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Evidence indicates that combinations of anti‐EGFR antibodies and KRAS p.G12C (c.34G>T) inhibitors can be an effective treatment strategy for advanced colorectal cancer. We hypothesized that KRAS c.34G>T (p.G12C)‐mutated colorectal carcinoma might be a distinct tumor subtype. We utilized a prospective cohort incident tumor biobank (including 1347 colorectal carcinomas) and detected KRAS c.34G>T (p.G12C) mutation in 43 cases (3.2%) and other KRAS mutations (in codon 12, 13, 61, or 146) in 467 cases (35%). The CpG island methylator phenotype (CIMP)‐low prevalence was similarly higher in KRAS c.34G>T mutants (52%) and other KRAS mutants (49%) than in KRAS‐wild‐type tumors (31%). KRAS c.34G>T mutants showed higher CIMP‐high prevalence (14%) and lower CIMP‐negative prevalence (33%) compared with other KRAS mutants (6% and 45%, respectively; p = 0.0036). Similar to other KRAS mutants, KRAS c.34G>T‐mutated tumors were associated with cecal location, non‐microsatellite instability (MSI)‐high status, BRAF wild type, and PIK3CA mutation when compared with KRAS‐wild‐type tumors. Compared with BRAF‐mutated tumors, KRAS c.34G>T mutants showed more frequent LINE‐1 hypomethylation, a biomarker for early‐onset colorectal carcinoma. KRAS c.34G>T mutants were not associated with other features, including the tumor tissue abundance of Fusobacterium nucleatum (F. animalis), pks+Escherichia coli, Bifidobacterium, or (enterotoxigenic) Bacteroides fragilis. Among 1122 BRAF‐wild‐type colorectal carcinomas, compared with KRAS‐wild‐type tumors, multivariable‐adjusted colorectal cancer‐specific mortality hazard ratios (95% confidence interval) were 1.82 (1.05–3.17) in KRAS c.34G>T (p.G12C)‐mutated tumors (p = 0.035) and 1.57 (1.22–2.02) in other KRAS‐mutated tumors (p = 0.0004). Our study provides novel evidence for clinical and tumor characteristics of KRAS c.34G>T (p.G12C)‐mutated colorectal carcinoma. [ABSTRACT FROM AUTHOR]

Background: Multiple diet patterns play a crucial role in the development of colorectal cancer and its precursor, colorectal adenoma, but mediating effect of plasma metabolite profiles is unclear. Methods: A total of 95,275 participants from UK Biobank with plasma metabolomics and dietary information were analyzed. Metabolite profile scores for 14 dietary patterns were estimated through elastic net regression. Cox regression analysis assessed the associations of dietary patterns and their metabolite profile scores with colorectal tumor risk. Mediating effects of identified metabolite profile scores were estimated in the associations. Results: Fourteen metabolite profile scores, including a range of 28 to 205 signatures, were weak to moderate correlation with dietary patterns (all p < 0.001). Multivariable Cox regression analyses revealed that five dietary patterns were significantly correlated with a decreased risk of colorectal tumor after FDR correction and adjustment for covariates. HRs (95% CIs) per 1 SD for these diet patterns were as follows: WCRF (0.93, 0.90–0.96), CRC score (0.94, 0.92–0.97), AHEI-2010 (0.95, 0.92–0.97), DASH (0.94, 0.91–0.97), and hPDI (0.95, 0.93–0.98). Similarly, metabolite profile scores for these five dietary patterns were inversely associated with colorectal tumor risk, with HRs (95% CIs) per 1 SD as follows: WCRF (0.59, 0.49–0.70), CRC score (0.67, 0.58–0.77), AHEI-2010 (0.73, 0.65–0.80), DASH (0.75, 0.66–0.84), and hPDI (0.56, 0.47–0.67). The mediation proportions of five metabolite profile scores between dietary patterns and colorectal tumor risk ranged from 6.37 to 27.23% (all p < 0.001). Conclusions: Five dietary patterns and their metabolite profile scores, were inversely correlated with colorectal tumor risk. These findings highlight the potential of metabolite profiles as mediators in the association between dietary patterns and the risk of colorectal tumor, further contributing to the prevention of colorectal cancer or adenoma and providing new insights for future research. [ABSTRACT FROM AUTHOR]

Introduction: Endoscopic submucosal dissection (ESD) has been popular worldwide to treat laterally spreading tumors and large polyps. Post-ESD coagulation syndrome (PECS) is more common than the two major ESD-related complications, perforation, and bleeding. The aim of this study was to assess the prevalence of PECS, identify the risk factors for PECS, and create a risk prediction model for PECS. Methods: Retrospective cross-sectional study analyzed a total of 986 patients who underwent colorectal ESD. Logistic regression models were used to assess risk factors with PECS. Each risk factor was scored, and the 3-step risk stratification index of prediction model was assessed. Results: The prevalence of PECS was 21.4% (95% confidence interval [CI] = 18.9–24.1%). The risk factors of PECS in the multivariate logistic regression were tumor size (+1 cm: odds ratio [OR], 1.29; 95% CI, 1.16–7.09), cecal lesion (OR, 1.96; 95% CI, 1.09–1.53), procedure time (+30 min: OR, 1.19; 95% CI, 1.02–1.39), and ESD with snaring (OR, 0.64; 95% CI, 0.43–0.95). Applying a simplified weighted scoring system based on adjusted OR increments of 1, the risk of PECS was 12.3% (95% CI, 0.3–16.0%) for the low-risk group (score ≤4) and was 36.0% (95% CI = 29.4–43.2%) for the high-risk group (score ≥8). Overall discrimination (C-statistic = 0.629; 95% CI = 0.585–0.672) and calibration (p = 0.993) of the model were moderate to good. Conclusion: PECS occurs frequently, and the prediction model can be helpful for effective treatment and prevention of PECS. [ABSTRACT FROM AUTHOR]

Abstract A positive resection margin after colorectal endoscopic submucosal dissection (ESD) is associated with an increased risk of recurrence. We aimed to identify the clinical significance of positive resection margins in colorectal neoplasms after ESD. We reviewed 632 patients who had en bloc colorectal ESD at two hospitals between 2015 and 2020. The recurrence rates and presence of residual tumor after surgery were evaluated. The rate of additional surgery after ESD and recurrence rate were significantly higher in patients with incomplete resection (n = 75) compared to patients with complete resection (n = 557). When focusing solely on non-invasive lesions, no significant differences in recurrence rates were observed between the groups with complete and incomplete resection (0.2% vs. 1.9%, p = 0.057). Among 84 patients with submucosal invasive carcinoma, 39 patients underwent additional surgery due to non-curative resection. Positive vertical margin and lymphovascular invasion were associated with residual tumor. Lymphovascular invasion was associated with lymph node metastasis. However, no residual tumor nor lymph node metastases were found in patients with only one unfavorable histological factor. In conclusion, a positive resection margin in non-invasive colorectal lesions, did not significantly impact the recurrence rate. Also, in T1 colorectal cancer with a positive vertical resection margin, salvage surgery can be considered in selected patients with additional risk factors.

Background and Aim: Recently, noninvasive fecal markers have been used as indicators of intestinal inflammation in patients with inflammatory bowel disease (IBD). We conducted a clinical validation study to measure fecal calprotectin (Cp), lactoferrin (Lf), and hemoglobin (Hb) levels using an all‐in‐one kit in patients with IBD and colorectal tumors and aimed to clarify the utility of these fecal markers. Methods: In this study, 104 patients were analyzed, including 25 patients with ulcerative colitis (UC), 20 with Crohn's disease (CD), 48 with colorectal tumors, and 13 healthy controls (HC). Of the 48 patients with colorectal tumors, 14 had invasive cancer. We validated the utility of fecal Cp, Lf, and Hb levels by simultaneously measuring fecal markers in patients with IBD and colorectal tumors. Results: Fecal Cp and Lf had almost equivalent abilities in detecting clinical remission in patients with UC; however, fecal Cp was slightly superior to Lf. Regarding colorectal tumors, fecal Cp and Lf levels tended to be higher in patients with adenomas and colorectal cancer than in HCs. Although fecal Hb alone had the best sensitivity and specificity for detecting colorectal cancer, it had relatively low sensitivity for detecting advanced neoplasms and colorectal cancer. Conclusion: Fecal Cp and Lf can be used as almost equivalent biomarkers to assess the clinical activity in patients with UC. Fecal Hb is the most useful marker for screening colorectal cancer; however, adding fecal Cp and Lf may compensate for the low sensitivity of detecting for advanced colorectal tumors based on Hb alone. [ABSTRACT FROM AUTHOR]

