BackgroundMany immunonutritional markers (INMs) have emerged as significant prognostic indicators in colorectal cancer (CRC); however, limited attention has been given to directly comparing these candidates to identify the most informative predictors.MethodsWe retrospectively analyzed 414 patients with stage I–III CRC who underwent curative resection. Seven INMs, including the C-reactive protein-albumin-lymphocyte (CALLY) index, the C-reactive protein-to-albumin ratio (CAR), and five other markers, were evaluated. The primary outcome was disease-free survival (DFS). Multivariable Cox proportional hazards regression was performed to identify independent predictors of DFS. The discriminatory performance of the resulting models was quantified using Harrell’s concordance index (C-index).ResultsIn univariable analysis, all seven INMs were significantly associated with DFS. However, after adjusting for T and N stages and other covariates, only the CALLY index (HR, 1.686; 95% confidence interval (CI), 1.038–2.738; p = 0.035) and CAR (HR, 2.089; 95% CI, 1.276–3.422; p = 0.004) remained independent predictors. Integrating these markers into the staging system significantly enhanced predictive accuracy. The C-index improved from 0.713 (95% CI, 0.657–0.764) for the stage-only model to 0.812 (95% CI, 0.781–0.867) for the CALLY + stage model and 0.809 (95% CI, 0.779–0.865) for the CAR + stage model.ConclusionThe CALLY index and CAR were the only INMs that retained independent prognostic significance after adjustment for T and N stages. Incorporating these continuous markers into the Tumor-Node-Metastasis (TNM) staging system substantially improved risk stratification and predictive accuracy in patients with non-metastatic CRC.

Purpose To identify long-term and late symptoms associated with impaired health-related quality of life (HRQoL) in Korean colorectal cancer (CRC) survivors, particularly those linked to worse HRQoL relative to the general population. Methods In this prospective cohort study, HRQoL and symptoms were assessed using the EORTC QLQ-C30, -CR29, -CIPN20, and -ELD14, EQ-5D, and EQ-VAS among 186 CRC survivors enrolled since October 2016 (derivation cohort, MKCCS-1) and 128 additional survivors (validation cohort, MKCCS-2) at a single tertiary cancer center in Korea. Exploratory factor analysis was used to identify clinically relevant symptom domains. HRQoL was subsequently compared with that of an age- and sex-matched general-population cohort (KNHANES-V) to identify specific survivorship symptoms associated with poorer perceived health status. Results After propensity-score matching, CRC survivors had lower mean EQ-5D index scores than the general population (0.823 vs. 0.881; p < 0.001). Abdominal pain, frequent bowel movements, sore perianal skin, fecal incontinence, and peripheral numbness were associated with HRQoL below the general-population mean EQ-VAS; decreased sexual interest and erectile dysfunction were additionally associated with lower HRQoL among men. Fourteen clinically relevant symptom items were grouped into four domains: abdominal/defecatory problems, peripheral neuropathy, voiding problems, and sexual problems (Cronbach’s α = 0.767; KMO = 0.718; p < 0.001). Conclusion Specific gastrointestinal, neuropathic, and sexual symptoms were associated with impaired HRQoL in Korean CRC survivors. These findings identify clinically actionable targets for symptom-focused assessment and supportive care in colorectal cancer survivorship.

