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Introduction: Colon cancer is the second most common cause of death in the United States. With an increasing number of patients diagnosed at younger ages, the disease remains a significant burden. However, recent data on early onset patients admitted with colon cancer are still limited. Methods: We utilized the 2016 to 2021 National Inpatient Sample to investigate trends and characteristics of colon cancer hospitalizations. Nonelective participants were divided into early onset and normal-age groups, with a cut point of 50 years old. In addition, we also investigated factors associated with the risk of inpatient mortality in the study population. Results: There were 26,903 early onset nonelective colon cancer hospitalizations in the population group, amounting to 11.91% of total colon cancer hospitalizations. No significant changes or trends were seen from 2016 to 2021. Compared to the normal-age population group, there was a disproportionate number of Blacks, Hispanics, and Asian Americans, as well as those with obesity and tobacco usage. Conclusion: Some demographic factors and comorbidities disproportionately affect early onset colon cancer patients when compared to the normal-age population group. Further investigations are necessary to combat the growing incidence of early onset colon cancer. [ABSTRACT FROM AUTHOR]

Objective: This large database study assessed whether extended pharmacologic prophylaxis for venous thromboembolism after colon cancer resection was associated with improved oncologic survival. Background: Heparin derivatives may confer an antineoplastic effect via a variety of mechanisms (eg, inhibiting angiogenesis in the tumor microenvironment). Studies evaluating the oncologic benefit of heparin and its derivatives have been limited in postsurgical patients. Multiple society guidelines recommend consideration of 30-day treatment with low molecular weight heparin to reduce venous thromboembolism risk after abdominopelvic cancer surgery. However, utilization of extended prophylaxis remains low. Methods: Surveillance, Epidemiology, and End Results-Medicare data were used to identify patients (age 65+) undergoing resection for nonmetastatic colon cancer from 2016 to 2017. The primary outcomes were overall and cancer-specific survival. Log-rank testing and multivariable Cox regression compared survival in patients who received extended prophylaxis versus those who did not in an inverse propensity treatment weighted cohort. Results: A total of 20,102 patients were included in propensity-weighting and analyzed. Eight hundred (3.98%) received extended pharmacologic prophylaxis. Overall survival and cancer-specific survival were significantly higher in patients receiving prophylaxis on log-rank tests (P=0.0017 overall, P= 0.0200 cancer-specific). Multivariable Cox regression showed improved overall survival [adjusted hazard ratio 0.66 (0.56-0.78)] and cancer-specific survival [adjusted hazard ratio 0.56 (0.39-0.81)] with prophylaxis after controlling for patient, treatment, and hospital factors. Conclusions: Extended pharmacologic prophylaxis after colon cancer resection was independently associated with improved overall and cancer-specific survival. These results suggest a potential antineoplastic effect from heparin derivatives when used in the context of preventing postsurgical venous thromboembolism. [ABSTRACT FROM AUTHOR]

Despite advances in diagnosis and treatment, racial disparities continue to exist in colorectal cancer (CRC) survival. This study aims to characterize the CRC survival differences among racial and ethnic minority groups. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify adults diagnosed with CRC from 2015 to 2019. Demographics, disease characteristics, surgical treatment, stages, and survival data for individuals who are Hispanic, Black, Southeast Asian, Chinese, American Indian and Alaskan Native (AIAN), Asian Indian and Pakistani (AIP), and Native Hawaiian and Other Pacific Islanders (NHOPI) were extracted. Survival analysis was done using the Kaplan-Meier survival curve. Multivariate analysis was done with the Cox proportional hazard model. There were 40 091 individuals with CRC. NHOPI had the youngest median age of 59 years, while Chinese individuals had the oldest median age of 65 years. From the total sample of their respective subgroups, 43.8% of Black patients and 36.7% of AIAN patients had a median household income of <$60 000, while 55.3% of Southeast Asian patients, 59.7% of Chinese patients, 55.8% of AIP patients, and 65.6% of NHOPI patient had a median household income >$70 000. The 1-year survival rate was lower for patients who were Hispanic (62.0%), Black (60.9%), and AIAN (63.1%). Even after multivariate analysis, Black patients had a significant hazard ratio (HR) of 1.21 (95% confidence interval [95% CI]: 1.05-1.38), while AIP had a HR of 0.68 (95% CI 0.55-0.84), compared to AIAN. Other significant variables that were linked with survival included older age, advanced stage of CRC, a median household income <$60 000, male sex, no surgery, subtotal colectomy/hemicolectomy, and total colectomy. Further studies are needed to elucidate the specific causes of these differences and create appropriate strategies to reduce this survival disparity. [ABSTRACT FROM AUTHOR]

Colonoscopy often is recommended after an episode of diverticulitis to exclude missed colorectal cancer (CRC). This is a controversial recommendation based on limited evidence. We estimated the prevalence and odds of CRC and advanced colorectal neoplasia on colonoscopy in patients with diverticulitis compared with CRC screening. Using data from the Gastrointestinal Quality Improvement Consortium registry, we performed a cross-sectional study with patients ≥40 years old undergoing outpatient colonoscopy for an indication of diverticulitis follow-up evaluation or CRC screening. The primary outcome was CRC. The secondary outcome was advanced colorectal neoplasia. Odds ratios (ORs) and 95% CIs were calculated. We identified 4,591,921 outpatient colonoscopies performed for screening and 91,993 colonoscopies for diverticulitis follow-up evaluation. CRC prevalence was 0.33% in colonoscopies for screening and 0.31% in colonoscopies for diverticulitis. Compared with screening, patients with diverticulitis were less likely to have CRC (adjusted OR, 0.84; 95% CI, 0.74–0.94). CRC prevalence decreased to 0.17% in colonoscopies performed for diverticulitis only. Compared with screening, patients with diverticulitis as the only indication were less likely to have CRC (adjusted OR, 0.49; 95% CI, 0.36–0.68). CRC prevalence increased to 1.43% in patients with complicated diverticulitis. Compared with screening, patients with complicated diverticulitis were more likely to have CRC (adjusted OR, 3.57; 95% CI, 1.59–8.01). The risk of CRC cancer is low in most patients with diverticulitis. Patients with complicated diverticulitis are the exception. Our results suggest that colonoscopy to detect missed CRC should include diverticulitis patients with a complication and those not current with CRC screening. [Display omitted] [ABSTRACT FROM AUTHOR]

Distant metastasis to the spleen is extremely rare. To the best of our knowledge, metastasis to the accessory spleen based on pathological findings has only been reported in four patients in the English literature, including one each of ovarian cancer, transitional cell carcinoma, breast cancer, and uterine carcinosarcoma after surgery. Furthermore, among these reported cases, only two reports (one each of transitional cell carcinoma and uterine carcinosarcoma) presented imaging findings. In this study, we report a case of colon cancer metastasis to the accessory spleen without involvement of the spleen in a 58-year-old male patient, providing imaging findings. This case emphasized the importance of considering the possibility of metastasis to the accessory spleen in patients with malignancy. [ABSTRACT FROM AUTHOR]

Nutrient availability is a key determinant of tumor cell behavior. While nutrient‐rich conditions favor proliferation and tumor growth, scarcity, and particularly glutamine starvation, promotes cell dedifferentiation and chemoresistance. Here, linking ribosome biogenesis plasticity with tumor cell fate, we uncover that the amino acid sensor general control non‐derepressible 2 (GCN2; also known as eIF‐2‐alpha kinase 4) represses the expression of the precursor of ribosomal RNA (rRNA), 47S, under metabolic stress. We show that blockade of GCN2 triggers cell death by an irremediable nucleolar stress and subsequent TP53‐mediated apoptosis in patient‐derived models of colon adenocarcinoma (COAD). In nutrient‐rich conditions, a cell‐autonomous GCN2 activity supports cell proliferation by stimulating 47S rRNA transcription, independently of the canonical integrated stress response (ISR) axis. Impairment of GCN2 activity prevents nuclear translocation of methionyl‐tRNA synthetase (MetRS), resulting in nucleolar stress, mTORC1 inhibition and, ultimately, autophagy induction. Inhibition of the GCN2–MetRS axis drastically improves the cytotoxicity of RNA polymerase I (RNA pol I) inhibitors, including the first‐line chemotherapy oxaliplatin, on patient‐derived COAD tumoroids. Our data thus reveal that GCN2 differentially controls ribosome biogenesis according to the nutritional context. Furthermore, pharmacological co‐inhibition of the two GCN2 branches and RNA pol I activity may represent a valuable strategy for elimination of proliferative and metabolically stressed COAD cells. [ABSTRACT FROM AUTHOR]

