A Randomized Controlled Trial of Epidermal Growth Factor Ointment for Treating Epidermal Growth Factor Receptor Inhibitor-Induced Skin Toxicities.

BACKGROUND: The efficacy of epidermal growth factor (EGF) receptor (EGFR) inhibitors in patients with non-small cell lung cancer (NSCLC), pancreatic cancer (PC), or colorectal cancer (CRC) has been demonstrated. However, dermatological reactions to these inhibitors can cause significant physical and psychosocial discomfort. The objective of the present study was to evaluate the efficacy of EGF ointment for EGFR inhibitor-related skin adverse events (ERSEs). MATERIALS AND METHODS: This placebo-controlled, double-blind, multicenter, pilot phase III trial enrolled patients with NSCLC, PC, or CRC treated with EGFR inhibitors. Patients with grade ≥2 ERSEs were included. Patients were randomized to three treatment arms: arm 1, placebo; arm 2, 1 ppm of EGF ointment; and arm 3, 20 ppm of EGF ointment. Patients applied ointment to their skin lesions twice daily. RESULTS: Efficacy evaluation was available for 80 patients (9 for PC, 28 for NSCLC, and 43 for CRC). Responses were 44.4% in arm 1, 61.5% in arm 2, and 77.8% in arm 3. There was a linear correlation between EGF concentrations and responses (p = .012). Quality of life (QoL) was assessed for 74 patients. Maximum changes in composite scores by Skindex-16 after treatment were significantly different among arms (mean ± SD: -5.2 ± 8.6 for arm 1, -11.7 ± 14.2 for arm 2, and - 18.6 ± 17.7 for arm 3; p = .008). EGF arms showed significant improvement in emotions (p = .005) and functioning (p = .044) scores over the placebo arm. CONCLUSION: EGF ointment is effective for managing ERSEs. It can also improve patients' QoL compared with placebo. Clinical trial identification number. NCT02284139 IMPLICATIONS FOR PRACTICE: Patients with non-small cell lung cancer, pancreatic cancer, or colorectal cancer who are treated with epidermal growth factor (EGF) receptor (EGFR) inhibitors may experience dermatologic reactions to their treatment. This study investigated the benefit of an EGF ointment in the treatment of these adverse events and observed the ointment to be effective in managing EGFR inhibitor-related skin adverse events.

Ablative fractional laser-assisted photodynamic therapy provides superior long-term efficacy compared with standard methyl aminolevulinate photodynamic therapy for lower extremity Bowen disease.

BACKGROUND: Ablative fractional laser (AFL)-assisted methyl aminolevulinate (MAL) photodynamic therapy (PDT) (AFL-MAL-PDT) has shown significantly higher efficacy and lower recurrence rates at 12 months than conventional methyl aminolevulinate photodynamic therapy (MAL-PDT) for the treatment of Bowen disease (BD). However, long-term follow-up data are not available. OBJECTIVE: To compare the 5-year efficacy and recurrence rates of AFL-MAL-PDT with those of conventional MAL-PDT for the treatment of lower extremity BD. METHODS: A total of 60 patients with 84 BD lesions were randomly assigned to a single session of AFL-MAL-PDT or 2 sessions of MAL-PDT with a 1-week interval between sessions. Patients were followed up at 3, 12, 24, 36, 48, and 60 months after treatment. Efficacy, recurrence rates, and risk factors for unsuccessful treatments were assessed. RESULTS: After 5 years, the overall clearance rate of AFL-MAL-PDT (84.78%) was significantly better than that of MAL-PDT (44.74%) for BD lesions. The recurrence rate was significantly lower for AFL-MAL-PDT (9.3%) than for MAL-PDT (41.38%). Diameters larger than 20 mm and lesions with a history of previous treatment were independent factors for treatment failure. LIMITATIONS: The small sample size and single-center study design were limitations. CONCLUSIONS: For patients with lower extremity BD lesions, AFL-MAL-PDT showed significantly higher long-term efficacy and lower recurrence rates than standard MAL-PDT.