BACKGROUND:Significant intraoperative blood loss (SIBL) and perioperative transfusion (PTF) are major concerns in colorectal cancer (CRC) surgery, yet they are often considered sequential events despite potentially distinct mechanisms. METHODS:We retrospectively analysed 706 patients who underwent curative resection for non-metastatic CRC. Logistic LASSO regression was used to identify predictors for SIBL (> 200 mL) and PTF. Model performance was evaluated using area under the curve (AUC), calibration metrics, and 1000 bootstrap validation. RESULTS:SIBL occurred in 18.1% of patients, and PTF was required in 12.3%. Independent predictors of SIBL included rectal cancer, preoperative radio- or chemotherapy, and surgeon experience less than 3 years, while minimally invasive surgery was associated with a reduced risk. In contrast, predictors of PTF included haemoglobin < 10.0 g/dL, albumin < 3.5 g/dL, CEA > 5 ng/mL, congestive heart failure, and renal dysfunction. cT4 stage, concurrent resection and platelet < 100 × 103/μL were common predictors in both models. The bootstrap-validated AUCs were 0.836 for SIBL and 0.934 for PTF, with calibration slopes of 0.886 and 0.893, respectively. In sensitivity analysis, PTF model showed an AUC of 0.897 (95% CI: 0.838-0.957) in patients without preoperative transfusion and SIBL defined as > 500 mL showed an AUC of 0.843 (95% CI: 0.763-0.924). CONCLUSION:Our findings suggest that SIBL and PTF arise from different risk factors. SIBL reflects surgical complexity, whereas PTF reflects impaired physiological reserve. Further research is warranted to validate these models in diverse cohorts to establish preventive strategies for these adverse outcomes.

Background/Objectives: The stool DNA-based SDC2 methylation (meSDC2) test has emerged as a promising noninvasive tool for the early detection of colorectal cancer (CRC). This study aimed to validate the clinical performance of the meSDC2 test for CRC detection in a multicenter hospital setting. Materials and Methods: This prospective, retrospective, multicenter, single-blind, case-control study was conducted at three tertiary medical centers. The primary endpoints were sensitivity and specificity for CRC detection. Secondary endpoints included test performance by tumor stage and location, and positivity rates in non-CRC lesions. Results: Among 636 participants, 260 (40.9%) had CRC, 173 (27.2%) had colorectal polyps, and 182 (28.6%) had normal colonoscopy findings. The meSDC2 test demonstrated a sensitivity of 87.7% (95% CI: 83.7-91.7%) and a specificity of 86.2% (95% CI: 82.7-89.7%) for CRC detection, with an AUC of 0.869 (95% CI: 0.841-0.895). Specificity among participants with negative colonoscopy findings was 91.8%. Positivity rates were 28.3% (95% CI: 15.3-41.3%) for advanced adenomas and 13.8% (95% CI: 6.6-21.0%) for non-advanced adenomas. Compared with the fecal immunochemical test (FIT), the meSDC2 test showed significantly higher sensitivity, whereas FIT demonstrated higher specificity. Combined testing improved sensitivity to 95.6% and 82.4% specificity. The meSDC2 test also showed significantly greater sensitivity than FIT for early-stage CRC (p = 0.037), while combined testing further improved sensitivity for both early- and late-stage CRC(p = 0.037 and p = 0.006, respectively). Conclusions: The stool-based meSDC2 test demonstrated high sensitivity, specificity, and consistent diagnostic performance across subgroups, supporting its clinical utility as a reliable and noninvasive CRC screening tool.

Small intestinal bacterial overgrowth (SIBO) is increasingly recognized as a clinically relevant condition characterized by excessive bacterial accumulation in the small intestine, contributing to a wide spectrum of gastrointestinal and systemic disorders. Recent advances in microbiome research have expanded our understanding of SIBO beyond a simple quantitative imbalance, highlighting its complex interactions with host physiology, immune regulation, and metabolic processes. This review summarizes current concepts of SIBO, focusing on its pathophysiological mechanisms, diagnostic challenges, and evolving therapeutic strategies. Key contributing factors include impaired gastrointestinal motility, disruption of mucosal defense systems, and alterations in the gut microbial ecosystem. Although jejunal aspirate culture remains the reference standard for diagnosis, its invasiveness limits clinical applicability. Noninvasive breath testing is widely used despite ongoing concerns regarding accuracy and standardization. In addition, this review discusses current treatment approaches, including antibiotic therapy such as rifaximin, as well as emerging strategies involving dietary modification, microbiome-targeted interventions, and integrative functional medicine frameworks.

Supplementary Table S2 shows that patients with an RHR ≥88 bpm had higher risks of all-cause and CRC-specific mortality compared to those with an RHR ≤66 bpm, after excluding patients who had died within 3-month of surgery.

