Colorectal Tumors Research Articles

Retracted: Application of Computer-Based Simulation Teaching Combined with PBL in Colorectal Tumor Hemorrhage.

[This retracts the article DOI: 10.1155/2022/1251388.].

Detection of Human cytomegalovirus UL55 Gene and IE/E Protein Expression in Colorectal Cancer Patients in Egypt

BackgroundA possible relation between Human cytomegalovirus (HCMV) and colorectal cancer (CRC) has been widely explored with an unclear role yet speculated.AimThe study aimed at detecting HCMV UL55 gene, immediate early and early (IE/E) proteins in colorectal tumor tissues and adjacent non neoplastic tissues (ANNT). Also, it aimed to correlate HCMV presence with CRC clinicopathological features.Subjects and methodsA prospective study of 50 HCMV seropositive patients with resectable CRC were enrolled in the study. Demographic, clinical, and radiological findings were recorded. Pathological assessment was done. Paired CRC tumorous and ANNT were examined for HCMV UL55 by PCR and for IE/ E proteins by immunohistochemistry (IHC).Results70% of CRC patients enrolled were females and 36% were elderly (> 60y). Adenocarcinoma was the prevalent histopathological type (92%) with Grade 2, higher stages, and nodal involvement accounting for (64%, 64% and 56%) respectively.HCMV detection was significantly higher in tumoral tissue versus ANNT by PCR and IHC (P < 0.001, P < 0.008) respectively. Moderate agreement was found between the two techniques (κ = 0.572, P < 0.001).Univariate analysis identified HCMV presence to be significantly higher in elderly patients, in tumors with higher stage and with nodal involvement (P = 0.041, P = 0.008, P = 0.018 respectively). In multivariate analysis, the latter two retained significance (P = 0.010, P = 0.008).ConclusionCRC tumor tissues are more infected by HCMV than ANNT. A significant association of HCMV presence with a higher CRC tumor stage and nodal involvement in an age-dependent manner was detected. HCMV oncomodulatory and a disease progression role is suspected.

Preoperative fluorescent clip marking vs. India ink tattooing for tumor identification during colorectal surgery.

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. 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. 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. In colorectal surgery, FCM provides better visibility than the conventional India ink tattooing method and is a simple and safe marking method. 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 .

Surgical approach to achieve R0 resections in primary and metastatic liver tumors: a literature review.

Primary and metastatic liver tumors are a significant cause of mortality worldwide. Regardless of the etiology of the tumor, macro- and microscopically clear margins (R0) while preserving adequate function of the remaining organ are the main goals after liver resections. However, technically challenging procedures are required to achieve R0 resection. Currently, there is no consensus of which should be the ideal minimal safety margin for liver tumor resections, with contrasting reports in regards of safety, tumor recurrence and overall outcomes following R0. Therefore, we aim to review current worldwide surgical practices to achieve R0 resections for primary and metastatic liver tumors in challenging surgical techniques and their reported outcomes. PubMed database, Google Scholar, and OVID Medline were searched for peer-reviewed original articles related to surgical techniques performed to achieve R0 resections in the setting of primary and/or metastatic liver tumors. An up-to-date review of English-language articles published between 2015 to July 2022 was performed. Primary and metastatic liver tumors can be effectively treated using hepatic resection. Current literature highlights that tumors involving major vascular structures are not uncommon. Surgical advances have allowed for vascular control techniques, as well as vascular resections to be performed in a feasible and safe manner to achieve R0 resections. Complex resections combining surgical techniques can be performed in certain population after a detailed evaluation. Liver transplantation (LT) have been used with varying degrees of success for treatment of patients with hepatocellular carcinoma, cholangiocarcinoma (CCA), colorectal liver metastases (CRLM), non-resectable CRLM and metastatic neuroendocrine tumors. Safety and feasibility of R0 resections have been reported for multiple techniques. Technical complexity should not be a limitation to achieve or pursue R0 tumor resection. However, there has to be a balance between patient risk/benefit in attempting R0 resections. Adequate training of surgeons on implementation of complex techniques, as well as transplant oncology techniques applied to hepato-pancreato-biliary (HPB) surgery represents as a promising path to improve short and long-term outcomes for liver-related oncology patients.