Clinical features and prognosis of Asian patients with acral lentiginous melanoma who have nodal nevi in their sentinel lymph node biopsy specimen.

BACKGROUND: Nodal melanocytic nevi (NNs) encountered during sentinel lymph node biopsy (SLB) for malignant melanoma are usually difficult to distinguish from metastatic melanoma. However, NNs have not been well studied in acral lentiginous melanoma (ALM) in Asian populations. OBJECTIVE: To investigate the clinical characteristics and significance of NNs in SLB specimens from patients with ALM. METHODS: We retrospectively analyzed 84 patients with ALM who underwent SLB between June 2010 and July 2017. RESULTS: Of the 84 patients with ALM, 9 (10.7%) had NNs in their SLB specimens. NNs were significantly more common in SLB specimens than in specimens not obtained by SLB. The presence of pre-existing melanocytic lesions was found to be associated with NNs (P < .001). The 5-year overall survival was significantly higher in patients with ALM with NNs than in patients with a positive SLB result (P = .047). Distant recurrence in patients with ALM with NNs was significantly lower than in patients a positive SLB result (P = .03). LIMITATIONS: The small sample size, single-center study design, and retrospective nature of the study were the limitations. CONCLUSION: In Asian populations, the prevalence of NNs in ALM is similar to that reported in Europe and the United States. The rates of distant recurrence and overall survival in patients with ALM who have NNs are similar to those of patients who do not have metastatic melanoma.

Comparison of the content of tobacco alkaloids and tobacco-specific nitrosamines in 'heat-not-burn' tobacco products before and after aerosol generation.

Standardized methods for collecting smoke and for measuring smoke components in heat not burn tobacco product (HTP) are yet to be established, and there is a lack of consensus as to whether the content of HTP cigarettes can be assayed in the same manner as for conventional cigarettes. Since HTPcigarettes do not generate ash when smoked, we compared the levels of tobacco alkaloids (TAs) and tobacco-specific nitrosamines (TSNAs) of HTP cigarettes before and after aerosol generation. HTP cigarettes were smoked according to two international standardization methods. The TAs and TSNAs contents of the cigarettes were analyzed by UPLC-Q-TOF and UPLC-MSMS, respectively. Smoking was found to significantly decrease the content of nicotine, nornicotine, anatabine, and anabasine by 53 ∼ 100% in all samples, and the maximum inhalable amounts of these entities were determined to be 4.24 mg/cig, 103.52 µg/cig, 258.72 µg/cig, and 33.03 µg/cig, respectively. By contrast, smoking significantly increased the content of NNK and NAB. we suggested that the reduced nicotine content minus the nicotine content remaining in the filter is an amount that could potentially be inhaled during smoking. The increase of NNK and NAB in HTP cigarette after aerosol generation is expected to be caused by the precursor, but more specific behavioral studies should be performed.

Phase II trial of epidermal growth factor ointment for patients with Erlotinib-related skin effects.

PURPOSE: The efficacy of erlotinib, the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has been demonstrated in patients with non-small cell lung cancer (NSCLC) and pancreatic cancer (PC). In the present study, we evaluated the effect of epidermal growth factor (EGF) ointment on erlotinib-related skin effects (ERSEs). METHODS: This was an open-label, non-comparative, multicenter, phase II trial. The patients included those diagnosed with NSCLC or PC who were treated with erlotinib. The effectiveness of the ointment was defined as follows: (1) grade 2, 3, or 4 ERSEs downgraded to ≤ grade 1 or (2) grade 3 or 4 ERSEs downgraded to grade 2 and persisted for at least 2 weeks. RESULTS: Fifty-two patients from seven institutes in Korea were enrolled with informed consent. The final assessment included 46 patients (30 males, 16 females). According to the definition of effectiveness, the EGF ointment was effective in 36 (69.2%) intention to treat patients. There were no statistically significant differences in the effectiveness of the EGF ointment by gender (p = 0.465), age (p = 0.547), tumor type (p = 0.085), erlotinib dosage (p = 0.117), and number of prior chemotherapy sessions (p = 0.547). The grading for the average National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) rating of rash/acne and itching improved from 2.02 ± 0.83 to 1.13 ± 0.89 and 1.52 ± 0.84 to 0.67 ± 0.90, respectively (p < 0.001). The most common reason for discontinuing the study was progression of cancer (37%). CONCLUSIONS: Based on the results, the EGF ointment is effective for ERSEs, regardless of gender, age, type of tumor, and dosage of erlotinib. The EGF ointment evenly improved all kinds of symptoms of ERSEs. CLINICAL TRIAL REGISTRATION NO: ClinicalTrials.gov identifier: NCT01593995.

