European recommendations for management of immune checkpoint inhibitors-derived dermatologic adverse events. The EADV task force 'Dermatology for cancer patients' position statement.

The introduction of immune checkpoint inhibitors (ICIs) opened a new era in oncologic therapy. The favourable profile of ICIs in terms of efficacy and safety can be overshadowed by the development of immune-related adverse events (irAEs). Dermatologic irAEs (dirAEs) appear in about 40% of patients undergoing immunotherapy and mainly include maculopapular, psoriasiform, lichenoid and eczematous rashes, auto-immune bullous disorders, pigmentary disorders, pruritus, oral mucosal lesions, hair and nail changes, as well as a few rare and potentially life-threatening toxicities. The EADV task force Dermatology for Cancer Patients merged the clinical experience of the so-far published data, incorporated the quantitative and qualitative characteristics of each specific dirAEs, and released dermatology-derived, phenotype-specific treatment recommendations for cutaneous toxicities (including levels of evidence and grades of recommendation). The basic principle of management is that the interventions should be tailored to serve the equilibrium between patients' relief from the symptoms and signs of skin toxicity and the preservation of an unimpeded oncologic treatment.

Photoadaptation to ultraviolet B TL01 in psoriatic patients.

BACKGROUND: In the biologic era, narrow-band ultraviolet B (NB-UVB) phototherapy still remains a valuable, effective, inexpensive, safe anti-psoriatic treatment. Patients can lose response to NB-UVB over time due to photoadaptation. This phenomenon is the tendency of the skin to respond to ultraviolet (UV) exposure by undergoing changes that may result in a decreased future response to an equivalent dose of radiation, thus leading to the need for an increased exposure during phototherapy course. AIM: To characterize and quantify the determinants of photoadaptation in NB-UVB treated psoriatic patients. METHODS: We enrolled 57 adult patients with moderate plaque psoriasis. Patients underwent 24 sessions of NB-UVB phototherapy delivered thrice a week. Dosing was started with 70% of the minimal erythema dose (MED) with percentage-based dose increments every two treatments. MED as well as change in the erythema and melanin index (MI) were measured at baseline and at the end of phototherapy course. Moreover, an adaptation factor (AF) was calculated for each patient. RESULTS: Adaptation factor was not influenced by both baseline MED and skin type. We found a weak correlation between higher cumulative dosages and the initial MED (Spearman's rho = 0.32, P = 0.0154) as well as with the mean initial MI (Spearman's rho = 0.25, P = 0.0624, statistically borderline). Clearance and mean number of treatments were correlated (Spearman's rho = 0.48, P < 0.001). CONCLUSION: Photoadaptation is a physiological skin response that negatively influences NB-UVB responsiveness and is not predictable by the baseline MED and skin type. Thus, starting with more aggressive protocols and increasing rapidly dosage progression to prevent AF may increase NB-UVB response.

Morphological and morphometric analysis of cutaneous squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa: a retrospective study.

BACKGROUND: Recessive dystrophic epidermolysis bullosa is a highly disabling genodermatosis characterized by skin and mucosal fragility and blistering. Cutaneous squamous cell carcinoma (cSCC) is one of the most devastating complications, having a high morbidity and mortality rate. Patients with recessive dystrophic epidermolysis bullosa were reported to have up to a 70-fold higher risk of developing cSCC than unaffected individuals. Immune cells play a role in cancer evolution. OBJECTIVE: The aim of our study was to evaluate immunohistological differences between cSCC in patients with and without recessive dystrophic epidermolysis bullosa. METHODS: A retrospective study of 25 consecutive cases was performed; five were biopsies of cSCC taken from five patients with recessive dystrophic epidermolysis bullosa; as controls we analysed 10 cSCC in subjects without recessive dystrophic epidermolysis bullosa (5 primitive, 3 postburns and 2 postradiotherapy), 5 cSCC in renal transplant recipients and 5 cutaneous pseudoepitheliomatous hyperplasia in patients with recessive dystrophic epidermolysis bullosa. RESULTS: A significant reduction of CD3+, CD4+ and CD68+ between the cSCC in patients with recessive dystrophic epidermolysis bullosa compared to primary cSCC and a significant reduction of CD3+, CD4+, CD8+ and CD20+ were observed in cSCC in patients with recessive dystrophic epidermolysis bullosa compared to secondary cSCC. On the contrary, there was no difference in CD3+, CD8+, CD20+ and CD68+ expression when comparing cSCC in patients with recessive dystrophic epidermolysis bullosa to cSCC in renal transplant recipients. No significant difference was found in size, histopathology, grading, number of mitoses and EGFR expression between the different groups. CONCLUSIONS: Our data show a reduction in immune cell peritumoral infiltration. Considering the well-known evolution of cSCC in patients with recessive dystrophic epidermolysis bullosa, as well as the younger age at diagnosis, it can be assumed that immune dysfunction might contribute to the cSCC aggressiveness in these patients.

Echo-guided SWL of vesical stones with Dornier MPL 9000 lithotripter in obstructed and unobstructed patients.

Sixty-one patients with vesical stones (38 with underlying obstructive conditions and 23 unobstructed) underwent SWL using ultrasound targeting under no regional or general anesthesia. A foley catheter was not routinely employed, and the bladder was filled in a physiologic way. Complete resolution was obtained in 47 patients (78%); in particular, 66% of the obstructed patients and 96% of the unobstructed patients became stone free in one to four SWL sessions. The average number of sessions for all patients was 1.28+/-0.63. Fragments were completely evacuated also in some patients with severe obstruction and in all three patients with neurogenic bladder dysfunction. The size and number of stones did not seem to play a limiting role in SWL effectiveness: the principal limiting factor was the hardness of the stone. No severe complications occurred. However, in six patients (10%), some fragments stopped in the urethra, causing acute urine retention, and endoscopic extraction was necessary. Echo-guided SWL of bladder stones is safe and highly effective in nonobstructed patients and can be considered the elective monotherapy method. In obstructed patients, SWL efficacy is lower, but the method may be suggested for patients who refuse or delay other, more invasive techniques.

Proliferating cell nuclear antigen/cyclin in incidental carcinoma of the prostate.

Monoclonal antibody to proliferating cell nuclear antigen (PCNA) has been used to identify the growth fraction in ten cases of benign prostatic hyperplasia (BPH), in 20 prostatic microcarcinomas (PMC) and in 30 cases of infiltrating prostatic carcinoma (PC). Ten year follow-up was available on all cases by means of clinical, serological, radiological and echographic examinations. The percentage of PCNA-staining nuclei was independently counted by two observers. Statistical analysis showed significant differences between PCNA/cyclin score of BPH and PMC without recurrences with respect to those of PMC with progression and of PC. PCNA immunostaining may represent a reliable method for assessing cellular proliferative activity. It may be used as a more powerful diagnostic hallmark of PMC than patterns of non-malignant microglandular proliferation and is also a useful additional test for assigning histological grades to PMC and PC. Statistical analysis indicated that PCNA/cyclin index was an independent significant prognostic indicator of predicting malignant progression (P < or = 0.01) and survival rates (P < or = 0.05) of PC and PMC (> 5 mm diameter).