Curcumin-loaded polypropylene/rice husk/SiO 2 composites were fabricated with tunable nano-SiO 2 filler loadings (0–10 wt%) via melt-blending and injection molding. XRD analysis revealed effective intercalation of nanoparticles and interaction with the polymer chains up to 6 wt% loading. Incorporation of SiO 2 fillers significantly enhanced mechanical strength with 6 % nano-SiO 2 formulation demonstrating 27 % higher tensile strength, 52 % increased flexural modulus and 51 % greater impact resistance. The silica nanoparticles also reduced heat release rate through protective charring and decreased moisture absorption by over 8 % due to hydrophilic surface groups. In vitro studies showed that curcumin nano-composites with 6 % nano-SiO 2 exhibited maximal cytotoxicity against HT-29 and HCT-116 colon cancer cells with CC50 values of 12.4±1.1 μg/ml and 10.3±0.9 μg/ml respectively, attributed to optimal drug release profile. The formulation arrested 22.1% cells in sub-G1 phase inducing apoptosis. Oral administration in tumor-bearing mice led to 3-fold increase in plasma exposure (Cmax 186±14 ng/ml) and relative bioavailability versus free curcumin, indicating capacity to evade presystemic clearance. The composites also enabled 3 times higher tumor accumulation highlighting potential for targeted colorectal cancer therapy via improved pharmacokinetics and site-specific action. Overall, precise tuning of nanostructured fillers augments mechanical and transport properties while potentiating anticancer performance. [ABSTRACT FROM AUTHOR]

Inefficient drug penetration hurdled by the stroma in the tumor tissue leads to a diminished therapeutic effect for drugs and a reduced infiltration level of immune cells. Herein, we constructed a PEGylated dendritic epirubicin (Epi) prodrug (Epi-P4D) to regulate the metabolism of cancer-associated fibroblasts (CAFs), thus enhancing Epi penetration into both multicellular tumor spheroids (MTSs) and tumor tissues in mouse colon cancer (CT26), mouse breast cancer (4T1) and human breast cancer (MDA-MB-231) models. Enhanced cytotoxicity against CT26 MTSs and remarkable antitumor efficacy of Epi-P4D were ascribed to reduced fibronectin, α -SMA, and collagen secretion. Besides, thinning of the tumor tissue stroma and efficient eradication of tumor cells promoted the immunogenic cell death effect for dendritic cell (DC) maturation and subsequent immune activation, including elevating the CD4+ T cell population, reducing CD4+ and CD8+ T cell hyperactivation and exhaustion, and amplifying the natural killer (NK) cell proportion and effectively activating them. As a result, this dendritic nanomedicine thinned the stroma of tumor tissues to enhance drug penetration and facilitate immune cell infiltration for elevated antitumor efficacy. A dendritic polymer-based nanomedicine was constructed to disturb the amino acid metabolism of cancer-associated fibroblasts for enhancing Epi penetration, boosting tumor immune cell infiltration, and elevating its therapeutic effect. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: This study aimed to identify risk criteria available before the point of treatment initiation that can be used to stratify the risk of obstruction in patients undergoing neoadjuvant chemotherapy (NAC) for high-risk colon cancer. Background: Global implementation of NAC for colon cancer, informed by the FOxTROT trial, may increase the risk of bowel obstruction. Methods: A case-control study, nested within an international randomized controlled trial (FOxTROT; ClinicalTrials.gov: NCT00647530). Patients with high-risk operable colon cancer (radiologically staged T3-4 N0-2 M0) that were randomized to NAC and developed large bowel obstruction were identified. First, clinical outcomes were compared between patients receiving NAC in FOxTROT who did and did not develop obstruction. Second, obstructed patients (cases) were age-matched and sex-matched with patients who did not develop obstruction (controls) in a 1:3 ratio using random sampling. Bayesian conditional mixed-effects logistic regression modeling was used to explore clinical, radiologic, and pathologic features associated with obstruction. The absolute risk of obstruction based on the presence or absence of risk criteria was estimated for all patients receiving NAC. Results: Of 1053 patients randomized in FOxTROT, 699 received NAC, of whom 30 (4.3%) developed obstruction. Patients underwent care in European hospitals including 88 UK, 7 Danish, and 3 Swedish centers. There was more open surgery (65.4% vs 38.0%, P=0.01) and a higher pR1 rate in obstructed patients (12.0% vs 3.8%, P= 0.004), but otherwise comparable postoperative outcomes. In the case-control-matched Bayesian model, 2 independent risk criteria were identified: (1) obstructing disease on endoscopy and/or being unable to pass through the tumor [adjusted odds ratio: 9.09, 95% credible interval: 2.34-39.66] and stricturing disease on radiology or endoscopy (odds ratio: 7.18, 95% CI: 1.84-32.34). Three risk groups were defined according to the presence or absence of these criteria: 63.4% (443/698) of patients were at very low risk (<1%), 30.7% (214/698) at low risk (<10%), and 5.9% (41/698) at high risk (>10%). Conclusions: Safe selection for NAC for colon cancer can be informed by using 2 features that are available before treatment initiation and identifying a small number of patients with a high risk of preoperative obstruction. [ABSTRACT FROM AUTHOR]

Objective: To create a recurrence prediction value (RPV) of high-risk factor and identify the patients with high risk of cancer recurrence. Background: There are several high-risk factors known to lead to poor outcomes. Weighting each high-risk factor based on their association with increased risk of cancer recurrence can provide a more precise understanding of risk of recurrence. Methods: We performed a multi-institutional international retrospective analysis of patients with stage II colon cancer patients who underwent surgery from 2010 to 2020. Patient data from a multi-institutional database were used as the Training data, and data from a completely separate international database from 2 countries were used as the Validation data. The primary endpoint was recurrence-free survival. Results: A total of 739 patients were included from Training data. To validate the feasibility of RPV, 467 patients were included from Validation data. Training data patients were divided into RPV low (n =564) and RPV high (n= 175). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low [hazard ratio (HR) 2.628; 95% confidence interval (CI) 1.887-3.660; P< 0.001). Validation data patients were divided into 2 groups (RPV low, n =420) and RPV high (n=47). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (HR 3.053; 95% CI 1.962-4.750; P<0.001). Conclusions: RPV can identify stage II colon cancer patients with high risk of cancer recurrence worldwide. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinase 9 (MMP‐9) is a member of the MMP family and has been recently identified as a nuclear protease capable of clipping histone H3 N‐terminal tails (H3NT). This MMP‐9‐dependent H3NT proteolysis is critical for establishing an active state of gene transcription during osteoclast differentiation and melanoma development. However, whether H3NT cleavage by MMP‐9 plays a similar role in other cellular events has not been explored. Here, we dissect the functional contribution of MMP‐9‐dependent H3NT clipping to colonic tumorigenesis by using a combination of genome‐wide transcriptome data, ChIP/ChIPac‐qPCR, CRISPR/dCas9 gene‐targeting system, and in vivo xenograft models. We show that MMP‐9 is overexpressed in colon cancer cells and catalyzes H3NT proteolysis to drive transcriptional activation of growth stimulatory genes. Our studies using knockdown and inhibition approaches clearly indicate that MMP‐9 mediates transcriptional activation and promotes colonic tumorigenesis in a manner dependent on its protease activity toward H3NT. Remarkably, artificial H3NT proteolysis at target gene promoters with dCAS9‐MMP‐9 is sufficient for establishing their transcriptional competence in colon cancer cells, underscoring the importance of MMP‐9‐dependent H3NT proteolysis per se in the transactivation process. Our data establish new functions and mechanisms for MMP‐9 in driving the oncogenic transcription program in colon cancer through H3NT proteolysis, and demonstrate how this epigenetic pathway can be exploited as a potential therapeutic target for cancer treatment. [ABSTRACT FROM AUTHOR]

