Development and external validation of a transfer learning-based system for the pathological diagnosis of colorectal cancer: a large emulated prospective study.

Background: The progress in Colorectal cancer (CRC) screening and management has resulted in an unprecedented caseload for histopathological diagnosis. While artificial intelligence (AI) presents a potential solution, the predominant emphasis on slide-level aggregation performance without thorough verification of cancer in each location, impedes both explainability and transparency. Effectively addressing these challenges is crucial to ensuring the reliability and efficacy of AI in histology applications. Method: In this study, we created an innovative AI algorithm using transfer learning from a polyp segmentation model in endoscopy. The algorithm precisely localized CRC targets within 0.25 mm² grids from whole slide imaging (WSI). We assessed the CRC detection capabilities at this fine granularity and examined the influence of AI on the diagnostic behavior of pathologists. The evaluation utilized an extensive dataset comprising 858 consecutive patient cases with 1418 WSIs obtained from an external center. Results: Our results underscore a notable sensitivity of 90.25% and specificity of 96.60% at the grid level, accompanied by a commendable area under the curve (AUC) of 0.962. This translates to an impressive 99.39% sensitivity at the slide level, coupled with a negative likelihood ratio of <0.01, signifying the dependability of the AI system to preclude diagnostic considerations. The positive likelihood ratio of 26.54, surpassing 10 at the grid level, underscores the imperative for meticulous scrutiny of any AI-generated highlights. Consequently, all four participating pathologists demonstrated statistically significant diagnostic improvements with AI assistance. Conclusion: Our transfer learning approach has successfully yielded an algorithm that can be validated for CRC histological localizations in whole slide imaging. The outcome advocates for the integration of the AI system into histopathological diagnosis, serving either as a diagnostic exclusion application or a computer-aided detection (CADe) tool. This integration has the potential to alleviate the workload of pathologists and ultimately benefit patients.

Performance of the fecal immunochemical test for colorectal cancer and advanced neoplasia in individuals under age 50.

The increased demand for colonoscopy combined with increased incidence of colorectal cancer (CRC) among younger populations presents a need to determine FIT performance among individuals in this age group. We conducted a systematic review to assess test performance characteristics of FIT in detecting CRC and advanced neoplasia in younger age populations. A search through December 2022 identified published articles assessing the sensitivity and specificity of FIT for advanced neoplasia or CRC among populations under age 50. Following the search, 3 studies were included in the systematic review. Sensitivity to detect advanced neoplasia ranged from 0.19 to 0.36 and specificity between 0.94 and 0.97 and the overall sensitivity and specificity were 0.23 (0.17-0.30) and 0.96 (0.94-0.98), respectively. Two studies that assessed these metrics in multiple age categories found similar sensitivity and specificity across all age groups 30-49. Sensitivity and specificity to detect CRC was assessed in one study and found no significant differences by age groups. These results suggest that FIT performance may be lower for younger individuals compared to those typically screened for CRC. However, there were few studies available for analysis. Given increasing recommendations to expand screening in younger age groups, more research is needed to determine whether FIT is an adequate screening tool in this population.

Short-chain fatty acids reprogram metabolic profiles with the induction of reactive oxygen species production in human colorectal adenocarcinoma cells.

Short-chain fatty acids (SCFAs) exhibit anticancer activity in cellular and animal models of colon cancer. Acetate, propionate, and butyrate are the three major SCFAs produced from dietary fiber by gut microbiota fermentation and have beneficial effects on human health. Most previous studies on the antitumor mechanisms of SCFAs have focused on specific metabolites or genes involved in antitumor pathways, such as reactive oxygen species (ROS) biosynthesis. In this study, we performed a systematic and unbiased analysis of the effects of acetate, propionate, and butyrate on ROS levels and metabolic and transcriptomic signatures at physiological concentrations in human colorectal adenocarcinoma cells. We observed significantly elevated levels of ROS in the treated cells. Furthermore, significantly regulated signatures were involved in overlapping pathways at metabolic and transcriptomic levels, including ROS response and metabolism, fatty acid transport and metabolism, glucose response and metabolism, mitochondrial transport and respiratory chain complex, one-carbon metabolism, amino acid transport and metabolism, and glutaminolysis, which are directly or indirectly linked to ROS production. Additionally, metabolic and transcriptomic regulation occurred in a SCFAs types-dependent manner, with an increasing degree from acetate to propionate and then to butyrate. This study provides a comprehensive analysis of how SCFAs induce ROS production and modulate metabolic and transcriptomic levels in colon cancer cells, which is vital for understanding the mechanisms of the effects of SCFAs on antitumor activity in colon cancer.