The clinical severity score of chronic actinic dermatitis correlates with in vivo photoallergic reactions and the immunologic parameters related to a shift towards Th2 immunity from the Th2/Th1 balanced status in patients with chronic actinic dermatitis.

BACKGROUND: Chronic actinic dermatitis (CAD) has a more complicated pathogenetic basis than others. The clinical grading system and its correlations with the clinical and immunological parameters still remained to be investigated to define the nature of CAD in a more detailed manner. OBJECTIVES: We investigated correlations of the clinical severity score of CAD (CSS-CAD) with the clinical and immunological parameters. METHODS: We evaluated 72 patients with CAD and classified them into three groups according to the CSS-CAD. We analysed total IgE level, peripheral blood (PB) eosinophil count, the ratio of Th2cell (CCR4 + CD4 +) percentage over Th1 cell (CXCR3 + CD4 +) percentage (Th2/Th1) and/or the sum of suppressor/cytotoxic T cells. RESULTS: The total IgE levels and the percentage of PB eosinophils were higher in the severer group than other groups. A shift towards Th2 from Th2/Th1 balanced status may be affected by total counts of suppressor T cells, and the patient with higher Th2/Th1 ratio than balanced status had the more proportion in the severer CSS-CAD group than other groups. CONCLUSION: The CSS-CAD correlates with total IgE level, PB eosinophil count and a shift towards Th2 immunity from Th2/Th1. So we suggest the Th1/Th2 dysbalance may be affected by the CSS-CAD.

Electrically tunable microlens arrays based on polarization-independent optical phase of nano liquid crystal droplets dispersed in polymer matrix.

Electrically tunable focusing microlens arrays based on polarization independent optical phase of nano liquid crystal droplets dispersed in polymer matrix are demonstrated. Such an optical medium is optically isotropic which is so-called an optically isotropic liquid crystals (OILC). We not only discuss the optical theory of OILC, but also demonstrate polarization independent optical phase modulation based on the OILC. The experimental results and analytical discussion show that the optical phase of OILC microlens arrays results from mainly orientational birefringence which is much larger than the electric-field-induced birefringence (or Kerr effect). The response time of OILC microlens arrays is fast~5.3ms and the tunable focal length ranges from 3.4 mm to 3.8 mm. The potential applications are light field imaging systems, 3D integrating imaging systems and devices for augment reality.

Film patterned retarder for stereoscopic three-dimensional display using ink-jet printing method.

We propose a film patterned retarder (FPR) for stereoscopic three-dimensional display with polarization glasses using ink-jet printing method. Conventional FPR process requires coating of photo-alignment and then UV exposure using wire-grid mask, which is very expensive and difficult. The proposed novel fabrication method utilizes a plastic substrate made of polyether sulfone and an alignment layer, poly (4, 4' - (9, 9 -fluorenyl) diphenylene cyclobutanyltetracarboximide) (9FDA/CBDA) in which the former and the latter aligns reactive mesogen along and perpendicular to the rubbing direction, respectively. The ink-jet printing of 9FDA/CBDA line by line allows fabricating the cost effective FPR which can be widely applied for 3D display applications.

