Optical coherence tomography-guided Nd:YAG laser treatment and follow-up of basal cell carcinoma.

OBJECTIVES: Basal cell carcinoma (BCC) is the most common skin tumor with an annually increasing incidence. Standard care requires several visits for diagnosis and treatment. Optical coherence tomography (OCT) as a diagnostic tool increases the sensitivity (95%) and specificity (77%) of the diagnosis of BCC. Although laser therapy is not the standard of care, the long-pulsed 1064 nm Nd:YAG laser seems to be a promising option. However, data are scarce. The published papers had a short follow-up (FU) time and used to some extent inferior methods to detect complete tumor clearance. To address this research gap, this study evaluates the efficiency of laser treatment by FU OCT. We pursue a patient-focused approach and combine OCT with Nd:YAG laser treatment in one procedure. MATERIALS AND METHODS: The study was conducted as a prospective, single-center trial that recruited biopsy-confirmed or OCT-proven BCC with a tumor thickness of less than 1.2 mm. Patients underwent two or three repeated sessions with the Nd:YAG laser (5-6 mm spot, fluence of 120-140 J/cm2 , pulse duration of 8-10 milliseconds). Each BCC was assessed at baseline, and 3 and 12 months after laser treatment by clinical image, dermoscopy, and OCT. Incomplete tumor clearance (ITC) was defined as a clearly detectable BCC on the OCT image or a biopsy-confirmed BCC in the treated area. RESULTS: Forty-five patients completed the 12-month FU (46.7% women; median age of 74.0 [52-88] years) with a total number of 78 BCC lesions. At baseline, all patients had their BCC diagnosed by OCT (tumor thickness of 0.6 [0.4; 0.8] mm), 15.4% lesions were additionally diagnosed by histopathology. The most common subtype of BCC was superficial (48.7%), followed by nodular (47.4%) and infiltrative (3.8%). ITC rate after the treatment using Nd:YAG laser was 30.8% (95% CI: 20.8%-42.2%) (24/78) after 3 months and 7.4% (95% CI: 2.1%-17.9%) (4/54) after 12 months. ITC was not associated with histological subtype, tumor thickness, or location. If ITC was detected, the lesion was treated again. Out of 19 lesions with at least one additional laser treatment, 7 lesions (36.8%) suffered from incomplete tumor removal. In 46.7% of the treated lesions, the cosmetic outcome was rated as moderate or severe scarring after 12 months. CONCLUSION: Our results demonstrate that the ITC rate of BCC treated with the Nd:YAG laser is much higher (up to one-third) than reported, although the laser settings were identical to prior studies. This is especially evident at the 3-month FU. In addition, we witnessed a larger number of side effects and a worse cosmetic outcome compared to previous studies.

Characterization of Amino Acid Substitutions and Deletions in Kindlin-1 FERM Domain: Relevance for Precision Medicine.

Kindler epidermolysis bullosa is a genodermatosis that manifests with cutaneous and mucosal fragility and with photosensitivity. No cure is available to date. Kindlin-1, a deficient protein, binds to ß-integrin and is required for its activation. Using a previously established experimental workflow, we addressed the consequences of three naturally occurring pathogenic variants, leading either to single amino acid substitutions p.Y293D and p.W559R or to a single amino acid deletion p.I623del in kindlin-1. We show that p.Y293D disrupts kindlin-1 localization to focal adhesions and cell spreading. Although treatment with a chemical chaperone increases the amount of mutant protein, spreading does not improve, and cellular stress increases, whereas the variants p.W559R and p.I623del do not interfere with kindlin-1 localization to focal adhesions and support cell adhesion and survival. These mutants are also responsive to the treatment with a chemical chaperone, and the increased mutant proteins improve cell spreading. These findings suggest that low levels of mutant kindlins p.W559R and p.I623del are able to rescue some important cellular functions. Patients carrying these mutations could benefit from treatment with promotors of proteostasis. Our results show that each pathogenic variant must be individually tested on genetic, molecular, and cellular levels to tailor personalized treatments for patients.