Colorectal cancer (CRC) is the third most common cancer worldwide and there is a controversy regarding the influence of laxative use on the incidence of CRC. Therefore, the present study aimed to investigate the effects of laxative use and different subtypes of laxatives on the incidence of CRC. To this aim, a comprehensive search of three databases (PubMed, Embase and the Cochrane Library) was conducted on April 12, 2022, using key words that included 'laxative' and 'CRC', which initially retrieved 305 records. Ultimately, 12 studies involving 415,313 patients met all eligibility criteria and were included in a meta-analysis. Subsequently, patients were categorized into the laxative use and non-laxative use groups. Stata 16.0 software was used for all data analyses. The results indicated that laxative use was not significantly associated with CRC risk [odds ratio (OR), 0.95; 95% confidence interval (CI), 0.75-1.20; P=0.65; I2=94.63%]. In the subgroup analyses, the effects of different laxative types were further examined. Notably, all types of laxatives except for fiber laxatives showed no significant influence on CRC risk (P>0.1). By contrast, fiber laxatives were associated with a reduced risk of CRC (OR, 0.74; 95% CI, 0.59-0.93; P=0.01; I2=32.15%), suggesting a potential protective effect of this medication. In conclusion, the findings of the present study suggest that the use of laxatives does not increase the risk of CRC. Moreover, the use of fiber laxatives may have a protective effect by reducing CRC incidence.

Colorectal cancer is the third most common cancer worldwide, accounting for approximately 10 % of all cancer cases. It is also the second leading cause of cancer-related deaths globally. Phloretin is a natural compound found in apples and other fruits. It has been studied for its potential health benefits, including antioxidant and anti-inflammatory properties. However, more research is needed to fully understand its impact on cancer prevention or treatment. This article aimed to prepare phloretin-nanospanlastics (Ph-NSLs) to evaluate their effects on dimethylhydrazine (DMH)-induced colon cancer in mice.

Morphology, Particle size, zeta potential, UV-vis, entrapment efficiency, polydispersity index, FT-IR spectra, and drug release of phloretin and Ph-NSLs at pH 6.8.were described. Ph-NSLs were also tested for their anti-cancer properties in DMH-induced colon cancer in mice. A 36 mice were divided into 6 groups; Normal control, DMH (20 mg/k.g.b.w.), DMH + Ph-NSLs (25 mg/k.g.b.w.), DMH + Ph-NSLs (50 mg/k.g.b.w.), DMH + 5-FU(20 mg/k.g.b.w.), DMH + Ph-NSLs (50 mg), 5-FU (20 mg). Ph-NSLs were tested for their anticancer properties in DMH-treated mice by evaluating the IC50, viability and inhibitory values of Ph-NSLs against Caco-2. Also, the effect of Ph-NSLs administration on number of surviving mice, number of tumors/mice, average of tumor size, Hb, RBCs, WBCs, C19-9, MDA, GSH, SOD, IL-2, TNF-α, TGF-β1, CEA, and P53 levels in mice treated DMH were estimated.

The synthesized Ph-NSLs were uniform, spherically shaped, and well dispersed, with a size, entrapment efficiency, and polydispersity index of approximately 114.06 ± 8.35 nm, 78.60 %, and 0.05, respectively. The zeta potential value of Ph-NSLs was measured at -21.5 ± 1.47 mV. Zeta potential reflects the surface charge of nanoparticles and affects their stability and interactions. UV spectra of phloretin and Ph-NSLs showed strong absorption peaks at 225 and 285 nm. These peaks correspond to specific wavelengths where the compound absorbs light. The percentage of Ph- NSLs release was found to be 56.87 ± 2.45 %. IC50 of Ph-NSLs was recorded 15.76 ± 0.42 μg/ml and the viability and inhibitory values of Ph-NSLs against Caco-2 cell lines was resorded 2.39, and 97.61 %, respectively at 100 μg/ml as well as 10.3, and 89.7 %, respectively at 50 μg/ml.Moreover, The combination of 5-FU and Ph-NSLs resulted in a moderate increase in survival and significantly reduces tumor size and number, showing enhanced anticancer efficacy compared to individual treatments as well as attenuated levels of hemoglobin (Hb), red blood cells (RBCs), and white blood cells (WBCs). Reduced plasma cancer antigen 19-9 (CA19-9) levels as well as improved of colon malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), interleukine-2 (IL-2), tumor necrosis factor-alpha (TNF-α), tumor growth factor-beta1 (TGF-β1), carcinoembryonic antigen (CEA), and tumor protein (P53) levels. Also, Ph-NSLs and 5FU, either alone or together, decreased the expression of the Akt and PI3K genes in the colon. The combination of Ph-NSLs and 5FU showed more pronounced anticancer activity than Ph-NSLs administered individually.

The combination of 5-FU and Ph-NSLs significantly enhances anticancer efficacy, reducing both the number of tumors and average tumor size more effectively than either treatment alone. This synergistic effect leverages 5-FU's inhibition of DNA synthesis and phloretin's induction of apoptosis and inhibition of cell proliferation, offering a promising approach for improved cancer treatment outcomes.

Colorectal cancer (CRC) involves the uncontrolled proliferation of glandular epithelial cells in the colon or rectum. The high mortality rate associated with CRC has driven extensive research into innovative diagnostic and therapeutic strategies. Among these, microRNAs (miRNA) have gained attention for their crucial role in regulating various cellular processes that contribute to the initiation, progression, and metastasis of CRC.

This systematic review aimed to assess the roles of various miRNAs in CRC by analyzing multiple studies. The PICO framework was followed to structure the study regarding miRNA involved in CRC development and progression compared to normal cases. The outcomes were measured according miRNAs impact on CRC progression, survival rates, and treatment response. Systematic review of studies published from 2000 to November 2023 were included. Data were collected from prominent databases, including Google Scholar, PubMed, ScienceDirect, Irandoc, SID, and Magiran, covering studies from 2000 to November 2023. Studies were managed using EndNote for citation management, and duplicates were removed. The remaining studies were evaluated based on predefined inclusion and exclusion criteria.

In our review, we categorized 28 miRNAs based on their potential tumor suppressor or oncogenic effects in CRC progression. Among them, 14 miRNAs were highlighted as important based on the assessment using TCGA data, with miR-200a also showing a significant effect on patient survival.

This study compiled and analyzed validated miRNAs associated with CRC progression. The findings suggest the potential of these miRNAs as non-invasive biomarkers, which may be used alone or in combination with traditional tumor markers for improved diagnostic and prognostic applications in CRC. This review contributes novel insights by updating the current understanding and offering a comprehensive evaluation of miRNAs in CRC.

Exploration of effective screening methods is imperative to improve current screening for colorectal cancer (CRC). Our aim was to systematically search the literature to identify and assess the diagnostic accuracy of both genetic and epigenetic biomarker panels for CRC detection using liquid biopsies for circulating tumour DNA (ctDNA) from stool, blood, or urine.

A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) with searches in Medline, Embase, CENTRAL, and Web Of Science from inception up to March 20, 2025, using pre-defined keywords. Study quality assessment was performed using QUADAS-2 tool (Quality Assessment for Diagnostic Accuracy Studies 2). Primary and secondary outcomes were panel performance (sensitivity and specificity) for CRC, advanced precancerous lesions (APL), and staging of disease.