Novel film patterned retarder utilizing in-plane electric field.

Conventional film patterned retarder (FPR) production requires a photo-alignment layer and a UV exposure process through a patterned wire-grid photo-mask, increasing the cost as well as limiting the resolution of FPR. We proposed a novel method for the fabrication of FPR without using the alignment layer and the photo-mask. Reactive mesogen (RM) was coated on a base film, and then the substrate with 2-domain interdigitated electrodes was contacted over the RM layer. The in-plane electric field reoriented the randomly orientated RM molecules to the field direction, generating the slow axes in each domain. Then, the UV light was exposed to the film, fixing the slow axes of the polymerized RM with orthogonal orientation between neighboring domains. Finally, an incident linearly polarized light gave rise to giving oppositely handed circular polarizations of light after passing the film.

The novel IGF-IR/Akt-dependent anticancer activities of glucosamine.

BACKGROUND: Recent studies have shown that glucosamine inhibits the proliferation of various human cancer cell lines and downregulates the activity of COX-2, HIF-1α, p70S6K, and transglutaminase 2. Because the IGF-1R/Akt pathway is a common upstream regulator of p70S6K, HIF-1α, and COX-2, we hypothesized that glucosamine inhibits cancer cell proliferation through this pathway. METHODS: We used various in vitro assays including flow cytometry assays, small interfering RNA (siRNA) transfection, western blot analysis, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, reverse transcription-polymerase chain reaction, and in vivo xenograft mouse model to confirm anticancer activities of glucosamine and to investigate the molecular mechanism. RESULTS: We found that glucosamine inhibited the growth of human non-small cell lung cancer (NSCLC) cells and negatively regulated the expression of IGF-1R and phosphorylation of Akt. Glucosamine decreased the stability of IGF-1R and induced its proteasomal degradation by increasing the levels of abnormal glycosylation on IGF-1R. Moreover, picropodophyllin, a selective inhibitor of IGF-1R, and the IGF-1R blocking antibody IMC-A12 induced significant cell growth inhibition in glucosamine-sensitive, but not glucosamine-resistant cell lines. Using in vivo xenograft model, we confirmed that glucosamine prohibits primary tumor growth through reducing IGF-1R signalling and increasing ER-stress. CONCLUSIONS: Taken together, our results suggest that targeting the IGF-1R/Akt pathway with glucosamine may be an effective therapeutic strategy for treating some type of cancer.

Efficacy of fluorescence diagnosis-guided Mohs micrographic surgery for pigmented vs non-pigmented basal cell carcinoma.

Pigmented basal cell carcinoma (PBCC) occurs more frequently in Asian population. The efficacy of fluorescence diagnosis (FD) for PBCCs treated with Mohs micrographic surgery has not yet been determined. This study enrolled 255 patients with 258 biopsy-proven BCC lesions: 199 PBCCs (77.1%) and 59 non-PBCCs (22.9%). We compared the clinicopathological and surgical features of the PBCCs and non-PBCCs. Each group was divided into 2 sub-groups, those assessed and not assessed by FD, to retrospectively analyse surgical features. Aggressive histological subtypes were less prevalent in PBCCs than in non-PBCCs. PBCCs required significantly fewer stages of Mohs excision, with significantly smaller surgical margins and surgical depth, than non-PBCCs. FD did not confer any benefits on PBCCs during Mohs micrographic surgery. However, non-PBCCs assessed by FD required significantly fewer Mohs stages, with significantly smaller surgical margins, than lesions not assessed by FD. These findings suggest that FD should be performed before Mohs micrographic surgery to delineate the margins of non-PBCCs in Asians.

Evaluating a combination treatment of NK cells and reovirus against bladder cancer cells using an in vitro assay to simulate intravesical therapy.