Ionizable polymeric nanocarriers for the codelivery of bi-adjuvant and neoantigens in combination tumor immunotherapy.

Ionizable lipid nanocarriers have made historical contribution to COVID-19 mRNA vaccines. Here, we report ionizable polymeric nanoparticles that co-deliver bi-adjuvant and neoantigen peptides for cancer immunotherapy in combination with immune checkpoint blockade (ICB). Current cancer ICB benefits only a small subset of patients, largely due to a lack of pre-existing target cells and checkpoint targets for ICB, tumor antigenic heterogeneity, and tumor immunosuppression. Therapeutic vaccines hold the potential to enhance ICB therapeutic efficacy by expanding antitumor cell repertoires, upregulating immune checkpoint levels and hence sensitizing ICB, and reducing tumor immunosuppression. Chemically defined peptide vaccines are attractive, but their current therapeutic efficacy has been limited due to 1) poor vaccine delivery to immunomodulatory lymph nodes (LNs) and antigen (Ag)-presenting cells (APCs), 2) poor immunostimulant adjuvant efficacy with restricted target cell subsets in humans, 3) limited adjuvant/Ag codelivery to enhance Ag immunogenicity, and 4) limited ability to overcome tumor antigenic heterogeneity. Here, we developed nanovaccines (NVs) using pH-responsive polymeric micellular nanoparticles (NPs) for the codelivery of bi-adjuvant [Toll-like receptor (TLR) 7/8 agonist R848 and TLR9 agonist CpG] and peptide neoantigens (neoAgs) to draining LNs for efficient Ag presentation in a broad range of APC subsets. These NVs potentiated the immunogenicity of peptide Ags and elicits robust antitumor T cell responses with memory, and remodeled the tumor immune milium with reduced tumor immunosuppression. As a result, NVs significantly enhanced ICB therapeutic efficacy for murine colorectal tumors and orthotopic glioblastoma multiforme (GBM). These results suggest marked potential of bi-adjuvant/neoAg-codelivering NVs for combination cancer immunotherapy.

Introducing novel key genes and transcription factors associated with rectal cancer response to chemoradiation through co-expression network analysis

Preoperative radiochemotherapy is a promising therapeutic method for locally advanced rectal cancer patients. However, the response of colorectal cancer (CRC) patients to preoperative radiotherapy varies widely. In this study, we aimed to identify novel biomarkers that could predict the response of colorectal tumors to treatment using a systems biology approach. We applied the Weighted Gene Co-Expression Network Analysis to construct co-expression networks and evaluated the correlation of these networks with radiation using the module-trait relationship. We then identified hub genes and related transcription factors in the selected co-expression module.Our analysis of seven constructed modules revealed that one module, which contained 113 nodes and 6066 edges, had the strongest correlation with radiation effects on CRC (correlation = 0.85; p-value = 6e-7). By analyzing the selected module with the CytoHubba plugin, we identified four hub genes, including ZEB2, JAM2, NDN, and PPAP2A. We also identified seven important transcription factors, including KLF4, SUZ12, TCF4, NANOG, POU5F1, SOX2, and SMARCA4, which may play essential roles in regulating the four hub genes.In summary, our findings suggest that ZEB2, JAM2, NDN, and PPAP2A, along with the seven transcription factors related to these hub genes, may be associated with the response of colorectal tumors to chemoradiotherapy.

Diagnostic and therapeutic strategies for colorectal tumor with positive muscle-retracting sign.

Endoscopic submucosal dissection (ESD) for colorectal tumors with positive muscle-retracting (MR) sign often results in incomplete resection or discontinuation owing to the difficulty of submucosal dissection. The present study aimed to evaluate the usefulness of endoscopic ultrasonography (EUS) in diagnosing the MR sign and performing ESD using the pocket-creation method (PCM). Thirty-six cases of colorectal tumors with positive MR sign during ESD between January 2015 and December 2021 were retrospectively reviewed. Cases were divided into two groups: 1) the conventional method (CM) group, comprising 29 cases, and 2) the PCM group with seven cases, in which preoperative EUS and ESD using PCM were performed. Treatment outcomes were compared between the groups. The diagnostic yield of EUS for the MR sign was evaluated among large sessile tumors >20 mm in which preoperative EUS was performed. Histologic diagnosis was adenoma or Tis carcinoma in 12 cases (33%), T1 carcinoma in 18 cases (50%), T2 carcinoma in four cases (11%), and unevaluable in two cases (6%). The sensitivity and specificity of the EUS-MR sign for large sessile tumors were 87.5% and 83.3%, respectively. ESD was achieved in all cases in the PCM group, although it was discontinued in eight cases (28%) in the CM group. There were significant differences between the PCM and CM groups in en bloc resection (100% vs. 48%, p = 0.013) and R0 resection rates (71% vs. 31%, p = 0.049). The MR sign can be predicted by preoperative EUS, and ESD using PCM allows en bloc resection.

