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Fibroblast growth factor receptor 4 (FGFR4) is known to induce cancer cell proliferation, invasion, and antiapoptosis through activation of RAS/RAF/ERK and PI3K/AKT pathways, which are also known as major molecular bases of colon cancer carcinogenesis related with epidermal growth factor receptor (EGFR) signaling. However, the interaction between FGFR4 and EGFR signaling in regard to colon cancer progression is unclear. Here, we investigated a potential cross‐talk between FGFR4 and EGFR, and the effect of anti‐EGFR therapy in colon cancer treatment. To explore the biological roles of FGFR4 in cancer progression, RNA sequencing was carried out using FGFR4 transfected colon cell lines. Gene ontology data showed the upregulation of genes related to EGFR signaling, and we identified that FGFR4 overexpression secretes EGFR ligands such as amphiregulin (AREG) with consequent activation of EGFR and ErbB3. This result was also shown in in vivo study and the cooperative interaction between EGFR and FGFR4 promoted tumor growth. In addition, FGFR4 overexpression reduced cetuximab‐induced cytotoxicity and the combination of FGFR4 inhibitor (BLU9931) and cetuximab showed profound antitumor effect compared to cetuximab alone. Clinically, we found the positive correlation between FGFR4 and AREG expression in tumor tissue, but not in normal tissue, from colon cancer patients and these expressions were significantly correlated with poor overall survival in patients treated with cetuximab. Therefore, our results provide the novel mechanism of FGFR4 in connection with EGFR activation and the combination of FGFR4 inhibitor and cetuximab could be a promising therapeutic option to achieve the optimal response to anti‐EGFR therapy in colon cancer. Our study has characterized the cross‐talk between fibroblast growth factor receptor 4 (FGFR4) and epidermal growth factor receptor (EGFR)/ErbB3 signaling by the contribution of EGFR ligands secreted from FGFR4. These findings provide experimental evidence for combined treatment with FGFR4 inhibitor and anti‐EGFR therapy in colon cancer.

Detecting anomalies in electrical equipment and improving maintenance efficiency are critical for ensuring operational safety, reliability, and sustainability. To address the structural limitations of conventional manual and visual inspection methods, this study developed an object-recognition-based automated damage diagnosis system for lightning rods and insulators (ADS-LI), which enabled non-contact and fully automated diagnosis of lightning rods and insulators. ADS-LI employs a dual-module architecture. The first module precisely detects lightning rods and insulators using the PointRend algorithm applied to drone-acquired aerial imagery. The second module is a formula-based diagnostic model that quantitatively determines structural anomalies using the geometric attributes of the detected objects. Specifically, anomalies in lightning rods are identified by analyzing variations in inclination derived from center-coordinate shifts (Δx), while insulator anomalies are evaluated based on the mask area conservation ratio (r). The performance of ADS-LI was validated using 90 independent test datasets, achieving a 0.89 F1-score and 99% overall accuracy. These results demonstrate that ADS-LI effectively automates labor-intensive diagnostic tasks that previously relied on skilled experts. Furthermore, by quantifying anomaly detection criteria, it ensures consistency and reproducibility for diagnostic outcomes. This study is also expected to contribute, in the long term, to the transition of elevated electrical installations toward a sustainable maintenance regime.

The aim of this study was to evaluate whether the use of fibrin glue as a sealant over an anastomosis is a risk factor for anastomotic leakage after laparoscopic rectal cancer surgery. Prospective data were collected from 223 patients with rectal cancer who underwent laparoscopic resection without defunctioning stoma. A total of 104 patients underwent laparoscopic rectal resection, followed by the application of fibrin glue over the stapled anastomosis, while 119 underwent surgery alone. No difference in clinically significant leakage was observed between the fibrin and the nonfibrin groups (5.8% vs 10.9%, P = .169). In multivariate analysis, extraperitoneal tumor location and operation duration >220 minutes were independently associated with anastomotic leakage. Significant predictors of anastomotic leakage include extraperitoneal tumor location and operation length >220 minutes. Fibrin glue application over the stapled anastomosis was not found to be significantly associated with anastomotic leakage.

