Potential Molecular Markers Related to Lymph Node Metastasis and Stalk Resection Margins in Pedunculated T1 Colorectal Cancers Using Digital Spatial Profiling: A Pilot Study with a Small Case Series.

There is a debate regarding the prediction of lymph node metastasis (LNM) in pedunculated T1 colorectal cancer (CRC). In this study with four cases of pedunculated T1 CRCs, we aimed to investigate gene expression variations based on the distance from the Haggitt line (HL) and identify potential molecular risk factors for LNM. By leveraging the Cancer Transcriptome Atlas and digital spatial profiling technology, we meticulously analyzed discrete regions, including the head, HL, proximal stalk region (300-1000 µm from HL), and distal stalk region (1500-2000 µm from HL) to identify spatially sequential molecular changes. Our findings showed significant overall gene expression variations among the head, proximal stalk, and distal stalk regions of pedunculated T1 CRCs compared to the control adenoma. Compared to LNM-negative T1 CRCs, LNM-positive T1 CRC showed that the expression of genes involved in immune-related pathways such as B2M, HLA-B, and HLA-E were significantly downregulated in the distal stalk region compared to the proximal stalk region. In summary, our results may tentatively suggest considering endoscopic resection of the stalk with a minimum 2000 µm margin from the HL, taking into account the gene expression alterations related to immune-related pathways. However, we acknowledge the limitations of this pilot study, notably the small case series, which may restrict the depth of interpretation. Further validation is imperative to substantiate these findings.

Oncologic relevance of genetic alterations in sporadic synchronous and solitary colorectal cancer: a retrospective multicenter study.

BACKGROUND: Oncologic impact of genetic alteration across synchronous colorectal cancer (CRC) still remains unclear. This study aimed to compare the oncologic relevance according to genetic alteration between synchronous and solitary CRC with performing systematic review. METHODS: Multicenter retrospective analysis was performed for CRC patients with curative resection. Genetic profiling was consisted of microsatellite instability (MSI) testing, RAS (K-ras, and N-ras), and BRAF (v-Raf murine sarcoma viral oncogene homolog B1) V600E mutation. Multivariate analyses were conducted using logistic regression for synchronicity, and Cox proportional hazard model with stage-adjusting for overall survival (OS) and disease-free survival (DFS). RESULTS: It was identified synchronous (n = 36) and solitary (n = 579) CRC with similar base line characteristics. RAS mutation was associated to synchronous CRC with no relations of MSI and BRAF. During median follow up of 77.8 month, Kaplan-meier curves showed significant differences according to MSI-high for OS, and in RAS, and BRAF mutation for DFS, respectively. In multivariable analyses, RAS and BRAF mutation were independent factors (RAS, HR = 1.808, 95% CI = 1.18-2.77, p = 0.007; BRAF, HR = 2.417, 95% CI = 1.32-4.41, p = 0.004). Old age was independent factor for OS (HR = 3.626, 95% CI = 1.09-12.00, p = 0.035). CONCLUSION: This study showed that oncologic outcomes might differ according to mutation burden characterized by RAS, BRAF, and MSI between synchronous CRC and solitary CRC. In addition, our systematic review highlighted a lack of data and much heterogeneity in genetic characteristics and survival outcomes of synchronous CRC relative to that of solitary CRC.

Different miRNAs Related to FBXW7 Mutations or High Mitotic Indices Contribute to Rectal Neuroendocrine Tumors: A Pilot Study.

