Exploring the Severity Strata of Disease Activity and Repigmentation in Vitiligo Based on Validated Physician Global Assessment (PGA) Scores.

Background/Objectives: There is currently no guidance on how to interpret the global degrees of activity (worsening) and repigmentation (improvement) in vitiligo. Stratification into global degrees can be completed for static evaluations (e.g., visible disease activity signs) and dynamic assessments (e.g., evolution over time). For the latter, the Vitiligo Disease Activity Score (VDAS15&60) and Vitiligo Disease Improvement Score (VDIS15&60) were recently validated. Methods: In the current study, a Physician Global Assessment (PGA) for disease activity (worsening) and repigmentation (improvement) was evaluated for validity (construct) and reliability (inter- and intrarater) based on a photo set of 66 patients. Subsequently, the PGA activity (worsening) and repigmentation (improvement) were used to stratify the Vitiligo Extent Score plus (VESplus), VDAS15&60 or VDIS15&60 into three global categories (slightly, moderately and much worse/improved), based on ROC analysis. Results: For the VESplus, cut-off values for the categories 'slightly, moderately and much worse' were >0.3%, >27.71% and >128.75% BSA (relative changes in the affected total BSA), respectively. For the categories 'slightly, moderately and much improved', they were >0%, >4.87% and >36.88% BSA (relative changes in the affected total BSA), respectively. The optimal cut-off values of the number of active (VDAS15) body areas were >0 areas for slightly worse, >2 areas for moderately worse and >7 for much worse. For VDIS15, the cut-off values for slightly improved and moderately improved were >0 and >1. For VDAS60 and VDIS60, the cut-off points were >0.5, >3, >9.5 and >0.5 and >1.5, respectively. The results should be interpreted with caution in patients with extensive vitiligo due to the rather limited disease extent of the included patient population (VESplus (median: 3.2%)). Conclusions: This research will aid in the development of more detailed international definitions.

Cost-of-Illness of Skin Cancer: A Systematic Review.

BACKGROUND: Skin cancer's rising incidence demands understanding of its economic impact. The current understanding is fragmented because of the various methodological approaches applied in skin cancer cost-of-illness studies. OBJECTIVE: This study systematically reviews melanoma and keratinocyte carcinoma cost-of-illness studies to provide an overview of the applied methodological approaches and to identify the main cost drivers. METHODS: This systematic review was conducted adhering to the 2020 PRISMA guidelines. PubMed, Embase, and Web of Science were searched from December 2022 until December 2023 using a search strategy with entry terms related to the concepts of skin cancer and cost of illness. The records were screened on the basis of the title and abstract and subsequently on full text against predetermined eligibility criteria. Articles published before 2012 were excluded. A nine-item checklist adapted for cost-of-illness studies was used to assess the methodological quality of the articles. RESULTS: This review included a total of 45 studies, together evaluating more than half a million patients. The majority of the studies (n = 36) focused on melanoma skin cancer, a few (n = 3) focused on keratinocyte carcinomas, and 6 studies examined both. Direct costs were estimated in all studies, while indirect costs were only estimated in nine studies. Considerable heterogeneity was observed across studies, mainly owing to disparities in study population, methodological approaches, included cost categories, and differences in healthcare systems. In melanoma skin cancer, both direct and indirect costs increased with progressing tumor stage. In advanced stage melanoma, systemic therapy emerged as the main cost driver. In contrast, for keratinocyte carcinoma no obvious cost drivers were identified. CONCLUSIONS: A homogeneous skin cancer cost-of-illness study design would be beneficial to enhance between-studies comparability, identification of cost drivers, and support evidence-based decision-making for skin cancer.

A critical re-evaluation of Mohs micrographic surgery for a facial basal cell carcinoma in older adults: Should we waive this treatment in certain patients?

