Novel Therapeutic Opportunities in Neoadjuvant Setting in Urothelial Cancers: A New Horizon Opened by Molecular Classification and Immune Checkpoint Inhibitors

Muscle invasive bladder cancer (MIBC) is a widespread malignancy with a worse prognosis often related to a late diagnosis. For early-stage MIBC pts, a multidisciplinary approach is mandatory to evaluate the timing of neoadjuvant chemotherapy (NAC) and surgery. The current standard therapy is platinum-based NAC (MVAC-methotrexate, vinblastine, doxorubicin, and cisplatin or Platinum–Gemcitabine regimens) followed by radical cystectomy (RC) with lymphadenectomy. However, preliminary data from Vesper trial highlighted that dose-dense NAC MVAC is endowed with a good pathological response but shows low tolerability. In the last few years, translational-based research approaches have identified several candidate biomarkers of NAC esponsiveness, such as ERCC2, ERBB2, or DNA damage response (DDR) gene alterations. Moreover, the recent consensus MIBC molecular classification identified six molecular subtypes, characterized by different sensitivity to chemo- or targeted or immunotherapy, that could open a novel procedure for patient selection and also for neoadjuvant therapies. The Italian PURE-01 phase II Trial extended data on efficacy and resistance to Immune Checkpoint Inhibitors (ICIs) in this setting. In this review, we summarize the most relevant literature data supporting NAC use in MIBC, focusing on novel therapeutic strategies such as immunotherapy, considering the better patient stratification and selection emerging from novel molecular classification

Assessing Vegetation Decline Due to Pollution from Solid Waste Management by a Multitemporal Remote Sensing Approach

Nowadays, the huge production of Municipal Solid Waste (MSW) is one of the most strongly felt environmental issues. Consequently, the European Union (EU) delivers laws and regulations for better waste management, identifying the essential requirements for waste disposal operations and the characteristics that make waste hazardous to human health and the environment. In Italy, environmental regulations define, among other things, the characteristics of sites to be classified as “potentially contaminated”. From this perspective, the Basilicata region is currently one of the Italian regions with the highest number of potentially polluted sites in proportion to the number of inhabitants. This research aimed to identify the possible effects of potentially toxic element (PTE) pollution due to waste disposal activities in three “potentially contaminated” sites in southern Italy. The area was affected by a release of inorganic pollutants with values over the thresholds ruled by national/European legislation. Potential physiological efficiency variations of vegetation were analyzed through the multitemporal processing of satellite images. Landsat 5 Thematic Mapper (TM) and Landsat 8 Operational Land Imager (OLI) images were used to calculate the trend in the Normalized Difference Vegetation Index (NDVI) over the years. The multitemporal trends were analyzed using the median of the non-parametric Theil–Sen estimator. Finally, the Mann–Kendall test was applied to evaluate trend significance featuring areas according to the contamination effects on investigated vegetation. The applied procedure led to the exclusion of significant effects on vegetation due to PTEs. Thus, waste disposal activities during previous years do not seem to have significantly affected vegetation around targeted sites

Desempenho linguístico de prematuros de 2 anos, considerando idade cronológica e idade corrigida

RESUMO Introdução O nascimento prematuro acarreta problemas que não se restringem à mortalidade perinatal. Alguns prematuros, mesmo na ausência de lesões cerebrais, apresentam consequências negativas em diversos aspectos do desenvolvimento, como dificuldades em adquirir linguagem. Objetivo O objetivo deste estudo foi verificar o desempenho linguístico de prematuros, na faixa etária de 2 anos, considerando a idade cronológica e a idade corrigida. Métodos Participaram do estudo 23 sujeitos prematuros e para verificar as habilidades linguísticas foi aplicado o Test of Early Language Development – TELD-3. Resultados Os sujeitos prematuros apresentaram desempenho total alterado no TELD-3 em 39,13% dos casos. Os prematuros também foram analisados considerando o atraso para a idade cronológica e a corrigida e não houve diferença no desempenho para os subtestes receptivo (p = 0,250) e expressivo (p = 1,000). Conclusão O grupo de prematuros aos 2 anos de idade constitui população de risco para alterações de linguagem que não podem ser compensadas com a correção da idade

Asymptomatic azygos vein overflow in a young patient with primary mediastinal seminoma