Recent studies suggest that miRNA may be involved in the development of rectal neuroendocrine tumors (NETs). We explored the frequency of clinicopathologically relevant mutations and miRNA expression in rectal NETs to examine molecular profiles related to prognosis and behavior. Twenty-four eligible specimens with endoscopically excised rectal NETs were selected. Next-generation sequencing and an miRNA expression assay were used to evaluate the expression profile relevant to common genetic mutations in rectal NETs. Kyoto Encyclopedia of Genes and Genomes analysis predicted that the possible target signaling pathways were correlated with dysregulated miRNAs. Nineteen rectal NETs harbored more than one mutation in the 24 cancer-related genes. Seven miRNAs (hsa-miR-769-5p, hsa-miR-221-3p, hsa-miR-34a-5p, hsa-miR-181c-5p, hsa-miR-1246, hsa-miR-324-5p, and hsa-miR-361-3p) were significantly down-regulated in tumors harboring the FBWX7 mutation. Unsupervised hierarchical clustering analysis showed that up-regulation of these seven miRNAs may result in high mitotic indices, indicating the role of miRNAs in tumor progression. Among the down-regulated miRNAs, hsa-miR-769-5p was strongly correlated with extracellular matrix-receptor interaction and lysine degradation. Among the clinicopathological factors, up-regulated hsa-miR-3934-5p was linked to an increased mitotic count. No change in miRNA expression was associated with a tumor size >1 cm, lymphovascular invasion, or Ki-67 index. In summary, we identified different miRNA signatures involved in FBXW7 mutations or high mitotic indices in rectal NETs, which may play a critical role in tumor behavior.

Clinical and oncologic outcomes of laparoscopic versus open surgery in elderly patients with colorectal cancer: a retrospective multicenter study.

BACKGROUND: Laparoscopic surgery is commonly used in elderly patients over 80 years old. The purpose of this study was to compare the perioperative and oncologic outcomes between laparoscopic surgery and open surgery in elderly patients with colorectal cancer. METHODS: We retrospectively analyzed the medical records of patients aged ≥ 80 years who underwent curative resection of colorectal cancer at six Hallym University-affiliated hospitals. The perioperative outcomes and oncologic outcomes were compared between laparoscopic and open surgery RESULTS: Of 294 elderly patients, 104 (35.3%) underwent open surgery and 190 (64.7%) underwent laparoscopic surgery. The postoperative hospital stay (P = 0.019) and time to soft diet (P = 0.009) were shorter in the laparoscopic group than in the open group. Postoperative complications were less frequent in the laparoscopic group than in the open group (P < 0.001), including wound infection (P = 0.005), ileus (P = 0.005), and pneumonia (P = 0.001). The 3-year overall survival (OS) (P = 0.982) and recurrence-free survival rates (RFS) (P = 0.532) were similar in both groups. In multivariable analyses, positive lymph node status was the only independent factor associated with OS (P = 0.019) and RFS (P = 0.012). Laparoscopic surgery was not associated with OS (P = 0.874) and RFS (P = 0.772). CONCLUSION: Laparoscopic surgery offers several perioperative advantages over open surgery and similar long-term oncological outcomes for elderly patients with colorectal cancer. Therefore, we suggest that laparoscopic surgery can be safely performed for the treatment of elderly patients (≥ 80 years old) with colorectal cancer.

Clinical Significance of Lymph Node Metastasis in the Mesentery of the Terminal Ileum in Patients With Right-sided Colon Tumors at Different Locations.

BACKGROUND: There are limited reports on peri-ileal lymph node metastasis in patients with right-sided colon cancer, and little is known about their clinical significance. OBJECTIVE: This study aimed to examine the role of tumor location in the prevalence and clinical significance of peri-ileal lymph node metastasis in patients with right-sided colon cancer. DESIGN: This is a retrospective study from a prospective cohort database. SETTINGS: The study was conducted at a tertiary referral hospital. PATIENTS: Patients with right-sided colon cancer treated with radical surgery in a hospital between May 2006 and September 2016 were included. MAIN OUTCOME MEASURES: The frequency of peri-ileal lymph node metastasis in the study cohort and the role of tumor location and the clinical characteristics of patients with peri-ileal lymph node metastasis were determined. RESULTS: We examined 752 cases with right-sided colon cancer including 82 cecal, 554 ascending colon, and 116 hepatic flexure cancer. Twenty patients (2.7%) had peri-ileal lymph node metastasis. The incidence of metastasis to peri-ileal lymph nodes was 7.3% (6/82) in patients with cecal cancer, 2.2% (12/554) in patients with ascending colon cancer, and 1.7% (2/116) in patients with hepatic flexure cancer. Three patients had stage III cancer and 17 had stage IV. All 3 patients with positive peri-ileal lymph nodes and stage III cancer had cecal tumors. In contrast, all patients with ascending colon or hepatic flexure cancer and positive peri-ileal lymph nodes had stage IV cancer. LIMITATIONS: The results were limited by the retrospective design of the study and the small number of patients with peri-ileal lymph node metastasis. CONCLUSIONS: Peri-ileal lymph node metastasis was rare even in right-sided colon cancer and occurred mainly in stage IV. However, it occurred in some patients with locally advanced cecal cancer. These results suggest that optimal resection of the mesentery of the terminal ileum might have clinical benefit, especially in curative surgery for cecal cancer. See Video Abstract at http://links.lww.com/DCR/A556.