BACKGROUND:Although lifestyle factors are associated with resting heart rate (RHR), its association with mortality in patients with colorectal cancer has not been fully understood. Therefore, we sought to determine whether RHR is associated with all-cause and colorectal cancer-specific mortality in patients with stage I to III colorectal cancer. METHODS:We included a total of 3,631 patients from the Severance Hospital Colorectal Cancer Registry (Seoul, South Korea) who underwent surgery for stage I to III colorectal cancer. RHR data were collected on the day of surgery. We utilized multivariable Cox proportional hazards models to estimate HRs and 95% confidence intervals (CI) for the association between RHR and all-cause and colorectal cancer-specific mortality. RESULTS:During a median follow-up of 3.0 years, there were 292 all-cause and 177 colorectal cancer-specific deaths. Patients in the highest quintile of RHR [≥88 beats per minute (bpm)] versus patients in the lowest quintile of RHR (≤66 bpm) showed a 3.33-fold increased risk of all-cause mortality (95% CI, 1.85-5.99) and a 2.98-fold increased risk of colorectal cancer-specific mortality (95% CI, 1.72-5.16). For every 10-bpm increase in RHR, there was a 1.44-fold increase in all-cause mortality (95% CI, 1.32-1.58) and a 1.50-fold increase in colorectal cancer-specific mortality (95% CI, 1.33-1.69). CONCLUSIONS:Elevated RHR on the day of surgery for colorectal cancer is associated with a higher risk of all-cause/colorectal cancer-specific mortality. IMPACT:Our data suggest that RHR may serve as a clinically relevant predictor of mortality in patients who undergo surgery for colorectal cancer.

Background/Objectives: Resistant starch intake has been shown to influence gut microbiota composition and affect metabolic markers. These effects may be partially attributed to enhanced short-chain fatty acid (SCFA)-mediated energy harvesting and hepatic lipogenesis induced by resistant starch fermentation. However, there is a lack of prospective research addressing these associations. To address this gap, we performed a double-blind, randomized dietary intervention study to investigate the impact of high versus low resistant starch consumption on metabolic markers and gut microbiota among adult women presenting with risk factors for metabolic syndrome. Methods: A total of 30 participants were randomly assigned to either the low-resistant starch (LRS) or high-resistant starch (HRS) diet groups. Each group, comprising 15 participants, consumed one food product per day enriched with either high or low resistant starch for 8 weeks. Changes in metabolic indices and gut microbiota were assessed and compared with baseline values, as assessed before diet (Week 0). Results: After 8 weeks of intervention, the HRS diet significantly increased body weight, body fat, and triglyceride (TG) level (mean change ≈ +40 mg/dL), while reducing blood pressure. Analysis of intestinal microbiota in the HRS group revealed a statistically significant increase in the genus Veillonella following the intervention. Conversely, the genus Marvinbryantia increased significantly in the LRS group. Conclusions: In women with metabolic risk factors, resistant starch supplementation elicited mixed metabolic responses-showing a modest reduction in blood pressure but concurrent increases in adiposity and TG concentrations. As the TG elevation reached a clinically meaningful magnitude, dietary interventions involving high-resistant starch should incorporate regular lipid monitoring to ensure cardiometabolic safety. Collectively, these findings highlight the complex interplay between SCFA-producing gut microbiota and host energy metabolism, suggesting that individualized dietary strategies may be required to optimize metabolic outcomes.

Supplementary Table S3 shows that patients with an RHR ≥88 bpm had higher risks of all-cause and CRC-specific mortality compared to those with an RHR ≤66 bpm, after excluding patients with a history of disease.