Association between the colorectal cancer screening status of primary care physicians and their patients: Evidence from the Swiss Sentinella practice-based research network.

Swiss health insurance reimburses screening for colorectal cancer (CRC) with either colonoscopy or fecal occult blood test (FOBT). Studies have documented the association between a physician's personal preventive health practices and the practices they recommend to their patients. We explored the association between CRC testing status of primary care physicians (PCP) and the testing rate among their patients. From May 2017 to September 2017, we invited 129 PCP who belonged to the Swiss Sentinella Network to disclose their CRC test status and whether they had been tested with colonoscopy or FOBT/other methods. Each participating PCP collected demographic data and CRC testing status from 40 consecutive 50- to 75-year-old patients. We analyzed data from 69 (54%) PCP 50 years or older and 2623 patients. Most PCP were men (81%); 75% were tested for CRC (67% with colonoscopy and 9% with FOBT). Mean patient age was 63; 50% were women; 43% had been tested for CRC (38%, 1000/2623 with colonoscopy and 5%, 131/2623, with FOBT or other non-endoscopic test). In multivariate adjusted regression models that clustered patients by PCP, the proportion of patients tested for CRC was higher among PCP tested for CRC than among PCP not tested (47% vs 32%; OR 1.97; 95% CI 1.36 to 2.85). Since PCP CRC testing status is associated with their patients CRC testing rates, it informs future interventions that will alert PCPs to the influence of their health decisions and motivate them to further incorporate the values and preferences of their patients in their practice.

Impact of genetic variants involved in the lipid metabolism pathway on progression free survival in patients receiving bevacizumab-based chemotherapy in metastatic colorectal cancer: a retrospective analysis of FIRE-3 and MAVERICC trials.

Background: Antiangiogenic drug (AAD)-triggered oxygen and nutrient depletion through suppression of angiogenesis switches glucose-dependent to lipid-dependent metabolism. Blocking fatty acid oxidation can enhance AAD-mediated anti-tumor effects in colorectal cancer (CRC). Therefore, we hypothesised that genetic variants in the lipid metabolism pathway may predict clinical outcomes [overall response rate (ORR), overall survival (OS) and progression-free survival (PFS)] in metastatic CRC (mCRC) patients receiving bevacizumab-based first-line treatment. Methods: Genomic DNA from blood samples of patients enrolled in FIRE-3 (a global, randomised, open-label, phase 3 trial, between 2007-6-23 and 2012-9-19, discovery cohort: FOLFIRI/bevacizumab arm, n = 107; control cohort: FOLFIRI/cetuximab arm, n = 129) and MAVERICC (a global, randomised, open-label, phase II study, between 2011-8 and 2015-7, in United States, Canada, Estonia, Ireland, Switzerland, Norway, and Portugal. Validation cohort: FOLFIRI/bevacizumab arm, n = 163) trials, was genotyped using the OncoArray-500 K beadchip panel. The impact on OS and PFS of 17 selected SNPs in 7 genes involved in the lipid metabolism pathway (CD36, FABP4, LPCAT1/2, CPT1A, FASN, ACACA) was analysed using Kaplan-Meier curves, the log-rank test for univariate analyses and likelihood ratio tests of Cox proportional hazards regression parameters for multivariable analyses. ORR and SNP associations were evaluated using Chi-square or Fisher's exact tests. Findings: In the discovery cohort, patients with FASN rs4485435 any C allele (n = 21) showed significantly shorter PFS (median PFS: 8.69 vs 13.48 months) compared to carriers of G/G (n = 62) in multivariable (HR = 2.87; 95%CI 1.4-5.9; p = 0.00675) analysis. These data were confirmed in the validation cohort in multivariable analysis (HR = 2.07, 95%CI: 1.15-3.74; p = 0.02), but no association was observed in the cetuximab cohort of FIRE-3. In the comparison of bevacizumab vs cetuximab arm in FIRE-3, a significant interaction was shown with FASN rs4485435 (p = 0.017) on PFS. Interpretation: Our study demonstrates for the first time, to our knowledge, that FASN polymorphisms may predict outcome of bevacizumab-based treatment in patients with mCRC. These findings support a possible role of the lipid metabolism pathway in contributing to resistance to anti-VEGF treatment. Funding: This work was supported by the National Cancer Institute [P30CA 014089 to H.-J.L.], Gloria Borges WunderGlo Foundation, Dhont Family Foundation, Victoria and Philip Wilson Research Fund, San Pedro Peninsula Cancer Guild, Ming Hsieh Research Fund, Eddie Mahoney Memorial Research Fund, Shanghai Sailing Program (22YF1407000), China National Postdoctoral Program for Innovative Talents (BX20220084), China Postdoctoral Science Foundation (2022M710768), National Natural Science Foundation of China (82202892).

