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Although there is a growing interest in developing circulating microRNA (miRNA) as noninvasive diagnostic biomarkers for the detection of high-risk colorectal adenomas and early-stage CRCs, but the comparative diagnostic significance of serum vs. exosomal miRNAs remains unexplored. Based upon published literature, we performed an initial discovery step by investigating the expression of a miRNA panel in 20 normal colonic mucosa, 27 adenomas, and 19 CRC tissues. We performed subsequent validation by quantifying expression of candidate miRNAs in total serum and in exosomes from 26 adenoma patients and 47 healthy controls, and evaluated their clinical significance and potential diagnostic value in colorectal adenomas. We observed that the expression of four miRNAs, miR-21, miR-29a, miR-92a, and miR-135b, was significantly higher in colorectal adenomas vs. normal colonic mucosa. During validation, expression of miR-21, miR-29a and miR-92a in serum was significantly higher in adenomas vs. healthy controls, significantly correlated with adenoma size and total adenoma number within the colorectum, and significantly discriminated patients with advanced adenomas. In contrast, although exosomal miR-21 and miR-29a levels in adenoma patients were significantly higher than those of healthy volunteers, only exosomal miR-21 significantly correlated with adenoma size and total adenoma number, and could discriminate patients with high-risk adenomas. Compared to exosomal miRNAs, serum levels of miR-21, miR-29a and miR-92a are superior diagnostic biomarkers in patients with high-risk adenomatous polyps.

Background Rac GTPase activating protein 1 (RacGAP1) plays a regulatory role in cell growth, transformation and metastasis. The aim of this study was to clarify the association between RacGAP1 expression and clinical outcome in patients with gastric cancer. Methods A total of 232 gastric cancer patients in our institute who underwent surgery without preoperative treatments were enrolled in this study. We investigated RacGAP1 expression using immunohistochemistry (IHC) and evaluated IHC scores calculated by the percentage of positive cells and intensity and its expression at the invasive front. RACGAP1 expression was also assessed. Results RacGAP1 expression was observed in the nuclei of gastric cancer cells. Evaluation by IHC score showed no significant correlations with clinicopathological variables except for histological differentiation. In transcriptional analyses, RACGAP1 expression was elevated in diffuse type gastric cancer than intestinal type without a significant difference. We observed significant correlations of RacGAP1 protein expression at the invasive front with older age, tumor size, lymph node metastasis, lymphatic invasion, vascular invasion and advanced stage. Patients with RacGAP1 protein expression at the invasive front had significantly poorer prognosis than those without it ( P  < 0.0001). In multivariate analysis, lymph node metastasis, distant metastasis and positive RacGAP1 expression at the invasive front were independent prognostic factors (lymph node metastasis: P  = 0.0106; distant metastasis: P  = 0.0012; RacGAP1: P  = 0.0011). Conclusions RacGAP1 expression at the invasive front in gastric cancer was significantly correlated with factors reflecting tumor progression and poor prognosis. Our data suggest that RacGAP1 might play important roles in the progression of gastric cancer.

Background L1 cell adhesion molecule (L1CAM) is highly expressed in malignant tumours and might play a pivotal role in tumour progression. Methods We analysed by immunohistochemistry L1CAM protein expression in formalin-fixed, paraffin-embedded specimens from 309 GC patients. We performed propensity score matching (PSM) analysis to clarify the prognostic impact of L1CAM in GC patients. We evaluated L1CAM gene expression in fresh frozen specimens from another group of 131 GC patients to establish its clinical relevance. The effects of changes in L1CAM were investigated in vitro and in vivo. Results L1CAM was mainly expressed in tumour cells of GC tissues. Elevated L1CAM expression was an independent prognostic factor for overall and disease-free survival, and an independent risk factor for distant metastasis in GC patients. PSM analysis showed that high L1CAM expression was significantly associated with poor prognosis. L1CAM gene expression using fresh frozen specimens successfully validated all of these findings in an independent cohort. Inhibition of L1CAM suppressed cell proliferation, cycle progress, invasion, migration and anoikis resistance in GC cells. Furthermore, L1CAM inhibition suppressed the growth of peritoneal metastasis. Conclusion L1CAM may serve as a feasible biomarker for identification of patients who have a high risk of recurrence of GC.