Clostridioides difficile infection (CDI) burdens hospitalized patients, particularly those with comorbidities. Colon cancer may worsen CDI severity and outcomes. We aimed to assess CDI outcomes in hospitalized colon cancer patients. A retrospective analysis of 2016 to 2020 National Inpatient Survey data identified adults with CDI, categorized by the presence of colon cancer. Hospitalization characteristics, comorbidities, and outcomes were compared between groups. Primary outcomes included in-hospital mortality, length of stay, and total hospital charges. The secondary outcomes were CDI complications. Multivariate logistic regression analysis was performed, with P values ≤0.05 indicating statistical significance. Among 1,436,860 CDI patients, 14,085 had colon cancer. Patients with colon cancer had a longer length of stay (10.77 vs 9.98 days; P < 0.001). After adjustment for confounders, colon cancer patients exhibited higher odds of acute peritonitis (adjusted odds ratio [aOR] 2.37; P = 0.009), bowel perforation (aOR 5.49; P < 0.001), paralytic ileus (aOR 2.12; P = 0.003), and colectomy (aOR 36.99; P < 0.001), but lower risks of mortality, sepsis, septic shock, acute kidney injury, cardiac arrest, and mechanical ventilation (all P < 0.001). Colon cancer significantly impacts CDI outcomes in hospitalized patients, highlighting the need for improved management strategies to reduce morbidity and mortality. [ABSTRACT FROM AUTHOR]

Tissue culture techniques were used to produce large amounts of bioactive compounds with medicinal potential, overcoming space and time constraints for cancer prevention. Rice callus suspension cultures (RCSC) and seed extracts prepared from aromatic rice varieties were used to evaluate the cytotoxic impact on human colon and lung cancer cell lines, as well as a normal control cell line, using Taxol as a positive control. RCSC and seed extracts from two Indian aromatic rice varieties were applied at different concentrations to treat the cancer cell lines and normal lung fibroblasts over varying time intervals. Apoptosis was assessed in 1:5 dilutions of the A549 and HT-29 cell lines treated with RCSC for 72 h, using propidium iodide staining and flow cytometry. RCSC showed a more potent cytotoxic effect than seed extracts with minimal effect on the normal cell line, in contrast to Taxol. Confocal microscopy and flow cytometry further confirmed the apoptotic effect of RCSC. Gas chromatography-mass spectrometry-based metabolic profiling identified metabolites involved in cytotoxicity and highlighted altered pathways. RCSC is proposed as an alternative source for the development of novel anticancer drugs with reduced side effects. [ABSTRACT FROM AUTHOR]

Introduction: Tumor budding (TB) is considered to be a morphological and prognostic factor relevant to colon cancer (CC). The aim of our study is to assess the TB and to evaluate its relationship to clinicopathological findings within stage II and III CC patients as a single center experience. Materials and methods: A total of 120 CC patients operated between 2018 and 2021 at the University Clinic of Digestive Surgery in Skopje, the Republic of North Macedonia were included in this retrospective, single center study. TB was evaluated by the magnification of 200x along the invasive front of the primary tumor on H&E and CKAE1/AE3 immunohistochemically stained sections. Two grades were used: low grade (TB1, 0-4 TBs) and high-grade, which includes intermediate (TB2, 5-9 TBs) and high grade (TB3 ≥10TBs) of TBs. Results: A statistically significant correlation has been identified between high-grade TB and age (p=0.05) of the patients. There was also a significantly higher occurrence of high-grade TB in patients within stage III CC. Statistically significant correlations were also found in lymph node status (p<0.01), vascular invasion (p<0.05), lymphatic invasion (p<0.01), postoperative relapse (p<0.01), and death (p<0.01). Tumor relapse and death were significantly more frequent in patients with high-grade TB than those with low-grade TB. Patients with registered high-grade TB demonstrated significantly lower relapse-free survival (RFS) and overall survival (OS) rates than patients with low-grade TB over the observation period (RFS: 53.8% vs. 98.5%, p<0.001; OS: 65.4% vs. 97.1%, p<0.001, respectively). Patients with lung and liver postoperative relapses had higher percentage of cases with high-grade TB (94.1%). Conclusion: Our results are highly suggestive that TB should be included as a histological biomarker in the pathology report of patients with stage II and stage III CC, because of its prognostic value. [ABSTRACT FROM AUTHOR]

Immunogenic dying tumor cells hold promising prospects as cancer vaccines to activate systemic immunity against both primary and metastatic tumors. Especially, X-ray- induced dying tumor cells are rich in highly immunogenic tumor-associated antigens and self-generated dsDNA as potent adjuvants. However, we found that the X-ray induction process can result in the excessive exposure of phosphatidylserine in cancer vaccines, which can specifically bind with the MerTK receptor on macrophages, acting as a "checkpoint" to facilitate immune silence in the tumor microenvironment. Therefore, we developed a novel strategy combining X-ray-induced cancer vaccines with UNC2250, a macrophage MerTK "checkpoint inhibitor," for treating peritoneal carcinomatosis in colon cancer. By incorporating UNC2250 into the treatment regimen, immunosuppressive efferocytosis of macrophages, which relies on MerTK-directed recognition of phosphatidylserine on vaccines, was effectively blocked. Consequently, the immune analysis revealed that this combination strategy promoted the maturation of dendritic cells and M1-like repolarization of macrophages, thereby simultaneously eliciting robust adaptive and innate immunity. This innovative approach utilizing X-ray-induced vaccines combined with a checkpoint inhibitor may provide valuable insights for developing effective cancer vaccines and immunotherapies targeting colon cancer. Frozen dying tumor cells (FDT) combined with efferocytosis inhibitors can mobilize dendritc cells and macrophages simultaneously, thereby eliciting robust innate and adaptive immunity against peritoneal carcinomatosis in colon cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

In this research, a novel biogenic strategy for decoration of silver nanoparticles (Ag NPs) on metal-organic frameworks (MOF) was suggested. The proposed protocol depended upon using of propolis as a green reducing agent for immobilization of Ag NPs on MOF. The XRD and SEM analyses were employed to identify the crystallinity and morphology of the fabricated MOF@Ag material, respectively. The MOF@Ag was utilized as an effective catalyst for the catalytic hydrogenation of 4-nitrophenol as a toxic pollutant using potassium borohydride. 4-Nitrophenol was completely reduced in 50 s, as confirmed by UV-Vis experiments. The relationship between the ln(A t /A 0) and reaction time was found to be linear, indicating that the reduction of 4-nitrophenol with the MOF@Ag nanocatalyst followed a pseudo-first-order kinetic. In addition, the green prepared nanocomposite exhibits consistent catalytic activity for a minimum of five cycles in the hydrogenation of target pollutant. The study also explored the anti-cancer property of the MOF@Ag on the common human colon cancer cell lines (HT-29 and HCT-116). The MTT assay studies on cell viability indicated that the MOF@Ag exhibited notable cytotoxicity versus colon cancer. The MOF@Ag composite fabricated in this study have proven to be efficient in the scopes of water purification and cancer therapy. [Display omitted] • Novel green strategy was proposed for decoration of Ag NPs on porous MOF support. • Remarkable catalytic property towards 4-nitrophenol reduction was obtained using the MOF@Ag. • The fabricated MOF@Ag illustrated a notable anti-cancer property versus colon cancer cell lines. [ABSTRACT FROM AUTHOR]

Background: Robotic surgery has been a revolution for colon cancer (CC) patients, with the increasing availability of different competitive robotic systems, but evidence of relevant oncologic outcomes is indeed scarce. Our goal was to compare the surgical quality and short-term oncologic outcomes of the Kangduo Surgical Robotic System and the da Vinci Si Robotic System in patients with CC. Methods: These are results from a subcohort of a multicenter randomized controlled noninferiority trial performed in three centers in China. Enrolled patients were randomly assigned to undergo surgery using either the KD-SR-01 system (KD group) or the da Vinci Si (DV) robotic system(DV group). Neither investigators nor patients weremasked to treatment allocation, but assessment of pathological outcomes was masked to treatment allocation. The primary endpoint was surgical success rate. The secondary endpoints were surgical outcomes, pathologic outcomes, and postoperative outcomes. The study is registered at www.chictr.org.cn (ChiCTR22000 63172). Although the long-term follow-up results were not a predefined endpoint for this study, late-stage work is in progress. Results: A total of 58 CC patients were included in this study, 28 in the KD group and 30 in the DV group. All patients were successfully operated without any intermediate open/conventional laparoscopic surgery and the success rate of surgery was 100%. Assessment of equipment docking task load and intraoperative operating sensation score were similar between the two groups. Adverse events and Clavien--Dindo grade II or higher grade complication rates were comparable between the two groups. Device arm docking time, robotic arm operation time, and intraoperative bleeding were not significantly different between the two groups. Similar results were obtained from postoperative pathological outcomes and internal environment indexes. Conclusions: The efficacy and safety of the Kangduo Robotic Surgical System has been proved, operation of the Kangduo Robotic System by experienced surgeons for CC is not less effective than the da Vinci robotic System. [ABSTRACT FROM AUTHOR]