Light‐Activatable Liquid Metal Immunostimulants for Cancer Nanotheranostics

AbstractGallium‐based liquid metal (LM) nanoparticles are among the most promising nanoscale materials for biomedicinal applications because of their outstanding physicochemical properties, including unique flexibility, easy surface modification, excellent photothermal conversion efficiency, and high biocompatibility. Further exploration of the modification and remote‐controlling performances of LM nanoparticles with functional bioactive molecules for the development of an innovative treatment modality for diseases is challenging. Herein, it is reported that near‐infrared (NIR) light‐activatable LM nanoparticle, which functionalized with immunological activators of T and dendritic cells, can work as highly immunogenic and photo‐exothermic nanoscale stimulants for cancer treatment. The synthesized LM nanostimulant, which has low toxicity, powerful photothermal conversion property, and high immunogenic features, can effectively eliminate cancer cells, cancer spheroids, and colorectal tumors in living mice under NIR laser illumination. Moreover, the fluorescent LM nanostimulant can express strong fluorescence as a reporter agent to identify the targeted tumors in living mice for optical cancer diagnosis. Therefore, such a smart nanostimulant represents a way toward combination photothermal immunotheranostics.

Loss of PERK function promotes ferroptosis by downregulating SLC7A11 (System Xc⁻) in colorectal cancer

Ferroptosis, a genetically and biochemically distinct form of programmed cell death, is characterised by an iron-dependent accumulation of lipid peroxides. Therapy-resistant tumor cells display vulnerability toward ferroptosis. Endoplasmic Reticulum (ER) stress and Unfolded Protein Response (UPR) play a critical role in cancer cells to become therapy resistant. Tweaking the balance of UPR to make cancer cells susceptible to ferroptotic cell death could be an attractive therapeutic strategy. To decipher the emerging contribution of ER stress in the ferroptotic process, we observe that ferroptosis inducer RSL3 promotes UPR (PERK, ATF6, and IRE1α), along with overexpression of cystine-glutamate transporter SLC7A11 (System Xc-). Exploring the role of a particular UPR arm in modulating SLC7A11 expression and subsequent ferroptosis, we notice that PERK is selectively critical in inducing ferroptosis in colorectal carcinoma. PERK inhibition reduces ATF4 expression and recruitment to the promoter of SLC7A11 and results in its downregulation. Loss of PERK function not only primes cancer cells for increased lipid peroxidation but also limits in vivo colorectal tumor growth, demonstrating active signs of ferroptotic cell death in situ. Further, by performing TCGA data mining and using colorectal cancer patient samples, we demonstrate that the expression of PERK and SLC7A11 is positively correlated. Overall, our experimental data indicate that PERK is a negative regulator of ferroptosis and loss of PERK function sensitizes colorectal cancer cells to ferroptosis. Therefore, small molecule PERK inhibitors hold huge promise as novel therapeutics and their potential can be harnessed against the apoptosis-resistant condition.

Current Status of Diagnosis and Treatment of Colorectal Cancer in Asian Countries: A Questionnaire Survey

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.

Dermatan Sulfate/Chitosan Nanoparticles Loaded with an Anti-Inflammatory Peptide Increase the Response of Human Colorectal Cancer Cells to 5-Fluorouracil.