Subsequent participation in organized FIT based screening following screen-derived colonoscopy - A Danish nationwide cohort study.

Introduction: In the Danish National Colorectal Cancer (CRC) screening program, participants with screen-detected low-risk adenomas are invited to a new faecal immunochemical test (FIT) screening after two years. However, participation rate in next FIT screening is unknown. We aimed to investigate this subsequent participation rate within the Danish CRC screening program. Methods: This nationwide register-based study included participants aged 50-72 years registered with FIT screening in the Danish CRC screening program between January 1, 2016, and June 30, 2017. Participants were included if their index FIT was negative or if it was positive and the subsequent colonoscopy detected low-risk adenomas. Invitees were categorized as subsequent participants if they returned a FIT within 135 days following the invitation to screening. We estimated the relative risk for participation depending on screening outcome, age, and sex. Result: 415,107 with a negative result and 5,550 with low-risk adenomas were included. 86.0% (85.9;86.1) of the invitees with a negative result participated in the subsequent screening, while 71.8% (70.6;73.0) of the invitees with low-risk adenomas participated subsequently. The risk of participation in the subsequent screening was significantly lower among all age groups of men and women with low-risk adenomas compared to similar groups with negative results. Conclusion: Invitees with low-risk adenomas detected at their initial colonoscopy are less likely to participate in the subsequent screening than invitees with negative results. This association was found in all age groups and for both sexes. Further studies are necessary to assess whether non-attendance is more pronounced in specific subgroups.

A new method for predicting the prognosis of colorectal cancer patients through a combination of multiple tumor-associated macrophage markers at the invasive front.

Tumor-associated macrophages (TAMs) are closely related to tumorigenesis and metastasis of multiple cancer types. The infiltration of TAMs is used for predicting the prognosis of cancers, including colorectal cancer (CRC). However, the density and prognostic significance of M1 and M2 TAM phenotypes in the intratumor versus the invasive front (IF) are largely unknown in CRC. In this study, CD68 was selected as a general marker of TAMs, CD11c, NOS2 and CXCL10 as markers for M1 phenotype and CD163, CD206, CD115 as markers for M2 phenotype. Firstly, immunohistochemistry staining and double-labeling immunofluorescence staining showed that M1 molecular markers (NOS2, CXCL10, CD11c) were lowly expressed at both IF and intratumor, while M2 molecular markers (CD163, CD206, CD115) were highly expressed mainly at IF. Moreover, we also demonstrated that three M1 molecular markers including NOS2, CXCL10 and CD11c were correlated to each other. Meanwhile, three M2 molecular markers including CD163, CD206, and CD115 were also correlated to each other. Patients with low expression of three M1 molecular markers (NOS2/CXCL10/CD11c) exhibited low overall survival (OS) rate, whereas patients with high expression of three M2 molecular markers (CD163/CD206/CD115) exhibited low OS rate. We also observed that the prognostic value of treble markers combination (NOS2/CXCL10/CD11c or CD163/CD206/CD115) was superior to that of single marker. Together, our results reveal the combination of treble TAMs markers (NOS2/CXCL10/CD11c or CD163/CD206/CD115) could better evaluate the prognosis of CRC patients, which might be used as a more comprehensive method for predicting the prognosis of CRC patients.

