Synthetic Retinoid Interventions and Outcomes in People with Cancer or Potentially Malignant Disorders of the Upper Aerodigestive Tract: A Systematic Review and Meta-analysis

Background & Aims: Retinoids may have a role in the chemoprevention of potentially malignant disorders of the upper aerodigestive tract. Therefore, we conducted a systematic review of randomised controlled trials to examine the effect of synthetic retinoid interventions in people with cancer or potentially malignant disorders of the upper digestive tract. Methods: We searched five electronic databases and reference lists to locate all eligible trials and analysed trial quality. Outcome measures were all-cause and cancer mortality, disease-free survival, second primary cancer, cancer and potentially malignant disorder recurrence and progression to cancer. Results of individual trials were combined by use of random-effects meta-analyses. Results & Conclusions: We identified 17 15 trials, eightnine in people with upper aerodigestive tract cancer and seven eight in people with potentially malignant disorders, respectively. The results provide little evidence that retinoids have a beneficial effect on disease-free survival (OR=0.74, 95% CI =0.51, 1.09), all cause mortality (OR = 1.28, 95% confidence interval [CI] =1.00 to 1.65), disease-free survival (OR=0.74, 95% CI =0.51, 1.09), recurrence of cancer (OR = 1.47, 95% CI = 0.95, 2.26), development of second primary cancers (OR = 0.96, 95% CI = 0.76, 1.20) or the progression to malignancy (OR = 0.69, 95% CIs = 0.22, 2.15). There was even a suggestion of harm for some outcomes. There was also a suggestion that retinoids may decrease the recurrence of potentially malignant disorders (OR = 0.22, 95% CIs = 0.03, 1.34). For now there is no evidence to support the use of retinoids in people with upper aerodigestive tract cancer

Pre-operative pulmonary assessment for patients with hip fracture

Hip fracture is a common injury among the elderly. Although patients who receive hip fracture surgery carry the best functional recovery compared to other treatment modalities, the presence of postoperative pulmonary complications, such as atelectasis, pneumonia, and pulmonary thromboembolism, may contribute to increased length of hospital stay, perioperative morbidity, and mortality. This review aims to provide evidence-based recommendations for preoperative assessment and perioperative strategies to reduce the risk of pulmonary complications after hip fracture surgery. Clinical assessment and basic laboratory results are sufficient to stratify the risk of postoperative pulmonary complications. Well-documented risk factors for pulmonary complications include advanced age, poor general health status, current infections, pre-existing cardiopulmonary diseases, hypoalbuminemia, and impaired renal function. Apart from optimizing the patient's medical conditions, interventions such as lung expansion maneuvers and thromboprophylaxis have been proven to be effective in reducing the risk of pulmonary complications after hip fracture surgery

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.ope

Comprehensive molecular characterization of the hippo signaling pathway in cancer

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era