The core–shell nanobombs integrating azo bonds (N N) and tetrasulfide bonds (S S S S) have been constructed and exhibit photothermal-thermodynamic effects, therapeutic H 2 S production, and biodegradation under the sensitive ignition by both near-infrared laser and tumor microenvironments, achieving a high efficacy against colorectal tumors. [Display omitted] • Rational design of nanobombs integrating azo and tetrasulfide bonds. • High and stable photothermal conversion due to the passivation of organosilica shell. • Photothermal-ignited nanobombs with the release of alkyl radicals. • Glutathione-ignited simultaneous H 2 S production and biodegradation due to tetrasulfide breaking. Reactive chemical bonds are associated with the generation of therapeutic radicals and gases under internal-external stimuli, which are highly attractive for cancer treatments. However, designing multifunctional nanostructures that incorporate multiple chemical bonds remains a significant challenge. Herein, novel core–shell nanobombs integrating azo (N N) and tetrasulfide bonds (S S S S) have been constructed with sensitive ignition by both near-infrared (NIR) laser and tumor microenvironments (TME) for treating colorectal tumors. The nanobombs (GNR/AIPH@MON@PVP, GAMP) were prepared by the in-situ growth of tetrasulfide-contained mesoporous organosilica nanoshell (MON) on gold nanorods (GNR) as the photothermal initiator, the load of azo compound (AIPH) as the radical producer and polymer modification. Upon NIR irradiation, the GNR core exhibits stable and high photothermal effects because of the passivation of the MON shell, leading to the thermal ablation of cancer cells. Simultaneously, the local hyperthermia ignites AIPH to release alkyl radicals to cause extensive oxidative stress without oxygen dependence. Moreover, the MON shell can be gradually decomposed in a reduced environment and release therapeutic H 2 S gas because of the cleavage of S S S S bonds by the glutathione (GSH) overexpressed in TME, causing mitochondrial injury. Owing to multifunctional functions, the GAMP significantly inhibits the growth rate of tumors upon NIR irradiation and achieves the highest efficacy among treatments. Therefore, this study presents activatable nanoagents containing multiple chemical bonds and provides insights into developing comprehensive antitumor strategies. [ABSTRACT FROM AUTHOR]

Introduction: Diagnostic and therapeutic methods for colorectal cancer (CRC) have advanced; however, they may be inaccessible worldwide, and their widespread use is challenging. This questionnaire survey investigates the current status of diagnosis and treatment of early-stage CRC in Asian countries. Methods: Responses to the questionnaire were obtained from 213 doctors at different institutions in 8 countries and regions. The questionnaire consisted of 39 questions on the following four topics: noninvasive diagnosis other than endoscopy (6 questions), diagnosis by magnification and image-enhanced endoscopy (IEE) including artificial intelligence (AI) (10 questions), endoscopic submucosal dissection (ESD), proper use among other therapeutic methods (11 questions), and pathologic diagnosis and surveillance (12 questions). Results: Although 101 of 213 respondents were affiliated with academic hospitals, there were disparities among countries and regions in the dissemination of advanced technologies, such as IEE, AI, and ESD. The NICE classification is widely used for the diagnosis of colorectal tumors using IEE, while the JNET classification with magnification was used in countries such as Japan (65/70, 92.9%) and China (16/22, 72.7%). Of the 211 respondents, 208 (98.6%) assumed that en bloc resection should be achieved for carcinomas, and 180 of 212 (84.9%) believed that ESD was the most suitable in cases with a diameter larger than 2 cm. However, colorectal ESD is not widespread in countries such as Thailand, the Philippines, and Indonesia. Conclusion: The promotion of advanced technologies and education should be continual to enable more people to benefit from them. [ABSTRACT FROM AUTHOR]

Abstract Background and Aim Recently, noninvasive fecal markers have been used as indicators of intestinal inflammation in patients with inflammatory bowel disease (IBD). We conducted a clinical validation study to measure fecal calprotectin (Cp), lactoferrin (Lf), and hemoglobin (Hb) levels using an all‐in‐one kit in patients with IBD and colorectal tumors and aimed to clarify the utility of these fecal markers. Methods In this study, 104 patients were analyzed, including 25 patients with ulcerative colitis (UC), 20 with Crohn's disease (CD), 48 with colorectal tumors, and 13 healthy controls (HC). Of the 48 patients with colorectal tumors, 14 had invasive cancer. We validated the utility of fecal Cp, Lf, and Hb levels by simultaneously measuring fecal markers in patients with IBD and colorectal tumors. Results Fecal Cp and Lf had almost equivalent abilities in detecting clinical remission in patients with UC; however, fecal Cp was slightly superior to Lf. Regarding colorectal tumors, fecal Cp and Lf levels tended to be higher in patients with adenomas and colorectal cancer than in HCs. Although fecal Hb alone had the best sensitivity and specificity for detecting colorectal cancer, it had relatively low sensitivity for detecting advanced neoplasms and colorectal cancer. Conclusion Fecal Cp and Lf can be used as almost equivalent biomarkers to assess the clinical activity in patients with UC. Fecal Hb is the most useful marker for screening colorectal cancer; however, adding fecal Cp and Lf may compensate for the low sensitivity of detecting for advanced colorectal tumors based on Hb alone.

The melanoma cell adhesion molecule, shed from endothelial and cancer cells, is a soluble growth factor that induces tumor angiogenesis and growth. However, the molecular mechanism accounting for its generation in a tumor context is still unclear. To investigate this mechanism, we performed in vitro experiments with endothelial/cancer cells, gene expression analyses on datasets from human colorectal tumor samples, and applied pharmacological methods in vitro/in vivo with mouse and human colorectal cancer cells. We found that soluble MCAM generation is governed by ADAM17 proteolytic activity and NOX1-regulating ADAM17 expression. The treatment of colorectal tumor-bearing mice with pharmacologic NOX1 inhibitors or tumor growth in NOX1-deficient mice reduced the blood concentration of soluble MCAM and abrogated the anti-tumor effects of anti-soluble MCAM antibodies while ADAM17 pharmacologic inhibitors reduced tumor growth and angiogenesis in vivo. Especially, the expression of MCAM, NOX1, and ADAM17 was more prominent in the angiogenic, colorectal cancer-consensus molecular subtype 4 where high MCAM expression correlated with angiogenic and lymphangiogenic markers. Finally, we demonstrated that soluble MCAM also acts as a lymphangiogenic factor in vitro. These results identify a role for NOX1/ADAM17 in soluble MCAM generation, with potential clinical therapeutic relevance to the aggressive, angiogenic CMS4 colorectal cancer subtype. [ABSTRACT FROM AUTHOR]

Background: Colorectal endoscopic resection (C-ER) is spreading due to the increase of colorectal cancer (CRC) in Japan. Gastric cancer (GC) sometimes occurs after C-ER. We aimed to analyze the status of GC after C-ER using large-scale data. Methods: We retrospectively used commercially anonymized health insurance claims data of 5.71 million patients from 2005 to 2018, and extracted 62,392 patients ≥ 50 years old who received C-ER. The incidence and risk factors of GC were analyzed. Additionally, subjects were divided into ≥ 2 cm group and < 2 cm group and risks of GC were analyzed. Results: The median age (range) was 58 (50–75) years and the overall rate of GC was 0.68% (423/62,392). Multivariate analysis showed that significant risk factors for GC [odds rates (OR), 95% confidence interval (CI)] were colorectal lesion size ≥ 2 cm (1.75, 1.24–2.47, p = 0.002), age ≥ 65 y.o. (1.65, 1.31–2.07, p < 0.001), male (2.35, 1. 76–3.13, p < 0.001), diabetes mellitus (1.40, 1.02–1.92, p = 0.035), liver disease (1.54, 1.06–2.24, p = 0.025), Helicobacter pylori infection (2.10, 1.65–2.67, p < 0.001), chronic atrophic gastritis (1.58, 1.14–2.18, p = 0.006), and CRC (1.72, 1.10–2.68, p = 0.017). The rate of GC in the ≥ 2 cm was significantly higher than that in < 2 cm groups (1.17% and 0.65%, p < 0.001). According to the number of significant risk factors, the rates of GC and the hazard ratios of GC (95%CI) were 0.64% and 3.64 (2.20–6.02) and 1.95% and 11.17 (6.57–19.00) for patient with 1–2 and ≥ 3 risk factors, compared with patients without risk factors. Conclusions: Using large-scale data, risk factors for GC, including colorecal lesions ≥ 2 cm after C-ER could be investigated. [ABSTRACT FROM AUTHOR]