Is MRI of the Liver Needed During Routine Preoperative Workup for Colorectal Cancer?

BACKGROUND: The clinical efficacy of gadoxetic acid-enhanced liver MRI as a routine preoperative procedure for all patients with colorectal cancer remains unclear. OBJECTIVE: The purpose of this study was to evaluate the efficacy of preoperative gadoxetic acid-enhanced liver MRI for the diagnosis of liver metastasis in patients with colorectal cancer. DESIGN: This was a retrospective analysis from a prospective cohort database. SETTINGS: All of the patients were from a subspecialty practice at a tertiary referral hospital. PATIENTS: Patients who received preoperative gadoxetic acid-enhanced liver MRI after CT and attempted curative surgery for colorectal cancer were included. MAIN OUTCOME MEASURES: The number of equivocal hepatic lesions based on CT and gadoxetic acid-enhanced liver MRI and diagnostic use of the gadoxetic acid-enhanced liver MRI were measured. RESULTS: We reviewed the records of 690 patients with colorectal cancer. Equivocal hepatic lesions were present in 17.2% of patients based on CT and in 4.5% based on gadoxetic acid-enhanced liver MRI. Among 496 patients with no liver metastasis based on CT, gadoxetic acid-enhanced liver MRI detected equivocal lesions in 15 patients and metastasis in 3 patients. Among 119 patients who had equivocal liver lesions on CT, gadoxetic acid-enhanced liver MRI indicated hepatic lesions in 103 patients (86.6%), including 90 with no metastasis and 13 with metastasis. Among 75 patients who had liver metastasis on CT, gadoxetic acid-enhanced liver MRI indicated that the hepatic lesions in 2 patients were benign, in contrast to CT findings. The initial surgical plans for hepatic lesions according to CT were changed in 17 patients (3%) after gadoxetic acid-enhanced liver MRI. LIMITATIONS: This study was limited by its retrospective design. CONCLUSIONS: The clinical efficacy of gadoxetic acid-enhanced liver MRI as a routine preoperative procedure for all patients with colorectal cancer is low, in spite of its high diagnostic value for detecting liver metastasis. However, this study showed gadoxetic acid-enhanced liver MRI was helpful in characterizing equivocal hepatic lesions identified in CT and could lead to change in treatment plans for some patients. See Video Abstract at http://links.lww.com/DCR/A420.

Clinicopathologic features of gastric cancer with synchronous and metachronous colorectal cancer in Korea: are microsatellite instability and p53 overexpression useful markers for predicting colorectal cancer in gastric cancer patients?

BACKGROUND: A large-scale study was performed to identify the risk factors for developing synchronous and metachronous colorectal cancer (CRC) in gastric cancer (GC) patients, including microsatellite instability (MSI) and p53 overexpression. METHODS: A total of 1041 GC patients who underwent endoscopic resection or surgery and underwent colonoscopy simultaneously or during surveillance for GC were consecutively enrolled. Clinicopathologic characteristics, MSI, and p53 overexpression were compared between the GC patients with and those without synchronous and metachronous CRC. RESULTS: Of the 1041 patients, CRCs were detected in 67 (6.4 %) patients with GC. Forty-six (4.4 %) had synchronous CRC and 21 (2.0 %) had metachronous CRC. Univariate analysis indicated that age ≥63 years (P < 0.001), male sex (P = 0.005), and p53 overexpression (P = 0.040) were significantly associated with a higher incidence of CRC. However, body mass index, smoking, tumor location, tumor multiplicity, tumor histology, TNM stage, and MSI were not significantly associated with the incidence of CRC. Age ≥63 years (OR: 5.881; 95 % CI: 3.083-11.221; P < 0.001) and male sex (OR: 2.933; 95 % CI: 1.307-6.584; P = 0.009) were risk factors for CRC in GC patients according to multivariate analysis. CONCLUSIONS: GC patients who are male and/or ≥63 years old are recommended to receive colonoscopy to detect CRC. MSI and p53 overexpression were not useful molecular markers for predicting CRC in GC.

