Pivotal articles that had been published between 2022 and 2023 on surgical and perioperative adjuvant treatments for locally advanced colorectal cancer (CRC) were reviewed. This review focuses on new evidence in the following areas: optimization of surgical procedures for colon cancer, minimally invasive surgery for rectal cancer, neoadjuvant treatments for colorectal cancer, and postoperative adjuvant chemotherapy for Stage II and III colon cancer.

Patients with pStage II/III colorectal cancer who undergo curative resection and demonstrate lower postoperative prognostic nutritional index (PNI) levels compared to preoperative PNI levels have poorer overall survival and recurrence-free survival. Therefore, perioperative PNI changes can serve as useful biomarkers for predicting survival and recurrence in these patients.

Statistical information is essential for clinical cancer research and policymaking processes. The essential information was summarized in this paper to help users of these statistics understand how these are made and what caution they need to take when interpreting the numbers.

This article reviewed a history of repeated revisions on tumor deposit (TD) definition and categorization in the tumor-node-metastasis (TNM) system, which may have failed to maximize the value of the TNM system because of the underused prognostic information of individual TDs. Recently, the potential value of an alternative staging method has been highlighted in several studies using the “counting method,” in which all nodular type TDs are individually counted together with positive LNs to derive the final pN. The treatment of TDs should be determined in terms of how it will maximize the prognostic value of TNM classification and its reproducibility, and it is time to initiate an international discussion on optimal treatment of TDs in tumor staging; otherwise, a proportion of patients end up missing an opportunity to receive the optimal adjuvant treatment.

This review article covers four topics that are important for surgeons to consider as they individualize multidisciplinary treatment for patients with colorectal liver metastases: parenchymal-sparing hepatectomy and/or ablation; two-stage hepatectomy; somatic gene alterations and canonical pathways; and posttreatment surveillance. The knowledge of tumor biology can alter treatment intensity, accurately predict patient prognosis, and help to determine whether extensive or repeated resection is justified. Also, the surveillance algorithm can be personalized according to tumor biology.

This review discusses the challenges around diagnosing EOCRC, why focusing on symptomatic patients is not enough and argues that reducing the age to start screening in younger patients is the best way to improve outcomes in EOCRC.

Australia's National Bowel Cancer Screening program is associated with increased colonoscopy and polypectomy rates, and a stage shift to earlier diagnosis.

An Asia-Pacific expert consensus panel developed eight evidence-based recommendations for the optimal management of BRAF^V600E-mutant metastatic colorectal cancer (mCRC). We recommend molecular testing to guide individualized therapy, propose treatment pathways according to microsatellite stability status, advocate for more frequent monitoring of BRAF^V600E-mutant mCRC, and discuss local treatment for oligometastatic disease.

We present a narrative review of the risk factors, histopathological profile, diagnostic biomarkers, treatment patterns, and survival of early-onset colorectal cancer patients. This review highlights the need for future research into immunotherapies, minimally invasive diagnostic biomarkers, and the survival and functional outcomes of early-onset colorectal cancer.

A systematic review was undertaken to determine the utility of resecting PALN metastases in colorectal cancer. PALN dissection was found to be associated with a survival benefit when compared to non-resection.

The case reported the histologic transformation from colon adenocarcinoma into large cell neuroendocrine carcinoma (LCNEC) after treatment. Notably, this case suggests that the phenotypic transformation into LCNEC might represent a novel mechanism of acquired resistance to antiangiogenesis and ICIs combination in metastatic colorectal cancer.

Flavonols are one of the most widespread dietary nutrients of the polyphenols-flavonoids and major constituent of Allium and Brassicaceae vegetables. Flavonols present in vegetables of Allium and Brassicaceae family are kaempferol, myricetin, quercetin, and isorhamnetin. These flavonols are claimed to have antiproliferative activity in vivo and in vitro against colorectal cancer.

Mismatch repair–deficient colorectal cancer patients are generally older, with often significant comorbidities, and only a limited portion of patients with metastatic tumors underwent oncological treatments. Many of the metastatic tumors present features that may impair response to PD-1 blockade therapy. High proportions of necrosis and stroma were common in metastatic tumors and were associated with worse survival; however, high Crohn's-like reaction density, T-cell proximity score, and CD68+/PD-L1+ cell number in the tumor center and invasive margin were independent prognostic immune factors for improved survival.

In order to evaluate the temporal recurrence dynamics of colorectal cancer, we conducted a systematic review of Phase III randomized controlled trials centered on Stage II–IV disease, finding that adjuvant cytotoxic chemotherapy improved early—but not remote—recurrence event rates over surgery-only controls. These results support the role of initially-dormant micrometastatic populations in disease relapse, and therefore the ongoing evaluation of cell-free DNA technologies to guide adjuvant treatment decisions and novel therapeutic strategies.

This study analyzed targeted sequencing of 6530 patients with metastatic Chinese colorectal cancer (CRC), identifying 36 novel driver genes with subgroup-specific implications, such as ERBB4 affecting only male CRC patient outcomes. Additionally, the study utilized network-based stratification to categorize microsatellite stable (MSS) and unstable (MSI) CRCs into distinct subtypes, revealing significant phenotypic and prognostic differences.

Colorectal cancer (CRC) tumors with high tumor mutation burden (TMB) often exhibit distinct molecular features, including lower KRAS and higher BRAF mutation frequencies, microsatellite instability (MSI), and a mutational signature linked to the CpG island methylator phenotype (CIMP). Analysis suggests that mutations in mismatch repair and DNA damage response genes may precede BRAF mutations, contributing to serrated pathway activation in these tumors.