Intravesical treatment using either reovirus or natural killer (NK) cells serves as an efficient strategy for the treatment of bladder cancer cells (BCCs); however, corresponding monotherapies have often shown modest cytotoxicity. The potential of a locoregional combination using high-dose reovirus and NK cell therapy in an intravesical approach has not yet been studied. In this study, we evaluated the effectiveness of reoviruses and expanded NK cells (eNK) as potential strategies for the treatment of bladder cancer. The anti-tumor effects of mono-treatment with reovirus type 3 Dearing strain (RC402 and RP116) and in combination with interleukin (IL)-18/-21-pretreated eNK cells were investigated on BCC lines (5637, HT-1376, and 253J-BV) using intravesical therapy to simulate in vitro model. RP116 and IL-18/-21-pretreated eNK cells exhibited effective cytotoxicity against grade 1 carcinoma (5637 cells) when used alone, but not against HT-1376 (grade 2 carcinoma) and 253J-BV cells (derived from a metastatic site). Notably, combining RP116 with IL-18/-21-pretreated eNK cells displayed effective cytotoxicity against both HT-1376 and 253J-BV cells. Our findings underscore the potential of a combination therapy using reoviruses and NK cells as a promising strategy for treating bladder cancer.

Survey on Resident Education for Surgical Dermatology in South Korea.

BACKGROUND: With the increasing demand for surgical procedures in dermatology, resident education in surgical dermatology has become important for delivering high-quality treatment. However, it remains unclear if a sufficient number of residency programs with quality standards exist, as there has been little research on this subject in South Korea. OBJECTIVE: To identify the status of surgical dermatology education among residents and assess dermatologists' perceptions of the subject. METHODS: A 35-question survey was developed and distributed to all resident training hospitals and local clinics listed by the Korean Society of Dermatologic Surgery. Only third- and fourth-year residents were included and board-certified specialists from training hospitals and local clinics responded to the surveys. RESULTS: Survey participants included 88 residents and 120 specialists of whom one-quarter of the residents attended regular monthly educational sessions. Most residents (93%) participated in cosmetic procedures, and many performed laser therapy. However, the opportunity for toxin or filler injection was rare, with only 12% of the residents having experience with filler injections. In response, 49% of residents and 32% of specialists said that more cosmetic training was required, whereas 28% of residents and 50% of specialists said that more training for both cosmetic and conventional surgeries was necessary. CONCLUSION: The survey demonstrated a need for more training programs in surgical dermatology during residency and a perception gap between residents and specialists. Therefore, developing educational residency programs that focus on basic dermatologic surgery principles and their applications in cosmetic procedures is essential.

Proactive treatment of adult facial seborrhoeic dermatitis with 0.1% tacrolimus ointment: randomized, double-blind, vehicle-controlled, multi-centre trial.

The effectiveness of intermittent topical tacrolimus to prevent relapse in patients with stabilized facial seborrhoeic dermatitis has not been evaluated. The aim of this study was to determine whether proactive use of 0.1% tacrolimus ointment can keep adult facial seborrhoeic dermatitis in remission. A total of 75 patients who had stabilized facial seborrhoeic dermatitis after 2 weeks' (open-label induction) treatment with 0.1% tacrolimus were randomized in a double-blind fashion to treatment with 0.1% tacrolimus once a week, twice a week, or vehicle twice a week, for 10 weeks (maintenance). Significant improvement in erythema, scaling and pruritus compared with baseline was maintained during the maintenance phase in both tacrolimus groups, but not in the vehicle group. The mean recurrence rate according to global assessment was significantly higher in the tacrolimus once-weekly group than in the twice-weekly group. In conclusion, twice-weekly treatment with 0.1% tacrolimus ointment had superior effects in keeping facial seborrhoeic dermatitis in remission.