Background and Aims: Underwater endoscopic submucosal dissection (U‐ESD) is a recently developed procedure that has the potential to prevent post‐ESD coagulation syndrome (PECS) owing to its heat‐sink effect. We aimed to clarify whether U‐ESD decreases the incidence of PECS compared with conventional ESD (C‐ESD). Methods: A total of 205 patients who underwent colorectal ESD (C‐ESD: 125; U‐ESD: 80) were analyzed. Propensity score matching analysis was performed to adjust for patient backgrounds. Ten C‐ESD and two U‐ESD patients with muscle damage or perforation during ESD were excluded when comparing PECS. The primary outcome was to compare the incidence of PECS between the U‐ESD and C‐ESD groups (54 matched pairs). Secondary outcomes were to compare procedural outcomes between the C‐ESD and U‐ESD groups (62 matched pairs). Results: Among the 78 patients who underwent U‐ESD, PECS occurred in only one patient (1.3%). Adjusted comparisons between the U‐ESD and C‐ESD groups demonstrated a significantly lower incidence of PECS in the U‐ESD group (0% vs 11.1%; P = 0.027). Median dissection speed was significantly faster in the U‐ESD than in the C‐ESD group (10.9 mm2/min vs 6.9 mm2/min; P < 0.001). En bloc and complete resection rates were 100% in the U‐ESD group. Although perforation and delayed bleeding occurred in one patient each (1.6%) as adverse events in the U‐ESD group, there were no differences compared with the C‐ESD group. Conclusions: Our study demonstrates that U‐ESD effectively decreases the incidence of PECS and is a faster and safer method for colorectal ESD. [ABSTRACT FROM AUTHOR]

Colorectal cancer is a malignant tumor with higher morbidity and mortality. The purpose of this study is to investigate whether inhibition of Protein Kinase, Membrane Associated Tyrosine/Threonine 1 (PKMYT1) affects tumor cell proliferation, survival and migration in colon tumors with high Cyclin E1 (CCNE1) expression. PcDNA3.1-CCNE1 vector and si-PKMYT1 were transfected in SW480 cells by Lipofectamine 2000. Q-PCR and western blot assay were processed to detect the expression. Transwell assay and Edu assay were undertaken to verify the migration and proliferation. CCNE1 promotes the proliferation and migration of SW480. Silencing of PKMYT1 inhibited the proliferation of tumor cells. Silencing the expression of PKMYT1 under the premise of overexpression of CCNE1, the level of Cyclin Dependent Kinase 1 (CDK1)-PT14 was reduced, indicating that the cell cycle was blocked. The expression of γH2AX increased significantly, indicating that the DDR pathway of tumor cells was activated and DNA damage accumulated. The results of immunofluorescence microscopy showed significantly increased expression of DNA damage-associated marker (γH2AX: H2AX Variant Histone). In CCNE1 amplificated colorectal tumor cells, knockdown of PKMYT1 reduced cells in S phase, inhibited cell proliferation and promoted cell apoptosis, confirming that PKMYT1 was a potential therapeutic target for colorectal tumor. This study may verify a potential therapeutic target and provide a new idea for the treatment of colorectal cancer in the future. [ABSTRACT FROM AUTHOR]

Purpose: Identifying tumor location is important in colorectal tumor resection. Preoperative endoscopic India ink marking is a widespread practice, but local injection of ink is an unstable procedure. Although it is often invisible, the ink may be sprayed into the peritoneal cavity and contaminate the surgical field. At our hospital, we introduced fluorescent clip marking (FCM) using the Zeoclip FS®, an endoscopic clip developed using near-infrared fluorescent resin. We tested the usefulness of FCM by retrospectively comparing cases in which FCM was used with cases in which conventional ink marking was used. Methods: We enrolled 305 patients with colorectal tumors who underwent colorectal surgery after preoperative marking from January 2017 to April 2022. We classified the patients into the FCM group (86 patients) and the India ink tattoo group (219 patients). Endoscopic marking was completed in the FCM group by the day before surgery, and fluorescence was evaluated during surgery with a fluorescent laparoscopic system. Patient backgrounds, marking visibility, adverse effects, and early postoperative results were retrospectively compared between groups. Results: Marking was visually confirmed in 80 patients in the FCM group (93.02%) and in 166 patients in the India ink tattoo group (75.80%) (p = 0.0006). In the group with India ink tattoos, contamination of the surgical field was observed in seven cases (3.20%). No adverse events were observed in the FCM group. Conclusion: In colorectal surgery, FCM provides better visibility than the conventional India ink tattooing method and is a simple and safe marking method. Clinical trial registration: Examination of fluorescence navigation for laparoscopic colorectal cancer surgery. Research Ethics Committee of the Kawaguchi Municipal Medical Center (Saitama, Japan) approval number: 2020-3. https://kawaguchi-mmc.org/wp-content/uploads/clinicalresearch-r02.pdf. [ABSTRACT FROM AUTHOR]

The development of an in vitro colorectal cancer (CRC) model that reconstructs the physiopathological microenvironment of human colorectal cancer shows great potential in accelerating the study of CRC mechanisms and the development of anti‐CRC drugs. To this end, a pathomimetic colorectal tumor‐on‐a‐chip (CRT‐chip) that can effectively recapitulate the in vivo dynamic physiology and pathology of primary CRC is proposed. It not only allows controllable seeding and cultivation of CRC cells to emulate the site‐specific occurrence of primary CRC, but also provides continuous low‐speed flows and peristalsis‐like deformation on colorectum epithelium to simulate the fluid shearing and peristalsis in human colorectum. Moreover, a channel that transports nutrients to CRC cells is designed specifically to mimic the function of tumor vessels. Based on the pathomimetic CRT‐chip, the therapeutic effect of a photothermal anticancer drug was tested and quantified, exhibiting its great potentials in in vitro evaluation of anti‐CRC drugs. [ABSTRACT FROM AUTHOR]

The naturally evolved and intestinal pathogenic Fusobacterium nucleatum (Fn)-induced drug resistance profoundly impaired the efficacy of chemotherapy against colorectal cancer (CRC). Alternative treatment modalities against Fn -associated CRC are desperately needed. Herein, we engineer an in situ-activated anti-tumor and antibacterial nanoplatform (Cu 2 O/BNN6@MSN-Dex) to allow photoacoustic (PA) imaging-guided photothermal and NO gas combinatorial therapy for enhanced Fn -associated CRC treatment. The nanoplatform is constructed by loading cuprous oxide (Cu 2 O) and nitric oxide (NO) donor (BNN6) into dextran-decorated mesoporous silica nanoparticles (MSN), which is finally surface-functionalized with dextran via dynamic boronate linkage. Cu 2 O can be sulfuretted in situ by endogenous hydrogen sulfide overexpressed in CRC to produce copper sulfide with remarkable PA and photothermal properties, enabling the generation of NO from BNN6 under 808 nm laser irradiation, which is eventually triggered to release by multiple biological cues in the tumor microenvironment. Cu 2 O/BNN6@MSN-Dex exhibits superior biocompatibility, as well as H 2 S-triggered near-infrared-controlled antibacterial and anti-tumor performance in vitro and in vivo via photothermal and NO gas combination therapy. Furthermore, Cu 2 O/BNN6@MSN-Dex provokes systemic immune responses, thereby promoting anti-tumor efficacy. This study provides a conbinational strategy to effectively inhibit tumors and intratumor pathogens for enhanced CRC treatment. An in situ-activated nanoplatform was demonstrated to achieve significant CRC inhibition via synchronous intratumor Fn elimination and anti-tumor immune activation under PA imaging-guided PTT/NO gas combinatorial therapy. [Display omitted] • An in situ-activated anti-tumor and antibacterial nanoplatform is developed for enhanced Fn -associated CRC treatment. • The nanoplatform allows in situ generation of copper sulfide with PA and photothermal properties in H 2 S-overexpressed CRC. • NO can be asymptotically produced under NIR irradiation and released via the trigger of clues in CRC microenvironment. • The nanoplatform inhibits CRC under PA imaging-guided PTT/NO gas therapy by eliminating Fn and provoking immune responses. [ABSTRACT FROM AUTHOR]

Abstract Background The development of multidrug resistance (MDR) during postoperative chemotherapy for colorectal cancer substantially reduces therapeutic efficacy. Nanostructured drug delivery systems (NDDSs) with modifiable chemical properties are considered promising candidates as therapies for reversing MDR in colorectal cancer cells. Selenium-doped manganese phosphate (Se-MnP) nanoparticles (NPs) that can reverse drug resistance through sustained release of selenium have the potential to improve the chemotherapy effect of colorectal cancer. Results Se-MnP NPs had an organic–inorganic hybrid composition and were assembled from smaller-scale nanoclusters. Se-MnP NPs induced excessive ROS production via Se-mediated activation of the STAT3/JNK pathway and a Fenton-like reaction due to the presence of manganese ions (Mn2+). Moreover, in vitro and in vivo studies demonstrated Se-MnP NPs were effective drug carriers of oxaliplatin (OX) and reversed multidrug resistance and induced caspase-mediated apoptosis in colorectal cancer cells. OX@Se-MnP NPs reversed MDR in colorectal cancer by down-regulating the expression of MDR-related ABC (ATP binding cassette) transporters proteins (e.g., ABCB1, ABCC1 and ABCG2). Finally, in vivo studies demonstrated that OX-loaded Se-MnP NPs significantly inhibited proliferation of OX-resistant HCT116 (HCT116/DR) tumor cells in nude mice. Conclusions OX@Se-MnP NPs with simple preparation and biomimetic chemical properties represent promising candidates for the treatment of colorectal cancer with MDR.