Factors associated with failure of enhanced recovery programs after laparoscopic colon cancer surgery: a single-center retrospective study.

BACKGROUND: Although enhanced recovery programs (ERPs) have been proven to be beneficial after laparoscopic colon surgery, they may result in adverse clinical outcomes following failure. This study analyzed risk factors associated with ERP failure after laparoscopic colon cancer surgery. METHODS: We analyzed the outcomes of 208 patients who underwent ERPs following laparoscopic colon cancer surgery between June 2007 and April 2013. The ERP included early oral feeding, early ambulation, and regular laxative administration. ERP failure was defined as postoperative hospital stay of more than 5 days related to postoperative complications, unplanned readmission within 30 days of surgery, or death. RESULTS: Surgical procedures included anterior resection (n = 101), right hemicolectomy (n = 90), and left hemicolectomy (n = 17). The mean postoperative hospital stay was 6.5 ± 2.3 days (range 3-24 days). ERP failure occurred in 36 patients (17.3%), with no mortality; reasons included ileus (n = 14), wound infection (n = 4), chylous drainage (n = 3), anastomotic bleeding (n = 3), pneumonia (n = 1), or readmission (n = 11) owing to delayed complications. Univariable analysis showed that ERP failure was associated with proximal colon cancer, side-to-side anastomosis, longer operation time, increased blood loss, and longer resected specimen length. Multivariable analysis showed that side-to-side anastomosis [odds ratio (OR) 4.534; 95% confidence interval (CI) 1.902-10.811; P = 0.001] and increased blood loss (OR 1.004; 95% CI 1.001-1.008; P = 0.041) were independent risk factors for ERP failure. CONCLUSIONS: We showed that increased blood loss and side-to-side anastomosis in comparison with end-to-end anastomosis were independent risk factors associated with ERP failure after laparoscopic colon cancer surgery. This suggests that intraoperative elements may be important determinants to obtain successful postoperative recovery in the era of ERP.

Effects of Preoperative Chemoradiotherapy on the Likelihood of Sphincter Preservation Surgery in Locally Advanced Distal Rectal Cancer: A Longitudinal Study Based on Pelvic Magnetic Resonance Imaging.

BACKGROUND: It is unclear whether preoperative chemoradiotherapy (pCRT) increases the rate of sphincter-preserving surgery (SPS), avoiding abdominoperineal resection (APR), for the treatment of distal rectal cancer. We examined whether pCRT increases the likelihood of SPS based on changes in tumor height using pelvic magnetic resonance imaging (MRI). METHODS: Between January 2009 and December 2013, 105 patients underwent long-course pCRT for locally advanced distal rectal cancer (≤5 cm from the anal verge) and were included in this study. The surgical procedures were analyzed in terms of radiologic findings, including the distance from the inferior margin of tumor to the superior margin of the anorectal ring (tumor height) measured by pelvic MRI before and after pCRT. RESULTS: Eighty-six (81.9 %) patients underwent SPS. Overall clinical downstaging occurred in 48 (45.7 %) patients. Tumor height increased significantly after pCRT (from 15.0 ± 15.3 to 18.1 ± 16.9 mm, change 3.1 ± 9.7 mm, p = 0.01). The mean change in tumor height was not significantly different between patients who underwent SPS or APR (mean change 3.3 ± 9.6 vs. 2.3 ± 10.5 mm, p = 0.68). The mean change was significantly greater in the double-stapled anastomosis group than in the handsewn anastomosis group (mean change 5.6 ± 9.9 vs. -0.6 ± 8.6 mm, p = 0.02). CONCLUSIONS: This was the first MRI-based longitudinal study to show that pCRT does not appear to increase the likelihood of SPS in locally advanced distal rectal cancer, although it could improve the potential of double-stapled anastomoses.

Cultural adaptation and validation of the Korean version of the EORTC QLQ-CR29 in patients with colorectal cancer.

