound margin images with BCC, 50 images of BCC-free margins and the corresponding skin surface images from 50 patients were compared with each other and with histopathological findings. Presence of confocal diagnostic criteria for BCC in images was analyzed. RESULTS: An overall sensitivity and specificity in detection of BCC in wound margins was 88.5%, and 91.7% compared to skin surface imaging and 97.8% and 90.7%, respectively, compared to histopathology. We identified all known confocal patterns of healthy skin and BCC in wound margin scans: damage of the epidermal layer above the lesion and cellular pleomorphism, elongated and monomorphic basaloid nuclei, nuclear polarization, an increased number of dilated blood vessels with high leukocyte traffic, inflammatory cells. CONCLUSIONS: The accuracy of in vivo RCM imaging of wound margins is comparable with a standard skin surface imaging. The intraoperative detection of BCC areas in wound margins is as precise as the standard skin imaging and may be supportive for surgical interventions.

Deep learning approach to predict sentinel lymph node status directly from routine histology of primary melanoma tumours.

AIM: Sentinel lymph node status is a central prognostic factor for melanomas. However, the surgical excision involves some risks for affected patients. In this study, we therefore aimed to develop a digital biomarker that can predict lymph node metastasis non-invasively from digitised H&E slides of primary melanoma tumours. METHODS: A total of 415 H&E slides from primary melanoma tumours with known sentinel node (SN) status from three German university hospitals and one private pathological practice were digitised (150 SN positive/265 SN negative). Two hundred ninety-one slides were used to train artificial neural networks (ANNs). The remaining 124 slides were used to test the ability of the ANNs to predict sentinel status. ANNs were trained and/or tested on data sets that were matched or not matched between SN-positive and SN-negative cases for patient age, ulceration, and tumour thickness, factors that are known to correlate with lymph node status. RESULTS: The best accuracy was achieved by an ANN that was trained and tested on unmatched cases (61.8% ± 0.2%) area under the receiver operating characteristic (AUROC). In contrast, ANNs that were trained and/or tested on matched cases achieved (55.0% ± 3.5%) AUROC or less. CONCLUSION: Our results indicate that the image classifier can predict lymph node status to some, albeit so far not clinically relevant, extent. It may do so by mostly detecting equivalents of factors on histological slides that are already known to correlate with lymph node status. Our results provide a basis for future research with larger data cohorts.

Factors influencing pain intensity during topical photodynamic therapy of complete cosmetic units for actinic keratoses.

BACKGROUND: Topical photodynamic therapy is a good treatment option for extensively photodamaged skin with multiple actinic keratoses. Pain is one of the major adverse effects during and after the treatment. OBJECTIVE: We sought to determine the pain intensity and its influencing factors during the extensive photodynamic treatment of complete cosmetic units. METHODS: In total, 104 patients with 411 treated fields were enrolled in this retrospective monocentric study. All patients had multiple actinic keratoses on the face, scalp, or back of hands and received an extensive treatment of the complete photodamaged area in our dermatologic outpatient department between February and May 2009. Pain was rated using a visual analog scale directly and 8 hours after photodynamic therapy. RESULTS: Multifactorial analysis of the data shows that pain intensity is dependent on sex of the patient (P = .030) and location of the treated field (P < .001). Visual analog scale scores were independent of the age and skin type of the patient. No significant difference in pain between the use of 5-amino-4-oxo-pentanoate (methylaminolevulinate) and 5-aminolevulinic acid was noticed. During treatment, mean visual analog scale scores +/- SEM of the different locations were 2.5 +/- 0.36 (hand), 3.6 +/- 0.35 (occiput), 5.2 +/- 0.19 (forehead), 5.9 +/- 0.20 (cheeks), and 7.4 +/- 0.48 (lips). Eight hours after treatment the mean pain +/- SEM in all locations was reduced significantly (P < .001) from 5.2 +/- 0.14 to 3.0 +/- 0.14. The rate of therapy interruptions showed a significant correlation (P = .044) with the location of the treated field. In all, 71% of the patients showed a good and 29% a poor clinical outcome. LIMITATIONS: Because of the retrospective study design not all factors that may influence pain (eg, protoporphyrin IX fluorescence) were recorded. CONCLUSION: These results show that pain intensity is dependent on the location of the treated field. Pain intensity is higher in male patients. After 8 hours pain decreases significantly.

Skin diseases and sexually transmitted diseases in HIV-infected patients on HAART compared to a non-infected population - results of a retrospective study.

BACKGROUND: The prevalence of skin diseases and sexually transmitted diseases has always played a special role in studying HIV infections, both because of immunosuppression and simultaneous transmission. In the early years of the HIV epidemic, skin diseases were often a pathognomonic sign in heavily immunosuppressed patients. With highly active antiretroviral therapy (HAART), HIV infection has become a treatable chronic disease. For this reason the spectrum as well as the prevalence of skin diseases has changed. Pathognomonic skin diseases have become rare and the wide spectrum today ranges from infectious to iatrogenic skin diseases. PATIENTS AND METHODS: From April to October 2007 166 HIV-infected patients and 173 patients of a comparison group were surveyed in retrospect by means of a questionnaire about skin diseases and sexually transmitted diseases that appeared over the entire year 2006. RESULTS AND CONCLUSIONS: The study confirmed the shift to a wide variety of mostly trivial skin diseases and away from severe opportunistic skin diseases. HIV-infected patients today have more numerous skin problems than the non-infected population and thus need regular dermatologic control examinations.