Colonic diverticulitis is a common gastrointestinal disease which can be acute or chronic in course. In this paper we report the management of a patient with chronic colonic diverticulitis. The patient had an atypical clinical presentation, whose imaging showed a high likelihood of occupying lesions. PET/CT showed hypermetabolism focus and colonoscopy saw mucosal thickening, pathological return of inflammation in the acute phase, which were difficult in differential diagnosis with colorectal cancer and inflammatory bowel disease. After comprehensive consideration, follow-up observation was recommended and the diagnosis was finally clarified. The management of this patient demonstrates the importance of evidence-based medicine in the diagnosis and treatment of diseases.

Abstract Background Macrophage infiltration in the tumor microenvironment participates in the regulation of tumor progression. Previous studies have found that Notch signaling pathway is involved in regulating the progression of colorectal cancer (CRC), however, the specific mechanism is still unclear. Methods The correlation between Notch signaling pathway and macrophage infiltration was investigated in TCGA database and verified in clinical samples of patients with CRC using immunohistochemistry. Gene Set Enrichment Analysis was used to find out genes related to Notch3 expression. Colony formation assay, and flow cytometry were utilized to test tumor growth and immune cell infiltration in vitro and in vivo. Results Using bioinformatics analysis and clinical sample validation, we found that Notch3 was highly expressed in colon tumor tissues compared to adjacent normal tissues, and it participated in regulating the recruitment of macrophages to the tumor microenvironment. Furthermore, we found that the Notch3 expression was positively correlated with the expression of macrophage recruitment-related cytokines in colon tumor tissues. Finally, we demonstrated that depletion of Notch3 had no significant effect on the growth of colon tumor cells in vitro, while, attenuated the growth of colon cancer tumors in vivo. Simultaneous, immunosuppressive cells, macrophages and myeloid-derived suppressor cell (MDSC) infiltration were dramatically reduced in the tumor microenvironment. Conclusion Our study illustrated that Notch3 could facilitate the progression of CRC by increasing the infiltration of macrophages and MDSCs to promote the immunosuppressive tumor microenvironment. Targeting Notch3 specifically is a potentially effective treatment for CRC.

Magnesium ions are essential elements to the human body, with a daily intake of about 350 mg for an adult. Recently, a meta-analysis reported that magnesium ion intake is related to a reduced risk of colorectal tumors. In addition, implantation of biodegradable magnesium pins after colorectal tumor resection could potentially inhibit the residual tumor cells. These impressive results implied that magnesium ions possess inhibitory properties against colorectal carcinoma. However, this hypothesis has yet to be confirmed by experimental results. In this work, different concentrations of magnesium ions were modulated to investigate their inhibitory effects on cell viability through cell cycle arrest, subsequently inducing apoptosis by activating the caspase-3 pathway. The animal experiments revealed that magnesium injection restricted tumor growth after 3 weeks of treatment compared to the control group. According to the immunohistochemistry and transmission electron microscopy results, the remarkable effect may be attributed to promoting the apoptotic rate of tumor cells. The evidence highlights the potential for the clinical use of magnesium implants to inhibit the growth of residual cells after colorectal tumor surgery. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T cell (CAR-T) is regarded as a promising therapy for malignancies. In our previous clinical trial targeted colorectal tumors, we found that CAR-T cells experienced poor proliferation and persistence in tumor sites. To improve the efficacy of CAR-T cells, we introduced CD27 co-stimulation signal into the established system and found that the CEA28BB27Z CAR-T cells exhibited enhanced proliferation and anti-tumor activity. Next, we demonstrated that the CEA28BB27Z CAR-T cells expressed less immune checkpoint receptors and generated more CD4+ and CD8+ memory stem T (TSCM) cells compared with other CARs during constant antigen stimulation. Furthermore, our data revealed that the different combination of co-stimulation signal affected the mitochondrial dynamics of CAR-T cells, and CEA28BB27Z CAR-T cells maintained more fused mitochondrial network compared with others. Finally, we validated the superior antitumor capacity of the CEA28BB27Z CAR-T cells in xenograft models. Our findings suggest that CD27 co-stimulation signals play a key role in improving the anti-tumor efficacy of CAR-T cells. [ABSTRACT FROM AUTHOR]

AimTo describe the currently available evidence regarding the efficacy and safety of preoperative tumor marking using indocyanine green (ICG) prior to laparoscopic or robotic colorectal resections.MethodsA systematic search for relevant studies was conducted using the following databases: Embase (OVID), MEDLINE® (OVID), APA PsycInfo (OVID), Global Health (OVID) and HMIC Health Management Information Consortium (OVID) through June 2022 reported according to PRISMA 2020 guidelines. Primary outcome was the detection rate of the tumor sites preoperatively marked with ICG. Secondary outcomes were timing of ICG injection in days prior to the operation and technique-related complications.ResultsEight single center studies, published between 2008 and 2022, were identified yielding a total of 1,061 patients, of whom 696 were preoperatively tattooed with ICG. Injection dosage of diluted ICG ranged from 0.1–1.5 ml. Four studies used the saline test injection method prior to ICG injection. When the marking was placed within one week, the visualization rate was 650/668 (97%), whereas when it was longer than one week, the detection rate was 8/56 (14%). No severe complications were reported.ConclusionPreoperative tumor marking using ICG prior to minimally invasive colorectal resections is safe and effective, allowing intraoperative tumor site location when performed up to a week prior to surgery without disturbing the surgical view in potential mild complications.

Background: The development of multidrug resistance (MDR) during postoperative chemotherapy for colorectal cancer substantially reduces therapeutic efficacy. Nanostructured drug delivery systems (NDDSs) with modifiable chemical properties are considered promising candidates as therapies for reversing MDR in colorectal cancer cells. Selenium-doped manganese phosphate (Se-MnP) nanoparticles (NPs) that can reverse drug resistance through sustained release of selenium have the potential to improve the chemotherapy effect of colorectal cancer. Results: Se-MnP NPs had an organic–inorganic hybrid composition and were assembled from smaller-scale nanoclusters. Se-MnP NPs induced excessive ROS production via Se-mediated activation of the STAT3/JNK pathway and a Fenton-like reaction due to the presence of manganese ions (Mn2+). Moreover, in vitro and in vivo studies demonstrated Se-MnP NPs were effective drug carriers of oxaliplatin (OX) and reversed multidrug resistance and induced caspase-mediated apoptosis in colorectal cancer cells. OX@Se-MnP NPs reversed MDR in colorectal cancer by down-regulating the expression of MDR-related ABC (ATP binding cassette) transporters proteins (e.g., ABCB1, ABCC1 and ABCG2). Finally, in vivo studies demonstrated that OX-loaded Se-MnP NPs significantly inhibited proliferation of OX-resistant HCT116 (HCT116/DR) tumor cells in nude mice. Conclusions: OX@Se-MnP NPs with simple preparation and biomimetic chemical properties represent promising candidates for the treatment of colorectal cancer with MDR. [ABSTRACT FROM AUTHOR]