Purpose To determine the methylation level of the miR-124 promoter in non-neoplastic rectal mucosa of patients with pediatric-onset ulcerative colitis (UC) to predict UC-associated colorectal cancer (UC-CRC). Methods Between 2005 and 2017, non-neoplastic rectal tissue specimens were collected from 86 patients with UC, including 13 patients with UC-CRC; cancer tissues were obtained from the latter group. The methylation status of the miR-124 promoter was quantified using bisulfite pyrosequencing and compared between pediatric- and adult-onset UC patients. Results Patients with pediatric-onset UC experienced a significantly shorter disease duration than those with adult-onset UC. The levels of miR-124 promoter methylation in non-neoplastic rectal mucosa were positively correlated with the age at the diagnosis and duration of UC. The rate of increase in miR-124 methylation was accelerated in patients with pediatric-onset UC compared to those with adult-onset UC. Furthermore, the miR-124 methylation levels in non-neoplastic rectal mucosa were significantly higher in patients with UC-CRC than in those with UC alone ( P  = 0.02). A receiver operating characteristic analysis revealed that miR-124 methylation in non-neoplastic tissue discriminated between patients with pediatric-onset UC with or without CRC. Conclusion miR-124 methylation in non-neoplastic rectal mucosa may be a useful biomarker for identifying patients with pediatric-onset UC who face the highest risk of developing UC-CRC.

Purposes The preoperative diagnosis of Hirschsprung disease (HD) requires a rectal mucosal biopsy and acetylcholinesterase (AchE) staining. However, the optimal timing for performing these procedures remains unclear. In this study, we assessed the most effective timing for a rectal biopsy and AchE staining to diagnose HD. Methods We retrospectively collected data from 57 patients who underwent radical surgery for HD at Mie University Hospital between January 2008 and April 2024. We reviewed all rectal biopsies, including those with multiple samples, and analyzed the biopsy date and the results of AchE staining (positive or negative). Results Among the 57 children with a confirmed HD diagnosis, 36 were included in the study. Fifty-two rectal biopsy sessions were performed in these 36 patients with HD, including 15 with multiple biopsies. A receiver operating characteristic analysis showed that the optimal age for diagnosing HD was older than 21 days. Biopsies performed at ≤ 3 weeks of age had a low diagnostic accuracy rate of 30.8%, whereas rectal biopsies performed at > 3 weeks of age showed a high positive diagnostic rate of 87.5%. Conclusions Rectal mucosal biopsies performed after 3 weeks of age show a higher diagnostic accuracy for HD. Clinical trial number Not applicable.

Aims The prognosis of colorectal cancer (CRC) has been historically reliant on the Tumor Node Metastasis (TNM) staging system, but there is variability in outcomes among patients at similar stages. Therefore, there is an urgent need for more robust biomarkers. The aim of this study was to assess the clinical feasibility of the recently reported Inflammatory Burden Index (IBI) for predicting short‐ and long‐term outcomes in patients with CRC. Methods This was a retrospective observational study of 555 CRC patients undergoing surgery for primary tumor resection. We determined the prognostic value of preoperative IBI for disease‐free and overall survival, and its predictive value for perioperative risk of infectious complications, including surgical site infection. Results Increased preoperative IBI was significantly associated with advanced disease stage and poor oncological outcome in CRC patients. Higher IBI was independently linked to poorer disease‐free and overall survival. Similar outcomes were observed in a subanalysis focused on high‐risk stage II and stage III CRC patients. Elevated preoperative IBI was significantly correlated with an increased risk of surgical site infection and other postoperative infectious complications. Propensity score‐matching analysis validated the impact of IBI on the prognosis in CRC patients. Conclusion We established preoperative IBI as a valuable predictive biomarker for perioperative risks and oncological outcomes in CRC patients. Preoperative IBI is useful for designing effective perioperative management and postoperative oncological follow‐up. This study emphasized the clinical importance of preoperative the Inflammatory Burden Index (IBI) as a robust biomarker for predicting both short‐ and long‐term outcomes in patients with colorectal cancer (CRC). We demonstrated significant associations between elevated preoperative IBI, disease progression, and postoperative infectious complications, which suggests a vital role for IBI in enhancing patient stratification and guiding more tailored perioperative management of CRC.

