Background and Objectives: This study aimed to evaluate surgical outcomes and identify prognostic factors associated with anastomotic leakage (AL), following rectal cancer resection. Materials and Methods: A retrospective cohort study included 415 patients who underwent rectal cancer surgery between 2020 and 2024. Patients were categorized by surgical approach (laparoscopic vs. open) and presence of AL. Results: Of the 415 patients, 160 (38.6%) underwent laparoscopic surgery, and 255 (61.4%) underwent open surgery. Operative time was significantly longer for laparoscopic surgery (213.0 ± 65.9 vs. 201.3 ± 60.4 min, p = 0.05), while stoma formation was more frequent in the open surgery group (60.0% vs. 48.1%, p = 0.018). Reoperation rate was higher in the laparoscopic group compared to the open group (13.1% vs. 6.7%, p = 0.027). The rate of AL was 20.5% in the laparoscopic group and 18.4% in the open surgery group (p = 0.434). Patients with AL had a significantly longer hospital stay (17 days, IQR 12.0–23.7 vs. 8 days, IQR 7.0–9.0, p < 0.001). The use of NOACs was associated with an increased risk of AL (p = 0.026). Multivariate analysis revealed that both a higher ASA score (p = 0.022) and older age (p = 0.044) were independent risk factors for AL, while the use of a diverting ileostomy was associated with a threefold reduction in the risk of AL (p = 0.049). Conclusions: AL rates were similar between approaches. Laparoscopic surgery had more reoperations and longer operative times. AL was associated with NOAC use, older age, and higher ASA scores. Diverting ileostomy reduced AL risk and warrants broader use in high-risk patients to improve outcomes.

Background and Objectives: Colorectal cancer (CRC) is a major global health challenge. The BRAF V600E mutation, found in 8–12% of CRC patients, exacerbates this by conferring poor prognosis and resistance to therapy. Our study focuses on the efficacy of the HAMLET complex, a molecular substance derived from human breast milk, on CRC cell lines and ex vivo biopsies harboring this mutation, given its previously observed selective toxicity to cancer cells. Materials and Methods: we explored the effects of combining HAMLET with the FOLFOX chemotherapy regimen on CRC cell lines and ex vivo models. Key assessments included cell viability, apoptosis/necrosis induction, and mitochondrial function, aiming to understand the mutation-specific resistance or other cellular response mechanisms. Results: HAMLET and FOLFOX alone decreased viability in CRC explants, irrespective of the BRAF mutation status. Notably, their combination yielded a marked decrease in viability, particularly in the BRAF wild-type samples, suggesting a synergistic effect. While HAMLET showed a modest inhibitory effect on mitochondrial respiration across both mutant and wild-type samples, the response varied depending on the mutation status. Significant differences emerged in the responses of the HT-29 and WiDr cell lines to HAMLET, with WiDr cells showing greater resistance, pointing to factors beyond genetic mutations influencing drug responses. A slight synergy between HAMLET and FOLFOX was observed in WiDr cells, independent of the BRAF mutation. The bioenergetic analysis highlighted differences in mitochondrial respiration between HT-29 and WiDr cells, suggesting that bioenergetic profiles could be key in determining cellular responses to HAMLET. Conclusions: We highlight the potential of HAMLET and FOLFOX as a combined therapeutic approach in BRAF wild-type CRC, significantly reducing cancer cell viability. The varied responses in CRC cell lines, especially regarding bioenergetic and mitochondrial factors, emphasize the need for a comprehensive approach considering both genetic and metabolic aspects in CRC treatment strategies.