Background
Hepatic immune-related adverse events (irAE) including elevated liver function tests (transaminases) occur in 1.4–22.3% of melanoma patients receiving immune checkpoint inhibitors (ICPI) ...and constitute a potentially serious toxicity that is challenging to treat. In contrast to the liver transaminases alanine aminotransferase (ALT) and aspartate aminotransferase (AST), only little is known about the frequency and impact of gamma-glutamyl transferase (GGT) elevations.
Methods
GGT determined prior to and during therapy of metastatic melanoma patients treated with ICPI were retrospectively assessed in two independent cohorts (PD-1:
n
= 218, Ipi + Nivo:
n
= 148). Overall survival (OS) and best objective response were analyzed according to baseline and immune-related GGT (irGGT) elevations during treatment.
Results
In multivariate analysis, OS was reduced in patients with elevated baseline GGT (PD-1 group: hazard ratio HR 1.76,
p
= .0073; Ipi + Nivo group: HR 1.77,
p
= .032). Immune-related GGT elevation was recorded in 17% (PD-1 group) and 38.5% (Ipi + Nivo group). Of these patients, the majority (81 and 68%, respectively) had normal ALT and AST and showed no clinical signs of hepatotoxicity. Patients who experienced irGGT elevation had superior response (PD-1 group: odds ratio OR 3.57,
p
= .00072; Ipi + Nivo group: OR 1.74,
p
= .12) and OS (PD-1 group: HR 0.37,
p
= .0016; Ipi + Nivo group: HR 0.33,
p
= .00050).
Conclusions
The frequency of hepatic irAE is currently underestimated. The addition of the sensitive enzyme GGT to the laboratory panel before and during therapy with ICPI allows to detect two to three times more patients developing hepatic or hepatobiliary toxicity than known so far. Immune-related GGT elevations correlate with response and favorable survival.
Precis for use in the Table of Contents
The frequency of hepatotoxicity under immune checkpoint blockade is currently underestimated. We suggest the addition of gamma-glutamyl transferase to the laboratory panel in checkpoint inhibitor patients for the detection of hepatobiliary toxicity.
Due to its antibacterial actions, silver sulfadiazine is widely used as a topical agent in the treatment of wounds, including burns. Widespread or prolonged topical application of silver sulfadiazine ...dressings can lead to argyria including systemic symptoms due to the resorption of silver. Here, we report a patient experiencing localized argyria due to sunlight exposure after topical use of silver sulfadiazine cream on his face.
At the early stages of the COVID-19 outbreak in 2020, Switzerland was among the countries with the highest number of SARS-CoV2-infections per capita in the world. Lockdowns had a remarkable impact on ...primary care access and resulted in postponed cancer screenings. The aim of this study was to investigate the effects of the COVID-19 lockdown on the diagnosis of melanomas and stage of melanomas at diagnosis. In this retrospective, exploratory cohort study, 1240 patients with a new diagnosis of melanoma were analyzed at five tertiary care hospitals in German-speaking Switzerland over a period of two years and three months. We compared the pre-lockdown (01/FEB/19-15/MAR/20, n = 655) with the lockdown (16/MAR/20-22/JUN/20, n = 148) and post-lockdown period (23/JUN/20-30/APR/21, n = 437) by evaluating patients' demographics and prognostic features using Breslow thickness, ulceration, subtype, and stages. We observed a short-term, two-week rise in melanoma diagnoses after the major lift of social lockdown restrictions. The difference of mean Breslow thicknesses was significantly greater in older females during the lockdown compared to the pre-lockdown (1.9 ± 1.3 mm,
= 0.03) and post-lockdown period (1.9 ± 1.3 mm,
= 0.048). Thickness increase was driven by nodular melanomas (2.9 ± 1.3 mm,
= 0.0021; resp. 2.6 ± 1.3 mm,
= 0.008). A proportional rise of advanced melanomas was observed during lockdown (
= 0.047). The findings provide clinically relevant insights into lockdown-related gender- and age-dependent effects on melanoma diagnosis. Our data highlight a stable course in new melanomas with a lower-than-expected increase in the post-lockdown period. The lockdown period led to a greater thickness in elderly women driven by nodular melanomas and a proportional shift towards stage IV melanoma. We intend to raise awareness for individual cancer care in future pandemic management strategies.
Rare T- or NK-cell lymphomas with cutaneous manifestation may display a highly aggressive clinical course and major diagnostic/therapeutic challenges. This report describes our experiences with ...different lymphomas of this rare category and the therapeutic options used. This retrospective, descriptive, monocentric, cross-sectional case study, identified 4 rare aggressive T-/NK-cell lymphomas with manifestation in the skin, which were diagnosed in a tertiary care centre over a period of 4 years. Two patients had an Epstein-Barr virus-associated extranodal NK/T-cell lymphoma and 2 patients had a primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma. Concomitant extracutaneous involvement was observed in 2 of all 4 patients. Two patients had fulminant disease progression and resistance to chemotherapy. Two patients underwent allogeneic haematopoietic stem cell transplantation, which resulted in one complete remission and one partial remission. This report emphasizes the importance of an early diagnostic work-up and a prompt aggressive therapeutic approach.