Development of a tongue image-based machine learning tool for the diagnosis of gastric cancer: a prospective multicentre clinical cohort study.

Background: Tongue images (the colour, size and shape of the tongue and the colour, thickness and moisture content of the tongue coating), reflecting the health state of the whole body according to the theory of traditional Chinese medicine (TCM), have been widely used in China for thousands of years. Herein, we investigated the value of tongue images and the tongue coating microbiome in the diagnosis of gastric cancer (GC). Methods: From May 2020 to January 2021, we simultaneously collected tongue images and tongue coating samples from 328 patients with GC (all newly diagnosed with GC) and 304 non-gastric cancer (NGC) participants in China, and 16 S rDNA was used to characterize the microbiome of the tongue coating samples. Then, artificial intelligence (AI) deep learning models were established to evaluate the value of tongue images and the tongue coating microbiome in the diagnosis of GC. Considering that tongue imaging is more convenient and economical as a diagnostic tool, we further conducted a prospective multicentre clinical study from May 2020 to March 2022 in China and recruited 937 patients with GC and 1911 participants with NGC from 10 centres across China to further evaluate the role of tongue images in the diagnosis of GC. Moreover, we verified this approach in another independent external validation cohort that included 294 patients with GC and 521 participants with NGC from 7 centres. This study is registered at ClinicalTrials.gov, NCT01090362. Findings: For the first time, we found that both tongue images and the tongue coating microbiome can be used as tools for the diagnosis of GC, and the area under the curve (AUC) value of the tongue image-based diagnostic model was 0.89. The AUC values of the tongue coating microbiome-based model reached 0.94 using genus data and 0.95 using species data. The results of the prospective multicentre clinical study showed that the AUC values of the three tongue image-based models for GCs reached 0.88-0.92 in the internal verification and 0.83-0.88 in the independent external verification, which were significantly superior to the combination of eight blood biomarkers. Interpretation: Our results suggest that tongue images can be used as a stable method for GC diagnosis and are significantly superior to conventional blood biomarkers. The three kinds of tongue image-based AI deep learning diagnostic models that we developed can be used to adequately distinguish patients with GC from participants with NGC, even early GC and precancerous lesions, such as atrophic gastritis (AG). Funding: The National Key R&D Program of China (2021YFA0910100), Program of Zhejiang Provincial TCM Sci-tech Plan (2018ZY006), Medical Science and Technology Project of Zhejiang Province (2022KY114, WKJ-ZJ-2104), Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer (JBZX-202006), Natural Science Foundation of Zhejiang Province (HDMY22H160008), Science and Technology Projects of Zhejiang Province (2019C03049), National Natural Science Foundation of China (82074245, 81973634, 82204828), and Chinese Postdoctoral Science Foundation (2022M713203).

Colorectal cancer screening barriers and facilitators among Jordanians: A cross-sectional study.

The factors affecting the adherence of Jordanians to colorectal cancer (CRC) screening remain underexplored. We examined the inhibitory and facilitating factors that influence the uptake of CRC screening among Jordanians. We conducted questionnaire interviews between April 2020 and June 2021 with 861 Jordanians aged 50-75. We analyzed the differences between proportions using the chi-square test. Binary logistic regression was conducted to determine factors associated with awareness of CRC and its screening. Of all participants, 41.7 % were aware of the necessity of screening for CRC, and 27.2 % were aware of at least one of the tests for CRC screening. However, only 17.2 % of participants underwent screening. In the multivariate analysis, participants with higher income (p-value < 0.001, odds ratio[OR] = 1.9, 95 % confidence interval [CI]: 1.4-2.7), higher level of education (p-value < 0.001, OR = 2.6, 95 % CI: 1.8-3.7), family history of colon cancer (p-value < 0.001, OR = 2.8, 95 % CI = 1.7-4.5), and those who had been screened for other cancers (p-value = 0.003, OR = 1.7, 95 % CI: 1.2-2.5) were more aware of the necessity of screening. Concerning barriers to screening, 'feeling well,' lack of physician endorsement, and difficult access to health care were the most commonly reported inhibitory factors (53.9 %, 52.3 %, and 31.9 %, respectively). The most commonly stated incentivizing factor was physician endorsement (82.3 %). Screening rates for CRC in eligible Jordanians remain low, albeit more than one-third of participants are aware of the necessity of screening. Enhanced awareness of barriers and incentivizing factors should help to prioritize national strategies to improve screening rates.