BACKGROUND: Skin cancer incidences are increasing. Treatment for basal cell carcinomas (BCCs) can be questioned in certain patients. Treatment options are various, but Mohs micrographic surgery (MMS) has the highest cure rate. It is, however, time-consuming and results in high logistical burden and treatment costs for both patients and society. OBJECTIVES: This study critically re-evaluates MMS for facial BCCs in older adults. The main objective is to examine all clinical, tumour and patient characteristics in relation to safety and survival to detect a subgroup in which MMS was not the best choice. The overall aim is to identify characteristics that support clinical decision-making in daily practice. METHODS: Patients that received MMS between November 1998 and December 2012 were included. Only patients >75 years with a facial BCC were withheld for analysis. This is a retrospective cohort study, since evaluating the outcome of MMS in accordance with life expectancy is the main objective. Patient charts were evaluated towards comorbidities, complications and survival. RESULTS: This cohort comprises 207 patients. Median survival was 7.85 years. The age-adjusted Charlson comorbidity index (aCCI) was divided into low/medium scores (aCCI < 6) and high scores (aCCI ≥ 6). Median survival was 11.58 years in the low aCCI group and 3.60 years in the high aCCI group (p < 0.001). There was a very strong association between high aCCI and survival (HR, 6.25; 95% CI, 3.83-10.21). Other characteristics were not associated with survival. CONCLUSIONS: Clinicians should assess the aCCI in older patients presenting with a facial BCC before deciding if MMS is an eligible treatment option. High aCCI has shown to be an indicator for low median survival, even in MMS patients with usually high functional status. MMS should be waived as treatment in older patients with high aCCI scores in favour of other, less intensive and less expensive treatment options.

The therapeutic dilemma of basal cell carcinoma in older adults: A review of the current literature.

Skin cancer is known to be a significant health care threat due to the massively increasing numbers of diagnoses. In 2019, 4 million basal cell carcinoma (BCC) cases were diagnosed globally, making BCC the most frequent of all cancers worldwide in fair skinned populations. Given the increasing life-expectancy for all countries worldwide (by 2050, the world's population of people aged 60 years and older will have doubled), the incidence of BCC is expected to keep increasing in the future. Management of BCCs is challenging, especially among older adults, as mortality due to BCCs is extremely rare, whereas locally destructive growth can cause significant morbidity in certain cases. Therapeutic management in this population is further hampered because of the presence of comorbidities, frailty, and the heterogeneity of these aspects in older patients, leading to treatment dilemmas. A literature review was conducted to identify relevant patient, tumour, and treatment related factors that should be considered in the decision making for BCC treatment in older adults. This narrative review synthesizes all aspects concerning BCC treatment in older adults and aims to make some specific suggestions considering BCC treatment in older adults that can be used in daily practice. We found that nodular BCC was found to be the most common subtype in older adults, most frequently located in the head and neck region. In non-facial BCCs, current literature has shown no significant impact on the quality of life (QoL) in older patients. Besides comorbidity scores, functional status should guide clinicians in treatment decisions. Taking all aspects into account when making treatment decisions is of great importance. When treating superficial BCCs on difficult-to-reach lesions in older adults, a clinician-administered treatment should be suggested because of possible impaired mobility in these patients. Based on current literature, we recommend assessing the comorbidities, the functional status, and frailty in older patients with BCC to evaluate life expectancy. In patients with low-risk BCCs and a limited life expectancy (LLE), an active surveillance or watchful waiting strategy can be suggested.

Study protocol of the BASINEL Study: a pragmatic randomised controlled trial investigating treatment versus no treatment of low-risk basal cell carcinomas in older persons.

INTRODUCTION: Basal cell carcinomas (BCCs) represent 70% of all skin cancers. These tumours do not metastasise but are locally invasive if left untreated. There is a high incidence of BCC in the elderly, and clinicians frequently face important treatment dilemmas. The approach to BCC in the elderly should be investigated thoroughly. METHODS AND ANALYSIS: Data on health-related quality of life (HrQoL), survival and complication rate will be examined in a treatment and a non-treatment arm (1:1 allocation). In the non-treatment arm, in vivo biological behaviour of low-risk BCCs in elderly patients will be examined. The main objective is to combine tumour characteristics with demographic data, in order to determine whether treatment will positively affect the patients' HrQoL within a predetermined time frame. A monocentric randomised controlled trial (RCT) was designed at the Ghent University Hospital. The study population consists of patients with the minimum age of 75 years and a new diagnosis of (a) low-risk BCC(s). Patients in the treatment arm will receive standard care. Patients in the non-treatment arm will be closely monitored: the tumour will be intensively evaluated using multispectral dermoscopy, reflectance confocal microscopy and high-definition optical coherence tomography. All patients will be asked to fill in a questionnaire concerning their HrQoL at consecutive time points. Patient-reported side effects will be evaluated via an additional questionnaire.Primary outcomes will include the difference in HrQoL and the difference in complication risks (treatment vs non-treatment) at different time points of the study. Secondary endpoints are the evolution of the BCCs in the non-treatment arm and the long-term survival in both study arms. Tertiary endpoint is the treatment effectiveness in the treatment arm. The sample size calculation was performed and resulted in a target sample size of 272 patients in this study with a 1:1 allocation. ETHICS AND DISSEMINATION: Subjects can withdraw from participating in this study at any time for any reason without any consequences. Approval for this study was received from the Ethics Committee of the Ghent University Hospital on 26 August 2021.The results of this RCT will be submitted for publication in one or more international, peer-reviewed medical journals, regardless of the nature of the study results. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT05110924).