PURPOSE: We aimed to evaluate the psychometric properties of the Korean version of the European Organization for Research and Treatment of Cancer (EORTC) Colorectal Cancer-Specific Quality of Life Questionnaire (QLQ-CR29), based on a sample of patients with colorectal cancer. METHODS: A total of 123 patients treated for colorectal cancer participated in the validation study. Test-retest reliability was assessed using intra-class correlations from a random sample. Internal consistency reliability was estimated using Cronbach's α coefficient. Convergent and discriminant validity was analyzed with multi-trait scaling. Clinical validity was assessed in terms of clinical differences using known-group comparisons. Concurrent validity was determined by correlations with the EORTC QLQ-C30, which was a generic core questionnaire to evaluate issues common to different cancer sites and treatments. RESULTS: The test-retest, administered to 35 patients, showed acceptable reproducibility (0.62-1.00) except the constipation scale of the QLQ-C30 (0.43). Cronbach's α coefficient (0.70-0.87) exceeded the 0.7 criterion. Multi-trait scaling analysis showed that multi-item scales met standards of convergent and discriminant validity. The known-group comparisons showed quality of life (QOL) differences between groups of patients based on tumor location, receipt of neoadjuvant therapy, and with/without a stoma. Correlations between the scales of the QLQ-CR29 and QLQ-C30 were low in most areas, whereas correlations in several areas with related content were higher. CONCLUSION: This study shows that the Korean version of the EORTC QLQ-CR29 is a reliable and valid tool for measuring QOL, as determined by application to a sample of Korean colorectal cancer patients.

Performance reporting design in artificial intelligence studies using image-based TNM staging and prognostic parameters in rectal cancer: a systematic review.

PURPOSE: The integration of artificial intelligence (AI) and magnetic resonance imaging in rectal cancer has the potential to enhance diagnostic accuracy by identifying subtle patterns and aiding tumor delineation and lymph node assessment. According to our systematic review focusing on convolutional neural networks, AI-driven tumor staging and the prediction of treatment response facilitate tailored treat-ment strategies for patients with rectal cancer. METHODS: This paper summarizes the current landscape of AI in the imaging field of rectal cancer, emphasizing the performance reporting design based on the quality of the dataset, model performance, and external validation. RESULTS: AI-driven tumor segmentation has demonstrated promising results using various convolutional neural network models. AI-based predictions of staging and treatment response have exhibited potential as auxiliary tools for personalized treatment strategies. Some studies have indicated superior performance than conventional models in predicting microsatellite instability and KRAS status, offer-ing noninvasive and cost-effective alternatives for identifying genetic mutations. CONCLUSION: Image-based AI studies for rectal can-cer have shown acceptable diagnostic performance but face several challenges, including limited dataset sizes with standardized data, the need for multicenter studies, and the absence of oncologic relevance and external validation for clinical implantation. Overcoming these pitfalls and hurdles is essential for the feasible integration of AI models in clinical settings for rectal cancer, warranting further research.

A Retrospective Multicenter Study of the Clinicopathological Characteristics and Prognosis of Young Adult Patients with Colorectal Cancer: Effects of Chemotherapy on Prognosis.

BACKGROUND: The objective of this study was to evaluate clinicopathologic features of young patients with colorectal cancer (CRC) and to compare their prognosis with those of older patients Methods: We retrospectively reviewed the medical records of patients who underwent surgery for stage 0-III CRC at four university-affiliated hospitals between January 2011 and December 2020. The patients were divided into two groups, the young adult group (≤45 years) and the older group (>45 years). RESULTS: Of 1992 patients, 93 (4.6%) were young adults and 1899 (95.3%) were older patients. Young patients showed more symptoms (p = 0.014) and more poorly or undifferentiated adenocarcinoma (p = 0.047) than older patients. The young adult patients were more likely to receive adjuvant chemotherapy (p < 0.001) and multidrug agents (p = 0.029), and less likely to cease chemotherapy (p = 0.037). The five-year RFS (recurrence-free survival) rate was better in the young adults than in the older patients (p = 0.009). In the multivariable analysis, young age was a significant prognostic factor for better RFS (p = 0.015). CONCLUSIONS: Young patients with CRC had more symptoms, aggressive histological features than older patients. They received more multidrug agents and discontinued chemotherapy less often, resulting in better prognosis.

