A Novel DNA Variant in SMARCA4 Gene Found in a Patient Affected by Early Onset Colon Cancer.

Colorectal cancer is the third leading cause of death from neoplasia worldwide. Thanks to new screening programs, we are now seeing an increase in Early Onset of ColoRectal Cancer (EOCRC) in patients below the age of 50. Herein, we report a clinical case of a woman affected by EOCRC. This case illustrates the importance of genetic predisposition testing also in tumor patients. Indeed, for our patient, we used a combined approach of multiple molecular and cellular biology technologies that revealed the presence of an interesting novel variant in the SMARCA4 gene. The latter gene is implicated in damage repair processes and related, if mutated, to the onset of various tumor types. In addition, we stabilized Patient-Derived Organoids from the tumor tissue of the same patient and the result confirmed the presence of this novel pathogenic variant that has never been found before even in early onset cancer. In conclusion, with this clinical case, we want to underscore the importance of including patients even those below the age of 50 years in appropriate screening programs which should also include genetic tests for predisposition to early onset cancers.

Could Stoma Be Avoided after Laparoscopic Low Anterior Resection for Rectal Cancer? Experience with Transanal Tube in 195 Cases.

Anastomotic leakage is the most-feared complication of rectal surgery. Transanal devices have been suggested for anastomotic protection as an alternative to defunctioning stoma, although evidence is conflicting, and no single device is widely used in clinical practice. The aim of this paper is to investigate the safety and efficacy of a transanal tube for the prevention of leakage following laparoscopic rectal cancer resection. A transanal tube was used in the cases of total mesorectal excision with low colorectal or coloanal anastomosis, undamaged doughnuts, and negative intraoperative air-leak test. The transanal tube was kept in place until the seventh postoperative day. A total of 195 consecutive patients were retrieved from a prospective surgical database and included in the study. Of these, 71.8% received preoperative chemoradiotherapy. The perioperative mortality rate was 1.0%. Anastomotic leakage occurred in 19 patients, accounting for an incidence rate of 9.7%. Among these, 13 patients underwent re-laparoscopy and ileostomy, while 6 patients were managed conservatively. Overall, the stoma rate was 6.7%. The use of a transanal tube may be a suitable strategy for anastomotic protection following restorative rectal cancer resection. This approach could avoid the burden of a stoma in selected patients with low anastomoses.

Concomitant Notch activation and p53 deletion trigger epithelial-to-mesenchymal transition and metastasis in mouse gut.

Epithelial-to-mesenchymal transition-like (EMT-like) is a critical process allowing initiation of metastases during tumour progression. Here, to investigate its role in intestinal cancer, we combine computational network-based and experimental approaches to create a mouse model with high metastatic potential. Construction and analysis of this network map depicting molecular mechanisms of EMT regulation based on the literature suggests that Notch activation and p53 deletion have a synergistic effect in activating EMT-like processes. To confirm this prediction, we generate transgenic mice by conditionally activating the Notch1 receptor and deleting p53 in the digestive epithelium (NICD/p53(-/-)). These mice develop metastatic tumours with high penetrance. Using GFP lineage tracing, we identify single malignant cells with mesenchymal features in primary and metastatic tumours in vivo. The development of such a model that recapitulates the cellular features observed in invasive human colorectal tumours is appealing for innovative drug discovery.