BACKGROUND:Impaired fasting glucose (IFG), being a pre-diabetic condition, can increase the risk of overt diabetes; thus early detection and prediction of IFG are important to reduce the incidence of overt diabetes. Some predictive factors, including serum alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), have been reported in several studies, but none of the studies have investigated the effect of longitudinal changes in individual serum ALT and GGT levels on the risk of IFG. METHODS:We aimed to investigate the association between changes in the serum ALT and GGT levels and the risk of IFG using a checkup database between 1999 and 2014. RESULTS:A total of 3,598 males and 3,275 females were enrolled in the study. We performed a follow-up test of serum ALT or GGT in each individual, and classified the cases in which the serum ALT or GGT level was increased or decreased during the follow-up test compared to the baseline. According to the multivariate Cox proportional hazards model, the hazard ratio was 1.76 (95% confidence interval, 1.45-2.12; P < 0.001) in male subjects with an increased serum GGT level compared to male subjects with a decrease in the serum GGT level at follow-up compared to the baseline. However, the relationship between the serum ALT level and incidence of new-onset IFG was not statistically significant in both sexes; and in females, the relationship between the serum GGT level and incidence of new-onset IFG was also not statistically significant. CONCLUSION:We revealed that a longitudinal increase in serum GGT levels was related to an increased risk of IFG in males. Therefore, monitoring the changes in serum GGT levels is important for predicting new-onset IFG, and it can be used as an early indicator of onset of overt diabetes in males.

Supplementary Table S1 shows that patients with an RHR ≥90 bpm had higher risks of all-cause and CRC-specific mortality, respectively, compared to those with an RHR of 60–69 bpm.

PURPOSE:A high index of suspicion is crucial for early anastomotic leak (AL) diagnosis, enabling timely intervention and conservative management. Although recent studies have highlighted the potential of drain amylase (dAmy) as a predictive marker for AL, its application in colorectal surgery remains underexplored. MATERIALS AND METHODS:A retrospective study was conducted among patients who underwent colorectal resection between March 2020 and November 2023. A total of 299 patients with at least one dAmy and serum amylase (sAmy) measurement between postoperative days 1 to 5 were included, after excluding patients with fecal diversion. RESULTS:Multiple logistic regression identified the drain/serum amylase ratio (d/s Amy) as an independent predictor of AL (odds ratio 1.032, 95% confidence interval 1.009-1.056; p=0.007). The receiver operating characteristic curve demonstrated significant diagnostic ability for AL [area under the curve (AUC)=0.691], with a cut-off value of 2.54, a sensitivity of 48.4%, and a specificity of 94.2%. Patients with d/s Amy ≥2.54 had a significantly higher incidence of AL with a faster diagnosis compared to conventional methods (3.5 days vs. 5 days, p=0.006). In patients who underwent ileal anastomosis, the d/s Amy ratio had an AUC of 0.936, with a sensitivity of 87.5% and a specificity of 96.6%. CONCLUSION:The postoperative d/s Amy ratio is valuable for early AL detection in patients undergoing colorectal surgery, particularly in those with ileal anastomosis. This simple and noninvasive test can aid in timely diagnosis, offering earlier intervention compared with conventional methods.

PURPOSE:Previous studies have demonstrated that short-course radiotherapy (SCRT), followed by consolidation chemotherapy (CCT), produces oncologic outcomes comparable to those of long-course chemoradiotherapy (LCRT). However, more recent long-term data have raised concerns regarding the durability of these benefits. This study aimed to assess the long-term surgical and oncologic outcomes of SCRT with CCT vs. LCRT, using data from the ESCORT trial. MATERIALS AND METHODS:This comparative study included 62 patients with locally advanced rectal cancer. Patients in the SCRT group (n=27) were prospectively enrolled in the ESCORT trial (NCT03676517), a single-arm phase II study conducted from 2018 to 2020. They received five daily fractions of 5 Gy, followed by two cycles of XELOX, and surgery after 4 weeks. A matched cohort of 35 patients who underwent LCRT during the same period was retrospectively identified from institutional records. RESULTS:With a median follow-up of 4.75 years for the SCRT group and 4.94 years for the LCRT group, the 5-year overall survival rates were similar between the groups (SCRT: 100% vs. LCRT: 97.1%, p=0.382). The 5-year disease-free survival (DFS) rates were 83.6% for SCRT and 70.3% for LCRT (p=0.237). In multivariable analysis, SCRT was not associated with inferior DFS (hazard ratio, 0.53; 95% confidence interval, 0.14-2.04). Delayed anastomosis-related complications occurred at similar rates (18.5% vs. 20.0%; p=0.884). CONCLUSION:SCRT with CCT demonstrated long-term oncologic outcomes and surgical safety comparable to those of LCRT, supporting its role as a viable alternative, particularly in resource-constrained healthcare settings.