The gold standard drug for colorectal cancer treatment, 5-Fluorouracil (5-FU), induces pharmacological tolerance in long-term management. The transcriptional factor NFκB plays a key role in 5-FU resistance. The aim of this work is to study the capability of polyelectrolytes complex nanoparticles of dermatan sulfate (DS) and chitosan, loaded with the anti-inflammatory tripeptide IRW, to sensitize colorectal cancer cells to 5-FU. Fluorescence and flow cytometry studies confirmed the recognition by the nanoformlation, of CD44 receptor, involved the initiation and progression of colorectal tumors. Dynamic light scattering and flow cytometry reinforced the importance of DS and CD44 receptor in the interaction, as the addition of DS or anti CD44 antibody blocked the binding. Moreover, the nanoformulation also interacts with 3D colon cancer cultures, namely colonospheres, enriched in cancer stem cells, subpopulation responsible for drug resistance and metastasis. To evaluate the consequences of this interaction, the subcellular distribution of the transcriptional factor NFκB, was determined by immunofluorescence analysis. Internalization and the intracellular release of IRW inhibited nuclear translocation of NFκB and increased cellular sensitivity to 5-FU. Altogether, the nanoformulation could provide a selective delivery platform for IRW distribution to colorectal tumors, being an innovative strategy towards overcoming 5-FU resistance in colorectal cancer therapy. This article is protected by copyright. All rights reserved.

Novel heavily fucosylated glycans as a promising therapeutic target in colorectal cancer

BackgroundColorectal cancer (CRC) is highly prevalent and lethal globally, and its prognosis remains unsatisfactory. Drug resistance is regarded as the main cause of treatment failure leading to tumor recurrence and metastasis. The overexpression of fucosylated epitopes, which are usually modifications of glycoproteins, was reported to occur in various epithelial cancers. However, the effects of treatments that target these antigens in colorectal cancer remain unclear.MethodsThis study investigated the expression of heavily fucosylated glycans (HFGs) in 30 clinical samples from patients with CRC and other normal human tissues. The complement-dependent cytotoxicity was explored in vitro through treatment with anti-HFG monoclonal antibody (mAb) alone or in combination with chemotherapeutic agents. In vivo inhibitory effects were also examined using a xenograft mouse model.ResultsImmunohistochemistry staining and western blotting revealed that HFG expression was higher in human colorectal cancer tissues than in normal tissues. In DLD-1 and SW1116 cells, which overexpress fucosylated epitopes, anti-HFG mAb produced observable cytotoxic effects, especially when it was combined with chemotherapeutic agents. The xenograft model also demonstrated that anti-HFG mAb had potent and dose-dependent inhibitory effects on colorectal tumor growth.ConclusionsAs a novel cancer antigen, HFGs are a promising treatment target, and the implementation of anti-HFG mAb treatment for CRC warrants further investigation.

Precision Medicine in the Era of Genetic Testing: Microsatellite Instability Evolved.

The recognized importance of microsatellite instability (MSI) in cancer has evolved considerably in the past 30 years. From its beginnings as a molecular predictor for Lynch syndrome, MSI first transitioned to a universal screening test in all colorectal and endometrial cancers, substantially increasing the identification of patients with Lynch syndrome among cancer patients. More recently, MSI has been shown to be a powerful biomarker of response to immune checkpoint blockade therapy across a diversity of tumor types, and in 2017 was granted Food and Drug Administration approval as the first tumor histology-agnostic biomarker for a cancer therapy. Focusing on colorectal cancer specifically, immune checkpoint blockade therapy has been shown to be highly effective in the treatment of both MSI-high (MSI-H) colon and rectal cancer, with data increasingly suggesting an early role for immune checkpoint blockade therapy in MSI-H colorectal tumors in the neoadjuvant setting, with the potential to avoid more toxic and morbid approaches using traditional chemotherapy, radiation therapy, and surgery. The success of MSI as an immune checkpoint blockade target has inspired ongoing vigorous research to identify new similar targets for immune checkpoint blockade therapy that may help to one day expand the reach of this revolutionary cancer therapy to a wider swath of patients and indications.