Forty-four studies were included. Exceptional performance for both CRC (sensitivity and specificity) and APL (sensitivity) was displayed by biomarker panels including methylated SDC2 with methylated SFRP1/2 (CRC: 91.5%/97.3%, APL: 89.2%) or methylated TFPI2 (CRC: 94.9%/98.1%, APL: 100%), and a 5-biomarker panel of mutational targets APC, Bat-26, KRAS, L-DNA, and p53 (CRC: 91.0%/93.0%, APL: 82.0%). Suboptimal APL sensitivities up to 57.0% were exhibited by Cologuard and variant panels (including KRAS, methylated BMP3, methylated NDRG4, FIT), and 47.8% for combinations including methylated SEPT9.

High-performance, candidate ctDNA biomarker panels with exceptional diagnostic accuracy for both CRC and APL have been identified. Further work should focus on the development of large-scale studies to justify their clinical implementation.

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, with KRAS mutations playing a significant role in its tumorigenesis. Among the KRAS variants, the G13D mutation is associated with poor prognosis and distinctive biological behaviors. This study focuses on the role of HER2, a critical prognostic and predictive biomarker, in modulating the unique characteristics of KRASG13D-mutated CRCs. We identified a novel transcriptional regulatory network involving HER2, ELF3, and KRAS, with ELF3 acting as a key transcription factor (TF) that regulates KRAS expression under conditions of HER2 overexpression. Our findings reveal that this HER2-ELF3-KRAS axis is exclusively activated in KRASG13D, driving aggressive oncogenic features and conferring resistance to cetuximab (CTX) therapy. Through comprehensive analysis of gene expression profiles, we demonstrated that HER2 is a crucial therapeutic target specifically for KRASG13D CRCs. To explore this further, we introduced YK1, a small molecule inhibitor designed to disrupt the ELF3-MED23 interaction, leading to the transcriptional downregulation of HER2 and KRAS. This intervention significantly attenuated the HER2-ELF3-KRAS axis, sensitizing KRASG13D CRCs to CTX and reducing their tumorigenic potential by inhibiting the epithelial-to-mesenchymal transition process. Our study underscores the importance of HER2 as a key determinant in the unique biological characteristics of KRASG13D CRCs and highlights the therapeutic potential of targeting the HER2-ELF3-KRAS axis. By presenting YK1 as a novel pharmacological approach, we provide a promising strategy for developing tailored interventions for KRASG13D CRCs, contributing to the ongoing efforts in precision medicine for CRCs.

Colorectal cancer (CRC) is the third-most common cancer and the second-leading cause of mortality due to cancer worldwide. The underlying regulatory mechanism of CCNA2 in CRC was explored through multiomics and experimental analyses, thus facilitating diagnosis, therapy and prognosis. Two gene expression datasets (i.e., GSE9348 and GSE110223) were extracted from GEO. Differentially expressed genes (DEGs) were identified via GEO2R, which were used for enrichment analyses through DAVID. PPI network of DEGs was constructed by STRING, and the core genes were identified. CCNA2, a prognostic core gene for CRC, was validated in TCGA and HPA via transcriptomics and proteomics. ROC analysis was performed to evaluate the diagnostic value of CCNA2 in CRC. The therapeutic value of CCNA2 was evaluated in DGIdb through pharmacogenomics. The correlation between CCNA2 and immune infiltration was determined in TIMER by immunomics. TF-mRNA and miRNA-mRNA networks for CCNA2 were constructed in miRnet and miRDB via transcriptomics. The role and mechanism of CCNA2 in CRC were investigated both in vitro and in vivo. The miR-548x-3p/CCNA2 regulatory axis in CRC was investigated in vitro. CCNA2 showed excellent diagnostic, therapeutic, and prognostic value in CRC. CCNA2 was closely associated with tumor-infiltrating immunocytes, TFs, and miRNAs. The upregulation of CCNA2 was observed in CRC, and the knockdown of CCNA2 inhibited the proliferation, migration, and invasion while inducing apoptosis of CRC cells. The knockdown of CCNA2 could inhibit epithelial-mesenchymal transition (EMT) pathway. CCNA2 acted as a target of miR-548x-3p in regulating the biological behavior of CRC cells via the EMT-signaling pathway. CCNA2 is a potential biomarker for the diagnosis, treatment, and prognosis of CRC and is associated with immune infiltration, TF, and miRNA. The miR-548x-3p/CCNA2 axis plays a pivotal role in regulating the tumorigenesis of CRC through the EMT-signaling pathway.

This study aims to investigate temporomandibular joint dysfunction (TMD) in patients with breast cancer-related lymphedema (BCRL) and to determine the relationship between TMD severity and posture, range of motion (ROM), psychological status, and lymphedema (LE).

Sociodemographic characteristics and previous treatments of 38 individuals included in the study were recorded. The Craniomandibular Dysfunction Index for Clinical (CMDIC) and visual analog scale (VAS) evaluated TMD symptoms, signs, and pain. Patients were divided into three groups: mild, moderate, and advanced TMD, according to CMDIC results. LE stages of the patients were recorded. The severity of LE, range of motion (ROM), anxiety and depression, and posture analysis were evaluated with circumference measurement, goniometer, Turkish version of the Hospital Anxiety and Depression Scale (HAD), photogrammetric assessment method, and inclinometer, respectively.

Different degrees of TMD were detected in all patients. There was a significant difference between the groups regarding post-op period duration, work status, posture, and ROM (p < 0.05). The groups' LE stage, LE severity, and scores of HAD and VAS were similar (p > 0.05).

According to the results of this study, TMD is highly prevalent in BCRL patients. It is necessary to monitor TMD and its impact on the range of motion and posture. The post-op period duration can determine the development of TMD in this patient group.

NCT06669910, date of registration: 01.11.2024, "retrospectively registered".

Black Americans experience a higher incidence of colorectal cancer than Whites despite undergoing prevention screenings similar to those of Whites since 2010. We compared the colorectal adenoma status of Black and White patients at screening colonoscopy, a measure of colorectal cancer risk.

Using cross-sectional, observational data, we studied colorectal adenomas at first-time screening colonoscopy in average-risk patients aged 40 to 89 years, screened between September 2001 and July 2016 in South Carolina. We analyzed the age-adjusted odds of Black men and women (vs. White) having adenomas, advanced adenomas, ≥3 nonadvanced adenomas, and right hyperplastic polyps, and compared their total polyp burden (the sum of the diameters of all adenomas and right polyps detected).

Among 28,100 patients (58.4% Black and 53.8% women), we found that Black patients had lower age- and gender-adjusted odds than White patients of having adenoma (OR = 0.88, P < 0.01) and right hyperplastic polyp (OR = 0.74, P < 0.01), with a similar pattern within gender groups. Black and White patients were similar about advanced adenoma and 3+ nonadvanced adenoma. Among patients with lesions, mean polyp burden ranged from 8.5 mm (±7.2) for Black women aged 40 to 49 years to 12.3 mm (±7.4) for Black men aged more than 70 years. Age-adjusted polyp burden was 0.4 mm higher for Black men than for White men and 0.3 mm lower for Black women than for White women patient groups (P < 0.01).

In a large, racially balanced patient sample, Black and White patients showed similar polyp profiles.

Given similar adenoma status, other evidence-supported clinical factors associated with suboptimal polyp detection should be explored to understand the continuing colorectal cancer disparities affecting Black Americans.

