The role of liver surgery in simultaneous synchronous colorectal liver metastases and colorectal cancer resections: a literature review of 1730 patients underwent open and minimally invasive surgery.

INTRODUCTION: Colorectal cancer (CRC) is the third most common malignant neoplastic disease in the world. Approximately 25-35% of patients affected by CRC will develop liver metastasis, and a percentage of 15-25% occurred in synchronous liver metastases (SCRLM) at the moment of CRC diagnosis or previously. Our aim is to investigate through an extensive literature review the effectiveness and safety of simultaneous SCRLM and CRC in open, laparoscopic and robotic surgery analyzing pre-, intra- and post-operative surgical outcomes and 1-, 3- and 5- years overall survival and disease-free survival. EVIDENCE ACQUISITION: A literature review was carried out on PubMed (Medline) and Cochrane libraries until 16th of April 2022. EVIDENCE SYNTHESIS: Forty-one articles were included and subjected to a qualitative and quantitative analysis. A total of 3038 patients were included; 1730 out of 3038 (56.94%) patients who underwent a simultaneous resection for SCRLM were identified. The mean age was 61.10±9.95 and a 1170 of males and 840 of females emerges. The mean blood loss was 422.23±238.31 mL, the mean operative time was 368.94±88.47 min. The mean Length of Stay was 14.21±6.06 days; 126 (12.79%) patients were Clavien-Dindo grade ≥III complications. CONCLUSIONS: Minimally invasive surgery (MIS) for simultaneous SCRLM and CRC resections shows peri-operative advantages over open surgery. Furthermore, considering postoperative benefits and long-term outcome, MIS could be the choice treatment in these patients.

Identification of Sp1 and GC-boxes as transcriptional regulators of mouse Dag1 gene promoter.

Dystroglycan is a widely expressed adhesion complex that anchors cells to the basement membrane and is involved in embryonic development and differentiation. Dystroglycan expression is frequently reduced in human dystrophies and malignancies, and its molecular functions are not completely understood. Several posttranslational mechanisms have been identified that regulate dystroglycan expression and/or function, while little is known about how expression of the corresponding Dag1 gene is regulated. This study aimed to clone the Dag1 gene promoter and to characterize its regulatory elements. Analysis of the mouse Dag1 gene 5'-flanking region revealed a TATA and CAAT box-lacking promoter including a GC-rich region. Transfection studies with serially deleted promoter constructs allowed us to identify a minimal promoter region containing three Specificity protein 1 (Sp1) sites and an E-box. Sp1 binding was confirmed by chromatin immunoprecipitation assay, and Sp1 downregulation reduced dystroglycan expression in muscle cells. Treatment with 5-aza-2'-deoxycytidine and/or the histone deacetylase inhibitor trichostatin A increased Dag1 mRNA expression levels in myoblasts, and methylation decreased promoter activity in vitro. Furthermore, Dag1 gene promoter methylation was reduced while its expression increased during differentiation of C(2)C(12) myoblast cells in myotubes. In conclusion, for the first time we have characterized the activity of the mouse Dag1 gene promoter, confirming a complex regulation by Sp1 transcription factor, DNA methylation, and histone acetylation, which might be relevant for a better understanding of the physiopathology of the dystroglycan complex.

Influence of Ggamma-158C --> and beta- (AT)x(T)y globin gene polymorphisms on HbF levels in Italian beta-thalassemia carriers and wild-type subjects.

Clinical manifestations of beta-thalassemia (beta-thal) intermedia phenotypes are influenced by the persistence of fetal hemoglobin (HbF) and by several polymorphisms located in the promoters of A- and beta-globin genes. The aim of this study was to evaluate the distribution of the -158Ggamma (C-->T) polymorphism and of the (AT)x(T)y configuration, as well as their eventual association with elevated levels of HbF in 188 beta-thal carriers and 229 wild-type individuals of Italian descent. The -158GgammaT and the (AT)9(T)5alleles were found to be associated with increased levels of HbF in beta-thal carriers, but not in wild-type subjects.