Prognostic Value of Artificial Intelligence-Driven, Computed Tomography-Based, Volumetric Assessment of the Volume and Density of Muscle in Patients With Colon Cancer.

OBJECTIVE: The prognostic value of the volume and density of skeletal muscles in the abdominal waist of patients with colon cancer remains unclear. This study aimed to investigate the association between the automated computed tomography (CT)-based volume and density of the muscle in the abdominal waist and survival outcomes in patients with colon cancer. MATERIALS AND METHODS: We retrospectively evaluated 474 patients with colon cancer who underwent surgery with curative intent between January 2010 and October 2017. Volumetric skeletal muscle index and muscular density were measured at the abdominal waist using artificial intelligence (AI)-based volumetric segmentation of body composition on preoperative pre-contrast CT images. Patients were grouped based on their skeletal muscle index (sarcopenia vs. not) and muscular density (myosteatosis vs. not) values and combinations (normal, sarcopenia alone, myosteatosis alone, and combined sarcopenia and myosteatosis). Postsurgical disease-free survival (DFS) and overall survival (OS) were analyzed using univariable and multivariable analyses, including multivariable Cox proportional hazard regression. RESULTS: Univariable analysis showed that DFS and OS were significantly worse for the sarcopenia group than for the non-sarcopenia group (P = 0.044 and P = 0.003, respectively, by log-rank test) and for the myosteatosis group than for the non-myosteatosis group (P < 0.001 by log-rank test for all). In the multivariable analysis, the myosteatotic muscle type was associated with worse DFS (adjusted hazard ratio [aHR], 1.89 [95% confidence interval, 1.25-2.86]; P = 0.003) and OS (aHR, 1.90 [95% confidence interval, 1.84-3.04]; P = 0.008) than the normal muscle type. The combined muscle type showed worse OS than the normal muscle type (aHR, 1.95 [95% confidence interval, 1.08-3.54]; P = 0.027). CONCLUSION: Preoperative volumetric sarcopenia and myosteatosis, automatically assessed from pre-contrast CT scans using AI-based software, adversely affect survival outcomes in patients with colon cancer.

Differentiation of Adipose-Derived Stem Cells into Smooth Muscle Cells in an Internal Anal Sphincter-Targeting Anal Incontinence Rat Model.

OBJECTIVE: Studies on development of an anal incontinence (AI) model targeting smooth muscle cells (SMCs) of the internal anal sphincter (IAS) have not been reported. The differentiation of implanted human adipose-derived stem cells (hADScs) into SMCs in an IAS-targeting AI model has also not been demonstrated. We aimed to develop an IAS-targeting AI animal model and to determine the differentiation of hADScs into SMCs in an established model. MATERIALS AND METHODS: The IAS-targeting AI model was developed by inducing cryoinjury at the inner side of the muscular layer via posterior intersphincteric dissection in Sprague-Dawley rats. Dil-stained hADScs were implanted at the IAS injury site. Multiple markers for SMCs were used to confirm molecular changes before and after cell implantation. Analyses were performed using H&E, immunofluorescence, Masson's trichrome staining, and quantitative RT-PCR. RESULTS: Impaired smooth muscle layers accompanying other intact layers were identified in the cryoinjury group. Specific SMC markers, including SM22α, calponin, caldesmon, SMMHC, smoothelin, and SDF-1 were significantly decreased in the cryoinjured group compared with levels in the control group. However, CoL1A1 was increased significantly in the cryoinjured group. In the hADSc-treated group, higher levels of SMMHC, smoothelin, SM22α, and α-SMA were observed at two weeks after implantation than at one week after implantation. Cell tracking revealed that Dil-stained cells were located at the site of augmented SMCs. CONCLUSIONS: This study first demonstrated that implanted hADSc restored impaired SMCs at the injury site, showing stem cell fate corresponding to the established IAS-specific AI model.

Self-expandable metallic stents as a bridge to surgery in obstructive right- and left-sided colorectal cancer: a multicenter cohort study.

