There still is no evidence which neoadjuvant therapy regimen for stage II–III rectal cancer is superior. The aim of this study was to compare results achieved after long-course chemoradiotherapy (CRT) with short-term radiotherapy (RT) followed by delayed surgery. A randomized trial was carried out between 2007–2013. One hundred fifty patients diagnosed with stage II–III rectal cancer were randomized into one of two neoadjuvant treatment arms: conventional chemoradiotherapy (CRT) and short-term radiotherapy (RT) followed by surgery after 6–8 weeks. Primary endpoints of this trial were downstaging and pathological complete response rate. Secondary endpoints were local recurrence rate and overall survival. The pathological complete response was found in 3 (4.4%) cases after RT and 8 (11.1%) after CRT (P = 0.112). Downstaging (stage 0 and I) was observed in 21 (30.9%) cases in RT group vs. 27 (37.5%) cases in CRT group (P = 0.409). Median follow-up time was 39.7 (range 4.9–79.7) months. 3-years overall survival (OS) was 78% in RT group vs. 82.4% in CRT group (P = 0.145), while disease-free survival (DFS) differed significantly – 59% in RT group vs. 75.1% in CRT group (P = 0,022). Hazard ratio of cancer progression for RT patients was 1.93 (95% CI: 1.08–3.43) compared to CRT patients. Three-years disease-free survival was better in CRT group comparing with RT group with no difference in overall survival. http://clinicaltrials.gov identifier NCT00597311. January 2008.

Background: The aim of this study is to evaluate the role of NADPH oxidase in primary intestinal epithelial cells during the active phase of UC. Methods: The primary human colonic epithelial cells were isolated from 19 patients with mild to moderate inflammatory activity of UC and 14 controls using chelation method. The cells were cultivated under the effect of mediators. Viability of cells was assessed by fluorescent microscopy. Production of reactive oxygen species (ROS) by the cells was measured fluorimetrically using Amplex Red. Production of TNF-α cytokine by the colonic epithelial cells was analysed by ELISA. Results: The results of our study showed that unstimulated cells of UC patients had a decreased viability, increased ROS production, but similar TNF-α level when compared to the controls. Stimulation with LPS increased hydrogen peroxide and TNF-α level in the UC group. Treatment of colonic epithelial cells with NADPH oxidase inhibitor increased cell viability decreased the levels of ROS and TNF-α in the LPS-treated cells isolated from UC patients. Conclusions: Our study showed that bacterial endotoxins induced NADPH oxidase activation in the colonic epithelial cells. Moreover, we revealed that treatment with NADPH oxidase inhibitors had a protective effect against pro-inflammatory action of LPS in human colonic epithelium cells during inflammation.

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.

Background and Objectives: In this study, we aimed to evaluate pain intensity in patients after pilonidal disease surgeries of varying extent using pressure algometry and the visual analog scale and to explore potential correlations between these methods. Materials and Methods: A total of 78 adult patients with symptomatic pilonidal cysts were enrolled in this study. The patients were divided into two groups based on the type of surgery assigned to each patient at the pre-hospital consultation: pit-picking surgery (n = 39) and radical excision (n = 39). The pain levels at the surgical site were assessed and compared using the visual analog scale (VAS) and pressure algometry the morning before surgery and the day after the operation. Results: There was no statistically significant difference (p > 0.05) in VAS measurement results between surgical groups when comparing pain intensity experienced by patients before, during, and after surgery. Notably, specific pressure algometry variables (pressure pain tolerance left 2.05 ± 1.46 compared to 1.42 ± 0.73 kg/cm², p = 0.02; maximum pressure pain tolerance left 2.91 ± 1.33 compared to 2.32 ± 1.14 kg/cm², p = 0.04; maximum pressure pain tolerance center 2.51 ± 1.07 compared to 1.91 ± 0.91 kg/cm², p = 0.01; interval of pressure pain tolerance center 0.98 ± 0.62 compared to 0.59 ± 0.39 kg/cm², p = 0.00) on the first postoperative day were significantly lower in the “pit-picking” group compared to the excision group. Furthermore, no statistically significant correlation was found between VAS and pressure algometry measurements either before surgery or on the first postoperative day. Conclusions: In the early postoperative period following pilonidal disease surgery of varying extents, pain measured with the VAS does not differ. In contrast, the pressure algometry method showed greater pain in the minimally invasive surgery cohort on the first postoperative day. However, further larger studies are needed to compare these pain assessment methods in reporting pain intensity experienced during patient movement.

Background and Objectives: Rectal cancer management has changed substantially over the past two decades. We evaluated 20-year trends in stage at diagnosis, treatment patterns, and survival at a Lithuanian tertiary referral centre. Materials and Methods: This retrospective cohort study included 839 patients who underwent resection for stage I–III rectal cancer between 2004 and 2023, divided into two periods: 2004–2013 (n = 426) and 2014–2023 (n = 413). Survival was analysed with Kaplan–Meier estimates and Cox proportional hazards regression, truncated at 60 months. Results: Patients in the later cohort were diagnosed at an earlier clinical stage (stage I: 12.6% vs. 2.4%) and more often received neoadjuvant or perioperative therapy (55.2% vs. 37.1%; p < 0.001). Among clinical stage III patients, receipt of neoadjuvant chemoradiotherapy or total neoadjuvant treatment rose from 15.9% to 70.9% (p < 0.001), while pathological complete response among treated patients remained stable (10.8% vs. 10.7%; p = 0.98). Five-year overall survival increased from 64.8% to 71.3% (HR 0.77; 95% CI 0.60–0.99; p = 0.039) and cancer-specific survival from 70.4% to 80.8% (HR 0.60; 95% CI 0.45–0.80; p = 0.0005). The cohort effect persisted after multivariable adjustment for CSS (HR 0.62; 95% CI 0.45–0.85; p = 0.003), with clinical stage explaining only ~13% of the crude effect; stage III sensitivity analysis confirmed the CSS gain (67.9% to 77.3%; p = 0.009). Conclusions: Cancer-specific survival improved substantially and independently of stage migration. The gain coincided with markedly wider and better-targeted delivery of effective neoadjuvant therapy rather than with improved per-patient tumour responsiveness. As an observational comparison of two historical cohorts, this study demonstrates association rather than causation; nonetheless, it provides real-world evidence consistent with the hypothesis that systematic implementation of evidence-based rectal cancer pathways translates into measurable survival benefit.