Colonoscopy is essential for diagnosing and managing colorectal conditions, and is recognized as the gold standard for early cancer detection and removal of precancerous lesions. The American Society for Gastrointestinal Endoscopy and the American College of Gastroenterology have established benchmark indicators to minimize the risk of interval colorectal cancer. Despite their importance, research on these metrics in Saudi Arabia is limited. This study analyzes key intraprocedural indicators of colonoscopies at a tertiary care center to evaluate adherence to care standards.

This retrospective study examined 3763 colonoscopies conducted by adult gastroenterologists at Johns Hopkins Aramco Healthcare from January 2021 to December 2022. Procedures were categorized as screening and non-screening, with demographic data collected alongside withdrawal time (WT), cecal intubation rate (CIR), polyp detection rate (PDR), adenoma detection rate (ADR), Boston Bowel Preparation Scale (BBPS), polyp retrieval rate, rectal retroflexion, and adverse events.

The mean age of participants was 54.13 years, with 81.56% of them Saudis and 44.6% female. The average WT was 10 min. The overall CIR was 93.6% (94.78% for screening), with a PDR of 33.9% and a retrieval rate of 96.6%. ADR for screening participants was 25.63%, and 88.94% of participants achieved a BBPS score of 6 or more. The adverse event rate was at 0.2%, primarily due to bleeding.

The study indicates that colonoscopy procedures adhere to care standards, with ADR among male screening patients approaching 30%. Further research is necessary to evaluate pre- and post-procedural indicators.

Recent increases in colorectal cancer (CRC) incidence and mortality under age 50 have led the US to recommend starting screening at age 45 years instead of 50. Several other countries are now also reconsidering the age to start CRC screening.

To aid decision makers in making an informed decision about lowering the starting age of CRC screening in their jurisdictions.

In this article, we present the clinical and modeling evidence for the optimal age to start CRC screening and provide a checklist of considerations for decisions on age to start CRC screening.

Two observational studies showed that detection of advanced neoplasia in those aged 45-49 years undergoing colonoscopy was at least as high as in those aged 50-54 years. One Taiwanese study reported a 22% reduction in CRC incidence and a 39% reduction in CRC mortality from FIT screening in those 40-49 years compared to those 50 years and older. Nine modeling studies concluded that lowering the age to start screening to age 45 was cost-effective. However, lowering the start age can have negative spill-off effects, such as increased wait times for diagnostic colonoscopy for symptomatic individuals and decreased screening participation. In an effort to support decision making and prevent negative spill-off, the National Colorectal Cancer Screening Network in Canada proposed a Worksheet to determine the resource impact of earlier screening initiation.

Lowering the age to start CRC screening to 45 years likely leads to a reduction in CRC incidence and mortality but requires additional healthcare resources. Policy makers can use the worksheet to assess the expected increase and assess the feasibility within their jurisdictions.

Colon cancer is a common malignancy of the digestive tract. An estimated 1148515 new cases of colon cancer were reported in 2020 worldwide. Chronic myeloid leukemia (CML) is a malignant tumor formed by the clonal proliferation of bone marrow hematopoietic stem cells, with an annual incidence rate of 1-2 cases per 100000 people worldwide. Leukemia can be secondary to solid tumors, and vice versa. Reports on CML secondary malignant tumors account for 8.7% but CML secondary to malignancy is extremely rare. Therapy-related CML is a rare but potentially fatal adverse event of chemotherapy or radiotherapy. Herein, we report a case of CML with colon cancer and discuss this unique patient population. Our findings can provide effective raw data and guidance for the diagnosis of this clinical disease.

A 61-year-old male patient attended our hospital due to leukocytosis for 5 days. In February 2020, the patient was diagnosed with colon cancer and underwent radical surgery and conventional chemotherapy with a stable condition. He was diagnosis was CML-chronic phase (Sokal score of 0.72) after examination. He was treated with imatinib (400 mg daily). When his conditions improved, the patient was discharged from our hospital and visited the outpatient department for follow-up twice a month.

CML in patients with colon cancer is extremely rare. Secondary hematological tumors may be multifactorial, and the exact mechanism is currently unknown. Owing to the slow progression of the disease, patients with CML show no symptoms in the early stage. However, with disease progression, obvious but non-specific symptoms may appear, including fever, anemia, bleeding tendency, and hypertrophy. Therefore, complete blood count monitoring for routine examination is recommended after cancer treatment for early detection of occult hematological tumors.

This study aimed to evaluate the association between cholecystectomy and colonic bubble formation during colonoscopy, METHODS: A single-center retrospective cohort study was conducted at Staten Island University Hospital. Researchers reviewed 348 colonoscopy reports, comparing patients with (n = 56) and without (n = 292) a history of cholecystectomy. Colonic bubble formation was assessed using a 0-3 scale (0 = no bubbles, 3 = severe bubbles). Secondary endpoints included polyp and adenoma detection, withdrawal and procedure times, bowel preparation quality, and repeat procedures. Statistical analysis included t-tests, Mann-Whitney U tests, and χ2 tests.

Patients with prior cholecystectomy had significantly higher incidence of severe bubble formation (score 3; 28.6% vs. 12%, p = 0.001), longer withdrawal times (18 ± 8 vs. 15 ± 5 min, p = 0.024), and increased need for repeat colonoscopies (10.7% vs. 2.1%, p = 0.001). No significant differences were found in adenoma detection, polyp detection, or bowel preparation quality between the two groups.

Cholecystectomy is associated with increased colonic bubble formation during colonoscopy, leading to longer withdrawal times and higher rates of repeat procedures. While this study did not find a difference in adenoma detection rates, the impaired visualization caused by bubbles may necessitate tailored bowel preparation strategies for patients with a history of cholecystectomy to optimize colonoscopy effectiveness.

Immunotherapy for gastrointestinal cancers has elicited considerable amount of attention as a viable therapeutic option for several cancer types. Gut microbiome as a whole plays a critical role in shaping immune responses and influencing cancer progression. Recent evidence suggests that Helicobacter pylori (H. pylori), may influence immunotherapy efficacy by modulating the tumor microenvironment. Infection with H. pylori is common as it affects approximately 50% of the global population and remains the leading risk factor for gastric cancer. Interestingly, recent clinical and preclinical data has associated H. pylori with colorectal cancer carcinogenesis. Gut microbiome appears to be a modulator of the relationship between the immune system, gastrointestinal cancer development and existing therapies. Infection with H. pylori may affect immunotherapy results in both gastroesophageal and colorectal cancer; favorable results were noticed in H. pylori positive patients with gastric cancer, while in colorectal cancer patients the pathogen seemed to impede immunotherapy's action. This article aims to review current data on the role of H. pylori in triggering gastric inflammation and cancer, as well as its potential involvement in colorectal cancer development. Additionally, it seeks to highlight the impact of H. pylori infection on the response to immunotherapy in gastrointestinal cancers.