ABSTRACT
Merkel cell carcinoma (MCC) is a rare and difficult-to-treat cutaneous malignancy with a poor prognosis. Treatment protocols for localized MCC are well established. Until recently, ...metastatic MCC has generally been treated with chemotherapy, which was often associated with poor clinical responses and significant toxicity. In this report, the case of a patient with metastatic MCC who received avelumab, an immune checkpoint inhibitor, after an inadequate response to first-line radiotherapy and chemotherapy, is presented. Nine months after the initiation of the treatment with avelumab, the patient achieved a partial remission with no treatment-related adverse events. After a follow-up of 17 months, a systematically ongoing partial response was reported. In conclusion, this case study offers a clinical insight into the patient’s case and highlights the importance of immunotherapy as a first-line therapy for metastatic MCC.
Purpose: Topical corticosteroids concerns (TCC) are common in dermatology patients, possibly leading to non-adherence to topical corticosteroids (TCS) and poor disease control. Clinicians play a key ...role in that context, as they can reduce or reinforce these concerns. It is unknown, if clinicians have accurate knowledge of TCC to appropriately address this issue and whether they have concerns themselves to use TCS. This questionnaire-based study aimed to assess these two aspects.
Materials and methods: Accuracy of knowledge was defined by how close the clinicians' estimates were to reference values of our previous study, in which we had examined TCC in dermatology outpatients. Moreover, clinicians indicated whether they have concerns themselves to use TCS.
Results: Totally 202 clinicians participated. They underestimated both the prevalence of TCC and the resulting non-adherence. Whereas most clinicians correctly estimated characteristics of patients with TCC and the impact of patient information, only 31% of clinicians knew that skin atrophy was the leading concern, and only 30% correctly ranked the reasons for TCC. 74% of the clinicians had at least minor concerns themselves.
Conclusion: The majority of clinicians may have inaccurate knowledge of certain aspects of TCC and own concerns to use TCS.
A specific association with mixed lineage leukemias suggests that MLL oncoproteins may selectively target early multipotent hematopoietic progenitors or stem cells. We demonstrate here that a ...representative MLL fusion protein, MLL-GAS7, impairs the differentiation and enhances the in vitro growth of murine hematopoietic cells with multipotent features. The multilineage differentiation potential of these cells was suggested by their immuno-phenotypes and transcriptional programs and confirmed by their ability to induce three pathologically distinct leukemias in mice, including an acute biphenotypic leukemia (ABL) that recapitulates the distinctive hallmark features of many MLL-associated leukemias in humans. This experimental modeling of ABL in mice highlights its origin from multipotential progenitors that arrest at a bipotential stage specifically targeted or induced by
MLL oncogenes.
Toxic epidermal necrolysis (TEN) is a rare, life-threatening drug-induced skin disease with a mortality rate of approximately 30%. The clinical hallmark of TEN is a marked skin detachment caused by ...extensive keratinocyte cell death associated with mucosal involvement. The exact pathogenic mechanism of TEN is still uncertain. Recent advances in this field have led to the identification of several factors that might contribute to the induction of excessive apoptosis of keratinocytes. In addition, specific human leukocyte antigen types seem to be associated with certain drugs and the development of TEN. As well-controlled studies are lacking, patients are treated with various immunomodulators (e.g. intravenous immunoglobulin) in addition to the best supportive care.
Decorative tattooing is a procedure in which exogenous pigment and/or dye is introduced into the dermis with the aim of creating a permanent skin decoration. The increasing prevalence of tattooed ...individuals leads to more reported tattoo-related complications. Pseudolymphomatous reaction is a benign reactive proliferation of lymphocytes that may uncommonly occur secondary to tattooing. We describe the clinical, histological, and molecular aspects of a pseudolymphomatous reaction to red tattoo pigment.
Merkel cell carcinoma (MCC) is a malignant neuroendocrine neoplasm which shares structural and immunohistochemical features with neuroectodermally derived cells. One hypothesis claims that it arises ...from Merkel cells, highly innervated neuroendocrine cells involved in mechanoreception in the skin. The incidence rate of this cancer increases with age and sun exposure as well as after immunosuppression. Recently, the clonal integration of a newly identified polyomavirus called Merkel cell polyomavirus (MCPyV) was reported in up to 80% of MCC tissue. Here we report the incidence rate of MCPyV in MCC patients in Switzerland.
We performed polymerase chain reaction in a collection of 32 samples obtained from pathology institutes around Switzerland. We used three different published primer sets. As control groups we used 7 squamous cell carcinoma samples and 11 normal skin samples.
We detected viral DNA in 20 out of 30 cases of MCC and in 0 out of 19 control samples. The presence of viral DNA in 66.6% of our MCC tissue specimens confirms the high prevalence of MCPyV in MCC patients described in American, German, French and Hungarian patient collections.
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