Risk factors analysis and prediction model construction of submucosal deep infiltration of early colorectal tumor

Objective: To investigate the risk factors for the development of deep infiltration in early colorectal tumors (ECT) and to construct a prediction model to predict the development of deep infiltration in patients with ECT. Methods: The clinicopathological data of ECT patients who underwent endoscopic treatment or surgical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences from August 2010 to December 2020 were retrospectively analyzed. The independent risk factors were analyzed by multifactorial regression analysis, and the prediction models were constructed and validated by nomogram. Results: Among the 717 ECT patients, 590 patients were divided in the within superficial infiltration 1 (SM1) group (infiltration depth within SM1) and 127 patients in the exceeding SM1 group (infiltration depth more than SM1). There were no statistically significant differences in gender, age, and lesion location between the two groups (P>0.05). The statistically significant differences were observed in tumor morphological staging, preoperative endoscopic assessment performance, vascular tumor emboli and nerve infiltration, and degree of tumor differentiation (P<0.05). Multivariate regression analysis showed that only erosion or rupture (OR=4.028, 95% CI: 1.468, 11.050, P=0.007), localized depression (OR=3.105, 95% CI: 1.584, 6.088, P=0.001), infiltrative JNET staging (OR=5.622, 95% CI: 3.029, 10.434, P<0.001), and infiltrative Pit pattern (OR=2.722, 95% CI: 1.347, 5.702, P=0.006) were independent risk factors for the development of deep submucosal infiltration in ECT. Nomogram was constructed with the included independent risk factors, and the nomogram was well distinguished and calibrated in predicting the occurrence of deep submucosal infiltration in ECT, with a C-index and area under the curve of 0.920 (95% CI: 0.811, 0.929). Conclusion: The nomogram prediction model constructed based on only erosion or rupture, local depression, infiltrative JNET typing, and infiltrative Pit pattern has a good predictive efficacy in the occurrence of deep submucosal infiltration in ECT.

The prognostic ability of radiotherapy of different colorectal cancer histological subtypes and tumor sites

The prognostic significance of radiotherapy (RT) for colorectal cancer (CRC) has shown conflicting results, particularly among different pathological subtypes, including adenocarcinoma (AC), mucinous adenocarcinoma (MC), and signet-ring cell carcinoma (SR). This study analyzed the prognosis of three pathological CRC types and focused on the prognostic significance of RT on three CRC histological subtypes. Patients diagnosed with AC (n = 54,174), MC (n = 3813), and SR (n = 664) in the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database (2010–2017) were evaluated. Cox regression models and competitive risk models were built to assess the effect of RT on the risk of CRC-associated death. Potential interactions between RT and stratified variables including age, sex, and tumor location were examined by multiplicative models. Compared with AC patients, SR patients had the worst overall survival (OS) among 3 subtypes of CRC (log-rank test, p < 0.001). Compared with patients who did not receive radiotherapy, RT was associated with a 1.09-fold (HR = 1.09, 95%[CI]: 1.03, 1.15) elevated risk of death among AC patients. In the SR group, RT significantly reduced the risk of death by 39% (HR = 0.61, 95%[CI]: 0.39–0.95). However, RT did not appear to independently influence survival in the MC group (HR = 0.96, 95%[CI]: 0.77, 1.21). In the subgroup analysis, tumor location (colon and rectum) significantly modified the association between RT and the risk of death among the AC and SR patients (p for interaction < 0.05). SR patients exhibited a worse OS (overall survival) than AC patients, and the effect of RT varied according to CRC histological subtypes. This can ultimately lead to more personalized and effective treatment strategies for CRC patients.

In silico analysis reveals mir-98-5p as a potential inhibitor of tumor cell proliferation and metastasis in colorectal cancer by targeting the fzd3 receptor of the Wnt signaling pathway

BackgroundColorectal Cancer (CRC) is the third most common cancer type and the second leading cause of cancer-related deaths worldwide. However, the existing treatment, as well as prognosis strategies for CRC patients, need to be improved in order to increase the chance of survival. Targeted therapies of CRC, as opposed to ordinary therapies, target key biological features and pathways of cancerous cells hence minimizing the subsequent damage to normal cells. MicroRNAs have been reported to play a crucial role in inhibiting and/or suppressing major pathways in various cancer types by targeting transcripts of key genes in such pathways. MethodsThe purpose of this study was to analyze in silico the differentially expressed genes from five microarray datasets of patients with CRC. Furthermore, miRNAs were investigated to inhibit cancer cell proliferation and metastasis by targeting a key gene—frizzled receptor 3 (FZD3) in the Wnt signaling pathway. ResultsThe Wnt pathway receptor FZD3 is upregulated in CRC along with other pathway genes, which play a critical role in tumorigenesis. In contrast, miR-98-5p inhibits the activity of FZD3 by binding directly to the 3′UTR of its mRNA, therefore exerting a suppressor effect on colorectal tumors. ConclusionThe study reveals miR-98-5p as a novel target of FZD3 and an inhibitor of the Wnt signaling pathway hence being a potential candidate for developing targeted therapies against CRC.