p15INK4B is an alternative marker of senescent tumor cells in colorectal cancer.

Senescent tumor cells are nonproliferating tumor cells which are closely related to cancer progression by secreting senescence-related molecules, called senescence-associated secreting phenotypes. Therefore, the presence of senescent tumor cells is considered a prognostic factor in various cancer types. Although senescence-associated ß-galactosidase staining is considered the best marker for detection of senescent tumor cells, it can only be performed in fresh-frozen tissues. p16INK4A, a cyclin-dependent inhibitor, has been used as an alternative marker to detect senescent tumor cells in formalin-fixed paraffin-embedded tissues. However, other reliable markers to detect senescent tumor cells is still lacking. In the present study, using public single-cell RNA-sequencing data, we found that p15INK4B, a cyclin-dependent kinase inhibitor, is a novel marker for detection of senescent tumor cells. Moreover, p15INK4B expression was positively correlated with that of p16INK4A in colorectal cancer tissues. In in vitro studies, mRNA expression of p15INK4B was increased together with that of p16INK4A in H2O2- and therapy-induced cancer senescence models. However, the mRNA level of p15INK4B did not increase in the oncogene-induced senescence model in primary colonic epithelial cells. In conclusion, p15INK4B is a potential alternative marker for detection of senescent tumor cells together with conventional markers in advanced stages of colorectal cancer.

Single-cell analysis of multiple cancer types reveals differences in endothelial cells between tumors and normal tissues.

Endothelial cells (ECs) play an important role in tumor progression. Currently, the main target of anti-angiogenic therapy is the vascular endothelial growth factor (VEGF) pathway. Some patients do benefit from anti-VEGF/VEGFR therapy; however, a large number of patients do not have response or acquire drug resistance after treatment. Moreover, anti-VEGF/VEGFR therapy may lead to nephrotoxicity and cardiovascular-related side effects due to its action on normal ECs. Therefore, it is necessary to identify targets that are specific to tumor ECs and could be applied to various cancer types. We integrated single-cell RNA sequencing data from six cancer types and constructed a multi-cancer EC atlas to decode the characteristic of tumor ECs. We found that tip-like ECs mainly exist in tumor tissues but barely exist in normal tissues. Tip-like ECs are involved in the promotion of tumor angiogenesis and inhibition on anti-tumor immune responses. Moreover, tumor cells, myeloid cells, and pericytes are the main sources of pro-angiogenic factors. High proportion of tip-like ECs is associated with poor prognosis in multiple cancer types. We also identified that prostate-specific membrane antigen (PSMA) is a specific marker for tip-like ECs in all the cancer types we studied. In summary, we demonstrate that tip-like ECs are the main differential EC subcluster between tumors and normal tissues. Tip-like ECs may promote tumor progression through promoting angiogenesis while inhibiting anti-tumor immune responses. PSMA was a specific marker for tip-like ECs, which could be used as a potential target for the diagnosis and treatment of non-prostate cancers.

Comparison of radiofrequency ablation and ablative external radiotherapy for the treatment of intrahepatic malignancies: A hybrid meta-analysis.