Clinical benefits of immunotherapy in colorectal cancer (CRC) are limited due to the low immunogenicity and immunosuppressive tumor microenvironment. Fusobacterium nucleatum (Fn) is discovered to colonize CRC tumors and dampen immunotherapy by fostering an immunosuppressive TME. Herein, a controllable "Shielding-deshielding" N-acetylgalactosamine (GalNAc)-derived photothermal nanotherapeutic is developed to mediate cascade targeting toward tumor and intratumoral Fn for enhanced photothermal-immunotherapy. This nanotherapeutic can in situ generate near infrared-II laser-activatable photothermal agent by reacting with endogenous hydrogen sulfide in CRC. The Schiff bond-tethered hyaluronic acid coating not only facilitates precise localization within CRC but shieldes GalNAc-mediated liver targeting, which can be deshielded upon a slightly acidic TME to anchor Fn by binding to its lectin Fap2. This cascade-targeting nanotherapeutic enables efficacious tumor accumulation and reinforces photothermal therapy (PTT) efficacy. Notably, PTT efficiently induces immunogenic cell death in CRC cells, leading to augmented immunogenicity and CD8+ T cell activation. Meanwhile, synchronous eradication of Fn facilitates M1 macrophage polarization, and promotes intratumoral infiltration of CD8+ T cell by reducing succinic acid level, thereby further boosting antitumor immunity against both primary and distant tumors. Overall, this study involving cascade targeting-reinforced PTT and intratumoral microorganism modulation offers new insight into effective CRC immunotherapy.

Programs to improve health care for adults with criminal legal involvement, including those who have been released from incarceration in jails or prisons or who are under court or community supervison, understandably focus on treatment for mental illness, drug overdose, and suicide. However, criminal legal-involved adults also have higher risk of developing and dying from medical conditions, such as cancer, relative to the general population. Colorectal cancer (CRC) screening among legal-involved adults, particularly those who have been incarcerated, might be delayed or missed.

We conducted an observational study of national Veterans Health Administration (VHA) electronic health record data to compare the CRC screening rate between legal-involved Veterans, identified through their contact with the Veterans Justice Programs, and non-legal-involved Veterans. We included patients ages 46 to 75 eligible for average-risk screening in fiscal year 2022. Our main outcome of guideline-concordant CRC screening included stool-based testing, CT colonography, flexible sigmoidoscopy, and colonoscopy. Comparisons were estimated using an unadjusted multilevel logistic regression model with a random intercept for facility. Secondary analyses included examining associations between patient-level factors and screening receipt using adjusted models as well as assessing the variation in screening rates across 129 VHA facilities.

There were 27,597 legal-involved and 3,467,396 non-legal-involved patients who met screening eligibility. Only 47% of legal-involved patients were up to date with screening, compared to 54% of non-legal-involved patients (OR = 0.77 [95% CI: 0.75 to 0.79]; risk difference = -6.5% [95% CI: -7.1% to -5.9%]). Adjusted odds of screening were higher for patients with an assigned primary care provider (OR = 2.49 [95% CI: 2.48 to 2.51]). Screening rates varied widely across facilities, ranging from 24 to 75% for legal-involved patients and from 30 to 68% for non-legal-involved patients. Legal-involved patients had significantly lower screening rates at 49 facilities and a higher rate at two facilities, compared to non-legal-involved patients.

Nearly half of VHA patients were behind on recommended CRC screening, and legal-involved VHA patients had even lower rates. Current VHA efforts to improve legal-involved patients' connection to primary care providers may result in improved screening rates.

Noninvasive stool DNA-based methylation testing has emerged as an effective strategy for the early colorectal cancer (CRC) detection. Syndecan-2 ( SDC2 ) methylation frequently occurs in all stages of CRC; therefore, the aim of this study was to evaluate the clinical performance of a stool DNA-based SDC2 methylation test for detecting CRC in asymptomatic or high-risk CRC populations.

This multicenter prospective study was conducted to determine the clinical performance of the SDC2 methylation test on stool DNA using real-time polymerase chain reaction. Stool samples were collected from asymptomatic individuals before colonoscopy, and the test results were independently analyzed through comparison with colonoscopic findings and pathological outcomes as reference standards.

Of the 1,124 evaluable participants, 20 had CRC, 73 had advanced adenomatous polyps (≥1.0 cm), 469 had nonadvanced adenomatous polyps (<1.0 cm), 178 had non-neoplastic polyps, and 384 had negative colonoscopy results. The stool SDC2 methylation test had a sensitivity and specificity of 95.0% and 81.5%, respectively, for detecting CRC, while the sensitivity for detecting advanced adenomatous polyps and CRC was 58.1%. The rate of adenoma detection increased with polyp size ( P < 0.01), and sensitivity was not associated with CRC stage ( P = 0.864).

The stool DNA-based SDC2 methylation test attained a high sensitivity for CRC detection in an asymptomatic high-risk population. Further large-scale clinical studies are required to validate the clinical utility of this test as a population-based CRC screening tool.

Almost 70 years have passed since the molecular mechanism of carcinogenesis was hypothesized to involve multiple gene mutations. More than 1,000 cancer-related genes, including oncogenes and tumor suppressor genes, accelerate carcinogenesis by altering molecular functions and gene expression through mutations and epigenetic changes and have been shown to cause multistep carcinogenesis in several organ cancers. The elucidation of cancer-related gene abnormalities has led to the development of molecular-targeted therapies that focus on driver molecules, known as precision medicine, in addition to conventional treatments such as surgery, radiotherapy, and chemotherapy. Now that the mechanism of cancer development has been largely elucidated, options for cancer treatment and its outcomes have improved, and cancer research is moving to the next stage: cancer prevention. Cancer prevention using chemicals was first proposed approximately 50 years ago. It is the concept of stabilizing, arresting, or reverting precancerous lesions to normal tissues using synthetic vitamin A analogs (retinoids). Cancer chemoprevention is now considered to consist of three elements: "primary prevention," which prevents the development of tumors and prevents benign tumors converting into more malignant ones; "secondary prevention," which aims for early detection through cancer screening and treatment; and "tertiary prevention," which reduces the risk of recurrence and extends the time until death from cancer through treatment. Consequently, there is no clear boundary between the prevention and treatment strategies. Therefore, chemoprevention targets the entire process, from normal cells to precancerous lesions, malignant progression of tumors, and death by cancer. Basic and clinical research has revealed that cancer prevention is influenced by race, regional, and national differences, as well as individual differences such as genetic factors, environmental factors, and lifestyle habits. This review provides an overview of the progress made in cancer prevention and summarizes future directions.

Colorectal cancer (CRC) refers to cancer that develops in the colon or rectum, parts of the large intestine. It ranks as the third most prevalent form of cancer globally. Colorectal cancer is responsible for the morbidity of millions and the loss of hundreds of thousands of lives worldwide although the incidence varies significantly depending on geographical location. In recent years, CRC has decreased in high-income countries due to technological advancements in diagnosis and treatment. However, there is an increased occurrence of CRC morbidity and mortality in low- and middle-income countries. Colorectal cancer is becoming an emerging public health concern in Ethiopia. We noticed that the incidence rates have been lower compared to more developed countries, but recent years have seen a noticeable increase. This rise is attributed to factors such as changes in diet, lifestyle, and an aging population. Common risk factors include dietary shifts towards processed foods and red meat, physical inactivity, obesity, smoking, and alcohol consumption. Unfortunately, in Ethiopia, screening programs for CRC are not widespread, and limited access to diagnostic facilities, lack of public awareness, and insufficient healthcare infrastructure contribute to late-stage diagnoses or left without diagnosis. Treatment options, including surgery, chemotherapy, and radiotherapy, are available but not uniformly accessible across the country, posing challenges for timely and effective treatment. Addressing colorectal cancer in Ethiopia requires a comprehensive approach to enhance public awareness, improve screening and early detection, expand treatment facilities, and train healthcare professionals to provide effective care.