Genomic features of renal cell carcinoma with venous tumor thrombus.

A venous tumor thrombus (VTT) is a potentially lethal complication of renal cell carcinoma (RCC) but virtually nothing is known about the underlying natural history. Based on our observation that venous thrombi contain significant numbers of viable tumor cells, we applied multiregion whole exome sequencing to a total of 37 primary tumor and VTT samples including normal tissue specimens from five consecutive patients. Our findings demonstrate mutational heterogeneity between primary tumor and VTT with 106 of 483 genes (22%) harboring functional SNVs and/or indels altered in either primary tumor or thrombus. Reconstruction of the clonal phylogeny showed clustering of tumor samples and VTT samples, respectively, in the majority of tumors. However, no new subclones were detected suggesting that pre-existing subclones of the primary tumor drive VTT formation. Importantly, we found several lines of evidence for "BRCAness" in a subset of tumors. These included mutations in genes that confer "BRCAness", a mutational signature and an increase of small indels. Re-analysis of SNV calls from the TCGA KIRC-US cohort confirmed a high frequency of the "BRCAness" mutational signature AC3 in clear cell RCC. Our findings warrant further pre-clinical experiments and may lead to novel personalized therapies for RCC patients.

Epidemiology, causes, evolution and outcome in a single-center cohort of 1116 critically ill patients with hypoxic hepatitis.

BACKGROUND: Hypoxic hepatitis (HH) is a type of acute hepatic injury that is histologically characterized by centrilobular liver cell necrosis and that is caused by insufficient oxygen delivery to the hepatocytes. Typical for HH is the sudden and significant increase of aspartate aminotransferase (AST) in response to cardiac, circulatory or respiratory failure. The aim of this study is to investigate its epidemiology, causes, evolution and outcome. METHODS: The screened population consisted of all adults admitted to the intensive care unit (ICU) at the Ghent University Hospital between January 1, 2007 and September 21, 2015. HH was defined as peak AST > 5 times the upper limit of normal (ULN) after exclusion of other causes of liver injury. Thirty-five variables were retrospectively collected and used in descriptive analysis, time series plots and Kaplan-Meier survival curves with multi-group log-rank tests. RESULTS: HH was observed in 4.0% of the ICU admissions at our center. The study cohort comprised 1116 patients. Causes of HH were cardiac failure (49.1%), septic shock (29.8%), hypovolemic shock (9.4%), acute respiratory failure (6.4%), acute on chronic respiratory failure (3.3%), pulmonary embolism (1.4%) and hyperthermia (0.5%). The 28-day mortality associated with HH was 45.0%. Mortality rates differed significantly (P = 0.007) among the causes, ranging from 33.3% in the hyperthermia subgroup to 52.9 and 56.2% in the septic shock and pulmonary embolism subgroups, respectively. The magnitude of AST increase was also significantly correlated (P < 0.001) with mortality: 33.2, 44.4 and 55.4% for peak AST 5-10× ULN, 10-20× ULN and > 20× ULN, respectively. CONCLUSION: This study surpasses by far the largest cohort of critically ill patients with HH. HH is more common than previously thought with an ICU incidence of 4.0%, and it is associated with a high all-cause mortality of 45.0% at 28 days. The main causes of HH are cardiac failure and septic shock, which include more than 3/4 of all episodes. Clinicians should search actively for any underlying hemodynamic or respiratory instability even in patients with moderately increased AST levels.