Background: Macrophage infiltration in the tumor microenvironment participates in the regulation of tumor progression. Previous studies have found that Notch signaling pathway is involved in regulating the progression of colorectal cancer (CRC), however, the specific mechanism is still unclear. Methods: The correlation between Notch signaling pathway and macrophage infiltration was investigated in TCGA database and verified in clinical samples of patients with CRC using immunohistochemistry. Gene Set Enrichment Analysis was used to find out genes related to Notch3 expression. Colony formation assay, and flow cytometry were utilized to test tumor growth and immune cell infiltration in vitro and in vivo. Results: Using bioinformatics analysis and clinical sample validation, we found that Notch3 was highly expressed in colon tumor tissues compared to adjacent normal tissues, and it participated in regulating the recruitment of macrophages to the tumor microenvironment. Furthermore, we found that the Notch3 expression was positively correlated with the expression of macrophage recruitment-related cytokines in colon tumor tissues. Finally, we demonstrated that depletion of Notch3 had no significant effect on the growth of colon tumor cells in vitro, while, attenuated the growth of colon cancer tumors in vivo. Simultaneous, immunosuppressive cells, macrophages and myeloid-derived suppressor cell (MDSC) infiltration were dramatically reduced in the tumor microenvironment. Conclusion: Our study illustrated that Notch3 could facilitate the progression of CRC by increasing the infiltration of macrophages and MDSCs to promote the immunosuppressive tumor microenvironment. Targeting Notch3 specifically is a potentially effective treatment for CRC. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a common malignancy worldwide, and the gut microbiota and metabolites play an important role in its initiation and progression. In this study, we constructed a mouse model of inflammation-induced colorectal tumors, with fixed doses of azoxymethane/dextran sulfate sodium (AOM/DSS). We found that colorectal tumors only formed in some mice treated with certain concentrations of AOM/DSS (tumor group), whereas other mice did not develop tumors (non-tumor group). 16S rDNA amplicon sequencing and liquid chromatography-mass spectrometry (LC-MS)/MS analyses were performed to investigate the microbes and metabolites in the fecal samples. As a result, 1189 operational taxonomic units (OTUs) were obtained from the fecal samples, and the non-tumor group had a relatively higher OTU richness and diversity. Moreover, 53 different microbes were identified at the phylum and genus levels, including Proteobacteria, Cyanobacteria, and Prevotella. Furthermore, four bacterial taxa were obviously enriched in the non-tumor group, according to linear discriminant analysis scores (log10) > 4. The untargeted metabolomics analysis revealed significant differences between the fecal samples and metabolic phenotypes. Further, the heatmaps and volcano plots revealed 53 and 19 dysregulated metabolites between the groups, in positive and negative ion modes, respectively. Styrene degradation and amino sugar-nucleotide sugar metabolism pathways were significantly different in positive and negative ion modes, respectively. Moreover, a correlation analysis between the metabolome and microbiome was further conducted, which revealed the key microbiota and metabolites. In conclusion, we successfully established a tumor model using a certain dose of AOM/DSS and identified the differential intestinal microbiota and characteristic metabolites that might modulate tumorigenesis, thereby providing new concepts for the prevention and treatment of CRC. [ABSTRACT FROM AUTHOR]

Background/Aims For the treatment of advanced colorectal neoplasms, colon endoscopic submucosal dissection (ESD) is an essential technique; however, it is time-consuming. The purpose of this study was to evaluate the efficacy of a recently developed one-step knife (OSK) in colon ESD and compare it with a conventional knife. Methods Between July 2020 and November 2021, patients scheduled to undergo colorectal ESD were randomly assigned to the OSK group (Endo-UpexTM Onestep knife) or conventional-knife (CK) group (Olympus DualKnife™). The primary outcome was the total submucosal injection time. Additionally, total procedure time, treatment outcome, adverse events, and operator convenience were compared and analyzed. Results A total of 53 patients (28 in the OSK group and 25 in the CK group) were finally analyzed. The mean total injection time was marginally significant reduced in the OSK group compared to CK group (186 [interquartile range {IQR}: 116.8 – 249.5] vs. 265 [IQR: 130.5 – 553.0] sec, p=0.082). Total procedure time tended to have a shorter duration in the OSK group than in the CK group (15.5 [IQR: 11.3 – 22.8] vs. 20 [IQR: 13.5 – 42.5] min, p=0.110). Resection rate and adverse events did not differ between the two groups. A greater proportion of endoscopists expressed high contentment with the utilization of endoscopic knives (OSK), particularly in regards to injection (67.9% vs. 32.0%, p=0.013). Conclusion In comparison to CK, the use of OSK for colorectal ESD marginally significant decreased the total injection and procedure time. It is believed that the use of this newly developed endoscopic knife will be helpful in performing colorectal ESD treatment more effectively [ABSTRACT FROM AUTHOR]

The melanoma cell adhesion molecule, shed from endothelial and cancer cells, is a soluble growth factor that induces tumor angiogenesis and growth. However, the molecular mechanism accounting for its generation in a tumor context is still unclear. To investigate this mechanism, we performed in vitro experiments with endothelial/cancer cells, gene expression analyses on datasets from human colorectal tumor samples, and applied pharmacological methods in vitro/in vivo with mouse and human colorectal cancer cells. We found that soluble MCAM generation is governed by ADAM17 proteolytic activity and NOX1-regulating ADAM17 expression. The treatment of colorectal tumor-bearing mice with pharmacologic NOX1 inhibitors or tumor growth in NOX1-deficient mice reduced the blood concentration of soluble MCAM and abrogated the anti-tumor effects of anti-soluble MCAM antibodies while ADAM17 pharmacologic inhibitors reduced tumor growth and angiogenesis in vivo. Especially, the expression of MCAM, NOX1, and ADAM17 was more prominent in the angiogenic, colorectal cancer-consensus molecular subtype 4 where high MCAM expression correlated with angiogenic and lymphangiogenic markers. Finally, we demonstrated that soluble MCAM also acts as a lymphangiogenic factor in vitro. These results identify a role for NOX1/ADAM17 in soluble MCAM generation, with potential clinical therapeutic relevance to the aggressive, angiogenic CMS4 colorectal cancer subtype.

Cheng-Tao Yu,1,&ast; Tongqing Chen,1,&ast; Sicheng Lu,1,&ast; Wenlong Hu,1 Qinchang Zhang,1 Jiani Tan,1 Dongdong Sun,1 Liu Li,1 Xin Sun,1 Changliang Xu,1 Yueyang Lai,1 Minmin Fan,1 Zhengjie Shen,2 Weixing Shen,1 Haibo Cheng1 1The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Medical Oncology Department, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weixing Shen; Haibo Cheng, The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China, Tel +86 13815857118, Fax +86 2585811006, Email haibocheng@njucm.edu.cn; weixingshen@njucm.edu.cnPurpose: Colorectal cancer (CRC) remains the third most common tumor worldwide. Ulcerative colitis (UC) could cause chronic inflammation and ulcers in the colon and rectum. UC is a risk factor for a high incidence of CRC, and the incidence of UC-associated CRC (UC-CRC) is still increasing. Chinese medicine prescription, Xian-Lian-Jie-Du decoction (XLJDD), has been proven its efficacy in some UC-CRC patients. However, the mechanism of XLJDD in treating UC-CRC remains unknown. This study aimed to investigate the mechanism of XLJDD in treating UC-CRC.Methods: We constructed an AOM/DSS mouse model that could simulate the various stages of UC-CRC in humans. XLJDD and its 5 main components are used to treat the AOM/DSS model, respectively. With the power of high-throughput sequencing technology, we described the mechanism of XLJDD from transcriptomics, proteomics, and single-cell transcriptomics.Results: Our results showed that XLJDD could effectively suppress the occurrence and development of colorectal tumors. Using the weighted correlation network analysis (WGCNA), several mRNA and protein modules that respond to XLJDD have been identified. Moreover, two essential genes, Mfsd2a and Ccdc85c, were caught our attention. They were prognostic markers in CRC patients, and their expression could be significantly modulated by XLJDD, showing their potential as effective targets of XLJDD. In addition, we also discovered that XLJDD could affect the cell composition of the colorectal tumor environment, especially in the infiltration of B cells.Conclusion: We demonstrated that XLJDD could prevent the initiation and development of colorectal tumors by modulating the expression of Mfsd2a and Ccdc85c and reducing the infiltration of B cells in the tumor microenvironment of colorectal tumor.Keywords: colorectal tumor, Mfsd2a, Ccdc85c, inflammation pathway, B cell infiltration