Cancer mortality has decreased over time, but the contributions of different interventions across the cancer control continuum to averting cancer deaths have not been systematically evaluated across major cancer sites.

To quantify the contributions of prevention, screening (to remove precursors [interception] or early detection), and treatment to cumulative number of cancer deaths averted from 1975 to 2020 for breast, cervical, colorectal, lung, and prostate cancers.

In this model-based study using population-level cancer mortality data, outputs from published models developed by the Cancer Intervention and Surveillance Modeling Network were extended to quantify cancer deaths averted through 2020. Model inputs were based on national data on risk factors, cancer incidence, cancer survival, and mortality due to other causes, and dissemination and effects of prevention, screening (for interception and early detection), and treatment. Simulated or modeled data using parameters derived from multiple birth cohorts of the US population were used.

Primary prevention via smoking reduction (lung), screening for interception (cervix and colorectal) or early detection (breast, cervix, colorectal, and prostate), and therapy (breast, colorectal, lung, and prostate).

The estimated cumulative number of cancer deaths averted with interventions vs no advances.

An estimated 5.94 million cancer deaths were averted for breast, cervical, colorectal, lung, and prostate cancers combined. Cancer prevention and screening efforts averted 8 of 10 of these deaths (4.75 million averted deaths). The contribution of each intervention varied by cancer site. Screening accounted for 25% of breast cancer deaths averted. Averted cervical cancer deaths were nearly completely averted through screening and removal of cancer precursors as treatment advances were modest during the study period. Averted colorectal cancer deaths were averted because of screening and removal of precancerous polyps or early detection in 79% and treatment advances in 21%. Most lung cancer deaths were avoided by smoking reduction (98%) because screening uptake was low and treatment largely palliative before 2014. Screening contributed to 56% of averted prostate cancer deaths.

Over the past 45 years, cancer prevention and screening accounted for most cancer deaths averted for these causes; however, their contribution varied by cancer site according to these models using population-level cancer mortality data. Despite progress, efforts to reduce the US cancer burden will require increased dissemination of effective interventions and new technologies and discoveries.

An initial analysis of population-based cancer survival data from Georgia revealed lower CRC survival rates compared to high-income countries. We conducted the study to address this issue and propose strategies for enhancing CRC care.

We analyzed CRC statistics, reviewed screening programs, and examined published CRC research in Georgia. Finally, we surveyed 16 oncologists from major institutions all over the country to assess molecular testing, treatment standards, and access to modern medications.

Despite CRC screening being available in Georgia, late diagnoses persist, with over a 1/3 of cases presenting with acute intestinal obstruction. As a result, 65 % of CRC patients are diagnosed at locally advanced or metastatic stages. All 16 oncologists reported limited molecular testing due to costs, with 13 not routinely performing MSI/MMR and NRAS/KRAS/BRAF testing. Consequently, only 15 % of patients receive anti-EGFR therapy. Oxaliplatin-based therapy is almost universally used for metastatic CRC as the first-line treatment. No CRC clinical trials have been conducted in Georgia over the past three years. Treatment for locally advanced rectalcancer typically includes chemoradiotherapy followed by surgery, with notable variation in multidisciplinary team meeting practices.

Study provides several practical recommendations: it is crucial to promote CRC screening programs, enhance access to modern treatment options, and standardize national diagnostic/treatment protocols. There is an urgent need for more clinical trials to increase access to modern therapeutics, as well as to strengthen MDT meetings. These measures are expected to improve CRC care with a further reduction in CRC mortality rates.

Colorectal cancer (CRC) ranks third in terms of global cancer prevalence and is the second most common cause of cancer-related mortality. Although CRC rates are decreasing in the United States, inequalities still exist despite the effectiveness of invasive screening methods, such as colonoscopy, flexible sigmoidoscopy, and computed tomography (CT) colonography in detecting colorectal cancer. Many current interventions promoting CRC screening do not utilize a modern theory-based approach, which has led to the low utilization of these screening methods. This cross-sectional study aims to address the lack of theory-based treatments for promoting visual CRC screening examinations by applying the multi-theory model (MTM) of health behavior change to explicate the health-related factors for individuals to seek visual colorectal cancer screening examinations for CRC screening. A 57-item validated questionnaire assessing MTM constructs and CRC screening was administered online. The survey questionnaire was administered to a sample of 640 adults from the United States. The participants were between the ages of 45 and 75 years. Hierarchical multiple regression was used to assess the relationship between MTM constructs with the initiation and sustenance of CRC screening behaviors. Out of the total participants in this nationwide sample, 71.4% (n = 457) reported that they had undergone a visual CRC screening examination. MTM subscales, specifically participatory dialogue, changes in the physical environment along with age, recommendation for CRC screening from a healthcare provider, and previous experience with colonoscopy, were found to be significant factors in predicting the initiation of visual CRC screening behavior. These factors accounted for 22% of the variation in initiation among this group (R2 = 0.222, F = 3.521, p < 0.001). The MTM can be a valuable framework for designing educational media, information media, social media platforms, and clinical interventions to promote visual colorectal cancer screening examinations.

Cancer is a major cause of mortality. Timely information about cancer mortality trends is essential for prioritizing health programs.

This study aims to use a Joint point regression model to predict the mortality rates of the top 10 common cancers in Babol City.

This cross-sectional study considered all registered cancer-related deaths from 2013 to 2021 in the Babol University of Medical Sciences' death registration and classification system. Crude and age-standardized rates and cancer trends were calculated and predicted for the next 5 years, overall and by type of cancer and gender.

Over these 9years, 2417 deaths from the 10 common cancers were recorded. We observed an increase in mortality rates with a slope of 12.05% from 2013 to 2016, and a gentler slope of 3.2% from 2016 to 2021. Cancer mortality rates are predicted to increase by 6.43% in the next 5 years without intervention. Detailed analysis indicates that breast cancer will have the highest mortality rate during 2022-2026, rising by 13.6% annually. Predictions based on gender indicate that, breast cancer mortality will increase by 13.6% annually for women. Also, stomach cancer mortality rates will increase by 0.15% in men annually.

Cancer mortality in Babol remains a significant public health issue with an increasing trend. Nevertheless, these rising mortality rates require urgent interventions, including cancer prevention programs, increased access to medical services, and improved quality of life.

Immunotherapy, particularly immune checkpoint inhibitor (ICIs) therapy, stands as an innovative therapeutic approach currently garnering substantial attention in cancer treatment. It has become a focal point of numerous studies, showcasing significant potential in treating malignancies, including lung cancer and melanoma. The objective of this research is to analyze publications regarding immunotherapy for colorectal cancer (CRC), investigating their attributes and identifying the current areas of interest and cutting-edge advancements. We took into account the publications from 2002 to 2022 included in the Web of Science Core Collection. Bibliometric analysis and visualization were conducted using CiteSpace, VOSviewer, R-bibliometrix, and Microsoft Excel. The quantity of publications associated with this domain has been steadily rising over the years, encompassing 3753 articles and 1498 reviews originating from 573 countries and regions, involving 19,166 institutions, 1011 journals, and 32,301 authors. In this field, China, the United States, and Italy are the main countries that come forward for publishing. The journal with the greatest impact factor is CA-A Cancer Journal for Clinicians. Romain Cohen leads in the number of publications, while Le Dt stands out as the most influential author. The immune microenvironment and immune infiltration are emerging as key hotspots and future research directions in this domain. This research carries out an extensive bibliometric examination of immunotherapy for colorectal cancer, aiding researchers in understanding current focal points, investigating possible avenues for research, and recognizing forthcoming development trends.