Sulfation is a crucial and prevalent conjugation reaction involved in cellular processes and mammalian physiology. 3′-Phosphoadenosine 5′-phosphosulfate (PAPS) synthase 2 (PAPSS2) is the primary enzyme to generate the universal sulfonate donor PAPS. The involvement of PAPSS2-mediated sulfation in adenomatous polyposis coli (APC) mutation-promoted colonic carcinogenesis has not been reported. Here, we showed that the expression of PAPSS2 was decreased in human colon tumors along with cancer stages, and the lower expression of PAPSS2 was correlated with poor prognosis in advanced colon cancer. Gut epithelial-specific heterozygous Apc deficient and Papss2 -knockout (Apc Δgut-Het Papss2 Δgut) mice were created, and the phenotypes were compared to the spontaneous intestinal tumorigenesis of Apc Δgut-Het mice. Apc Δgut-Het Papss2 Δgut mice were more sensitive to gut tumorigenesis, which was mechanistically accounted for by the activation of Wnt/ β -catenin signaling pathway due to the suppression of chondroitin sulfation and inhibition of the farnesoid X receptor (FXR)-transducin-like enhancer of split 3 (TLE3) gene regulatory axis. Chondroitin sulfate supplementation in Apc Δgut-Het Papss2 Δgut mice alleviated intestinal tumorigenesis. In summary, we have uncovered the protective role of PAPSS2-mediated chondroitin sulfation and bile acids–FXR–TLE3 activation in the prevention of gut carcinogenesis via the antagonization of Wnt/ β -catenin signaling. Chondroitin sulfate may be explored as a therapeutic agent for Papss2 deficiency-associated colonic carcinogenesis. Intestinal PAPSS2 or sulfation represents a potential therapeutic target for colon cancer and chondroitin sulfate may be explored for its use in the prevention and treatment of PAPSS2 deficiency-associated colon cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: To determine long-term survival in patients undergoing robot-assisted surgery (RAS) or laparoscopic surgery (LAS) for colon cancer. Background: The potential long-term benefits of RAS compared with LAS for colon cancer are not well examined. Using a register-based approach, we aimed to compare these 2 surgical platforms in an analysis of long-term outcomes, including recurrence-free survival and all-cause- and colon cancer-specific mortality. Methods: A nationwide register-based cohort study of patients with Union for International Cancer Control stage I-III colon cancer undergoing planned RAS or LAS from 2010 through 2018. Patient demographic, clinical, and pathological data were retrieved from Danish national registers. Survival and recurrence rates were estimated by Cox proportional hazard multivariate regression analysis adjusting for baseline covariates. Results: A total of 7565 patients [LAS = 6905 (91%) and RAS = 660 (9%)] were included in the complete case survival analysis. Patients undergoing LAS had a significantly increased risk of cancer recurrence [LAS = 1178 (17.1%), RAS = 82 (12.4%), P = 0.002] with a mean follow-up time of 4.93 years (standard deviation 2.47). The survival analysis of recurrence-free survival favored RAS [hazard ratioadjusted = 0.80, 95% CI (0.64-1.00), P = 0.049]. No associations between the 2 surgical platforms were evident regarding all-cause [hazard ratioadjusted = 0.98, 95% CI (0.82-1.17), P = 0.783] or colon cancer-specific mortality [hazard ratioadjusted = 0.89, 95% CI (0.67-1.18), P = 0.405]. Conclusions: Adopting RAS for colon cancer was associated with improved recurrence-free survival. However, it did not cause a lower all-cause- or colon cancer-specific mortality. [ABSTRACT FROM AUTHOR]

Combination immunotherapy strategies targeting OX40, a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation, differentiation, and effector function of tumor-infiltrating T cells, have attracted much attention for their excellent therapeutic effects. In this study, we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core virus-like particles (HBc VLPs) therapy using a mouse colon cancer model. Humanized B-hOX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-hOX40 antibody. Tumor growth was monitored. Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors. The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth, suggesting that a potent antitumor immunity was induced by the combination therapy. Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells (Teffs) and a significant decrease in regulatory T cells (Tregs) in the tumor microenvironment (TME), which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs. Combination therapy of anti-hOX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice, which may represent a potential design strategy for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA) is involved in diverse biological and physiological processes of tumors. Dysregulation of miRNA will induce a series of human diseases. miR-129-2-3p has vital effects in the pathogenesis of various tumors. However, the regulatory function of miR-129-2-3p in colon cancer remains to be clarified. This study investigated the role of miR-129-2-3p targeting BZW1 in proliferation, apoptosis, migration, and invasion of colon cancer. Here, RT-qPCR was applied to measure the miR-129-2-3p levels in colon cancer tissues. The predicted targets of miR-129-2-3p were identified by bioinformatics and verified using luciferase reporter assay. The effects of miR-129-2-3p on colon cancer were detected by CCK-8, colony formation, transwell chamber test, wound healing, and flow cytometry assays. Finally, the influence of miR-129-2-3p on tumor growth was studied. Nude mice were xenografted with transfected Lovo cells by subcutaneous injection of 5 × 105 cells in 100 µl. HE staining and TUNEL were used to assess metastasis ability. miR-129-2-3p level in colon cancer tissue was significantly reduced. Furthermore, it was verified that BZW1 was a target of miR-129-2-3p, and its expression in colon cancer cells was inhibited by miR-129-2-3p. Additionally, miR-129-2-3p inhibited colon cancer cell proliferation, colony formation, mobility ability and tumor growth, and promoted cell apoptosis by targeting BZW1. miR-129-2-3p overexpression in tumor xenografts in vivo decreased BZW1 expression, and suppressed tumor growth. Collectively, these findings indicated that miR-129-2-3p exerts a suppressive role in colon cancer cells by directly targeting BZW1, and may have significant therapeutic implications for patients with colon cancer. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The principal aim of this research is to investigate the variables that exert a discernible impact on the overall survival (OS) of individuals afflicted with colorectal cancer (CRC) harboring pathologic stages 2-3, as delineated within the TNM staging schema tailored to CRC, an established framework governed by the American Joint Committee on Cancer (AJCC). PATIENTS AND METHODS: Patients with preoperative stages 1 and 4, patients with a history of other organ malignancy, patients who could not undergo curative resection, patients with systemic malignant diseases (leukemia, lymphoma, etc.), patients with synchronous tumors, and patients with positive surgical margins were excluded from the study. Notable pathological parameters, including tumor grade, perforation status, lymphovascular invasion, perineural invasion, the presence of mucinous components, and tumor size, were ascertained through pathological examination of resected specimens. RESULTS: Curative resection was performed on 241 patients. The mean age of all patients was calculated to be 65.67±16.04. The average tumor size was measured as 5.03±2.22 cm. The 1-year survival rate of the patients was found to be 84.3%, 3-year survival rate was 69.0%, and 5-year survival rate was 52.9%. According to the COX regression analysis, the categorical variables that were found to be significantly associated with OS were grade (p=0.046), emergency surgery (p<0.001), and tumor localization (p=0.015). CONCLUSIONS: The initial patient and tumor characteristics at baseline have demonstrated substantial predictive capacity regarding patient outcomes following disease recurrence. Survival analyses showed that undergoing emergency surgery, having the tumor located in the rectum, and having a "poor" tumor grade adversely affected survival. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a common and lethal disease; it remains the third most frequently occurring cancer among both genders. In Egypt, colon cancer represents the ninth most common cancer while rectal cancer ranks the 18th most common cancer by incidence. The application of cancer stem cells (CSC) as prognostic markers in CRC is now studied, among which is CD44, which is implicated in cellular growth, differentiation, survival as well as the metastatic behavior of cancer cells. The prognostic role of CD44 in CRC is still controversial. The study aims at inspecting CD44 immunoreactivity in the epithelium of colorectal cancer specimens and to detect its association with the patients' clinicopathological features as well as its prognostic significance. This retrospective cross-sectional study included 85 CRC specimens and 16 adenoma specimens collected from the Pathology Department, South Egypt Cancer Institute, during the period from 2018 to 2020. All specimens were stained by anti-CD44 antibody. CD44 epithelial expression in colon cancer tissue specimens was substantially higher than in normal mucosa. It was observed that 95% (n = 81) of the studied colorectal carcinoma cases showed positive CD44 epithelial expression compared to distant normal mucosa as controls as well as adenoma cases where only 43.8% (n = 7) of adenoma cases showed positivity with highly significant p-value P = 0.000 and it correlates with cancer progression and aggressiveness. Low H score expression H ≤ 150 had better 3 years disease-free survival DFS estimated by 83.3% compared to 79.6% with high H score expression with significant P-value (P = 0.041). Our current study showed a statistically significant association between CD44 expression and tumor size (T), lymph node metastasis (N) as well as disease stage with P-values (P = 0.009), (p = 0.000) and (p = 0.000), respectively. CD44 epithelial immunostaining showed to be of an adverse prognostic significance in early CRC associated with more aggressive behavior and worse survival. [ABSTRACT FROM AUTHOR]

