A scoping review of unexpected weight loss and cancer: risk, guidelines, and recommendations for follow-up in primary care.

BACKGROUND: Cancer diagnoses often begin with consultations with general practitioners (GPs), but the nonspecific nature of symptoms can lead to delayed diagnosis. Unexpected weight loss (UWL) is a common nonspecific symptom linked to undiagnosed cancer, yet guidelines for its diagnostic assessment in general practice lack consistency. AIM: To synthesise evidence on the association between UWL and cancer diagnosis, and to review clinical guidelines and recommendations for assessing patients with UWL. DESIGN AND SETTINGS: Systematic search and analysis of studies conducted in primary care. METHOD: Four databases searched for peer-reviewed literature from 2012 to 2023. Two reviewers conducted all the steps. A narrative review was conducted detailing the evidence for UWL as a risk factor for undiagnosed cancer, existing clinical guidance, and recommended diagnostic approach. RESULTS: We included 25 studies involving 916,092 patients; 92% provided strong evidence of an association between UWL and undiagnosed cancer. The National Institute for Health Care and Excellence Cancer Guideline in the UK was frequently cited. General suggestions encompassed regular weight monitoring, family history, risk factor evaluation, additional signs and symptoms, and a comprehensive physical examination. Commonly recommended pathology tests included C-reactive protein, complete blood count, alkaline phosphatase, and thyroid-stimulating hormone. Immunochemical faecal occult blood test, abdominal ultrasound, and chest X-ray were also prevalent. One large cohort study provided age, sex, and differential diagnosis-specific recommendations. CONCLUSION: This evidence review informs recommendations for investigating patients with UWL and will contribute to a computer decision support tool implementation in primary care, enhancing UWL assessment and potentially facilitating earlier cancer diagnosis.

Mesenchymal stromal cell therapy reduces lung inflammation and vascular remodeling and improves hemodynamics in experimental pulmonary arterial hypertension.

BACKGROUND: Experimental research has reported beneficial effects of mesenchymal stromal cell (MSC) therapy in pulmonary arterial hypertension (PAH). However, these studies either were based on prophylactic protocols or assessed basic remodeling features without evaluating possible mechanisms. We analyzed the effects of MSC therapy on lung vascular remodeling and hemodynamics and its possible mechanisms of action in monocrotaline (MCT)-induced PAH. METHODS: Twenty-eight Wistar rats were randomly divided into two groups. In the PAH group, animals received MCT 60 mg/kg intraperitoneally, while a control group received saline (SAL) instead. On day 14, both groups were further randomized to receive 105 adipose-derived MSCs or SAL intravenously (n = 7/group). On day 28, right ventricular systolic pressure (RVSP) and the gene expression of mediators associated with apoptosis, inflammation, fibrosis, Smad-1 levels, cell proliferation, and endothelial-mesenchymal transition were determined. In addition, lung histology (smooth muscle cell proliferation and plexiform-like injuries), CD68+ and CD163+ macrophages, and plasma levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) were evaluated. RESULTS: In the PAH group, adipose-derived MSCs, compared to SAL, reduced mean RVSP (29 ± 1 vs 39 ± 2 mmHg, p < 0.001), lung tissue collagen fiber content, smooth muscle cell proliferation, CD68+ macrophages, interleukin-6 expression, and the antiapoptotic mediators Bcl-2 and survivin. Conversely, expression of the proapoptotic mediator procaspase-3 and plasma VEGF increased, with no changes in PDGF. In the pulmonary artery, MSCs dampened the endothelial-mesenchymal transition. CONCLUSION: In MCT-induced PAH, MSC therapy reduced lung vascular remodeling, thus improving hemodynamics. These beneficial effects were associated with increased levels of proapoptotic markers, mesenchymal-to-endothelial transition, reduced cell proliferation markers, and inflammation due to a shift away from the M1 phenotype.

The role of perioperative radiotherapy in gastric cancer.

Gastric cancer is one of the most common neoplasms and a main cause of cancer-related mortality worldwide. Surgery remains the mainstay for cure and is considered for all patients with potentially curable disease. However, despite the fact that surgery alone usually leads to favorable outcomes in early stage disease, late diagnosis usually means a poor prognosis. In these settings, multimodal therapy has become the established treatment for locally advanced tumors, while the high risk of locoregional relapse has favored the inclusion of radiotherapy in the comprehensive therapeutic strategy. We provide a critical, non-systematic review of gastric cancer and discuss the role of perioperative radiation therapy in its treatment.