Data on the global, regional and national changes in the trends of colorectal cancer (CRC) are analyzed to understand the trends in its burden, in order to assist policymakers in allocating healthcare resources and developing prevention and control strategies.

This study analyzed trends in age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and disability-adjusted life years (DALYs) for CRC from 1990 to 2021 using data from the Global Burden of Disease (GBD) 2021 database. The trends of burden and effectiveness of control strategies were assessed using jointpoint regression analysis, decomposition analysis and frontier analysis.

Globally, the ASMR and age-standardized DALYs for CRC have shown a declining trend, but the ASIR was still increasing. The number of new cases of CRC in 2021 was higher in males than in females, the values were 1,263.46 thousands [95% confidence interval (95% CI): 1,146.50, 1,400.38] vs. 930.68 thousands (95% CI: 824.67, 1,017.65). The change in DALYs was mainly due to population growth (111.42%). The high socio-demographic index (SDI) region had an ASIR of 40.52 (95% CI: 37.45, 42.45), and the low SDI region had an ASIR of 7.39 (95% CI: 6.65, 8.19). The ASIR for CRC showed an upward trend in all SDI regions before age of 40 years. Among the four world regions, only America showed a downward trend in ASIR, with an estimated annual percentage change (EAPC) of -0.62 (95% CI: -0.71, -0.53). Among the 204 countries and territories, Netherlands, Monaco, and Bermuda were the top 3 countries with the highest ASIR in 2021. In the frontier analysis of DALYs, the 10 countries with the longest effective distances all had SDI levels above 0.70.

Although ASMR and age-standardized DALYs are declining, ASIR is still increasing globally and in many regions. The burden of CRC varies significantly across the globe, and more targeted screening strategies and prevention measures are needed to address the problem of CRC.

The Canadian Screening for Colorectal Cancer Research Network (CanSCCRN) recently set out to develop a national CRC screening research agenda and identify priority research areas. The specific objectives were to (1) identify evidence gaps relevant to CRC screening and the barriers and facilitators to evidence generation and uptake by CRC screening programs, (2) establish high-priority collaborative research ideas to inform best CRC screening practices, and (3) identify one to two research topics for grant development and submission within 12 to 18 months. Three focus groups were conducted with network members and relevant parties (n = 15) to identify evidence gaps, barriers, and facilitators to evidence generation and uptake. Three workshops were subsequently held to discuss focus group findings and develop an action plan for research. An electronic survey was used to prioritize the evidence gaps to be addressed. Overall, five categories of barriers and six categories of facilitators to evidence uptake and generation were identified, as well as 23 evidence gaps to be addressed. Screening participation, post-polypectomy surveillance, and screening age range were identified as research priority research areas. Adequate resourcing and infrastructure, as well as partnerships with knowledge end users, are integral to addressing these research areas and advancing CRC screening programs in Canada and beyond.

Macrophages play a crucial role in tumor initiation and progression, while macrophage-associated gene signature in colorectal cancer (CRC) patients has not been investigated. Our study aimed to identify macrophage-related molecular subgroups and develop a macrophage-related risk model to predict CRC prognosis. The mRNA expression profile and clinical information of CRC patients were obtained from TCGA and GEO databases. CRC patients from TCGA were divided into high and low macrophage subgroups based on the median macrophage score. The ESTIMATE and CIBERSORT algorithms were used to assess immune cell infiltration between subgroups. GSVA and GSEA analyses were performed to investigate differences in enriched pathways between subgroups. Univariate and LASSO Cox regression were used to build a prognostic risk model, which was further validated in the GSE39582 dataset. A high macrophage score subgroup was associated with poor prognosis, highly activated immune-related pathways and an immune-active microenvironment. A total of 547 differentially expressed macrophage-related genes (DEMRGs) were identified, among which seven genes (including RIMKLB, UST, PCOLCE2, ZNF829, TMEM59L, CILP2, DTNA) were identified by COX regression analyses and used to build a risk score model. The risk model shows good predictive and diagnostic values for CRC patients in both TCGA and GSE39852 datasets. Furthermore, multivariate Cox regression analysis showed that the risk score was an independent risk factor for overall survival in CRC patients. Our findings provided a novel insight into macrophage heterogeneity and its immunological role in CRC. This risk score model may serve as an effective prognostic tool and contribute to personalised clinical management of CRC patients.

This review investigates the disparities in colorectal cancer screening, treatment, and outcomes among different racial, ethnic, socioeconomic, and geographic groups. Although there has been progress, notable disparities continue to exist as a result of socioeconomic status, access to healthcare, and systemic prejudices. Approaches to tackle these challenges involve expanding screening access, enhancing healthcare utilization, addressing socioeconomic obstacles, ensuring fair treatment, and boosting representation in research.

LSM-83177, a phenoxy acetic acid derivative, is a small molecule reported for its promising anti-tumor properties. Via inhibiting the interaction between MDM2 and p53, LSM-83177 can elevate the active p53 levels within cells, thereby promoting apoptosis and inhibiting tumor growth. Also, LSM-83177 has been shown to inhibit GST activity in colorectal cancer HT29 cells. In the current work, novel LSM-83177 hydrazone analogs 5a-f, 7a-b, 10a-e, and 13a-b have been designed according to the structure features of LSM-83177 and their binding mode in the active site of MDM2. The anti-cancer activity of the newly synthesized analogs is evaluated against the HT29 cell line. The most potent compounds, 7a and 10a, showed IC50 = 12.48 and 10.44 µg/ml, respectively, when compared with Cisplatin (IC50 = 11.32 µg/ml) as a reference drug. Compounds 7a and 10a were introduced for further inspection for p53-MDM2 protein-protein interaction, where they displayed IC50 values of 3.65 and 11.08 µg/ml, respectively. Furthermore, hydrazones 7a and 10a increased the p-53 expression levels by 3.22- and 4.25-fold, respectively; in addition, they effectively reduced the GST expression levels in HT29 cancer cells with 0.56- and 0.30-fold increments in comparison to the untreated control.

Understanding the molecular signaling pathways of colorectal cancer (CRC) can be accepted as the first step in treatment strategy. Permanent mTOR signaling activation stimulates the CRC process via various biological processes. It supplies the survival of CRC stem cells, tumorigenesis, morbidity, and decreased response to drugs in CRC pathogenesis. Therefore, inhibition of the mTOR signaling by numerous bioactive components may be effective against CRC. The study aims to discuss the therapeutic capacity of various polyphenols, terpenoids, and alkaloids on CRC via the PI3K/Akt/mTOR pathway. The potential molecular effects of bioactive compounds on the mTOR pathway's upstream and downstream targets are examined. Each bioactive component causes various physiological processes, such as triggering free radical production, disruption of mitochondrial membrane potential, cell cycle arrest, inhibition of CRC stem cell migration, and suppression of glycolysis through mTOR signaling inhibition. As a result, carcinogenesis is inhibited by inducing apoptosis and autophagy. However, it should be noted that studies are primarily in vitro dose-dependent treatment researchers. This study raises awareness about the role of phenolic compounds in treating CRC, contributing to their future use as anticancer agents. These bioactive compounds have the potential to be developed into food supplementation to prevent and treat various cancer types including CRC. This review has the potential to lead to further development of clinical studies. In the future, mTOR inhibition by applying several bioactive agents using advanced drug delivery systems may contribute to CRC treatment with 3D cell culture and in vivo clinical studies.