Aim The clinical significance of the geriatric nutritional risk index (GNRI) in locally advanced rectal cancer (LARC) patients undergoing preoperative chemoradiotherapy (CRT) followed by curative surgery has not been comprehensively evaluated. Methods This retrospective study enrolled 93 LARC patients diagnosed with clinical lymph node metastasis. The GNRI formula was as follows: 1.489 × albumin (g/l) + 41.7 × current weight/ideal weight. Patients were categorized as GNRI low (GNRI < 104.25) or high (GNRI > 104.25) according to the receiver operating characteristic (ROC) curve for survival analysis. The impact of GNRI status on the prognostic outcomes of curative surgery for LARC was examined. Results There were 55 (59.14%) and 38 (40.86%) patients in the GNRI high and low groups, respectively. Of the investigated demographic factors, age, pathological tumor invasion, and presence of recurrence were significantly associated with the GNRI value. In Kaplan–Meier analysis, overall survival (OS) and disease-free survival (DFS) were significantly shorter in the GNRI low group (OS: p  = 0.00020, DFS: p  = 0.0044, log-rank test). Multivariate analysis using a Cox proportional hazards model showed that a low GNRI was an independent risk factor for poor OS (hazard ratio (HR) = 3.22; 95% confidence interval (CI), 1.37–8.23; p  = 0.0068) and DFS (HR = 2.32; 95%CI = 1.15–4.79; p  = 0.018). Although use of adjuvant therapy has no impact on prognosis (OS: p  = 0.26, DFS: p  = 0.29), low GNRI showed shorter OS and DFS in patients with pathological lymph node metastasis [ypN(+)] (OS: p  = 0.033, DFS: p  = 0.032, log-rank test). Conclusions GNRI is a useful marker for LARC patients diagnosed with clinical lymph node metastasis and treated by preoperative CRT followed by curative surgery. GNRI is a useful tool to identify high risk of recurrence for improving the survival in LARC patients.

Background Sarcopenia frequently occurs in metastatic cancer patients. Emerging evidence has revealed that various secretory products from metastatic tumours can influence host organs and promote sarcopenia in patients with malignancies. Furthermore, the biological functions of microRNAs in cell‐to‐cell communication by incorporating into neighbouring or distal cells, which have been gradually elucidated in various diseases, including sarcopenia, have been elucidated. Methods We evaluated psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC) using pre‐operative computed tomography imaging in 183 colorectal cancer (CRC) patients. miR‐203 expression levels in CRC tissues and pre‐operative serum were evaluated using quantitative polymerase chain reaction. Functional analysis of miR‐203 overexpression was investigated in human skeletal muscle cells (SkMCs), and cells were analysed for proliferation and apoptosis. Expressions of several putative miR‐203 target genes (CASP3, CASP10, BIRC5, BMI1, BIRC2, and BIRC3) in SKMCs were validated. Results A total of 183 patients (108 men and 75 women) were included. The median age of enrolled patients at diagnosis was 68.0 years (range 35–89 years). High IMAC status significantly correlated with female gender (P = 0.004) and older age (P = 0.0003); however, no other clinicopathological factors correlated with IMAC status in CRC patients. In contrast, decreased PMI significantly correlated with female gender (P = 0.006) and all well‐established disease development factors, including advanced T stage (P = 0.035), presence of venous invasion (P = 0.034), lymphovascular invasion (P = 0.012), lymph node (P = 0.001), distant metastasis (P = 0.002), and advanced Union for International Cancer Control tumour–node–metastasis stage classification (P = 0.0004). Although both high IMAC status and low PMI status significantly correlated with poor overall survival (IMAC: P = 0.0002; PMI: P < 0.0001; log‐rank test) and disease‐free survival (IMAC: P = 0.0003; PMI: P = 0.0002; log‐rank test), multivariate Cox's regression analysis revealed that low PMI was an independent prognostic factor for both overall survival (hazard ratio: 4.69, 95% confidence interval (CI): 2.19–10, P = 0.0001) and disease‐free survival (hazard ratio: 2.33, 95% CI: 1.14–4.77, P = 0.021) in CRC patients. Serum miR‐203 expression negatively correlated with pre‐operative PMI level (P = 0.0001, ρ = −0.25), and multivariate logistic regression analysis revealed that elevated serum miR‐203 was an independent risk factor for myopenia (low PMI) in CRC patients (odds ratio: 5.16, 95% CI: 1.8–14.8, P = 0.002). Overexpression of miR‐203 inhibited cell proliferation and induced apoptosis via down‐regulation of BIRC5 (survivin) expression in human SkMC line. Conclusions Assessment of serum miR‐203 expression could be used for risk assessment of myopenia, and miR‐203 might be a novel therapeutic target for inhibition of myopenia in CRC.