The azygos system is the most important pathway for decompression of the superior vena cava (SVC) when a blood flow obstruction to the right atrium is present. Thoracic and mediastinal malignancies, mainly lung cancers, are responsible for 60%-85% of superior vena cava syndrome (SVCS) cases. An uncommon origin of SVCS is primary malignant mediastinal germ cell tumor (PMMGCT) which represent 1%-4% of all mediastinal tumors and can be divided into two broad groups: seminomas and nonseminomatous germ cell tumors (NSGCTs). Primary mediastinal seminomas clinical presentation is often nonspecific, even if the majority of patients present with superior vena cava involvement. Here, we present the radiologic features of asymptomatic azygos system overflow in a patient with primary mediastinal seminoma

Novel Therapeutic Opportunities in Neoadjuvant Setting in Urothelial Cancers: A New Horizon Opened by Molecular Classification and Immune Checkpoint Inhibitors

Muscle invasive bladder cancer (MIBC) is a widespread malignancy with a worse prognosis often related to a late diagnosis. For early-stage MIBC pts, a multidisciplinary approach is mandatory to evaluate the timing of neoadjuvant chemotherapy (NAC) and surgery. The current standard therapy is platinum-based NAC (MVAC-methotrexate, vinblastine, doxorubicin, and cisplatin or Platinum–Gemcitabine regimens) followed by radical cystectomy (RC) with lymphadenectomy. However, preliminary data from Vesper trial highlighted that dose-dense NAC MVAC is endowed with a good pathological response but shows low tolerability. In the last few years, translational-based research approaches have identified several candidate biomarkers of NAC esponsiveness, such as ERCC2, ERBB2, or DNA damage response (DDR) gene alterations. Moreover, the recent consensus MIBC molecular classification identified six molecular subtypes, characterized by different sensitivity to chemo- or targeted or immunotherapy, that could open a novel procedure for patient selection and also for neoadjuvant therapies. The Italian PURE-01 phase II Trial extended data on efficacy and resistance to Immune Checkpoint Inhibitors (ICIs) in this setting. In this review, we summarize the most relevant literature data supporting NAC use in MIBC, focusing on novel therapeutic strategies such as immunotherapy, considering the better patient stratification and selection emerging from novel molecular classification

Immunotherapy for head and neck cancer: Present and future

: Immunotherapy has changed the treatment landscape of Head and Neck cancer (HNC). Different immune checkpoint inhibitors targeting PD-1/PD-L1 axis have been approved for different disease settings and many others, alone or in combination, are currently under investigation. Otherwise, as in other cancer types, efficacy, and resistance mechanisms, are not clearly understood. Considering the heterogeneity of the benefit reported in clinical trials, cost-efficacy analysis and the development of an effective patient selection are encouraged. Different pathways involving innate immunity, regulatory T lymphocytes and microbiome are emerging as new potential biomarkers, supported by preclinical and translational data. In this review we report current evidence on immunotherapy in HNC with updates from the main 2021 oncology events as ASCO, AACR and ESMO meetings. We focus on clinical trials results of single agent and combination immunotherapy in different clinical scenario, from (neo)adjuvant to metastatic setting, describing also novel evidence about efficacy and resistance biomarkers

Circulating vitamin D level before initiating chemotherapy impacts on the time-to-outcome in metastatic colorectal cancer patients: systematic review and meta-analysis

Abstract Background Vitamin D (VD) is implicated in various health conditions, including colorectal cancer (CRC). To investigate potential relationships between pre-chemotherapy VD levels and the time-to-outcome in metastatic CRC patients, we conducted a systematic review and meta-analysis. Methods Following the PRISMA 2020 guidelines, we performed thorough searches in PubMed/MEDLINE and Scopus/ELSEVIER databases (covering the years 2002 to 2022). Inclusion criteria mandated studies to report on individuals aged 18 years and above with histologically confirmed stage IV CRC. Additionally, studies needed to provide data on VD levels before chemotherapy, along with hazard ratios (HR) and 95% confidence intervals (CIs) for overall survival (OS) and/or progression-free survival (PFS). Five articles were identified with the aim of establishing a combined risk estimate for death and progression based on pre-chemotherapy VD levels. Heterogeneity among studies and publication bias were evaluated using Tau2, I2 statistics, and a Funnel plot. Results Although no significant heterogeneity was observed in time-to-outcome among the selected studies, variations in technical assessments and serum VD concentration measurements were noted. The pooled analysis, involving 1712 patients for OS and 1264 patients for PFS, revealed a 47% increased risk of death (HR: 1.47, 95% CI: 1.21–1.79) and a 38% increased risk of progression (HR: 1.38, 95% CI: 1.13–1.70) for patients with lower VD levels, as indicated by fixed-effects models. Conclusions Our results emphasize the adverse effects of low VD concentration on the time-to-outcome in metastatic CRC patients. This underscores the importance of investigating VD supplementation as an innovative approach in this clinical setting to enhance patient outcomes