T cell migration and effector function differences in familial adenomatous polyposis patients with APC gene mutations.

Familial adenomatous polyposis (FAP) is an inherited disease characterized by the development of large number of colorectal adenomas with high risk of evolving into colorectal tumors. Mutations of the Adenomatous polyposis coli (APC) gene is often at the origin of this disease, as well as of a high percentage of spontaneous colorectal tumors. APC is therefore considered a tumor suppressor gene. While the role of APC in intestinal epithelium homeostasis is well characterized, its importance in immune responses remains ill defined. Our recent work indicates that the APC protein is involved in various phases of both CD4 and CD8 T cells responses. This prompted us to investigate an array of immune cell features in FAP subjects carrying APC mutations. A group of 12 FAP subjects and age and sex-matched healthy controls were studied. We characterized the immune cell repertoire in peripheral blood and the capacity of immune cells to respond ex vivo to different stimuli either in whole blood or in purified T cells. A variety of experimental approaches were used, including, pultiparamater flow cytometry, NanosString gene expression profiling, Multiplex and regular ELISA, confocal microscopy and computer-based image analyis methods. We found that the percentage of several T and natural killer (NK) cell populations, the expression of several genes induced upon innate or adaptive immune stimulation and the production of several cytokines and chemokines was different. Moreover, the capacity of T cells to migrate in response to chemokine was consistently altered. Finally, immunological synapses between FAP cytotoxic T cells and tumor target cells were more poorly structured. Our findings of this pilot study suggest that mild but multiple immune cell dysfunctions, together with intestinal epithelial dysplasia in FAP subjects, may facilitate the long-term polyposis and colorectal tumor development. Although at an initial discovery phase due to the limited sample size of this rare disease cohort, our findings open new perspectives to consider immune cell abnormalities into polyposis pathology.

Development and validation of an online calculator to predict the pathological nature of colorectal tumors.

No single endoscopic feature can reliably predict the pathological nature of colorectal tumors (CRTs). To establish and validate a simple online calculator to predict the pathological nature of CRTs based on white-light endoscopy. This was a single-center study. During the identification stage, 530 consecutive patients with CRTs were enrolled from January 2015 to December 2021 as the derivation group. Logistic regression analysis was performed. A novel online calculator to predict the pathological nature of CRTs based on white-light images was established and verified internally. During the validation stage, two series of 110 images obtained using white-light endoscopy were distributed to 10 endoscopists [five highly experienced endoscopists and five less experienced endoscopists (LEEs)] for external validation before and after systematic training. A total of 750 patients were included, with an average age of 63.6 ± 10.4 years. Early colorectal cancer (ECRC) was detected in 351 (46.8%) patients. Tumor size, left semicolon site, rectal site, acanthosis, depression and an uneven surface were independent risk factors for ECRC. The C-index of the ECRC calculator prediction model was 0.906 (P = 0.225, Hosmer-Lemeshow test). For the LEEs, significant improvement was made in the sensitivity, specificity and accuracy (57.6% vs 75.5%; 72.3% vs 82.4%; 64.2% vs 80.2%; P < 0.05), respectively, after training with the ECRC online calculator prediction model. A novel online calculator including tumor size, location, acanthosis, depression, and uneven surface can accurately predict the pathological nature of ECRC.

Association between primary tumor characteristics and histopathological growth pattern of liver metastases in colorectal cancer.

