What's new about the tumor microenvironment of urothelial carcinoma?

Urothelial carcinoma is a significant global health concern that accounts for a substantial part of cancer diagnoses and deaths worldwide. The tumor microenvironment is a complex ecosystem composed of stromal cells, soluble factors, and altered extracellular matrix, that mutually interact in a highly immunomodulated environment, with a prominent role in tumor development, progression, and treatment resistance. This article reviews the current state of knowledge of the different cell populations that compose the tumor microenvironment of urothelial carcinoma, its main functions, and distinct interactions with other cellular and non-cellular components, molecular alterations and aberrant signaling pathways already identified. It also focuses on the clinical implications of these findings, and its potential to translate into improved quality of life and overall survival. Determining new targets or defining prognostic signatures for urothelial carcinoma is an ongoing challenge that could be accelerated through a deeper understanding of the tumor microenvironment.

Characteristics and Outcomes of COVID-19 Cancer Patients Admitted to a Portuguese Intensive Care Unit: A Case-Control Study.

Cancer patients appear to be a vulnerable group in the COVID-19 pandemic. This study aims to compare clinical characteristics and outcomes of cancer and non-cancer patients with COVID-19 admitted to the ICU. All COVID-19 cancer patients (cases) admitted to a Portuguese ICU between March 2020 and January 2021 were included and matched on age, sex and comorbidities with COVID-19 non-cancer patients (controls); 29 cases and 29 controls were enrolled. Initial symptoms were similar between the two groups. Anemia was significantly superior among cases (76% vs. 45%; p = 0.031). Invasive mechanical ventilation (IMV) need at ICU admission was significantly higher among cases (48% vs. 7%; odds ratio (OR) = 12.600, 95% CI: 2.517-63.063, p = 0.002), but there were no differences for global need for IMV during all-length of ICU stay and mortality rates. In a multivariate model of logistic regression, the risk of IMV need at ICU admission among cases remained statistically significant (adjusted OR = 14.036, 95% CI: 1.337-153.111, p = 0.028). Therefore, compared to critical non-cancer patients, critical cancer patients with COVID-19 had an increased risk for IMV need at the moment of ICU admission, however, not for IMV need during all-length of ICU stay or death.

Impact of Immune-Related Adverse Events on Immune Checkpoint Inhibitors Treated Cancer Patients' Survival: Single Center Experience and Literature Review.

Immune-related adverse events have emerged as a new challenge and its correlation with survival remains unclear. The goal of our study was to investigate the effect of irAE on survival outcomes in solid tumor patients receiving ICI treatment. This was a retrospective, single-center study at a university hospital involving patients with malignancy who received immune checkpoint inhibitors. Chart review was performed on each patient, noting any irAE, including new events or worsening of previous autoimmune condition after starting treatment with ICI. A total of 155 patients were included, 118 (76.1%) were male, with median age of 64 years. Median follow up time was 36 months. Seventy patients (45.2%) had at least one irAE. Of all irAE, nine (8.1%) were classified as grade 3 or higher according to the CTCAE version 5.0. There was one death secondary to pneumonitis. Median ICI cycles until first irAE onset was 4 (range: 2-99). The objective response rate was higher for patients who developed irAE (18.7% vs. 9.0%; p = 0.001), as was median overall survival (18 months (95% CI, 8.67-27.32) vs. 10 (95% CI, 3.48-16.52) months; p < 0.016) and progression free survival (10 months (95% CI, 5.44-14.56) vs. 3 months (95% CI, 1.94-4.05); p = 0.000). The risk of death in patients with irAE was 33% lower when compared to patients without such events (hazard ratio (HR): 0.67; 95% CI, 0.46-0.99; p = 0.043). Development of irAE predicted better outcomes, including OS in patients with advanced solid tumors treated with ICI. Further prospective studies are needed to explore and validate this prognostic value.

Ewing Sarcoma Developed at the Site of Previous Mast Cell Proliferation.

KIT gene mutations in Ewing sarcomas are rare; however, they are much more frequent in other neoplasms, namely mastocytosis. We describe a case of an adult male with a one-year duration of recurrent episodes of pain, swelling, and redness on the proximal phalanx of the third finger of his right hand. A core biopsy suggested a possible mastocytosis. After four years of recurrent episodes and worsening symptoms, an incisional biopsy revealed an Ewing sarcoma with a KIT gene mutation (M541L, on exon 10). KIT gene mutations with gain-of-function were identified in 2.6% of Ewing sarcomas. In this case, the detection of a KIT mutation in an Ewing sarcoma developed at the site of previous mast cell proliferation raises the hypothesis of a possible sarcomatous evolution of the original lesion. To the best of our knowledge, similar cases are not described in the current literature. This is also the first report describing the KIT M541L mutation (exon 10) in Ewing sarcoma.

Pleural empyema due to Rhodotorula mucilaginosa: A rare yet severe complication of a previously undiagnosed cancer patient.

Rhodotorula mucilaginosa (R. mucilaginosa) has been increasingly recognized as an emerging opportunistic pathogen causing invasive fungal infection, mainly in immunosuppressed patients. We report the case of a previously undiagnosed lung cancer patient with a pleural empyema due to R. mucilaginosa.