Efficacy of photodynamic diagnosis-guided Mohs micrographic surgery in primary squamous cell carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) usually has ill-defined margins because of its irregular invasive patterns. OBJECTIVE: To evaluate the surgical efficacy of photodynamic diagnosis (PDD) in primary cSCC treated using Mohs micrographic surgery (MMS). METHODS & MATERIALS: We examined 67 cases of biopsy-proven primary facial cSCC treated with MMS. The 67 SCC were divided into the two groups depending on PDD application: PDD group (n = 38, 56.7%) and non-PDD group (n = 29, 43.3%). We analyzed the differences in surgical features between the PDD and non-PDD groups. RESULTS: The PDD group required fewer Mohs stages (1.37 vs 1.83, p = .02) and smaller surgical margins (8.03 vs 11.24 mm, p = .03). PDD showed additional benefits in terms of surgical margin and Mohs stage, especially in low-risk SCC, including thin (≤4 mm), small (≤20 mm), well-differentiated, and nonulcerative tumors (p < .05) but did not show beneficial effects in high-risk SCC (p > .05) during MMS. CONCLUSION: PDD can increase surgical efficacy of primary cSCC during MMS. These benefits are more pronounced in low-risk SCC. We recommend PDD as a simple and useful technique for delineating the margins of low-risk SCC before MMS.

Histone deacetylase inhibitors enhance the apoptotic activity of insulin-like growth factor binding protein-3 by blocking PKC-induced IGFBP-3 degradation.

Overexpression of insulin-like growth factor binding protein (IGFBP)-3 induces apoptosis of cancer cells. However, preexisting resistance to IGFBP-3 could limit its antitumor activities. This study characterizes the efficacy and mechanism of the combination of recombinant IGFBP-3 (rIGFBP-3) and HDAC inhibitors to overcome IGFBP-3 resistance in a subset of non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC) cells. The effects of the combination of rIGFBP-3 and a number of HDAC inhibitors on cell proliferation and apoptosis were assessed in vitro and in vivo by using the MTT assay, a flow cytometry-based TUNEL assay, Western blot analyses and the NSCLC xenograft tumor model. Combined treatment with HDAC inhibitors and rIGFBP-3 had synergistic antiproliferative effects accompanied by increased apoptosis rates in a subset of NSCLC and HNSCC cell lines in vitro. Moreover, combined treatment with depsipeptide and rIGFBP-3 completely suppressed tumor growth and increased the apoptosis rate in vivo in H1299 NSCLC xenografts. Evidence suggests that HDAC inhibitors increased the half-life of rIGFBP-3 protein by blocking protein kinase C (PKC)-mediated phosphorylation and degradation of rIGFBP-3. In addition, combined treatment of IGFBP-3 with an HDAC inhibitor facilitates apoptosis through upregulation of rIGFBP-3 stability and Akt signaling inhibition. The ability of HDAC inhibitors to decrease PKC activation may enhance apoptotic activities of rIGFBP-3 in NSCLC cells in vitro and in vivo. These results indicated that combined treatment with HDAC inhibitor and rIGFBP-3 could be an effective treatment strategy for NSCLC and HNSCC with highly activated PKC.

Removal of arsenic from aqueous solution by iron-coated sand and manganese-coated sand having different mineral types.

In this study, the effects of the coating temperature during the preparation of manganese-coated sand (MCS) and iron-coated sand (ICS) on the removals of As(III) and As(V) were evaluated. The mineral type of manganese oxide on MCS-150, prepared at 150 °C, was identified as a mixture of pyrolusite and ramsdellite, which changed to high crystalline pyrolusite above 300 °C. The mineral type of ICS-150, prepared at 150 °C, was a mixture of goethite and hematite, which changed to high crystalline goethite above 300 °C. The adsorption efficiency was determined according to the mineral type which depended on the coating temperature. The As(III) oxidation efficiency of MCS-150 and As(V) adsorption efficiency of ICS-150 were approximately 77 and 70% higher compared with those of MCS-600 and ICS-600, respectively, prepared at 600 °C. Regardless of the coating temperature, the amounts of manganese and iron coated on the sand substrates were similar.