Background: Multiple diet patterns play a crucial role in the development of colorectal cancer and its precursor, colorectal adenoma, but mediating effect of plasma metabolite profiles is unclear., Methods: A total of 95,275 participants from UK Biobank with plasma metabolomics and dietary information were analyzed. Metabolite profile scores for 14 dietary patterns were estimated through elastic net regression. Cox regression analysis assessed the associations of dietary patterns and their metabolite profile scores with colorectal tumor risk. Mediating effects of identified metabolite profile scores were estimated in the associations., Results: Fourteen metabolite profile scores, including a range of 28 to 205 signatures, were weak to moderate correlation with dietary patterns (all p < 0.001). Multivariable Cox regression analyses revealed that five dietary patterns were significantly correlated with a decreased risk of colorectal tumor after FDR correction and adjustment for covariates. HRs (95% CIs) per 1 SD for these diet patterns were as follows: WCRF (0.93, 0.90-0.96), CRC score (0.94, 0.92-0.97), AHEI-2010 (0.95, 0.92-0.97), DASH (0.94, 0.91-0.97), and hPDI (0.95, 0.93-0.98). Similarly, metabolite profile scores for these five dietary patterns were inversely associated with colorectal tumor risk, with HRs (95% CIs) per 1 SD as follows: WCRF (0.59, 0.49-0.70), CRC score (0.67, 0.58-0.77), AHEI-2010 (0.73, 0.65-0.80), DASH (0.75, 0.66-0.84), and hPDI (0.56, 0.47-0.67). The mediation proportions of five metabolite profile scores between dietary patterns and colorectal tumor risk ranged from 6.37 to 27.23% (all p < 0.001)., Conclusions: Five dietary patterns and their metabolite profile scores, were inversely correlated with colorectal tumor risk. These findings highlight the potential of metabolite profiles as mediators in the association between dietary patterns and the risk of colorectal tumor, further contributing to the prevention of colorectal cancer or adenoma and providing new insights for future research., Competing Interests: Declarations. Ethics approval and consent to participate: The UK Biobank had approval from the North West Multi-Centre Research Ethics Committee (MREC) as a Research Tissue Bank (RTB) approval. All participants provided written informed consent before enrolment in the study, which was conducted following the Declaration of Helsinki. This approval means that other researchers do not require separate ethical clearance and can operate under the RTB approval. Consent for publication: All the authors agreed on this manuscript for publication. Competing interests: The authors declare that they have no conflict of interest., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract Background In Japan, endoscopic submucosal dissection (ESD) is standardized for large colorectal tumors. However, its validity in the elderly population is unclear. We aimed to evaluate the safety and efficacy of ESD for colorectal tumors in elderly patients aged over 80 years. Methods ESD was performed on 178 tumors in 165 consecutive patients aged over 80 years between December 2008 and December 2018. We retrospectively evaluated the clinicopathological characteristics and clinical outcomes of ESD. We also assessed the prognosis of 160 patients followed up for more than 12 months. Results The mean patient age was 83.7 ± 3.1 years. The number of patients with comorbidities was 100 (62.5%). Among all patients, 106 (64.2%) were categorized as class 1 or 2 according to the American Society of Anesthesiologists classification of physical status (ASA-PS), and 59 (35.8%) were classified as class 3. The mean procedure time was 97.7 ± 79.3 min. The rate of histological en bloc resection was 93.8% (167/178). Delayed bleeding in 11 cases (6.2%) and perforation in 7 cases (3.9%) were treated conservatively. The 5-year survival rate was 89.9%. No deaths from primary disease (mean follow-up time: 35.3 ± 27.5 months) were observed. Overall survival rates were significantly lower in the non-curative resection group that did not undergo additional surgery than in the curative resection group (P = 0.0152) and non-curative group that underwent additional surgery (P = 0.0259). Overall survival rates were higher for ASA-PS class 1 or 2 patients than class 3 patients (P = 0.0105). Metachronous tumors (> 5 mm) developed in 9.4% of patients. Conclusions ESD for colorectal tumors in patients aged over 80 years is safe. Colorectal cancer-associated deaths were prevented although comorbidities pose a high risk of poor prognosis.

Importance: Postoperative gastrointestinal dysfunction (POGD) may be caused by postoperative vagus nerve tension inhibition and systemic inflammation. Dexmedetomidine (Dex) increases vagus nerve tone and affords an anti-inflammatory property, which may play a role in pathogenesis. Objective: To investigate whether a higher dose of Dex enhances gastrointestinal function recovery. Design: In this retrospective study, patients receiving colorectal surgery at the First Affiliated Hospital of Xi'an Jiaotong University from 2017 to 2019 were included. We evaluated the postoperative flatus time between recipients who received loading plus maintenance dose of DEX (LMD group, 237 recipients) and those who recieved maintenance dose of DEX (MD group, 302 recipients). Data were analyzed by logical regression and stratified and interaction analyses. The simulated pharmacokinetics of two DEX regimens was compared using the Tivatrainer software. Thirty paired blood samples from patients whose propensity scores matched with POGD-related factors at 24 h postoperatively were randomly selected, and their tumor necrosis factor- α (TNF-α), cyclooxygenase-2 (COX-2), d-lactate (DLA), acetylcholine (Ach), interleukin (IL)-10, lipopolysaccharide (LPS), IL-6, and inducible nitric oxide synthase (iNOS) levels were measured. Setting: Operating rooms and general surgery wards. Participants: Among the 644 patients undergoing colorectal surgery, 12 who had a colostomy, 26 without Dex infusion, 20 whose Dex administration mode cannot be classified, and 47 with a history of intestinal surgery were excluded. A total of 539 patients were included. Result: Compared with the MD group, the LMD group had a shorter recovery time to flatus; lower incidences of nausea, vomiting, abdominal distension, and abdominal pain (p < 0.05); and a slightly decreased heart rate. The LMD group was the independent factor of POGD (OR = 0.59, 95% CI = 0.41–0.87, p = 0.007) without being reversed in stratified and interaction analyses and had higher Dex plasma concentration from skin incision to 8 h postoperatively. The LMD group had a 39% and 43% increase in Ach and IL-10 levels, respectively, and a 33%–77% decrease in TNF-α, IL-6, COX-2, iNOS, LPS, and DLA levels (p < 0.05). Conclusion: Adding an extra loading dose of Dex can increase parasympathetic tone and decrease inflammation; hence, it can enhance postoperative gastrointestinal function recovery following colorectal surgery. [ABSTRACT FROM AUTHOR]

Abstract Background An educational and training program is required for generalization of Japan NBI Expert Team (JNET) classification. However, there is no detailed report on the learning curve of the diagnostic accuracy of endoscopists using JNET classification. We examined the effect of an educational lecture on beginners and less experienced endoscopists for improving their diagnostic accuracy of colorectal lesions by JNET classification. Methods Seven beginners with no endoscopy experience (NEE group), 7 less experienced endoscopists (LEE group), and 3 highly experienced endoscopists (HEE group) performed diagnosis using JNET classification for randomized NBI images of colorectal lesions from 180 cases (Type 1: 22 cases, Type 2A: 105 cases, Type 2B: 33 cases, and Type 3: 20 cases). Next, the NEE and LEE groups received a lecture on JNET classification, and all 3 groups repeated the diagnostic process. We compared the correct diagnosis rate and interobserver agreement before and after the lecture comprehensively and for each JNET type. Results In the HEE group, the correct diagnosis rate was more than 90% with good interobserver agreements (kappa value: 0.78–0.85). In the NEE and LEE groups, the correct diagnosis rate (NEE: 60.2 → 68.0%, P

Importance: Postoperative gastrointestinal dysfunction (POGD) may be caused by postoperative vagus nerve tension inhibition and systemic inflammation. Dexmedetomidine (Dex) increases vagus nerve tone and affords an anti-inflammatory property, which may play a role in pathogenesis.Objective: To investigate whether a higher dose of Dex enhances gastrointestinal function recovery.Design: In this retrospective study, patients receiving colorectal surgery at the First Affiliated Hospital of Xi’an Jiaotong University from 2017 to 2019 were included. We evaluated the postoperative flatus time between recipients who received loading plus maintenance dose of DEX (LMD group, 237 recipients) and those who recieved maintenance dose of DEX (MD group, 302 recipients). Data were analyzed by logical regression and stratified and interaction analyses. The simulated pharmacokinetics of two DEX regimens was compared using the Tivatrainer software. Thirty paired blood samples from patients whose propensity scores matched with POGD-related factors at 24 h postoperatively were randomly selected, and their tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), d-lactate (DLA), acetylcholine (Ach), interleukin (IL)-10, lipopolysaccharide (LPS), IL-6, and inducible nitric oxide synthase (iNOS) levels were measured.Setting: Operating rooms and general surgery wards.Participants: Among the 644 patients undergoing colorectal surgery, 12 who had a colostomy, 26 without Dex infusion, 20 whose Dex administration mode cannot be classified, and 47 with a history of intestinal surgery were excluded. A total of 539 patients were included.Result: Compared with the MD group, the LMD group had a shorter recovery time to flatus; lower incidences of nausea, vomiting, abdominal distension, and abdominal pain (p < 0.05); and a slightly decreased heart rate. The LMD group was the independent factor of POGD (OR = 0.59, 95% CI = 0.41–0.87, p = 0.007) without being reversed in stratified and interaction analyses and had higher Dex plasma concentration from skin incision to 8 h postoperatively. The LMD group had a 39% and 43% increase in Ach and IL-10 levels, respectively, and a 33%–77% decrease in TNF-α, IL-6, COX-2, iNOS, LPS, and DLA levels (p < 0.05).Conclusion: Adding an extra loading dose of Dex can increase parasympathetic tone and decrease inflammation; hence, it can enhance postoperative gastrointestinal function recovery following colorectal surgery.