Background & Aims: Radiofrequency ablation (RFA) and ablative external beam radiotherapy (ablative RT) are commonly used to treat small intrahepatic malignancies. We meta-analysed oncologic outcomes and systematically reviewed the clinical consideration of tumour location and size. Methods: PubMed, Medline, Embase, and Cochrane Library databases were searched on February 24, 2022. Studies comparing RFA and ablative RT, providing one of the endpoints (local control or survival), and encompassing ≥5 patients in each arm were included. Results: Twenty-one studies involving 4,638 patients were included. Regarding survival, the odds ratio (OR) was 1.204 (p = 0.194, favouring RFA, not statistically significant) among all studies, 1.253 (p = 0.153) among hepatocellular carcinoma (HCC) studies, and 1.002 (p = 0.996) among colorectal cancer metastasis studies. Regarding local control, the OR was 0.458 (p <0.001, favouring ablative RT) among all studies, 0.452 (p <0.001) among HCC studies, favouring the ablative RT arm, and 0.649 (p = 0.484) among colorectal cancer metastasis studies. Pooled 1- and 2-year survival rates for HCC studies were 91.8% and 77.7% after RFA, and 89.0% and 76.0% after ablative RT, respectively; and for metastasis studies were 88.2% and 66.4% after RFA and 82.7% and 60.6% after RT, respectively. Literature analysis suggests that ablative RT can be more effective than RFA for tumours larger than 2-3 cm or for specific sublocations in the liver (e.g. subphrenic or perivascular sites), with moderate quality of evidence (reference to the grading system of the American Society for Radiation Oncology Primary Liver Cancer Clinical Guidelines). The pooled grade ≥3 complication rates were 2.9% and 2.8% in the RFA and ablative RT arms, respectively (p = 0.952). Conclusions: Our study shows that ablative RT can yield oncologic outcomes similar to RFA, and suggests that it can be more effective for the treatment of tumours in locations where RFA is difficult to perform or for large-sized tumours. Systematic Review Registration: This study was registered with PROSPERO (Protocol No: CRD42022332997). Impact and implications: Radiofrequency ablation (RFA) and ablative radiotherapy (RT) are non-surgical modalities for the treatment of small intrahepatic malignancies. Ablative RT showed oncologic outcomes at least similar to those of RFA, and was more effective at specific locations (e.g. perivascular or subphrenic locations).

Factors influencing colorectal cancer screening decision-making among average-risk US adults.

Colorectal cancer (CRC) screening rates remain suboptimal in the US. We examined patient-focused concerns and influence of various factors (e.g., test attributes, provider recommendation) on CRC screening decision-making. We conducted a web survey with 1595 US adults aged 40-75 from a nationally representative panel in November 2019 (completion rate: 31.3 %). Analyses focused on individuals aged 45-75 years at average-risk for CRC (n = 1062). All participants rated their level of concern about various CRC screening test/procedure attributes. Participants who have screened previously designated the three most important attributes for choosing a screening method and rated how various factors influenced their decision to use a particular method. The top concern for participants who have not screened previously was having an invasive procedure (54.2 %) while the top concerns for participants who have screened previously were completing a colon prep (41.3 %) and test/procedure accuracy (41 %). Cost/insurance coverage was most frequently ranked among the most important attributes (48.5 %), followed by where the test can be taken (45.7 %) and test accuracy (43.6 %). Provider recommendation was reported as the major motivator across screening methods. Other factors that were frequently reported as very influential included convenience and comfort for the stool-based methods and scientific/clinical evidence and insurance coverage for colonoscopy. Variations by age, sex, and race/ethnicity were noted. Findings demonstrate that along with provider recommendation, patient preferences regarding test/procedure attributes and preparation requirements are influential in screening decision-making, highlighting the need for clinicians to involve patients in shared decision-making and incorporate patient needs and preferences in establishing screening strategies.

N1-methyladenosine modification in cancer biology: Current status and future perspectives.

Post-transcriptional modifications in RNAs regulate their biological behaviors and functions. N1-methyladenosine (m1A), which is dynamically regulated by writers, erasers and readers, has been found as a reversible modification in tRNA, mRNA, rRNA and long non-coding RNA (lncRNA). m1A modification has impacts on the RNA processing, structure and functions of targets. Increasing studies reveal the critical roles of m1A modification and its regulators in tumorigenesis. Due to the positive relevance between m1A and cancer development, targeting m1A modification and m1A-related regulators has been of attention. In this review, we summarized the current understanding of m1A in RNAs, covering the modulation of m1A modification in cancer biology, as well as the possibility of targeting m1A modification as a potential target for cancer diagnosis and therapy.

