Long-Term Results of Bariatric Surgery in Adolescents with at Least 5 Years of Follow-up: a Systematic Review and Meta-Analysis.

OBJECTS: The purpose of this study was to investigate the long-term outcomes of bariatric surgery in adolescents with obesity by including studies with a follow-up of at least 5 years. METHODS: PubMed, EMBASE, and CENTRAL were systematically searched. Studies that met the criteria were included in the analysis. RESULT: We identified 29 cohort studies with a total population of 4970. Preoperative age ranged from 12 to 21 years; body mass index (BMI) ranged from 38.9 to 58.5 kg/m2. Females were the predominant gender (60.3%). After at least 5-year of follow-up, the pooled BMI decline was 13.09 kg/m2 (95%CI 11.75-14.43), with sleeve gastrectomy (SG) was 15.27 kg/m2, Roux-en-Y gastric bypass (RYGB) was 12.86 kg/m2, and adjustable gastric banding (AGB) was 7.64 kg/m2. The combined remission rates of type 2 diabetes mellitus (T2DM), dyslipidemia, hypertension (HTN), obstructive sleep apnea (OSA), and asthma were 90.0%, 76.6%, 80.7%, 80.8%, and 92.5%, (95%CI 83.2-95.6, 62.0-88.9, 71.5-88.8, 36.4-100, and 48.5-100), respectively. Postoperative complications were underreported. Combined with the current study, we found a low level of postoperative complications. Iron and vitamin B12 deficiencies were the main nutritional deficiency complications identified so far. CONCLUSION: For adolescents with severe obesity, bariatric surgery (especially RYGB and SG) is the independent and effective treatment option. After at least 5 years of follow-up, bariatric surgery in adolescents showed a desirable reduction in BMI and significant remission of T2DM, dyslipidemia, and HTN. Surgical and nutrition-related complications still need to be further explored by more long-term studies.

Crosstalk of Histone and RNA Modifications Identified a Stromal-Activated Subtype with Poor Survival and Resistance to Immunotherapy in Gastric Cancer.

Emerging evidence has revealed the pivotal role of epigenetic modifications in shaping the tumor microenvironment (TME). However, crosstalk between different modification types and their clinical relevance in cancers remain largely unexplored. In this study, using ChIP/MeRIP-seq data of seven human gastric cell lines, we systematically characterized the crosstalk of four epigenetic modification types including H3K4me1, H3K4me3, H3K27ac, and N6-methyladenosine (m6A) and identified a recurrent subtype with high FTO expression and low HDAC1 expression across three independent gastric cancer (GC) cohorts, which we named the epigenetic-modification-dysregulated (EMD) subtype. Patients of the EMD subtype were featured with poor survival, stromal activation, and immune suppression. Extensive relevance to clinical characteristics was observed in the EMD subtype, including the Lauren classification, MSI status, histological grade, TNM stage, the Asian Cancer Research Group classification, and the immune/fibrotic classification. An EMD score was then constructed using WGCNA and ssGSEA algorithms, to precisely recognize the EMD subtype and indicate prognosis and response to immunotherapy in multiple independent GC cohorts. Correlations of the EMD score with tumor mutation burden, tumor purity, aneuploidy score, tumorigenic pathways, TME characteristics, and FTO/HDAC1 ratio were measured. In vitro experiments were performed to demonstrate the correlation between FTO and the epithelial-mesenchymal transition pathway, which suggested FTO as a targetable vulnerability for GC patients with a high EMD score. Altogether, by comprehensively analyzing the epigenetic modification patterns of 1518 GC patients, we identified a novel stromal-activated subtype with poor survival and resistance to immunotherapy, which might benefit from the combined immune checkpoint inhibition therapy with FTO inhibition.

MRPS17 promotes invasion and metastasis through PI3K/AKT signal pathway and could be potential prognostic marker for gastric cancer.

In this study, the molecular mechanisms through which Mitochondrial Ribosomal Protein S17 (MRPS17) contributes to gastric cancer (GC) and its prognostic significance in GC have been explored. As a protein encoding gene, MRPS17 encodes a 28s proteins belonging the ribosomal protein S17P family. The specific roles and molecular mechanisms of MRPS17 in cancers remain ambiguous. It was revealed by analyzing data from TCGA and GEO that elevated expression of MRPS17 was significantly associated with invasion of GC and poor survival of GC patients. Then through univariate and multivariate Cox regression analyses it was demonstrated that MRPS17 an independent prognostic factor for GC patients (P<0.001). It was demonstrated by differentially expressed gene analysis and functional enrichment analysis that MPRS17 is related to PI3K/AKT pathway and Cell adhesion molecules (CAMs), while its function is mediated by collagen-containing extracellular matrix and receptor ligand/regulator activity. Then it was proven by in-vitro experiments that knocking down of MRPS17 gene in AGS and SGC7901 cells would significantly inhibit proliferation and invasion capability of these cells. Furthermore, it was revealed by cell immunofluorescence assay that as a ribosomalprotein, MRPS17 was mainly distributed in the cytoplasmic surface of cell membrane. Additionally, activation of PI3K/AKT pathway is responsible for malignant progression of glioma that was promoted by MRPS17. In conclusion, it was revealed in the present study that MRPS17 promoted invasion and metastasis of GC and potential molecular mechanisms through which it exerted its influences on GC were explored, suggesting its potential as a novel prognostic biomarker for GC.

Distinct Prognosis of High Versus Mid/Low Rectal Cancer: a Propensity Score-Matched Cohort Study.

BACKGROUND: Rectal cancers have long been treated as a single-entity disease; however, whether the prognosis of high rectal cancer (inferior margin located 10.1 to 15.0 cm from the anal verge) differs from that of mid/low rectal cancer (0 to 10.0 cm) remains disputed. METHODS: Patients with stages I-III rectal adenocarcinomas undergoing curative-intent surgery were enrolled between 2007 and 2013 in this retrospective analysis. Exclusion criteria were neoadjuvant therapy or concurrent cancers. Propensity score matching and Cox regression analysis were performed to compare a 5-year overall and cancer-specific survival between patients with high and mid/low rectal cancer. RESULTS: Of 613 patients who met the inclusion criteria, 199 (32.5%) and 414 (67.5%) had high and mid/low rectal cancer, respectively. After propensity score matching (187 cases for each group), the high group showed a better overall survival (70.9 vs. 56.9%, p = 0.042) and cancer-specific survival (77.4 vs. 60.3%, p = 0.028) at 5 years compared with the mid/low group with stage III disease. However, high rectal cancer did not demonstrate prognostic superiority in stages I-II disease. Multivariate analysis identified high tumor location as an independent prognostic factor for cancer-specific survival (hazards ratio = 0.422, 95% confidence interval 0.226-0.786, p = 0.007) and overall survival (hazards ratio = 0.613, 95% confidence interval 0.379-0.991, p = 0.046). CONCLUSIONS: Patients with stage III high rectal adenocarcinoma demonstrated better overall and cancer-specific survival than those with mid/low type, and tumor location was an independent prognostic factor for patients with rectal carcinomas.