Background/aim: The main aim of the study is to assess expression levels of CDH1, FHIT, PTEN, and TTPAL genes in tumors and peripheral bloods of colorectal cancer patients in staged I-IV. Materials and methods: Gene expression analysis of related genes were performed for tumor tissues and peripheral blood samples of 51 colorectal cancer patients and colon tissues and blood samples of 5 healthy individuals. The real-time-PCR reaction method was used for the analysis. Results: Alteration of mRNA levels of related genes in tumor tissues of colorectal cancer cases was determined compared to control tissues. GAPDH and TBP were used for the normalization. While the mRNA levels of CDH1 decreased, the mRNA level of the FHIT and TTPAL genes increased in the tumor tissues. There was no PTEN gene expression difference in tumor tissues (total). The mRNA levels of the CDH1 and PTEN genes were increased while the mRNA levels of FHIT and TTPAL genes decreased in the blood (total). The mRNA levels of the CDH1 gene decreased at each stage (I-IV) in the tumor tissues and increased at each stage (I-IV) in the blood. The PTEN gene mRNA levels at each stage were controversial. The mRNA levels of the FHIT gene increased at stage I-II-III, decreased at stage IV in the tissues and decreased at each stage (I-IV) in the blood. The mRNA levels of TTPAL gene increased at each stage (I-IV) in the tissues and decreased at each stage (I-IV) in the blood. Conclusion: Although related expression levels in tissue did not correlate with its expression in blood, consistent with previous studies FHIT and TTPAL genes upregulation and CDH1 downregulation, in especially tumoral tissues, may serve as predictive determinants for the patients with colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Colorectal and prostate cancers are the most common types of cancer in men worldwide. To diagnose colorectal and prostate cancer, a pathologist performs a histological analysis on needle biopsy samples. This manual process is time-consuming and error-prone, resulting in high intra- and interobserver variability, which affects diagnosis reliability. Objective: This study aims to develop an automatic computerized system for diagnosing colorectal and prostate tumors by using images of biopsy samples to reduce time and diagnosis error rates associated with human analysis. Methods: In this study, we proposed a convolutional neural network (CNN) model for classifying colorectal and prostate tumors from multispectral images of biopsy samples. The key idea was to remove the last block of the convolutional layers and halve the number of filters per layer. Results: Our results showed excellent performance, with an average test accuracy of 99.8% and 99.5% for the prostate and colorectal data sets, respectively. The system showed excellent performance when compared with pretrained CNNs and other classification methods, as it avoids the preprocessing phase while using a single CNN model for the whole classification task. Overall, the proposed CNN architecture was globally the best-performing system for classifying colorectal and prostate tumor images. Conclusions: The proposed CNN architecture was detailed and compared with previously trained network models used as feature extractors. These CNNs were also compared with other classification techniques. As opposed to pretrained CNNs and other classification approaches, the proposed CNN yielded excellent results. The computational complexity of the CNNs was also investigated, and it was shown that the proposed CNN is better at classifying images than pretrained networks because it does not require preprocessing. Thus, the overall analysis was that the proposed CNN architecture was globally the best-performing system for classifying colorectal and prostate tumor images. [ABSTRACT FROM AUTHOR]

Abstract Introduction The incidence of synchronous RCC and colorectal cancer is heterogeneous ranging from 0.03 to 4.85%. Instead, only one case of huge colon carcinoma and renal angiomyolipoma was reported. The treatment of synchronous kidney and colorectal neoplasm is, preferably, synchronous resection. Currently, laparoscopic approach has shown to be feasible and safe, and it has become the gold standard of synchronous resection due to advantages of minimally invasive surgery. We presented a case synchronous renal neoplasm and colorectal cancer undergone simultaneous totally robotic renal enucleation and rectal resection with primary intracorporeal anastomosis. As our knowledge, this is the first case in literature of simultaneous robotic surgery for renal and colorectal tumor. Case presentation A 53-year-old woman was affected by recto-sigmoid junction cancer and a solid 5 cm left renal mass. We performed a simultaneous robotic low anterior rectal resection and renal enucleation. Total operative time was 260 min with robotic time of 220 min; estimated blood loss was 150 ml; time to flatus was 72 h, and oral diet was administered 4 days after surgery. The patient was discharged on the eighth post-operative day without peri- and post-operative complication. The definitive histological examination showed a neuroendocrine tumor pT2N1 G2, with negative circumferential and distal resection margins. Renal tumor was angiomyolipoma. At 23 months follow-up, the patient is recurrence free. Discussion and conclusion As our knowledge, we described the first case in literature of simultaneous robotic anterior rectal resection and partial nephrectomy for treatment of colorectal tumor and renal mass. Robotic rectal resection with intracorporeal anastomosis surgery seems to be feasible and safe even when it is associated with simultaneous partial nephrectomy. Many features of robotic technology could be useful in combined surgery. This strategy is recommended only when patients’ medical conditions allow for longer anesthesia exposure. The advantages are to avoid a delay treatment of second tumor, to reduce the time to start the post-operative adjuvant chemotherapy, to avoid a second anesthetic procedure, and to reduce the patient discomfort. However, further studies are needed to evaluate robotic approach as standard surgical strategy for simultaneous treatment of colorectal and renal neoplasm.

Background and Aim Cases of colorectal endoscopic submucosal dissection (ESD) with poor maneuverability are often encountered. We aimed to evaluate the efficacy of balloon‐assisted endoscopy (BAE) for such cases. Methods We confirmed maneuverability preoperatively in 400 consecutive cases of colorectal ESD performed at a single center from April 2011 to April 2018. A total of 83 deep colon cases judged as having poor maneuverability were retrospectively reviewed; 54 cases underwent BAE with a single balloon endoscope (group B), and 29 cases underwent conventional procedures without BAE (group C). Tumor size, procedure duration, dissection speed, en bloc resection rate, histology, and associated complications were compared between groups. Results The mean tumor size, tumor invasiveness, fibrosis, and complications did not differ between groups. Although the en bloc resection rate did not differ (both 98%), the groups significantly differed with regard to the R0 resection rate (B: 96%; C: 83%; P = 0.048). Overall, the procedure duration (B: 51 min; C: 70 min; P = 0.17) and dissection speed (B: 19.4 mm2/min; C: 17.4 mm2/min; P = 0.13) were not significantly different between groups. However, the dissection speed for lesions in the cecum/ascending colon was significantly faster in group B than in group C (B: 22.3 mm2/min; C: 11.3 mm2/min; P = 0.037). Conclusions In cases of colorectal ESD with poor maneuverability, the use of BAE contributed to an improvement in the R0 resection rate. In addition, BAE contributed to a quicker dissection speed for lesions located in the cecum/ascending colon.

Due to the irregularity of colorectal tumor contours, it is a challenging task for clinicians to segment colorectal tumors manually in CT scans. To solve this problem, a novel algorithm based on a convolutional neural network with an attention mechanism is proposed to automatically achieve tumor segmentation. The proposed network consists of three major modules: an encoder module, which is fed CT scans to attain the feature map; a dual attention module, which includes a channel attention module and a position attention module to obtain more contextual information in the deep layer of the network; and a decoder module, which restores the feature map to the original size of the input images. We used 1131 CT slices of colorectal tumors to train and test the proposed network. Compared with U-Net and CE-Net, the Dice coefficient increased by 1.46% and 0.66% respectively, for our model. The comprehensive results show that the proposed network performs more effectively in colorectal tumor segmentation than the other methods.