The insertion of a self-expandable metal stent (SEMS) has been proposed as an alternative to emergent surgery (ES) for obstructive colorectal cancer (CRC). We aimed to evaluate the perioperative and oncologic outcomes of SEMS as a bridge to surgery in obstructive CRC, as compared with ES. We retrospectively reviewed the medical records of patients who underwent curative resection of obstructive CRC at four Hallym University-affiliated hospitals between January 2010 and December 2019. All patients were analyzed overall colon, then according to the side of obstruction (overall, right or left). Of 167 patients, 52 patients underwent ES and 115 underwent SEMS insertion and surgery (SEMS group). The postoperative hospital stay and time to soft diet were shorter in the SEMS group than in the ES group for overall and both sided cancer. The SEMS group had lower rates of stoma formation and severe complications for overall and for left-sided cancer. The 5-year overall survival (P = 0.682) and disease-free survival (P = 0.233) rates were similar in both groups. SEMS insertion as a bridge to surgery was associated with faster recovery, a lower rate of stoma formation with similar oncologic outcomes to those of ES.

Exosomes Derived from Colon Cancer Cells Promote Tumor Progression and Affect the Tumor Microenvironment.

Cancer-cell-derived exosomes confer oncogenic properties in their tumor microenvironment and to other cells; however, the exact mechanism underlying this process is unclear. Here, we investigated the roles of cancer-cell-derived exosomes in colon cancer. Exosomes were isolated from colon cancer cell lines, HT-29, SW480, and LoVo, using an ExoQuick-TC kit, identified using Western blotting for exosome markers, and characterized using transmission electron microscopy and nanosight tracking analysis. The isolated exosomes were used to treat HT-29 to evaluate their effect on cancer progression, specifically cell viability and migration. Cancer-associated fibroblasts (CAFs) were obtained from patients with colorectal cancer to analyze the effect of the exosomes on the tumor microenvironment. RNA sequencing was performed to evaluate the effect of the exosomes on the mRNA component of CAFs. The results showed that exosome treatment significantly increased cancer cell proliferation, upregulated N-cadherin, and downregulated E-cadherin. Exosome-treated cells exhibited higher motility than control cells. Compared with control CAFs, exosome-treated CAFs showed more downregulated genes. The exosomes also altered the regulation of different genes involved in CAFs. In conclusion, colon cancer-cell-derived exosomes affect cancer cell proliferation and the epithelial-mesenchymal transition. They promote tumor progression and metastasis and affect the tumor microenvironment.

A Retrospective Multicenter Study of Risk Factors, Stratification, and Prognosis of Lymph Node Metastasis in T1 and T2 Colorectal Cancer.

BACKGROUND: The objective of this study was to compare the long-term prognosis of patients with T1 and T2 colorectal cancer (CRC) according to lymph node metastasis (LNM) and to identify risk factors for LNM. METHODS: We retrospectively reviewed patients who underwent curative resection for T1 or T2 CRC at five University-affiliated hospitals between January 2012 and December 2021. The patients were divided into several groups depending on the presence of LNM or the number of risk factors. RESULTS: Of the total 765 patients, 87 (11.3%) patients had LNM. These patients had poorer recurrence-free survival (RFS) than patients without LNM (72.6% vs. 88.6%). The multivariable analysis showed that high-grade tumors (p = 0.003), lymphovascular invasion (p < 0.001), and rectal location (p = 0.049) were independent predictors of LNM. When divided into groups according to the number of the three risk factors, the risk of LNM increased from 5.4% (ultralow-risk group; no risk factor) to 60.0% (high-risk group; all three risk factors) and the 5-year RFS rate decreased from 96.3% in the ultralow-risk group to 60% in the high-risk group (p < 0.001). CONCLUSION: Radical surgery should be considered for T1 and T2 CRC patients with these risk factors.

A systematic review of translation and experimental studies on internal anal sphincter for fecal incontinence.

The complexity in the molecular mechanism of the internal anal sphincter (IAS) limits preclinical or clinical outcomes of fecal incontinence (FI) treatment. So far, there are no systematic reviews of IAS translation and experimental studies that have been reported. This systematic review aims to provide a comprehensive understanding of IAS critical role in FI. Previous studies revealed the key pathway for basal tone and relaxation of IAS in different properties as follows; calcium, Rho-associated, coiled-coil containing serine/threonine kinase, aging-associated IAS dysfunction, oxidative stress, renin-angiotensin-aldosterone, cyclooxygenase, and inhibitory neurotransmitters. Previous studies have reported improved functional outcomes of cellular treatment for regeneration of dysfunctional IAS, using various stem cells, but did not demonstrate the interrelationship between those results and basal tone or relaxation-related molecular pathway of IAS. Furthermore, these results have lower specificity for IAS-incontinence due to the included external anal sphincter or nerve injury regardless of the cell type. An acellular approach using bioengineered IAS showed a physiologic response of basal tone and relaxation response similar to human IAS. However, in both cellular and acellular approaches, the lack of human IAS data still hampers clinical application. Therefore, the IAS regeneration presents more challenges and warrants more advances.