BackgroundAnastomotic stricture following colorectal cancer surgery is not a rare complication, but proper management of anastomotic stricture located close to the anal verge is uncertain. This study aimed to investigate risk factors and management strategies for anastomotic stricture after ultralow anterior resection (ULAR).MethodsWe retrospectively reviewed a database of patients with rectal cancer who underwent surgery between January 2007 and June 2015, and included patients with an anastomosis within 4 cm from the anal verge. Clinical outcomes and risk factors for anastomotic stricture were investigated.ResultsAmong the 586 patients included, 46 (7.8%) were diagnosed as having anastomotic stricture. Multivariable logistic regression analysis revealed that intersphincteric resection (ISR) with hand-sewn anastomosis (odds ratio [OR] = 3.070; 95% confidence interval [CI] 1.247–7.557) and postoperative radiotherapy (OR 6.237; 95% CI 1.961–19.841) were independent risk factors of anastomotic stricture. Forty-one (89.1%) underwent anastomotic dilatation with a Hegar dilator; while three patients (6.5%) underwent endoscopic balloon dilatation and two (4.3%) underwent surgery initially. Among the patients with initial nonoperative management (n = 44), 21 (47.7%) were completely cured with nonoperative management alone, 12 (27.3%) experienced complications, such as bowel perforation, anastomotic rupture, and perirectal abscess; and 21 (47.7%) underwent further surgical management. Fifteen patients (32.6%) eventually had permanent stoma.ConclusionISR with a hand-sewn coloanal anastomosis, compared to ULAR with double-stapling anastomosis, and postoperative radiotherapy were independent risk factors of anastomotic stricture after surgery for very low-lying rectal cancer. Nonoperative anastomotic dilatation showed poor clinical outcome, with high complication rates, and subsequent surgical management. Therefore, nonoperative management of such patients should be carefully selected.

The oncologic impact of anastomotic leakage after rectal cancer surgery remains controversial. Between January 1999 and December 2010, 1,148 patients with rectal cancer who underwent curative surgery with sphincter preservation were retrospectively reviewed. Using the propensity score matching method, 328 patients with fibrin glue were matched to 328 patients without fibrin glue, and oncologic outcomes were compared in the matched groups. Anastomotic leakage was diagnosed in 76 patients (6.6%). On multivariate analysis, fibrin glue was the independent predictor of prevention of anastomotic leakage. In the 656 matched groups, patients with anastomotic leakage had significantly worse 5-year local recurrence-free survival and disease-free survival than those without leakage. Multivariate analysis confirmed that anastomotic leakage was an independent prognostic factor of both local recurrence and disease-free survival, but the use of fibrin glue was not associated with the long-term outcomes when controlling for confounders. Anastomotic leakage is a major independent prognostic factor for long-term outcomes. Fibrin glue has a protective effect of anastomosis, without oncologic advantages.

Wei Zheng and colleagues report the results of a large-scale genome-wide association study of colorectal cancer in East Asians. They identify six new susceptibility loci, including variants near TCF7L2 and TGFB1 . Known genetic loci explain only a small proportion of the familial relative risk of colorectal cancer (CRC). We conducted a genome-wide association study of CRC in East Asians with 14,963 cases and 31,945 controls and identified 6 new loci associated with CRC risk ( P = 3.42 × 10 −8 to 9.22 × 10 −21 ) at 10q22.3, 10q25.2, 11q12.2, 12p13.31, 17p13.3 and 19q13.2. Two of these loci map to genes ( TCF7L2 and TGFB1 ) with established roles in colorectal tumorigenesis. Four other loci are located in or near genes involved in transcriptional regulation ( ZMIZ1 ), genome maintenance ( FEN1 ), fatty acid metabolism ( FADS1 and FADS2 ), cancer cell motility and metastasis ( CD9 ), and cell growth and differentiation ( NXN ). We also found suggestive evidence for three additional loci associated with CRC risk near genome-wide significance at 8q24.11, 10q21.1 and 10q24.2. Furthermore, we replicated 22 previously reported CRC-associated loci. Our study provides insights into the genetic basis of CRC and suggests the involvement of new biological pathways.