Colorectal cancer (CRC) ranks third in global incidence and second in mortality. However, a comprehensive predictive model for CRC prognosis, immunotherapy response, and drug sensitivity is still lacking. Various types of programmed cell death (PCD) are crucial for cancer occurrence, progression, and treatment, indicating their potential as valuable predictors. Fourteen PCD genes were collected and subjected to dimensionality reduction using regression methods to identify key hub genes. Predictive models were constructed and validated based on bulk transcriptomes and single-cell transcriptomes. Furthermore, the tumor microenvironment, immunotherapy response, and drug sensitivity profiles among patients with CRC were explored and stratified by risk. A risk score incorporating the PCD genes FABP4, AQP8, and NAT1 was developed and validated across four independent datasets. Patients with CRC who had a high-risk score exhibited a poorer prognosis. Unsupervised clustering algorithms were used to identify two molecular subtypes of CRC with distinct features. The risk score was combined with the clinical features to create a nomogram model with superior predictive performance. Additionally, patients with high-risk scores exhibited decreased immune cell infiltration, higher stromal scores, and reduced responsiveness to immunotherapy and first-line clinical drugs compared with low-risk patients. Furthermore, the top ten non-clinical first-line drugs for treating CRC were selected based on their predicted IC50 values. Our results indicate the efficacy of the model and its potential value in predicting prognosis, response to immunotherapy, and sensitivity to different drugs in patients with CRC.

Sociodemographic disparities in colorectal cancer (CRC) surgical patients are known. Few studies, however, have examined the intersection of insurance type and median household income (MHI).

In this retrospective analysis of the National Inpatient Sample from 2000 to 2019, all CRC surgery patients between 50 and 64 y old were included. Patients were further stratified based on insurance type (commercial, Medicaid, and uninsured) as well as county-level MHI quartiles. Outcomes included nonelective surgery (primary outcome), inpatient mortality, complications, and blood transfusions. Multivariate logistic regression adjusted for sociodemographic variables, medical comorbidities, and hospital-level factors.

Of 108,606 patients, 80.5% of patients had commercial insurance, while 5.8% were uninsured. On multivariate analysis, Medicaid or no insurance, especially when living in a lower-income community, were associated with significantly higher odds of nonelective surgery (ORs: 1.11-4.54). There was a stepwise effect on nonelective surgery by insurance type (uninsured with lower odds than insured) and MHI (each lower quartile had higher odds). There were similar trends for inpatient blood transfusions, but there were no significant differences in mortality or complications.

Especially when considered together, noncommercial insurance and lower MHI were associated with worse outcomes in CRC patients. Insurance was more protective than MHI against worse outcomes. These findings among a screening-aged cohort have policy planning implications for insurance expansions and healthcare funding allocations. Further research is needed to understand the complex underlying mechanisms that create this interaction between insurance and MHI.

Hydrogen sulfide (H2S) is a critical molecule that participates in various molecular, physiological, and pathophysiological processes in biological systems. Emerging evidence has revealed that H2S is implicated in the progression of colon cancer and immune escape. Against this backdrop, the present study aimed to construct a prognostic risk feature for colon adenocarcinoma (COAD) by leveraging hydrogen sulfide-related genes (HSRG). Transcriptomic data and corresponding clinical-pathological information of colon cancer were obtained from The Cancer Genome Atlas and gene expression omnibus databases. Univariate Cox regression analysis was employed to assess the prognostic relevance of HSRG. Consensus clustering was utilized to perform molecular subtyping of COAD, followed by comparison of immune cell infiltration, drug sensitivity, and immune therapy response between subtypes. Differential expression gene and gene set enrichment analyses were conducted between subtypes. Univariate, lasso, and multivariate Cox regression analyses were applied to construct a prognostic model derived from HSRG. A nomogram model for predicting COAD prognosis was constructed and evaluated. In this study, we identified 12 HSRGs that were associated with COAD prognosis. Consensus clustering analysis revealed 3 COAD molecular subtypes that exhibited significant differences in terms of prognosis, tumor immune cell infiltration, drug sensitivity, and immune therapy response. Gene set enrichment analysis demonstrated that immunoregulatory processes were significantly suppressed in the poor-prognosis subtype while Wnt-related pathways and processes were significantly upregulated. Based on the differentially expressed genes between subtypes, we constructed a risk model comprising 11 genes that effectively distinguished high-risk patients from low-risk patients with significant associations with patient survival outcomes, drug treatment, pathological staging, and T staging. The HSRG-derived risk feature was an independent prognostic factor for COAD in drug treatment and pathological staging and could be integrated into a nomogram for prognosis prediction. Calibration curve, receiver operating characteristic curve, and decision curve analysis demonstrated excellent performance of the nomogram in evaluating COAD prognosis. Our study systematically assessed the prognostic significance of HSRG in COAD, identified HSRG-based molecular subtypes and risk features, and highlighted their potential utility in predicting prognosis and treatment response.

Blood-based biomarker tests can potentially change the landscape of colorectal cancer (CRC) screening. We characterize the conditions under which blood test screening would be as effective and cost-effective as annual fecal immunochemical testing or decennial colonoscopy.

We used the 3 Cancer Information and Surveillance Modeling Network-Colon models to compare scenarios of no screening, annual fecal immunochemical testing, decennial colonoscopy, and a blood test meeting Centers for Medicare & Medicaid (CMS) coverage criteria (74% CRC sensitivity and 90% specificity). We varied the sensitivity to detect CRC (74%-92%), advanced adenomas (10%-50%), screening interval (1-3 years), and test cost ($25-$500). Primary outcomes included quality-adjusted life-years (QALY) gained from screening and costs for a US average-risk cohort of individuals aged 45 years.

Annual fecal immunochemical testing yielded 125-163 QALY gained per 1000 at a cost of $3811-$5384 per person, whereas colonoscopy yielded 132-177 QALY gained at a cost of $5375-$7031 per person. A blood test with 92% CRC sensitivity and 50% advanced adenoma sensitivity yielded 117-162 QALY gained if used every 3 years and 133-173 QALY gained if used every year but would not be cost-effective if priced above $125 per test. If used every 3 years, a $500 blood test only meeting CMS coverage criteria yielded 83-116 QALY gained at a cost of $8559-$9413 per person.

Blood tests that only meet CMS coverage requirements should not be recommended to patients who would otherwise undergo screening by colonoscopy or fecal immunochemical testing because of lower benefit. Blood tests need higher advanced adenoma sensitivity (above 40%) and lower costs (below $125) to be cost-effective.