Background Tobacco ingestion is widely known to cause nicotine toxicity, which may result in severe symptoms. Two heated tobacco sticks, called TEREA™ and SENTIA™, were launched in 2021 by Philip Morris International (New York, NY, USA), and their ingestion is associated with a risk of bowel injury because they contain a partially pointed metallic susceptor. However, this risk is not well known to the general public or healthcare providers. To increase awareness of this risk, we herein report a case involving extraction of a metallic susceptor after ingestion of the heated tobacco stick TEREA™. Case presentation A 7-month-old girl presented to the emergency department of a nearby hospital because she was suspected to have accidentally swallowed heated tobacco. Although she presented with no symptoms related to nicotine poisoning, abdominal X-ray examination revealed a metal object in her stomach. According to a statement released by the Japan Poison Information Center, the TEREA™ heated tobacco stick contains a metallic susceptor with a rectangular shape and sharp corners. The patient was transferred to our department because of the risk of bowel injury, and upper gastrointestinal endoscopy was performed. No cigarettes were found by endoscopic observation; however, a metallic susceptor was located in the second part of the duodenum. We grasped it with biopsy forceps and carefully removed it using an endoscope with a cap attached to the tip. The post-endoscopic course was uneventful. Conclusions Some patients who ingest heated tobacco sticks might be exposed not only to the effects of nicotine but also to physical damage caused by a metallic susceptor. Infants and toddlers especially could swallow these sticks, therefore tobacco companies need to make the problem more public. Clinicians also should alert the problem, and pay attention to this risk in the clinical setting.

Aim The prognostic immune nutritional index (PINI) is increasingly recognized for its potential clinical utility. However, multifaceted evaluations of its ability to predict oncological outcomes in colorectal cancer (CRC) and its association with postoperative infectious complications remain limited. Methods We analyzed the preoperative PINI in 487 patients with CRC who underwent surgical treatment between 2006 and 2015 to clarify its clinical relevance. Results A low preoperative PINI was significantly associated with several clinicopathological factors indicative of disease progression, including advanced pathological T category (p < 0.001) and lymph node metastasis (p = 0.001). It was an independent prognostic factor for disease‐free survival (DFS) (hazard ratio [HR]: 1.91; 95% confidence interval [CI]: 1.22–3.00; p = 0.005) and overall survival (OS) (HR: 2.51; 95% CI: 1.50–4.18; p < 0.001). A low preoperative PINI was also an independent risk factor for total infection (odds ratio [OR]: 1.82; 95% CI: 1.11–3.00; p = 0.02), encompassing all postoperative infectious complications. In a subgroup analysis of patients with stage III and high‐risk stage II CRC, a low preoperative PINI was an independent prognostic factor for both DFS (HR: 2.03; 95% CI: 1.24–3.32; p = 0.005) and OS (HR: 3.64; 95% CI: 1.61–8.19; p = 0.002). Additionally, propensity score matching analysis demonstrated that patients with a low preoperative PINI had significantly worse DFS (p = 0.01) and OS (p = 0.02). Conclusion The preoperative PINI is a valuable biomarker for both perioperative risk assessment and long‐term oncological management in patients with CRC. This study investigated the prognostic value of the preoperative prognostic immune nutritional index (PINI) in colorectal cancer. A low preoperative PINI was significantly associated with both poor oncological outcomes and an increased risk of postoperative infectious complications. These findings suggest that PINI is a useful biomarker for improving perioperative risk stratification and patient management.