The microarchitecture of liver metastases (LMs), or histopathological growth pattern (HGP), has been demonstrated to be a significant prognostic factor in patients undergoing resection of colorectal liver metastases (CRLMs). Currently, however, HGP can be only determined on the operative specimen. Therefore, the development of new tools to predict the HGP of CRLMs before surgery and to understand the mechanisms that drive these patterns is important for improving individualization of therapeutic management. In this study, we analyzed data from a retrospective series of patients who underwent surgery for CRLMs to compare primary tumor characteristics, including markers of local aggressiveness and migratory capacity, and HGP of liver metastases. Data from a retrospective series of 167 patients who underwent curative-intent resection of CRLMs and in whom pathological samples from both primary tumor and liver metastases were available were reviewed. At the primary tumor level, KRAS mutational status, grade of differentiation, and tumor budding were assessed. HGP was scored in each resected CRLM, according to consensus guidelines, and classified as desmoplastic (dHGP) or non-desmoplastic (non-dHGP). Associations between primary tumor characteristics and HGP of CRLMs were evaluated using a binary logistic regression model. Overall survival and disease-free survival were evaluated using Kaplan-Meier and multivariable Cox regression analyses. CRLMs were classified as dHGP in 36% of the patients and as non-dHGP in 64%. Higher rates of moderately or poorly differentiated primary tumors were observed in the non-dHGP CRLM group (80%), as compared with the dHGP group (60%) (OR = 3.6; 95%CI: 1.6-7.05; p = 0.001). Higher rates of tumor budding were observed in the non-dHGP CRLM group, with a median tumor budding value of 4 as compared with 2.5 in the dHGP group (p = 0.042). In the entire series, 5-year overall and disease-free survival were 43% and 32.5%, respectively. The non-dHGP CRLM group had worse post-hepatectomy survival, with 5-year overall and disease-free survival of 32.2% and 24.6%, respectively, as compared with 60.8% and 45.9%, respectively, for the dHGP group (p = 0.02). Colorectal tumors with moderate or poor differentiation and those with high tumor budding are more frequently associated with CRLMs with a non-dHGP. This suggests that primary tumor characteristics of local aggressiveness and migratory capacity could preferentially promote the development of CRLMs with an infiltrating pattern and that these parameters should be considered as part of new scores for predicting HGP before surgery. This finding may stimulate new lines of research for more individualized therapeutic decision in patients with CRLM candidate to surgery.

Protective Effects of Long-Term Usage of Cyclo-Oxygenase-2 Inhibitors on Colorectal Cancer in Genetically Predisposed Individuals and Their Overall Effect on Prognosis: A Systematic Review.

Colorectal cancer (CRC) is a major global health concern, accounting for significant cancer-related morbidity and mortality worldwide. Despite advancements in early detection and treatment modalities, the prevention of CRC remains a critical goal. Cyclo-oxygenase-2 (COX-2) is an inducible enzyme involved in the production of pro-inflammatory prostaglandins, which play a crucial role in various cellular processes, including inflammation, cell proliferation, apoptosis, and angiogenesis. Elevated COX-2 expression has been consistently observed in colorectal tumors, indicating their role in the pathogenesis of cancer. COX-2 inhibitors, such as celecoxib and rofecoxib, have been studied as potentiallyeffective treatment modalities due to their ability to decrease prostaglandin levels, which are generally higher in cancer patients.Aberrant prostaglandin production is linked to the adenoma-carcinoma sequence, during which adenomas turn dysplastic and accumulate enough damage to become malignant. COX-2 inhibitors have also been shown to modulate various signaling pathways involved in CRC development, such as wingless-related integration site/β-catenin (Wnt/β-catenin), mitogen-activated protein kinase (MAPK), and phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) pathways. This systematic review aimed to evaluate the protective effects of long-term usage of COX-2 inhibitors on CRC in genetically predisposed individuals and their overall effect on the prognosis of the disease. The researchers conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and collected data from several databases, including PubMed, PubMed Central, Cochrane Library, and Web of Science. The search strategy combined keywords related to CRC, COX-2 inhibitors, protective effects, and prognosis. They identified 1189 articles and shortlisted 26 full-text articles that met the eligibility criteria. Quality assessment tools, such as the Assessment of Multiple Systematic Review (AMSTAR) for systematic reviews, the Cochrane bias assessment tool for randomized control trials, the scale for the assessment of narrative review articles(SANRA) checklist for narrative reviews, and the Joanna Briggs Institute (JBI) tool for cross-sectional studies and case reports, are used. This review's conclusions will assist in determining the effectiveness of COX-2 inhibitors to prevent CRC. This review may also contribute to developing guidelines for clinicians to manage genetically predisposed individuals with CRC. Furthermore, the results of this review will shed light on the potential of COX-2 inhibitors as a preventive measure against CRC in genetically predisposed individuals.