Predicting rectal tumor response to neoadjuvant chemoradiotherapy using plasma levels of carcinoembryonic antigen (CEA): Results from a tertiary center in Iran.

Objectives: Nonsurgical treatment of colorectal cancer, the third most prevalent cancer worldwide, through chemoradiotherapy (CRT) has been suggested to induce complete remission. Carcinoembryonic antigen (CEA) has been used as a candidate marker to predict treatment response. In this study, we aimed to assess the applicability of plasma levels of CEAs in predicting the response to CRT, particularly complete pathological response. Methods: We designed a retrospective, cross-sectional study in which tumor stage and plasma levels of CEAs before and after neoadjuvant CRT were extracted from the medical records of patients with rectal tumors who underwent neoadjuvant chemoradiotherapy before surgery at Sina Hospital, Tehran, Iran from 2010 to 2015. Results: Pre-CRT plasma levels of CEA positively correlated with tumor stage, and chemoradiotherapy significantly decreased plasma levels of CEA. Whereas lower pre-CRT plasma levels of CEA and tumor stage were significantly associated with complete response to CRT, post-CRT plasma levels of CEA showed no association with complete response. In addition, in ROC curve analysis, a CEA cut-off value of 2.6 ng/mL predicted complete response to CRT (specificity = 82.6%, sensitivity = 40.5%). Conclusion: Although several factors other than plasma levels of CEA and tumor stage are important in determining the response to CRT, preliminary plasma levels of CEA and tumor stage can be used as factors for determining complete response to neoadjuvant chemoradiotherapy in rectal cancer.

Carbon dots conjugated to SN38 for improved colorectal anticancer therapy.

Irinotecan (CTP-11) is one of the standard therapies for colorectal cancer (CRC). CTP-11 is enzymatically converted to the hydrophobic 7-ethyl-10-hydroxycamptothecin (SN38), a one hundred-fold more active metabolite. Conjugation of hydrophobic anticancer drugs to nanomaterials is a strategy to improve their solubility, efficacy, and selectivity. Carbon dots (CDs) have garnered interest for their small sizes (<10 â€‹nm), low toxicity, high water solubility, and bright fluorescence. This paper describes the use of CDs to improve drug vehiculation, stability, and chemotherapeutic efficiency of SN38 through a direct intracellular uptake in CRC. The covalent conjugation of SN38 to CDs via a carbamate bond provides a CD-SN38 hybrid material for slow, sustained, and pH-responsive drug release. CD-SN38 successfully penetrates the CRC cells with a release in the nucleus affecting first the cell cycle and then the cytoskeleton. Moreover, CD-SN38 leads to a deregulation of the extracellular matrix (ECM), one of the major components of the cancer niche considered a possible target therapy for reducing the cancer progression. This work shows the combined therapeutic and imaging potential of CD-based hybrid materials for the treatment of CRC. Future efforts for targeted therapy of chronic diseases characterized by altered ECM deposition, such as chronic kidney disease and chronic allograft nephropathy in kidney transplant patients are envisaged.

Dostarlimab: A breakthrough in the field of oncology.

Of the 19 million cancer cases reported worldwide in 2020, colorectal cancer (CRC) has a 10% prevalence and 9.4% mortality. A critical lack of cancer treatment facilities in third-world countries like Pakistan where a significant prevalence of CRC has been detected. The five FDA-approved drugs used for CCR therapy (Durvalumab, Atezolizumab, Nivolumab, Pembrolizumab, and Avelumab) have been associated with a high occurrence of grade 3-4 adverse side effects. Dostarlimab is a new drug previously used to treat endometrial cancers and has a mechanism of action that is in accordance with other PD-1/PD-L1 inhibitors. A recent clinical trial has found Dostarlimab to cure 100% of the CRC patients who were given this drug while also showing no adverse events of grade 3 or higher in any patient. The recent clinical trial has opened up doors for future clinical trials perhaps with bigger sample sizes and ones that also include CRC patients belonging to wider geo-economic backgrounds such as those of Pakistan and other Asian countries.