Recurrence-Free Survival Outcomes Based on Novel Classification Combining Lymphovascular Invasion, Perineural Invasion, and T4 Status in Stage II-III Colon Cancer.

Background: T4 tumor, lymphovascular invasion (LVI) and perineural invasion (PNI) are regarded as one of risk factors and associated with poor outcomes in colorectal cancer. The relationship between these three combined risk factors and the prognosis for colon cancer is not yet clear. The purpose of this study was to evaluate the prognostic value of combining the risk factors T4 tumor, LVI, and PNI in stage II-III colon cancer. Methods: Between January 2011 and December 2019, we retrospectively reviewed the medical records of patients who underwent curative resection for stage II-III colon cancer at four Hallym University-affiliated hospitals. These patients are categorized into three groups based on T4, LVI and PNI: no-risk group (no risk factors), low-risk group (one risk factor), and high-risk group (two or more risk factors). Results: Of 1684 patients, the incidence of no-, low-, and high-risk group were 49.3%, 32.6%, 18.0%, respectively. The median follow-up period was 48.9 months, and the 5-year recurrence-free survival (RFS) rate decreased from 78.5% to 58.7% as the number of risk factors increased (P < 0.001). Cox's proportional hazard regression models showed that T4 (P < 0.001), LVI (P = 0.043), and PNI (P = 0.018) were independent prognostic factors for poor RFS. In subgroup analysis in stage II colon cancer, patients with one or more risk factors showed the better 5-year RFS rate when they received adjuvant chemotherapy than in those who did not (P < 0.001). Poor/mucinous differentiation, obstruction, and lymph-node positivity were independent predictors in the high risk group. Conclusion: The present study showed the histological combination of LVI, PNI, and T4 indicates a poor prognosis for RFS in patients with stage II-III colon cancer. Therefore, patients with one of these risk factors should be considered for chemotherapy and have close follow-up.

Comparison of oncologic outcomes between patients with Lynch syndrome and sporadic microsatellite instability-high colorectal cancer.

PURPOSE: Long-term oncologic differences in outcome between groups of patients with Lynch syndrome (LS) colorectal cancer (CRC) and sporadic CRC with microsatellite instability-high (MSI-H) are the focus of investigation in the current study. METHODS: Patients registered in the Korean Hereditary Tumor Registry and 2 tertiary referral hospitals treated for stage I-III CRC between 2005 and 2015 were retrospectively analyzed. Detection for both groups was performed using pedigree, microsatellite instability, and mismatch repair (MMR) gene testing. Multivariate analyses for overall survival (OS) and disease-free survival (DFS) were conducted. RESULTS: Cases of LS (n = 77) and sporadic CRC with MSI-H (n = 96) were identified. LS CRC patients were younger in age and displayed tumor sidedness, typically involving left-sided colon and rectum, compared to patients with sporadic CRC with MSI-H. OS and DFS were lower for LS CRC relative to CRC with MSI-H (OS, 72.7% vs. 93.8%, P = 0.001; DFS, 71.4% vs. 88.5%, P = 0.001). In multivariate analyses, tumor sidedness, stage, and chemotherapy were independent factors for OS and DFS. LS CRC was a prognostic factor for poorer OS (hazard ratio, 2.740; 95% confidence interval, 1.003-7.487; P = 0.049), but not DFS. CONCLUSION: Our findings indicate that LS CRC is associated with poorer outcomes compared to sporadic CRC with MSI-H, presenting distinct clinical features. In view of the current lack of knowledge on genetic and molecular mechanisms, appropriate management taking into consideration the difficulty of identification of CRC with hypermutable tumors harboring heterogeneity is essential.