Background Perineural invasion (PNI) has emerged as an important factor related to colorectal cancer spread; however, the impact of neoadjuvant chemoradiotherapy (nCRT) on PNI remains unclear. Herein, we investigated the prognostic value of PNI, along with lymphovascular invasion (LVI), in rectal cancer patients treated with nCRT. Methods This single-center observational study of pathologic variables, including PNI and LVI, analyzed 1411 invasive rectal cancer patients (965 and 446 patients treated with primary resection and nCRT, respectively). Results The overall detection rates of LVI and PNI were 16.7 and 28.8%, respectively. The incidence of LVI was significantly lower in patients treated with nCRT (8.1 vs. 20.6%, P  < .001); this was confirmed by multivariate analysis. However, PNI was not affected by nCRT (with nCRT 28.3% vs. without nCRT 29.1%, P  = .786). In the 446 patients with nCRT, multivariate analysis revealed that PNI was an independent prognostic factor for both disease-free survival (DFS) and overall survival (OS). For the prediction of both 5-year DFS and OS, the C-index for the combinations of T-stage with the PNI (TPNI) system showed favorable result, especially in patients with a total number of harvested lymph nodes <8. Conclusion PNI is a meaningful prognostic factor for rectal cancer patients treated with nCRT, especially when <8 lymph nodes are harvested. The lack of influence of nCRT on the PNI incidence suggests that residual tumor cells with PNI are more radioresistant or biologically aggressive than those without.

Background This study was designed to investigate an association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of gastric and colorectal cancer in the Korean population. Methods We conducted a population-based large-scale case-control study involving 2,213 patients with newly diagnosed gastric cancer, 1,829 patients with newly diagnosed colorectal cancer, and 1,700 healthy controls. Genotyping was performed with peripheral blood DNA for MTHFR C677T polymorphisms. The statistical significance was estimated by logistic regression analysis. Results The MTHFR C677T frequencies of CC, CT, and TT genotypes were 35.2%, 47.5%, and 17.3% among stomach cancer, 34%, 50.5%, and 15.5% in colorectal cancer, and 31.8%, 50.7%, and 17.5% in the controls, respectively. The MTHFR 677TT genotype showed a weak opposite association with colorectal cancer compared to the homozygous CC genotype [adjusted age and sex odds ratio (OR) = 0.792, 95% confidence interval (CI) = 0.638-0.984, P = 0.035]. Subjects with the MTHFR 677CT showed a significantly reduced risk of gastric cancer compared whose with the 677CC genotype (age- and sex-adjusted OR = 0.810; 95% CI = 0.696-0.942, P = 0.006). We also observed no significant interactions between the MTHFR C677T polymorphism and smoking or drinking in the risk of gastric and colorectal cancer. Conclusions The T allele was found to provide a weak protective association with gastric cancer and colorectal cancer.

Background This study was aimed to evaluate the impact of multivisceral resection (MVR) on the oncologic outcomes of patients with locally advanced colorectal cancer. Methods We conducted a retrospective review of patients who underwent surgical resection between 2011 and 2020. Patients were divided into two groups: the MVR group and the standard resection group. Prognostic factors were compared, and the effect of MVR on oncologic outcomes was assessed. Results Among 625 patients, 108 underwent MVR. The MVR group showed a significantly lower rate of lymph node metastasis (51.9% vs. 72.5%, p  < 0.001), lymphovascular invasion (25.9% vs. 42.8%, p  = 0.001), and perineural invasion (45.4% vs. 73.2%, p  < 0.001) compared to the standard resection group. Postoperative complications were more frequent in the MVR group (57.4% vs. 26.9%, p  < 0.001). Three-year disease-free survival (68.6% vs. 62.7%, p  = 0.743) and overall survival (OS) (80.9% vs. 85.0%, p  = 0.290) were comparable between the two groups. Multivariable analysis identified lymph node metastasis, perineural invasion, R2 resection, and absence of adjuvant chemotherapy as independent poor prognostic factors for OS. Conclusions The MVR group showed a significantly lower rate of lymph node metastasis and comparable oncologic outcomes. Therefore, when adjacent organ invasion is suspected, an aggressive en-bloc MVR should be considered to achieve radical resection.