Ileal pouch-anal anastomosis (IPAA) is recommended for patients with ulcerative colitis (UC) in terms of surgical treatment. Measuring surgical complications of IPAA and long-term quality of life (QOL) are important to achieve an acceptable risk/benefit ratio for patients with UC. Patients with UC who underwent total proctocolectomy (TPC) with IPAA from February 2008 to July 2016 at our institute were included. Early surgical complications were defined as mechanical/infectious events within one month after IPAA. Assessment of QOL was performed using the Cleveland Global Quality of Life instrument (CGQL), with 50% improvement as a cut-off value. Demographic and clinical variables were compared with univariable analysis and step-wise logistic regression models were also performed. A total of 58 eligible patients had a median follow-up time of 78.5 months [interquartile range (IQR), 34.4-92.8] from February2008 to March 2017, including 25 cases (43.1%) developed early surgical complications. Age at pouch surgery and excessive blood loss were risk factors associated with early surgical complications (p < 0.05). In multivariate analysis, older age at surgery [odds ratio (OR), 1.05; 95% confidence interval (CI), 1.01-1.1] and significant blood loss (≧400 ml) (OR, 4.31; 95% CI, 1.21-16.87) were contributing factors for developing early surgical complications. The CGQL score was significantly increased after IPAA (0.728 ± 0.151 vs. 0.429 ± 0.173, p < 0.001). Early surgical complications (OR, 5.55; 95%CI, 1.44-21.37), older age at surgery (OR, 1.06; 95% CI, 1.01-1.12) and use of immunomodulatory (OR, 17.50; 95% CI, 1.52-201.39) were associated with poor long-term QOL. The study demonstrated that early surgical complications might contribute to develop a poor CGQL score, suggesting intentional control of risk factors associated with early surgical complications should be taken into consideration for patients with UC for pouch surgery.
P4HA2 has been implicated in various malignant tumors; however, its expression and functional role in colorectal cancer (CRC) remain poorly elucidated. This study aims to investigate the involvement of P4HA2 in CRC metastasis and progression, uncovering the underlying mechanisms. In colorectal cancer (CRC), P4HA2 exhibited overexpression, and elevated levels of P4HA2 expression were associated with an unfavorable prognosis. Functional assays demonstrated P4HA2's regulation of cell proliferation, and epithelial-mesenchymal transition (EMT) both in vitro and in vivo. Additionally, the AGO1 expression was correlated with P4HA2, and depletion of AGO1 reversed the proliferation and EMT function induced by P4HA2. Chromatin immunoprecipitation (ChIP) and luciferase assays suggested that the transcription factor SP1 binds to the promoter sequence of P4HA2, activating its expression in CRC. This study unveiled SP1 as a transcriptional regulator of P4HA2 in CRC and AGO1 is a probable target of P4HA2. In conclusion, P4HA2 emerges as a potential prognostic biomarker and promising therapeutic target in colorectal cancer.
19 July 2024 in World Journal of Surgical Oncology
Background: Microsatellite instability-high (MSI-H) tumors, with elevated tumor mutational burden and expression of neoantigens, represent a distinct immune-activated subpopulation in colorectal cancer (CRC), characterized by strong lymph node reaction, locally advanced tumor and higher total lymph nodes harvested (TLN), but less metastatic lymph nodes and fewer incidence of III-IV stage. Host immune response to tumor and lymph nodes may be an important prognostic factor. However, N stage and LNR (Lymph-Node Ratio) have limitations in predicting the prognosis of MSI-H patients. Negative lymph node count (NLC) provided a more precise representation of immune activation status and extent of tumor metastasis. The study aims to detect prognostic significance of NLC in MSI-H CRC patients, and compare it with N stage, TLN and LNR. Methods: Retrospective data of 190 consecutive MSI-H CRC patients who received curative resection were collected. Survival analyses were performed using the Kaplan–Meier method. Clinicopathological variables including NLC, N stage, TLN and LNR were studied in univariate and multivariate COX regression analyses. ROC (receiver operating characteristic curve) and concordance index were employed to compare the differences in predictive efficacy between NLC, N stage, TLN and LNR. Results: Patients with increased NLC experienced a significantly improved 5-years DFS and OS in Kaplan–Meier analysis, univariate analysis, and multivariate analysis, independent of potential confounders examined. Increased NLC corresponded to elevated 5-years DFS rate and 5-years OS rate. AUC (area under curve) and concordance index of NLC in DFS and OS predicting were both significantly higher than N stage, TLN and LNR. Conclusions: Negative lymph node is an important independent prognostic factor for MSI-H patients. Reduced NLC is associated with tumor recurrence and poor survival, which is a stronger prognostic factor than N stage, TLN and LNR.
In recent years, cancer immunotherapy has become a breakthrough method to solve solid tumors. It uses immune checkpoint inhibitors to interfere with tumor immune escape to coordinate anti-tumor therapy. However, immunotherapy has an individualized response rate. Moreover, immune-related adverse events and drug resistance are still urgent issues that need to be resolved, which may be attributed to the immune imbalance caused by immune checkpoint inhibitors. Microbiome research has fully revealed the metabolic-immune interaction relationship between the microbiome and the host. Surprisingly, sequencing technology further proved that intestinal microbiota could effectively intervene in tumor immunotherapy and reduce the incidence of adverse events. Therefore, cancer immunotherapy under the intervention of intestinal microbiota has innovatively broadened the anti-tumor landscape and is expected to become an active strategy to enhance individualized responses.