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Background: Combination of immune checkpoint inhibitors and mitogen-activated protein kinase (MAPK) pathway inhibitors (MAPKi) has been proposed to enhance the durability of anti-tumour responses induced by MAPKi. Here, we present phase I safety results from an open-label, phase I/II study of pembrolizumab (PEM), encorafenib (ENC) and binimetinib (BIN) triplet therapy in advanced, B-Raf proto-oncogene serine/threonine kinase (BRAF) V600 -mutated melanoma (IMMU-TARGET, NCT02902042)., Methods: The dose finding phase I part used a 3 + 3 design, starting with the approved doses of PEM (200 mg every three weeks), ENC (450 mg once daily [QD]) and BIN (45 mg twice daily [BID]) as dose level (DL) 0. Reduction of the ENC and BIN doses (300 mg QD and 30 mg BID at DL-1 and 200 mg QD and 30 mg BID at DL-2) was preplanned in case of ≥2 dose-limiting toxicities (DLTs). Primary objectives were to estimate the recommended phase II dose of the triplet combination, DLT and safety. As per the sponsor's decision, the study was terminated after the phase I part, as the clinical efficacy of the combination is currently being investigated in a pivotal, placebo-controlled (PEM mono), double-blinded phase III trial (STARBOARD,NCT04657991)., Results: Fifteen patients were enrolled. DLTs of DL0 were creatine phosphokinase (CPK) elevation plus cytokine release syndrome (n = 1) and gamma glutamyl transferase (GGT) increase (n = 1). No DLT was observed in further 3 + 3 patients at DL-1. One (isolated GGT elevations) DLT of DL0 was questionable, as the patient had further episodes of isolated GGT elevations after treatment discontinuation. Hence, further 6 patients were enrolled at DL0: here, no DLT occurred. In total, 13 of 15 patients (87%) experienced a treatment-related adverse event (TRAE) and 8 patients (53%), a grade ≥III TRAE; there were no TRAE-related deaths. Increases in aspartate aminotransferases, GGT (6/15 patients) and CPK elevations (4/15) were the most common grade III-IV TRAE. In median, patients received triplet therapy for 24 weeks (interquartile range [IQR], 12-45). Of the 14 patients evaluable for efficacy, the overall response rate was 64% (95% confidence interval [CI], 35-87). At a median follow-up of 25 months (IQR, 9-28), progression-free survival at 12 months was 41% (95% CI, 13-68)., Conclusions: Triplet therapy with PEM, ENC and BIN as used in the study was feasible and safe and led to clinically meaningful disease control., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: A more reliable classification of skin inflammation and severity of active disease results from ultrasound sonography and the new hidradenitis suppurativa/acne inversa (HS) classification system IHS4. However, an objective assessment of skin inflammation in a continuous mode is still the ultimate goal. Long-wave medical infrared thermography (MIT) may offer a blood flow and temperature differential assessment in inflammatory conditions., Objective: To evaluate the application of MIT in HS., Methods: Standardized photography of the areas involved or been candidates for HS involvement was performed and MIT pictures were taken simultaneously and superimposed on the photographs of 18 patients (11 female, 7 male, median age 38.75 years [95% confidence interval 28.5 and 51 years], Hurley score I 5.6%, Hurley score II 38.9%, and Hurley score III 55.5%). A modification of the Otsu's method facilitated the automatic lesion segmentation from the background, depicting the inflammation area. Moreover, MIT was administered in real-time mode during radical HS surgery., Results: A 1°C temperature difference from a corresponding symmetric body region was indicative of inflammation. MIT figures detected a gradual increase of skin temperature from 33.0°C in healthy skin on average to 35.0-36.6°C at the center of inflamma tory lesions in the axilla and to 35.4-36.9°C at the center of inflammation in the groin area. Real-time MIT assessment enabled the definition of the margins and depth of the surgical intervention during the procedure., Conclusion: MIT is a promising tool for the detection of inflammation severity in HS lesions and can be used as a clinical biomarker in evaluation studies of medical and surgical HS treatment., (© 2019 S. Karger AG, Basel.)

A 36-year-old homosexual man presented with a 3-week history of pin-head-sized vesicles on the lower lip followed by a tumorous infiltrate, cervical lymphadenopathy and episodic fevers. Laboratory findings included striking leukocytosis and elevated inflammatory markers. Serologically,anti-chlamydial antibodies (IgG, IgA,IgM) were present. The histological findings were compatible with a chlamydial infection; PCR examination of the tumor and lymph nodes was positive for Chlamydia trachomatis DNA. Treatment with doxycycline (2x 100 mg/daily p.o. for 3 weeks) led to rapid improvement. Lymphogranuloma venereum is a relatively rare, worldwide illness, more common in tropical and sub-tropical zones. In Germany, there are 10-50 cases reported annually but many cases go unreported. The causative organism is Chlamydia trachomatis, serotypes L1-3. The transfer occurs through skin or mucous membrane contact with an infected partner. In the advanced stage, the infection can lead to marked internal organ involvement. The special features of our case include the extragenital manifestation and the tumorous appearance of the illness which is very rarely diagnosed in Germany.

We report four patients with long-lasting therapy-resistant ulcus cruris, on which a new erysipelas was superimposed. In one case there was a total closure of the ulcers under the erysipelas. In three patients a reduction in size occurred. All ulcers became flatter. Other stimuli of wound healing were excluded. Because of the long-lasting existence and well known therapy resistance in each case, these changes suggest a positive effect of the erysipelas on the healing of the ulcers. We assume that serum cytokines could offer a possible explanation for this. The concentrations of the IL-6 and IL-2-receptor were initially raised and then later decreased in three of the four cases. Because of the complex stimulation and regulation mechanisms in the cytokine network which are triggered by inflammation, systemic and local effects of keratinocytes, monocytes/macrophages, fibroblasts and endothelium cells could also be assumed to support wound healing.

54 patients suffering from esophageal cancer have been treated in a period from 1990 to 1994. In 29 cases curative resection was possible, corresponding to a resection rate of 54%. Average age of resected patients was 62 years. According to pTNM-classification the stages T1 and T2 amounted to 45%, T3 and T4 to 55%. Lymphatic node metastases were discovered with an incidence of 55%. In patients treated conservatively more unfavourable stage distributions and increased rates of lymphatic node metastasis were shown. Transthoracal-transabdominal esophageal resection was preferred as curative management. Lethality amounted to 13.8%. In 3 of 4 lethal cases after resection autopsy confirmed absence of tumor. Lethal complications were two respiratory insufficiencies, one suture line dehiscence and one alcoholic delirium. Survival rates were calculated by life-table-method. We consider the transthoracal-transabdominal esophageal resection as an acceptable therapeutic option in esophageal cancer offering a real chance of enduring curing.