Irinotecan (CPT-11) is a widely utilized topoisomerase I inhibitor in the treatment of colorectal cancer and other malignant tumors. However, severe and even life-threatening dose-limiting toxicity-delayed diarrhea affects the clinical application of CPT-11. The standard treatment for CPT-11-induced delayed diarrhea is prompt use of loperamide (LPA), however LPA can also cause constipation, diarrhea and even intestinal obstruction and has a high failure rate. Carboxylesterase 2 (CES2) is the main enzyme in the intestinal transformation of CPT-11, which can convert CPT-11 into toxic metabolite SN-38 and produce intestinal toxicity. Inhibiting CES2 activity can block the hydrolysis process of CPT-11 in the intestine and reduce SN-38 accumulation. Additionally, Farnesoid X receptor (FXR) agonists have anti-inflammatory, anti-secretory, and protective functions on intestinal barrier integrity that could potentially alleviate diarrhea. In this study, we investigated for the first time the anti-delayed diarrhea effect of FXR agonists, and the first time identified LE-77 as a potent dual modulator that activates FXR and inhibits CES2 through high-throughput screening. In the CPT-11-induced delayed diarrhea model, LE-77 demonstrated a dual modulator mechanism by activating FXR and inhibiting CES2, thereby reducing the accumulation of SN-38 in the intestine, alleviating intestinal inflammation, preserving intestinal mucosal integrity, and ultimately alleviating delayed diarrhea.

A multitude of randomized controlled trials (RCTs) conducted in both the initial and subsequent treatment settings for patients diagnosed with metastatic colorectal cancer (mCRC) have provided clinical evidence supporting the efficacy of immunotherapy with the use of immune checkpoint inhibitors (ICIs). In light of these findings, the U.S. Food and Drug Administration (FDA) has authorized the use of several ICIs in specific subpopulations of mCRC patients. Nevertheless, there remains a dearth of direct comparative RCTs evaluating various treatment options. Consequently, the most effective ICI therapeutic strategy for microsatellite-stable (MSS) subgroup and microsatellite instability (MSI) subgroup in the first- and second-line therapies remains undefined. To address this gap, the present study employs a Bayesian network meta-analysis to ascertain the most effective first- and second-line ICI therapeutic strategies.

A comprehensive literature search was conducted across multiple databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, with the retrieval date ranging from the databases' inception to August 20, 2024. A total of 875 studies were identified, and seven were ultimately included in the analysis after a screening process. A systematic review and network meta-analysis were conducted on the basis of the search results.

This comprehensive analysis, comprising seven RCTs, evaluated first-line and second-line immunotherapy regimens in 1,358 patients diagnosed with mCRC. The treatments under investigation consisted of five initial treatments, including three focusing on MSS patients and two on MSI patients, as well as two secondary immunotherapy regimens, both focusing on MSS patients. A total of 1051 individuals underwent first-line treatment, while 307 received second-line treatment. The application of ICIs proved to offer varying degrees clinical benefits when compared to standard-of-care therapy alone, both in two subgroups of the first and the second treatment phases. Of particular note is the performance of Nivolumab combination with ipilimumab, which demonstrated superior efficacy in improving progression-free survival (PFS) (HR=0.21; 95% CI, 0.13-0.34),. Moreover, the treatment demonstrated an optimal safety profile, with a relatively low risk of adverse events (OR = 0.33; 95% CI, 0.19-0.56), compared to other first-line treatment modalities for MSI subgroup. Regarding MSS subgroup, the improvement of PFS by Nivolumab plus standard-of-care (SOC) was relatively significant (HR = 0.74; 95% CI, 0.53-1.02). In the realm of second-line therapies for MSS subgroup, the administration of Atezolizumab plus SOC has proven to be an effective approach for prolonging PFS, exhibiting an HR of 0.66 (95% CI, 0.44-0.99). These findings underscore the clinical benefits and safety profiles of ICIs in the treatment of mCRC across various treatment lines.

The clinical application of ICIs in both first- and second-line treatment strategies for patients with mCRC yields substantial therapeutic benefits. A detailed assessment in this study indicates that first-line treatment with Nivolumab combination with ipilimumab may represent an efficacious and well-tolerated therapeutic approach for MSI subgroup. In terms of MSS subgroup in first-line therapy, Nivolumab plus SOC may be a relative superior choice. In the context of second-line therapy for MSS subgroup, it is evident that a combination of Atezolizumab and SOC represents a preferable option for enhancing PFS. Furthermore, it is noteworthy that other ICIs treatment regimens also exhibit great value in various aspects, with the potential to inform the development of future clinical treatment guidelines and provide a stronger rationale for the selection of ICIs in both first- and second-line therapeutic strategies for mCRC.

https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42024543400.

Colorectal cancer (CRC) incidence has been increasing. Colonoscopy is still a gold standard method for its early diagnosis but using colonoscopy alone as a mass screening method is unrealistic. This study is to investigate whether combining fecal immunochemical test (FIT) and high-risk-factors questionnaire (HRFQ) with colonoscopy improve the cost-effectiveness of a mass CRC screening.

CRC screening protocol combining FITs and HRFQ in the first stage and colonoscopy in the second stage was used in 50 villages/towns in 2007-2015. Residents aged 40-74 years were eligible for this free screening. A total of 160 210 (76.12%) participants completed first-stage screening, and 28 679 (17.90%) participants were defined as positive, among which 21 715 (75.72%) participants completed colonoscopy and were included in the final analysis. Outcomes were followed up until 2020.

The compliance was 76.12% and 75.72% in the first and second screening stage, respectively. A total of 252 CRC, 4033 adenoma, 1234 advanced neoplasm, and 5534 total neoplasm cases were detected in the screening. The positive predictive values of CRC, adenoma, advanced neoplasm, and total neoplasm were higher in FITs+ than those in the HRFQ+ population, respectively. A total of 64.60% and 43.42% total neoplasm cases were found in FITs+ and HRFQ+ (8.02% for both), respectively. The total colorectal neoplasm and CRC cases detected by combining HRFQ and FITs increased by 55.08% and 40.00%, respectively, and their increases were higher compared to HRFQ. The detection cost per any neoplasm by combining HRFQ and FITs was <$5331, while that by FITs and HRFQ alone was <$4570 and $5380, respectively.

Combining FITs and HRFQ with colonoscopy improve the cost-effectiveness of a mass CRC screening program. This protocol can be recommended for most populations, especially those in the countries and areas with high population density and low physician/population ratio.

The purpose of this study is to evaluate the cost-effectiveness of increasing access to colorectal cancer (CRC) diagnosis, considering resource limitations in Thailand.

We analyzed the cost-effectiveness of increasing access to fecal immunochemical test screening (strategy I), symptom evaluation (strategy II), and their combination through healthcare and societal perspectives using Colo-Sim, a simulation model of CRC care. We extended our analysis by adding a risk-stratification score (RS) to the strategies. We analyzed all strategies under the currently limited annual colonoscopy capacity and sufficient capacity. We estimated quality-adjusted life-years (QALYs) and costs over 2023 to 2047 and performed sensitivity analyses.

Annual costs for CRC care will increase over 25 years in Thailand, resulting in a cumulative cost of 323B Thai baht (THB). Each strategy results in higher QALYs gained and additional costs. With the current colonoscopy capacity and willingness-to-pay threshold of 160 000 THB, strategy I with and without RS is not cost-effective. Strategy II + RS is the most cost-effective, resulting in 0.68 million QALYs gained with additional costs of 66B THB. Under sufficient colonoscopy capacity, all strategies are deemed cost-effective, with the combined approach (strategy I + II + RS) being the most favorable, achieving the highest QALYs (1.55 million) at an additional cost of 131 billion THB. This strategy also maintains the highest probability of being cost-effective at any willingness-to-pay threshold above 96 000 THB.

In Thailand, fecal immunochemical test screening, symptom evaluation, and RS use can achieve the highest QALYs; however, boosting colonoscopy capacity is essential for cost-effectiveness.