Objective: To determine the timeframe and associated changes in the microenvironment that promote the development of a diet-induced local-regional recurrence in a mouse model of colorectal surgery. Background: Postoperative recurrence and metastasis occur in up to 30% of patients undergoing attempted resection for colorectal cancer (CRC). The underlying mechanisms that drive the development of postoperative recurrences are poorly understood. Preclinical studies have demonstrated a diet and microbial-driven pathogenesis of local-regional recurrence, yet the precise mechanisms remain undefined. Methods: BALB/C mice were fed a western diet (WD) or standard diet (SD), underwent a colon resection and anastomosis, given an Enterococcus faecalis enema on postoperative day (POD) 1, and subjected to a CT26 cancer cell enema (mimicking shed cancer cells) on POD2. Mice were sacrificed between POD3 and POD7 and cancer cell migration was tracked. Dynamic changes in gene expression of anastomotic tissue that were associated with cancer cell migration was assessed. Results: Tumor cells were identified in mice fed either a SD or WD in both anastomotic and lymphatic tissue as early as on POD3.Histology demonstrated that these tumor cells were viable and replicating. In WD-fed mice, the number of tumor cells increased over the early perioperative period and was significantly higher than in mice fed a SD. Microarray analysis of anastomotic tissue found that WD-fed mice had 11 dysregulated genes associated with tumorigenesis. Conclusions: AWD promotes cancer cells to permeate a healing anastomosis and migrate into anastomotic and lymphatic tissue forming viable tumor nodules. These data offer a novel recurrence pathogenesis by which the intestinal microenvironment promotes a CRC local-regional recurrence. [ABSTRACT FROM AUTHOR]

Background: The tumor area may be a potential prognostic indicator. The present study aimed to determine and validate the prognostic value of tumor area in curable colon cancer. Methods: This retrospective study included a training and validation cohorts of patients who underwent radical surgery for colon cancer. Independent prognostic factors for overall survival (OS) and disease-free survival (DFS) were identified using Cox proportional hazards regression models. The prognostic discrimination was evaluated using the integrated area under the receiver operating characteristic curves (iAUCs) for prognostic factors and models. The prognostic discrimination between tumor area and other individual factors was compared, along with the prognostic discrimination between the tumor-node-metastasis (TNM) staging system and other prognostic models. Two-sample Wilcoxon tests were carried out to identify significant differences between the two iAUCs. A two-sided P < 0.05 was considered statistically significant. Results: A total of 3051 colon cancer patients were included in the training cohort and 872 patients in the validation cohort. Tumor area, age, differentiation, T stage, and N stage were independent prognostic factors for both OS and DFS in the training cohort. Tumor area had a better OS and DFS prognostic discrimination characteristics than T stage, maximal tumor diameter, differentiation, tumor location, and number of retrieved lymph nodes. The novel prognostic model of T stage + N stage + tumor area (iAUC for OS, 0.714, P < 0.001; iAUC for DFS, 0.694, P < 0.001) showed a better prognostic discrimination than the TNM staging system (T stage + N stage; iAUC for OS, 0.664; iAUC for DFS, 0.658). Similar results were observed in an independent validation cohort. Conclusions: Tumor area was identified as an independent prognostic factor for both OS and DFS in curable colon cancer patients, and in cases with an adequate number of retrieved lymph nodes. The novel prognostic model of combining T stage, N stage, and tumor area may be an alternative to the current TNM staging system. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the association between distress at initial diagnosis and disease-free survival in patients with resectable colon cancer. Summary Background Data: Considerable research has examined the psychological impact of having a confirmed diagnosis of cancer, but relatively limited research has examined the impact of distress during the diagnostic phase on oncological outcomes. Methods: This is a retrospective cohort study. We included newly diagnosed colon cancer patients who had resectable surgery and underwent distress screening between July 2014 and July 2021 (N=1,362). The Korean versions of the Distress Thermometer were used to assess distress and related problems. Patients were categorized into 3 groups based on distress score: low (<4), moderate (4–7), and severe (≥8). The primary outcome was disease-free survival. Results: The mean distress was 5.1 (SD=2.4) and 61%, and 15% of patients had moderate and severe distress at diagnosis, respectively. The severe distress group was more likely to report fear, sadness, and concerns regarding insurance/finance, work, and childcare than the low distress group. Compared with the low distress group, the severe distress group had worse disease-free survival (Hazard Ratio=1.84, 95% CI=1.03, 3.29). The association was more evident in patients with stage IV disease (Hazard Ratio=2.53, 95% CI=1.02, 6.25). Conclusions: A substantial number of patients with colon cancer experience distress at diagnosis, and severe distress has a negative impact on oncologic outcomes. Active monitoring and appropriate management of distress at diagnosis should be adopted at clinical settings. [ABSTRACT FROM AUTHOR]

Purpose To investigate whether CT-based tumor regression grade (ctTRG) can be used to predict the response to neoadjuvant chemotherapy (NAC) in colon cancer. Materials and Methods A total of 53 patients were enrolled. Two radiologists independently assessed the ctTRG using the length, thickness, layer pattern, and luminal and extraluminal appearance of the tumor. Changes in tumor volume were also analyzed using the 3D Slicer software. We evaluated the association between pathologic TRG (pTRG) and ctTRG. Patients with Rödel's TRG of 2, 3, or 4 were classified as responders. In terms of predicting responder and pathologic complete remission (pCR), receiver operating characteristic was compared between ctTRG and tumor volume change. Results There was a moderate correlation between ctTRG and pTRG (ρ = -0.540, p < 0.001), and the interobserver agreement was substantial (weighted к = 0.672). In the prediction of responder, there was no significant difference between ctTRG and volumetry (Az = 0.749, criterion: ctTRG ≤ 3 for ct- TRG, Az = 0.794, criterion: ≤ -27.1% for volume, p = 0.53). Moreover, there was no significant difference between the two methods in predicting pCR (p = 0.447). Conclusion ctTRG might predict the response to NAC in colon cancer. The diagnostic performance of ctTRG was comparable to that of CT volumetry. [ABSTRACT FROM AUTHOR]