BACKGROUND:Lymph node (LN) examination is important for staging colorectal cancer. Examining < 12 LN has been associated with a poor prognosis. However, surgical and pathological advances have led to increase examined LN, necessitating the reassessment of the best cutoff for prognosis. PATIENTS AND METHODS:We reviewed patients with stage II-III colon cancer from the Yonsei Cancer Center Registry (YCC) database and the Netherlands Cancer Registry (NCR). The optimal LN cutoff was determined by comparison with hazard ratio (HR) in 12 LN. We compared higher vs. lower LN cutoff effects on a 6-year overall survival (OS). RESULTS:From 2005 to 2015, the proportion with < 12 LN decreased significantly (P < .001). There was no significant association between 6-year OS and LN yield in all stages II-III patients (HR = 1.21, P = .116), stage II (HR = 1.39, P = .068), and stage III (HR = 1.18, P = .297) colon cancer based on the standard 12 LN examined, whereas the 20 LN cutoff examined was associated with a significant increase in 6-year OS in all patients (HR = 1.51, P < .001). Multivariate regression revealed a significant decrease in 6-year OS in stage II (HR = 1.39, P = .026) and stage III (HR = 1.47, P < .001) with < 20 LN yield. In the NCR, < 20 LN was associated with poorer 6-year OS in stage II-III patients (HR = 1.25, P < .001), stage II (HR = 1.43, P < .001), and stage III (HR = 1.13, P = .007). CONCLUSION:Over the past decade, inadequate LN examinations have significantly decreased. Compared to < 12 LN, < 20 LN examined is more associated with a worse prognosis in patients who underwent surgery.

Supplementary Table S4 shows that patients with an RHR ≥88 bpm had higher risks of all-cause and CRC-specific mortality compared to those with an RHR ≤66 bpm, after excluding patients who received neoadjuvant therapy.

Background: Heart rate variability (HRV) is a well-established marker of autonomic nervous system function and resistant starch (RS) is known to modulate gut microbiota and promote short-chain fatty acid production. This study aimed to investigate whether RS consumption improves HRV by modulating autonomic function in individuals with metabolic syndrome risks. Methods: This randomized controlled trial included 30 women with metabolic syndrome, recruited from a university hospital. Participants were randomly assigned to either the high-resistant starch (HRS) group or the low-resistant starch (LRS) group. The intervention lasted for 8 weeks. The primary analysis of this study focused on participants in the lower 50% of baseline total power (TP), assessing the differential effects of HRS intake on autonomic function in this subgroup. Statistical analyses, including the Wilcoxon rank-sum test, were performed to compare differences between groups. Results: In the subgroup with baseline TP in the lower 50%, the HRS group showed an increase in TP (median ΔTP: 435 ms², interquartile range [IQR]: 964 ms²), while the LRS group showed a decrease (-30.9 ms², IQR: 146 ms²). The between-group difference in TP change was statistically significant (P=0.03). Similarly, low frequency (LF) power increased significantly in the HRS group compared to the LRS group (P=0.03). Although high frequency and very low frequency also showed greater improvement in the HRS group, these changes did not reach statistical significance. Conclusion: RS intake was associated with significant improvements in TP and LF in individuals with lower baseline HRV, suggesting its potential role in autonomic nervous system modulation.