Background: With the continuous progress of colorectal cancer treatment technology, the survival rate of patients has improved significantly, but the problem of postoperative neurocognitive dysfunction has gradually attracted attention., Aim: To analyze the risk factors for delayed postoperative neurocognitive recovery (DNR) after laparoscopic colorectal cancer surgery and constructed a risk prediction model to provide an evidence-based reference for the prevention and treatment of DNR after laparoscopic colorectal cancer surgery., Methods: The clinical data of 227 patients with colorectal cancer who underwent laparoscopic surgery and regional cerebral saturation oxygenation (rScO 2 ) monitoring at our hospital from March 2020 to July 2022 were retrospectively analyzed. Common factors and potential factors affecting postoperative DNR were used as analysis variables, and univariate analysis and multifactor analysis were carried out step by step to determine the predictors of the model and construct a risk prediction model. The predictive performance of the model was assessed by the receiver operating characteristic (ROC) curve, the calibration curve was used to assess the fit of the model to the data, and a nomogram was drawn. In addition, 30 patients who met the inclusion and exclusion criteria from January 2023 to July 2023 were selected for external verification of the prediction model., Results: The incidence of postoperative DNR in the modeling group was 15.4% (35/227). Multivariate analysis revealed that age, years of education, diabetes status, and the lowest rScO 2 value were the independent influencing factors of postoperative DNR (all P < 0.05). Accordingly, a DNR risk prediction model was constructed after laparoscopic colorectal cancer surgery. The area under the ROC curve of the model was 0.757 (95%CI: 0.676-0.839, P < 0.001), and the Hosmer-Lemeshow test of the calibration curve suggested that the model was well fitted ( P = 0.516). The C-index for external validation of the row was 0.617., Conclusion: The DNR risk prediction model associated with rScO 2 monitoring can be used for individualized assessment of patients undergoing laparoscopic colorectal cancer surgery and provides a clinical basis for the prevention of DNR after surgery., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Colorectal cancer (CRC) is one of the most common malignant tumors, and early screening is crucial to improving the survival rate of patients. The combination of colonoscopy and immune fecal occult blood detection has garnered significant attention as a novel method for CRC screening. Colonoscopy and fecal occult blood tests, when combined, can improve screening accuracy and early detection rates, thereby facilitating early intervention and treatment. However, certain risks and costs accompany it, making the establishment of a risk classification model crucial for accurate classification and management of screened subjects., Aim: To evaluate the feasibility and effectiveness of colonoscopy, immune fecal occult blood test (FIT), and risk-graded screening strategies in CRC screening., Methods: Based on the randomized controlled trial of CRC screening in the population conducted by our hospital May 2020 to May 2023, participants who met the requirements were randomly assigned to a colonoscopy group, an FIT group, or a graded screening group at a ratio of 1:2:2 (after risk assessment, the high-risk group received colonoscopy, the low-risk group received an FIT test, and the FIT-positive group received colonoscopy). The three groups received CRC screening with different protocols, among which the colonoscopy group only received baseline screening, and the FIT group and the graded screening group received annual follow-up screening based on baseline screening. The primary outcome was the detection rate of advanced tumors, including CRC and advanced adenoma. The population participation rate, advanced tumor detection rate, and colonoscopy load of the three screening programs were compared., Results: A total of 19373 subjects who met the inclusion and exclusion criteria were enrolled, including 8082 males (41.7%) and 11291 females (58.3%). The mean age was 60.05 ± 6.5 years. Among them, 3883 patients were enrolled in the colonoscopy group, 7793 in the FIT group, and 7697 in the graded screening group. Two rounds of follow-up screening were completed in the FIT group and the graded screening group. The graded screening group (89.2%) and the colonoscopy group (42.3%) had the lowest overall screening participation rates, while the FIT group had the highest (99.3%). The results of the intentional analysis showed that the detection rate of advanced tumors in the colonoscopy group was greater than that of the FIT group [2.76% vs 2.17%, odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.01-1.65, P = 0.037]. There was no significant difference in the detection rate of advanced tumors between the colonoscopy group and the graded screening group (2.76% vs 2.35%, OR = 1.9, 95%CI: 0.93-1.51, P = 0.156), as well as between the graded screening group and the FIT group (2.35% vs 2.17%, OR = 1.09%, 95%CI: 0.88-1.34, P = 0.440). The number of colonoscopy examinations required for each patient with advanced tumors was used as an index to evaluate the colonoscopy load during population screening. The graded screening group had the highest colonoscopy load (15.4 times), followed by the colonoscopy group (10.2 times), and the FIT group had the lowest (7.8 times)., Conclusion: A hierarchical screening strategy based on CRC risk assessment is feasible for screening for CRC in the population. It can be used as an effective supplement to traditional colonoscopy and FIT screening programs., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

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Background: In Japan, endoscopic submucosal dissection (ESD) is standardized for large colorectal tumors. However, its validity in the elderly population is unclear. We aimed to evaluate the safety and efficacy of ESD for colorectal tumors in elderly patients aged over 80 years.Methods: ESD was performed on 178 tumors in 165 consecutive patients aged over 80 years between December 2008 and December 2018. We retrospectively evaluated the clinicopathological characteristics and clinical outcomes of ESD. We also assessed the prognosis of 160 patients followed up for more than 12 months.Results: The mean patient age was 83.7 ± 3.1 years. The number of patients with comorbidities was 100 (62.5%). Among all patients, 106 (64.2%) were categorized as class 1 or 2 according to the American Society of Anesthesiologists classification of physical status (ASA-PS), and 59 (35.8%) were classified as class 3. The mean procedure time was 97.7 ± 79.3 min. The rate of histological en bloc resection was 93.8% (167/178). Delayed bleeding in 11 cases (6.2%) and perforation in 7 cases (3.9%) were treated conservatively. The 5-year survival rate was 89.9%. No deaths from primary disease (mean follow-up time: 35.3 ± 27.5 months) were observed. Overall survival rates were significantly lower in the non-curative resection group that did not undergo additional surgery than in the curative resection group (P = 0.0152) and non-curative group that underwent additional surgery (P = 0.0259). Overall survival rates were higher for ASA-PS class 1 or 2 patients than class 3 patients (P = 0.0105). Metachronous tumors (> 5 mm) developed in 9.4% of patients.Conclusions: ESD for colorectal tumors in patients aged over 80 years is safe. Colorectal cancer-associated deaths were prevented although comorbidities pose a high risk of poor prognosis. [ABSTRACT FROM AUTHOR]

Background: Endoscopic submucosal dissection (ESD) is a technically difficult and time-consuming procedure for the treatment of large colorectal tumors. In Japan, the ball-tip bipolar-current needle-knife (BB-knife) has been used in ESD as a safe device that minimizes the damage to deeper tissues of colorectal neoplasms. In May 2012, a BB-knife combined with a water jet function (Jet B-knife) was newly developed. Methods: This retrospective study was aimed at examining the effectiveness and safety of the Jet B-knife. The BB-knife was used in 276 lesions (BB-knife group), while the Jet B-knife was used in 245 lesions (Jet B-knife group). We evaluated tumor characteristics and the results of the ESD procedures, including the size of the resected tumor, histological diagnosis, time required for resection, frequency of using other electrical devices, en bloc resection rate, and incidence rate of associated complications. Then, the data obtained were compared between the two groups. Results: The histological evaluation of the resected tumors revealed that the incidence of cancer was not significantly different between the two groups. The median time required for resection was 103 min (45–255) in the BB-knife group and 51 min (28–210) in the Jet B-knife group. The difference was statistically significant (p < 0.05). Furthermore, the median tumor diameters were 23.1 mm (18–50) and 26.2 mm (20–60) in the BB-knife and Jet B-knife groups, respectively, demonstrating a statistically significant difference (p < 0.05). Multivariate logistic regression analysis revealed that short resection time (p < 0.001) and reduced use of hemostatic devices (p < 0.01) were independent favorable features of Jet B-knife. The en bloc resection rate and the perforation rate were not statistically significant between the two groups. Conclusions: Use of the Jet B-knife may contribute to the development of a time-saving, cost-effective, and safe procedure for ESD of colorectal tumors. [ABSTRACT FROM AUTHOR]

Purpose: Endoscopic clipping closure after colorectal endoscopic submucosal dissection (ESD) did not reduce the incidence of post-ESD coagulation syndrome (PECS) in our recent randomized controlled trial (RCT); however, the definition of PECS is still controversial. The aim of this study is to establish optimal definition of PECS with additional analysis of RCT based on another definition. Methods: In this multicenter, single-blind RCT, individuals were randomly assigned to colorectal ESD followed by endoscopic clipping closure or non-closure. In this post hoc analysis, the definition of PECS was modified as both localized abdominal pain on visual analogue scale and inflammatory response (fever or leukocytosis), from either localized abdominal pain or inflammatory response in the original study. All participants underwent a computed tomography after ESD, and PECS was classified into type I, conventional PECS without extra-luminal air, and type II, PECS with peri-luminal air. Results: A total of 155 patients (84 in the non-closure group and 71 in the closure group) were analyzed. As a result of criteria modification, 21 type I PECS and four type II PECS cases in the original study, which included patients with clear pain and inflammatory response, were downgraded to no adverse event and simple peri-luminal air, respectively. The frequency of PECS showed no significant difference between non-closure and closure groups. Conclusion: Clipping closure after colorectal ESD does not reduce the incidence of PECS regardless of the diagnostic criteria. Either localized abdominal pain or inflammatory response might be optimal criteria of PECS (UMIN000027031). Trial registration number: UMIN000027031 Date of registration: April 18, 2017 [ABSTRACT FROM AUTHOR]