We describe improvements to the previously proposed "U-tied anastomosis" with the aim of broadening its indications, especially in left hemicolectomy. After bowel mobilization and vascular ligation, the proximal and distal colon were aligned in a U-shape using a ligature. An anastomosis was constructed using a linear stapler through the common enterotomies. Following resection of the bowel using laparoscopic coagulation shears, the common opening was closed using 3-0 barbed sutures. Eight consecutive patients underwent colectomy using the U-tied semi-manual technique between May and July 2023. In all cases, the U-tied procedures were completed using one cartridge and two sutures. No complications or mortality were observed after one month of follow-up. The U-tied semi-manual anastomosis is a straightforward and effective method for intracorporeal anastomosis. The simplified reconstruction technique of U-tied series, together with the minimization of technique variability, results in consistent outcomes when performed by surgeons with different levels of experience. The streamlined process enhances the homogeneity of the intracorporeal anastomosis while reducing cartridge use. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to explore the effects of sodium butyrate (NaB), grape seed proanthocyanidin extract (GSPE), or their combination against dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) formation, which is a proxy for colon carcinogenesis in the rat colon. Results: After inducing colon cancer, all treatments markedly decreased the overall numbers of ACF, with the NaB–GSPE combination eliciting the most pronounced reduction. All the treatments significantly inhibited cell proliferation as indicated by the lower percentages of Ki67-positive cells in the colonic mucosa. Also, caspase-3-immunolabeled cells were found to be significantly increased after all treatments, indicating more apoptotic activity in the initiated colonocytes. Further, the treatments significantly modulated the levels of antioxidant biomarkers, including malondialdehyde, superoxide dismutase, reduced glutathione, and total antioxidant capacity, suggesting a potently induced antioxidant activity, especially after the combination treatment. All treatments, especially the combination, dramatically downregulated the expression of COX-2 and APC, both of which are directly linked to colon cancer. Conclusions: NaB and GSPE exert potent anti-carcinogenic effects, both alone but more effectively in combination, in a rat colon cancer model. They could be important for colon cancer treatment and for adjuvant therapy in humans. [ABSTRACT FROM AUTHOR]

To develop and validate a computed tomography (CT)-based radiomics nomogram for the preoperative prediction of tumor deposits (TDs) and clinical outcomes in patients with colon cancer. This retrospective study included 383 consecutive patients with colon cancer from two centers. Radiomics features were extracted from portal venous phase CT images. Least absolute shrinkage and selection operator regression was applied for feature selection and radiomics signature construction. The multivariate logistic regression model was used to establish a radiomics nomogram. The performance of the nomogram was assessed by using receiver operating characteristic curves, calibration curves and decision curve analysis. Kaplan‒Meier survival analysis was used to assess the difference of the overall survival (OS) in the TDs-positive and TDs-negative groups. The radiomics signature was composed of 11 TDs status related features. The AUCs of the radiomics model in the training cohort, internal validation and external validation cohorts were 0.82, 0.78 and 0.78, respectively. The radiomics nomogram that incorporated the radiomics signature and clinical independent predictors (CT-N, CEA and CA199) showed good calibration and discrimination with AUCs of 0.88, 0.80 and 0.81 in the training cohort, internal validation and external validation cohorts, respectively. The radiomics nomogram-predicted high-risk groups had a worse OS than the low-risk groups (p < 0.001). The radiomics nomogram-predicted TDs was an independent preoperative predictor of OS. The radiomics nomogram based on CT radiomics features and clinical independent predictors could effectively predict the preoperative TDs status and OS of colon cancer. CT-based radiomics nomogram may be applied in the individual preoperative prediction of TDs status in colon cancer. Additionally, there was a significant difference in OS between the high-risk and low-risk groups defined by the radiomics nomogram, in which patients with high-risk TDs had a significantly worse OS, compared with those with low-risk TDs. [ABSTRACT FROM AUTHOR]

Colon cancer is the third most commonly diagnosed cancer in the world. Most colon AdenoCArcinoma (ACA) arises from pre-existing benign polyps in the mucosa of the bowel. Thus, detecting benign at the earliest helps reduce the mortality rate. In this work, a Predictive Modeling System (PMS) is developed for the classification of colon cancer using the Horizontal Voting Ensemble (HVE)method. Identifying different patterns inmicroscopic images is essential to an effective classification system. A twelve-layer deep learning architecture has been developed to extract these patterns. The developedHVE algorithm can increase the system's performance according to the combined models from the last epochs of the proposed architecture. Ten thousand (10000) microscopic images are taken to test the classification performance of the proposed PMS with the HVE method. The microscopic images obtained from the colon tissues are classified intoACAor benign by the proposed PMS. Results prove that the proposed PMS has ~8% performance improvement over the architecture without using the HVE method. The proposed PMS for colon cancer reduces the misclassification rate and attains 99.2% of sensitivity and 99.4% of specificity. The overall accuracy of the proposed PMS is 99.3%, and without using the HVE method, it is only 91.3%. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that lncRNAs impact cancer progression. The lncRNA AC125611.3 (also referred to as RP11-161H23.5) is highly expressed in colon cancer but rarely studied; understanding its regulation may provide novel insights on treating colon cancer. qRT-PCR was performed to quantify RNAs. CCK-8 and EdU assays were performed to assess cell proliferation. Western blot analysis was used to detect levels of proteins related to cell apoptosis and EMT. Wound healing assay and Transwell invasion assay were conducted to evaluate cell migratory and invasive capabilities, respectively. Luciferase reporter assay, RIP assay, and pull-down assay were used to verify RNA-RNA and RNA-protein interactions. AC125611.3 was highly overexpressed in colon cancer cells. AC125611.3 depletion curbed cell proliferative, invasive, migratory, and EMT processes while enhancing apoptosis. Furthermore, AC125611.3 activated the Wnt signaling pathway in colon cancer cells by regulating catenin beta-1 (CTNNB1). Moreover, AC125611.3 recruited dyskeratosis congenita 1 (DKC1) to stabilize CTNNB1. AC125611.3 recruits DKC1 to stabilize CTNNB1 and activate Wnt signaling, thereby promoting the progression of colon cancer. [ABSTRACT FROM AUTHOR]

Colorectal cancer is the third most common cancer and is anticipated to cause 52,580 deaths in 2022 in the United States. Despite the effectiveness of colorectal cancer screening (CRCS), only 74% of adults eligible for CRCS complete the screening. Community pharmacists are well positioned to provide preventive care education and recommendations to the general population. This study aimed to evaluate overall participants' knowledge, perceptions, and barriers on CRCS before and after receiving pharmacist-led education in the outpatient, community pharmacy setting and to assess the impact of pharmacist intervention on screening uptake with the stool-based DNA test. A 16-item prequestionnaire/postquestionnaire was administered by clinical pharmacists in a grocery store pharmacy chain in the Kansas City area. The questionnaire assessed participants' knowledge, perceptions, barriers, CRCS intentions, and demographics. After completing the prequestionnaire, participants received verbal and written education. For those participants interested in the stool-based DNA test, a facsimile transmission was sent to the participant's provider. The postquestionnaire was administered by the pharmacist coach at visit two 6 to 10 weeks later. Participant demographics were assessed using descriptive statistics. Wilcoxon signed rank test was used to assess prechanges/postchanges in perceptions, awareness, and knowledge. We reported the stool-based DNA test completion rate as an overall percentage. Participants' knowledge of CRCS reached statistical significance after pharmacist-led education (score 4.5-6, P = 0.003). There was no change in perception pre/post. The 3 most common reported barriers were cost of screening, not being concerned with colon cancer, and lack of follow-up from a physician. Of 42 participants, 23 (54.8%) were indicated for CRCS and 4 (17%) completed screening during the study. Not all eligible participants completed CRCS, but pharmacists improved participants' knowledge of CRCS. [ABSTRACT FROM AUTHOR]

We aimed to investigate manual subtraction computed tomography angiography (MS-CTA) to further confirm the distribution and classification of LCA (left colic artery) ascending/descending branches, then observe the postoperative blood flow path to illustrate how the above branches evolved to postoperative blood path. 89 patients with distal sigmoid and rectal cancer were referred in our observation and underwent MS-CTA between June 2020 and March 2022. We classified the distribution of LCA and confirmed whether there exists AMCA (accessory middle colic artery). Then we planned blood flow path based on the classification of LCA branches before operation. High ligation was applied in regular radical surgery. During operation, we carefully protect the bifurcation of ascending and descending LCA. Then we compared the planned blood flow path with the actual postoperative blood flow path to verify the mechanism we proposed previously. Of 89 patients, 82 cases met our criteria, we summarized 6 distribution pattens of LCA ascending and descending branches. These preoperative pattens are consistent with the inspection during operation. The postoperative blood flow path of 6 pattens is evolved from the above adjacent anastomotic branches and is consistent with the planned blood flow path. We also found 2 cases with IMA stenosis and 1 case with SMA stenosis under pathological condition, and their compensatory blood flow path is in accordance with our theory. The rate of the anastomotic leakage in our study group is relatively low (7.3%). MS-CTA could confirm the distribution of LCA and AMCA, display accurate postoperative blood reconstruction path after IMA high ligation, and it further verified the mechanism we proposed previously, which is the proximal anastomotic branches forming new blood flow path from high-pressure area to the low-pressure area. This mechanism might be helpful for performing accurate laparoscopic sigmoid and rectal cancer surgery. [ABSTRACT FROM AUTHOR]

Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy. Cannabidiol (CBD) is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects, including neuroprotective, antiemetic, anti-inflammatory, and antineoplastic activities. This study aimed to elucidate the specific anticancer mechanism of CBD by single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) technologies. Here, we report that CBD inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment (TME). Our single-cell transcriptome and ATAC sequencing results showed that CBD suppressed M2-like macrophages and promoted M1-like macrophages in tumors both in strength and quantity. Furthermore, CBD significantly enhanced the interaction between M1-like macrophages and tumor cells and restored the intrinsic anti-tumor properties of macrophages, thereby preventing tumor progression. Mechanistically, CBD altered the metabolic pattern of macrophages and related anti-tumor signaling pathways. We found that CBD inhibited the alternative activation of macrophages and shifted the metabolic process from oxidative phosphorylation and fatty acid oxidation to glycolysis by inhibiting the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and related downstream target genes. Furthermore, CBD-mediated macrophage plasticity enhanced the response to anti-programmed cell death protein-1 (PD-1) immunotherapy in xenografted mice. Taken together, we provide new insights into the anti-tumor effects of CBD. [Display omitted] • CBD shapes the TME to prevent tumor progression. • CBD-induced metabolic reprogramming inhibits alternative activation of macrophage. • CBD inhibits PI3K-Akt signaling to downregulate anti-inflammatory gene expression. • CBD enhances the response to anti-PD-1 immunotherapy. [ABSTRACT FROM AUTHOR]

Key summary points: Aim: To evaluate the health-related quality of life (HR-QoL) trajectory during the first year after cancer treatment in patients with resectable primary colon cancer. Findings: On average, HR-QoL recovered to baseline level one year after start of treatment. However, 1 out of 7 patients, particularly older patients who received adjuvant chemotherapy, were at risk of non-resilience or a late decline in HR-QoL. Message: Our findings provide insight in risks for a permanent loss of HR-QoL which may support patients and physicians in the treatment decision-making process to optimize tailored cancer care. Purpose: This study aims to evaluate quality of life trajectory during the first year after surgical treatment in patients with resectable primary colon cancer. Methods: Patients with resectable primary colon cancer diagnosed between 2013 and 2019 who received surgical treatment and adjuvant chemotherapy if indicated were selected from the Prospective Dutch ColoRectal Cancer cohort study (PLCRC). Health-related quality of life (HR-QoL) was assessed using EORTC-QLQ-C30 questionnaire before surgery, and three and twelve months after surgery. HR-QoL scores varied between 0 and 100 and outcomes were compared according to age (< 70 years, ≥ 70 years), comorbidity (yes, no) and treatment type (adjuvant chemotherapy, surgical treatment only). The extent of resilience, defined as a recovery of HR-QoL to baseline level after a clinically relevant decline in HR-QoL at months, was calculated twelve months post-surgery. Results: For all 458 patients, the mean age was 66.4 years (SD 9.5), 40% were aged 70 years and older and 68% were men. Baseline level of HR-QoL summary score was relatively high with a mean of 87.9 (SD 11.5), and did not significantly differ between older and younger patients. The strongest decline of HR-QoL compared to baseline was observed at three months with a gradual recovery over time. Fourteen percent of all patients were non-resilient or showed a late decline at twelve months post-surgery. Compared to younger patients, older patients who received adjuvant chemotherapy were less resilient (respectively, 53 and 32%, p = 0.07) and at risk of a late decline in HR-QoL 1 year post-surgery (respectively, 3% versus 16%, p = 0.02). Comorbidity status had no significant impact on the HR-QoL trajectory. Conclusion: Colon cancer treatment was associated with a decline in HR-QoL three months post-surgery, but most patients return to baseline level within twelve months. Still, particularly older patients who received adjuvant chemotherapy were less resilient and at risk of a late decline in HR-QoL. These data could help in patients counselling regarding colon cancer treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Colon cancer is a primary human cancer that accounts for approximately one-tenth of all cancers and is one of the three most common cancers in incidence and mortality. This study investigated the relationship between serum preoperative carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), patient characteristics and lymph node (LND) involvement in early-stage colon cancer. PATIENTS AND METHODS: A total of 154 patients who had undergone surgery for early-stage colon cancer were included in this study. Patient demographics regarding age and gender, laboratory parameters, tumor size, and tumor laterality were recorded. CEA and CA19-9 positivity was defined as patients whose tumor markers were above the cut-off values, and patients were grouped according to CEA and CA19-9 positivity. Patients were compared according to the CEA and CA19-9 status and pathological LND involvement. RESULTS: We found that patients in the CEA (+) and CA19-9 (+) groups were significantly older than the others. Our study detected LND involvement in histopathological examination in 25% of patients. LND pathological participation was significantly higher in the CEA (+) CA19-9 (+) group, and being age 65 years or older was found to be a risk factor for pathological LND involvement. CONCLUSIONS: Clinicians should pay more attention to LND involvement when both CEA and CA19-9 are elevated preoperatively in early-stage colon cancer patients. Preoperative CEA and CA19-9 status of patients is important in predicting LND involvement and, as a result, the prognosis of these patients. [ABSTRACT FROM AUTHOR]

Cancers of the breast, prostate and intestinal tract account for most cancer-associated deaths in humans and represent several of the highest incidence human neoplasms. Therefore, understanding the underlying pathophysiology, including the formation and propagation of these cancers, is key to designing potential treatments. Over the last 50 years or more, genetically engineered mouse models (GEMMs) have been instrumental platforms to our discovery of neoplastic disease as many follow near-identical molecular and histological progression as human tumours. In this mini review, we summarize three key preclinical models and focus on some of the major findings in relation to clinical care. We discuss the MMTV-PyMT (polyomavirus middle T antigen) mouse, TRAMP (transgenic adenocarcinoma mouse prostate) mouse and APCMin (multiple intestinal neoplasm mutation of APC gene) mouse, which mimic breast, prostate and intestinal cancers, respectively. We aim to describe the significant contributions these GEMMs have made to our collective understanding of high-incidence cancers as well as briefly discuss the limitations of each model as a device for therapeutic discovery. [ABSTRACT FROM AUTHOR]

Exosomes derived from colon cancer cells has been found to elevate viability and metastasis of recipient cells. Berberine is a plant-derived natural compound that has shown anti-colon cancer potential. However, berberine's impacts on the tumorigenic functions of tumor exosomes have yet to be evaluated. To elucidate whether berberine modulates exosomal pro-tumor activity, we evaluated the effects of exosomes released by berberine-treated colon cancer cells against viability, migration, and invasion of recipient cancer cells. The human colon cancer HCT116 cells were treated or not treated with berberine, and culture media were collected following 48 h of treatment. Exosomes released by treated or untreated cells were isolated from collected media via ultracentrifugation. To study effects of berberine on tumor exosomes, HCT116 cells were co-cultured with exosomes derived from berberine-treated and non-treated cells, followed by monitoring changes in cell viability, migration, and invasion. The treatment with 100, 150, and 200 µ g/ml of berberine-primed exosomes could dose-dependently decrease the viability [by -35.4% (p < 0.0001), -47% (p < 0.0001), and -65.5% (p < 0.0001), respectively], migration [by -24% (p = 0.0001), -43.5% (p = 0.0001), and -65.2% (p = 0.0001), respectively], and invasion [by -29% (p < 0.0001), -58.8% (p < 0.0001), and -69.7% (p < 0.0001), respectively] of HCT116 cells compared to the control. However, non-primed exosomes exerted significant inducing effects on the viability and metastatic ability of HCT116 cells. In conclusion, berberine can reverse the tumorigenic function of colon cancer exosomes and, thus, exert a remarkable suppressive impact against the survival and metastatic ability of colon cancer cells. [ABSTRACT FROM AUTHOR]