Purpose The purpose of this qualitative study was to use semi-structured interviews and thematic analysis to elicit key influencing factors (i.e., behavioral, normative, and control beliefs) related to physical activity and exercise in colorectal cancer survivors. Methods Colorectal cancer survivors ( N = 17) were recruited from exercise programs designed for colorectal cancer survivors at the Yonsei Cancer Center, Seoul, South Korea. A purposive sampling method was used. Interview questions were informed by the theory of planned behavior (TPB). Semi-structured face-to-face interviews were conducted, and open-ended questions addressed the research question. Interviews were transcribed verbatim and analyzed using thematic analysis. Results Participants were on average 2.2 years post-treatment. The mean age of the sample was 55.9 years. Key behavioral, normative, and control beliefs emerged in the data. For behavioral beliefs, colorectal cancer survivors believed that exercise would result in physical and psychological improvements, and improve their bowel problems. For normative beliefs, most colorectal cancer survivors wanted their oncologists’ approval for participation of exercise. Family members, more specifically the spouse, were also influencing factors for colorectal cancer survivors adopting physical activity. The most frequently mentioned control belief was that supervised exercise with an exercise specialist made exercise participation easier. Conclusions and implications Beliefs identified in this study can inform TPB-based physical activity interventions tailored for colorectal cancer survivors. While information alone may not lead to behavior change, integrating these beliefs with other influential factors can potentially enhance intervention efficacy and promote physical activity in this population.

Background: Combining radiotherapy (RT) with immune checkpoint inhibitors (ICIs) is a promising strategy that can enhance the therapeutic efficacy of ICIs. However, little is known about RT-induced changes in the expression of immune checkpoints, such as PD-L1, and their clinical implications in colorectal cancer (CRC). This study aimed to investigate the association between responsiveness to RT and changes in PD-L1 expression in human CRC tissue and cell lines. Methods: Tissue specimens from preoperative biopsy via sigmoidoscopy and surgical resection were obtained from 24 patients with locally advanced rectal cancer (LARC) who underwent neoadjuvant chemoradiation therapy (CRT) between August 2016 and December 2017. Immunohistochemistry for PD-L1 in formalin-fixed paraffin-embedded tissue was performed from the endoscopic biopsy and surgical specimens. RNA sequencing was performed using 11 pairs of human LARC tissues before and after irradiation. After exposing human CRC cells to radiation, we investigated changes in the expression levels of PD-L1 and its regulatory signaling pathways. Results: Patients were classified by tumor regression grade into responders (grade 2; 9 patients, 37.5 %) and non-responders (grades 3, 4, or 5; 15 patients, 62.5 %). In the non-responder group, 13 patients had low PD-L1 expression, but neoadjuvant CRT increased PD-L1 expression in 7 patients (53.9 %) (McNemar’s test, p=0.034). CRT up-regulated PD-L1 in non-responder LARC tissues. Similarly, radiation increased PD-L1 in radioresistant DLD-1 cells more than in radiosensitive HCT116 cells, also affecting PD-L1-regulating genes and immune checkpoints in CRC cells. Conventional fractionated radiation treatment further increased PD-L1 in DLD-1 cells compared to HCT116 cells. Conclusions: This study demonstrated that radiation induces an increase in PD-L1 expression, which is more pronounced in radioresistant CRC, proving the theoretical framework for a combined treatment strategy with a PD-L1 blockade for locally advanced rectal cancer.

Purpose Despite advances in neoadjuvant chemoradiotherapy and anal sphincter-preserving surgery for rectal cancer, bowel dysfunction is still unavoidable and negatively affects patients’ quality of life. In this longitudinal study, we aimed to investigate the changes in bowel function with follow-up time and the effect of neoadjuvant chemoradiotherapy on bowel function following low anterior resection for rectal cancer. Methods In this study, 171 patients with upper or middle rectal cancer who underwent low anterior resection between 2012 and 2018 were included. Bowel function was assessed longitudinally with Memorial Sloan Kettering Cancer Center Bowel Function Instrument and Wexner scores every 6 months after restoration of bowel continuity. Patients with at least 2 follow-up visits were included. Results Overall, 100 patients received neoadjuvant chemoradiotherapy. Urgency, soilage, and fecal incontinence were noted within 24 months in the patients treated with neoadjuvant chemoradiotherapy. After 2 years of follow-up, significant bowel dysfunction and fecal incontinence were observed in the neoadjuvant chemoradiotherapy group. Low tumor level and neoadjuvant chemoradiotherapy were associated with delayed bowel dysfunction. Conclusion Neoadjuvant chemoradiotherapy in combination with low tumor level was significantly associated with delayed bowel dysfunction even after 2 years of follow-up. Therefore, careful selection and discussion with patients are paramount.