Introduction: Permanent colostomy is, under certain conditions and characteristics, one of the means of treatment of colorectal cancer. The multidimensional effects of this therapeutic method affect cancer patients and their families. Purpose: To assess the quality of life of patients with colostomy and identify the factors affecting it. Methodology: A literature review was conducted at Google Scholar, Scopus, Cross Ref, Science Direct and Pubmed. The articles had to concern an adult population, being published between 2012 and 2022 and used Greek and English language. Results: The effects of colostomy to the patients are related to their personal, social and sex life, their adaptation to the new reality, the psychology, the management of possible complications, the stoma care and the coverage of basic daily needs. In addition, implications are also found on the professional and economic life of patients. Conclusions: Permanent colostomy disturbs the balance of the patient's and family's daily live, facing them with a number of issues that affect the quality of life. [ABSTRACT FROM AUTHOR]

Colon adenocarcinoma mainly occurs in older patients. Oxaliplatin-based adjuvant chemotherapy improved disease-free survival after stage III colon cancer resection, but this improvement was not demonstrated in older patients. The purpose of ADAGE-PRODIGE 34, randomized open phase III trial is to compare in patients over 70 years oxaliplatin plus fluoropyrimidine with fluoropyrimidine alone in fit patients (Group 1) and fluoropyrimidine with observation in frail patients (Group 2) after resection of stage III colon adenocarcinoma. We report a preliminary tolerance analysis on 50% of the first patients enrolled. The analysis was conducted on 491 patients (378 in Group 1 and 113 in Group 2). Patients in Group 2 were older and showed more frailty criteria than those in Group 1. Cumulative grade 3–5 toxicities were more frequent in patients treated with oxaliplatin in Group 1 or with fluoropyrimidine in Group 2 than in patients treated with fluoropyrimidine in Group 1. At least one course was deferred in more than half of the patients in all groups. Early treatment cessation was more frequent in Group 2. No safety concerns were raised for the continuation of accrual. The frailty criteria distribution suggests that the investigator's evaluation for group allocation was accurate. [ABSTRACT FROM AUTHOR]

The published literature presents conflicting results regarding the impact of bariatric surgery on the incidence of colorectal cancer. There are important new studies that have addressed this question with longer follow-up. To investigate the effect of bariatric surgery on the risk of developing colorectal cancer in patients with obesity. Meta-analysis. PubMed and Scopus were searched for relevant articles. Articles published by November 2021 were retrieved; data were extracted according to the evidence-based PICO (population, intervention, control, outcome) model and analyzed using a random-effects model to estimate the pooled relative risk (RR) and its 95% confidence interval. The heterogeneity of studies was tested and quantified using Cochran's Q. The initial search yielded 327 articles. After evaluation, 13 studies were analyzed. The thorough evaluation resulted in 13 articles, which were analyzed. A total number of 3,233,044 patients were included in the meta-analysis. The mean time of follow-up was 9.5 ± 7.9 years. The pooled estimate of the adjusted RR was.63 (95% confidence interval,.50–.79). Heterogeneity χ2 was 107.96 (df = 12; P <.001; I2 = 89%). Patients who underwent bariatric surgery had a 37% reduction in the risk of developing colorectal cancer compared with patients with obesity who had no surgery. • Patients who underwent bariatric surgery had a 37% reduction in the risk of developing colorectal cancer compared with patients with obesity who had no surgery • The sub-analysis of studies with minimum 10 years of follow-up showed 32% decrease in risk of developing colorectal cancer compared with patients with obesity who had no surgery [ABSTRACT FROM AUTHOR]

Objective: We evaluated the prognostic value of tumor deposit (TD) counts and incorporated them with the number of positive lymph nodes to develop a revised nodal staging. Summary Background Data: The current American Joint Committee on Cancer (AJCC) staging on colon cancer includes the TDs only for nodenegative patients, as N1c, and their counts are not considered. Methods: We included consecutive patients with stage III colorectal cancer who underwent curative resections between January 2010 and December 2019. The patients were grouped as TD 0, TD 1, TD 2, or TD ≥3 based on their TD counts. Disease-free survival and overall survival were compared. Results: Of 2446 eligible stage III patients, 658 (26.9%) had TDs. Among them, 500 (76.0%) patients concurrently had positive lymph nodes (LNs). TD counts were significantly related to worse disease-free survival (DFS) and overall survival regardless of pT stages or the number of positive LNs. The patients were restaged based on the integrated number of TD counts and positive LNs. The N3 stage, which had ≥10 integrated TDs and positive LNs, was newly classified. Among the patients who completed 6 months of adjuvant chemotherapy, those upstaged to N2 from an initial stage of N1 experienced significantly worse DFS than those confirmed as N1 in the revised N staging. The newly N3-staged patients showed significantly worse DFS than the patients initially staged as N2. Conclusions: Revised N staging using the integrated number of TD counts and positive LNs could predict DFS more accurately than current staging. It would also draw greater attention to the patients with high-risk stage III colon cancer staged as N3. [ABSTRACT FROM AUTHOR]

In patients with left-sided obstructive colon cancer (LSOCC), a stoma is often constructed as part of primary treatment, but with a considerable risk of becoming a permanent stoma (PS). The aim of this retrospective multicentre cohort is to identify risk factors for a PS in LSOCC and to develop a pre- and postoperative prediction model for PS. Data was retrospectively obtained from 75 hospitals in the Netherlands. Patients who had curative resection of LSOCC between January 1, 2009 to December 31, 2016 were included with a minimum follow-up of 6 months after resection. The interventions analysed were emergency resection, decompressing stoma or stent as bridge-to-elective resection. Main outcome measure was presence of PS at the end of follow-up. Multivariable logistic regression analysis was performed to identify risk factors for PS at primary presentation (T 0) and after resection, in patients having a stoma in situ (T 1). These risk factors were used to construct a web-based prediction tool. Of 2099 patients included in the study (T 0), 779 had a PS (37%). A total of 1275 patients had a stoma in situ directly after resection (T 1), of whom 674 had a PS (53%). Median follow-up was 34 months. Multivariable analysis showed that older patients, female sex, high ASA-score and open approach were independent predictors for PS in both the T 0 and T 1 population. Other predictors at T 0 were sigmoid location, low Hb, high CRP, cM1 stage, and emergency resection. At T 1 , subtotal colectomy, no primary anastomosis, not receiving adjuvant chemotherapy and high pTNM stage were additional predictors. Two predictive models were built, with an AUC of 0.74 for T 0 and an AUC of 0.81 for T 1. PS is seen in 37% of the patients who have resection of LSOCC. In patients with a stoma in situ directly after resection, 53% PS are seen due to non-reversal. Not only baseline characteristics, but also treatment strategies determine the risk of a PS in patients with LSOCC. The developed predictive models will give physicians insight in the role of the individual variables on the risk of a PS and help in informing the patient about the probability of a PS. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the impact of preoperative immunonutrition on the outcomes of colon cancer surgery. Background: Although current guidelines recommend that immunonutrition should be prescribed for malnourished patients before major gastrointestinal surgery, the benefit of preoperative immunonutrition remains debatable. Methods: Between April 2019 and October 2020, 176 patients with primary colon cancer were enrolled and randomly assigned (1:1) to receive preoperative immunonutrition plus a normal diet (n = 88) or a normal diet alone (n = 88). Patients in the immunonutrition group received oral nutritional supplementation (400 mL/d) with arginine and ω-3 fatty acids for 7 days before elective surgery. The primary endpoint was the rate of infectious complications, and the secondary endpoints were the postoperative complication rate, change in body weight, and length of hospital stay. Results: The rates of infectious (17.7% vs 15.9%, P = 0.751) and total (31.6% vs 29.3%, P = 0.743) complications were not different between the two groups. Old age was the only significant predictive factor for the occurrence of infectious complications (odds ratio = 2.990, 95% confidence interval 1.179–7.586, P = 0.021). The length of hospital stay (7.6 ± 2.5 vs 7.4 ± 2.3 days, P = 0.635) and overall change in body weight (P = 0.379) were similar between the two groups. However, only the immunonutrition group showed weight recovery after discharge (+0.4 ± 2.1 vs −0.7 ± 2.3 kg, P = 0.002). Conclusions: Preoperative immunonutrition was not associated with infectious complications in patients undergoing colon cancer surgery. Routine administration of immunonutrition before colon cancer surgery cannot be justified. [ABSTRACT FROM AUTHOR]