We characterized the functional states of T and B cells in colorectal cancer post-renal transplantation compared with non-transplant CRC. In CRC post renal transplantation, cytotoxic T cells exhibited significantly weakened tumor-killing capabilities while Tregs immunosuppressive potential enhanced. Elevated CTLA4 expression contributes to the maintenance of this suppressive state.

We demonstrated that the overall spectrum of mutations in our Japanese stage III colorectal cancer cohort (534 patients) was largely similar to that in Western populations, but the frequencies of mutation for TP53 (75.3%), SOX9 (11.8%), and FBXW7 (18.5%) were higher, and the proportion of hypermutated tumors (5.8%) was lower. We also revealed that poorer relapse-free survival was seen with mutant KRAS (hazard ratio 1.66; p = 0.011) and mutant RNF43 (2.17; p = 0.055) as well as hypermutated tumors (0.53; p = 0.229), whereas better relapse-free survival was seen with mutant COL6A3 (0.35; p = 0.040) and mutant NOTCH3 (0.18; p = 0.093), suggesting that tumor genomic profiling has the potential to support precision medicine for patients with colorectal cancer.

PLOD2 enhances proliferation and metastasis in CRC. PLOD2 interacts with USP15 by inhibiting protein degradation of ubiquitination in the cytoplasm. USP15 subsequently activates the phosphorylation of the AKT/mTOR signaling pathway to promote tumor growth and migration.

This paper describes the most commonly encountered and clinically significant difficulties in the histological assessment of risk factors for regional lymph node metastases in locally resected early (i.e. pT1) colorectal cancer (CRC). These are illustrated using four examples that were received by our department during routine diagnostic practice.

This systematic review compares LNM+, LNM + TD+ and LNM + ENE+ cases using network meta-analyses. As LNM+TD+ has a worse outcome than LNM +E NE+ and both groups perform worse than cases with LNM only, more emphasis on both ENE and TD in the TNM classification is needed, with the most prominent role for TD.

Protocols for the pathological examination of colorectal cancer specimens now recommend assessment of a number of microscopic findings that are associated with prognosis, including venous invasion. Here we prospectively identify an approach to gross dissection and sectioning of these cases to maximise sensitivity for detection of this important histological feature.

We report pathology findings from the first 10 years of the faecal-occult blood-based Northern Ireland Bowel Cancer Screening Programme. ‘Real world’ pathology data demonstrate programme success in the form of shift to early cancer stage and reduced endoscopic diagnoses of cancer and interesting trends with respect to serrated polyp diagnoses.

What's new?

The highest rates of colorectal cancer are in highly developed countries, but rates are on the rise in low- and middle-income countries. Here, the authors analyze trends in CRC incidence in sub-Saharan Africa. Using data from 12 population-based registries in 11 countries covering a period of at least 12 years, they found a steady rise in CRC across all regions, possibly due to wider adoption of a western lifestyle, including consumption of more meat, sugars, and alcohol. This highlights the need for prevention, early diagnosis, and management strategies in these regions.

What's new?

There is strong evidence that dairy intake is associated with a reduced risk of developing colorectal cancer. However, its relation to the risk of colorectal cancer recurrence remains unclear. Combining data from two prospective cohort studies of patients with stage I–III colorectal cancer, this study found that a higher intake of low-fat dairy was associated with a reduced risk of recurrence in men, where as a higher intake of high-fat dairy was associated with an increased risk of recurrence in people with colon cancer. With a global transition towards more plant-based diets and increasing numbers of colorectal cancer survivors, the findings may contribute to more personalised dietary guidelines.

What's new?

Single-cell transcriptomics is a standard means of assessing cell heterogeneity and cell hierarchies in cancer tissues. However, single-cell datasets are complex and contain cancer and non-cancer lineage cells. Here, the authors compared different strategies to analyze gene expression and genomic information and retrace the origins of epithelial cell transcriptomes in colorectal cancer (CRC) cells. Haplotype-aware copy number inference combined with a novel method to assess somatic single nucleotide variants exhibited high accuracy in differentiating between cancerous and genetically normal cells found within cancer tissue. The findings offer a novel approach to account for biological and genetic features of CRC.

What's new?

MCL-1, an anti-apoptotic protein required for intestinal homeostasis, has been associated with chemoresistance in colorectal cancer. This study provides novel insights into the molecular profile and tumor microenvironment of colorectal cancer according to MCL-1 mRNA expression. High MCL-1 expression in colorectal cancer samples was associated with the upregulation of PD-L1, several immune-related genes, B cells, natural killer cells, T-reg cells, and M1 and M2 macrophages. High MCL-1 expression was linked to improved patient survival. The findings reveal a correlation between distinct immune biomarkers, tumor microenvironment cell infiltration, and MCL-1 in colorectal cancer and highlight MCL-1 as a potential biomarker.

What's new?

Innate-like immune γδT-cells infiltrate into human tumors of colorectal cancer and widely participate in the antitumor immune response. However, the immune landscape and functional states of tumor-infiltrating γδT-cells in the colorectal cancer tumor microenvironment remain unclear. In our study, tumor-infiltrating γδT-cells exhibited exhaustion phenotypes and displayed more severe functional exhaustion than tumor-infiltrating CD8⁺T-cells or NK-cells in the tumor microenvironment of colorectal cancer. scRNA-seq analysis demonstrated that the tumor-infiltrating γδT-cell population was heterogeneous, and that exhausted cells were the dominant subset. Moreover, transcriptional factor c-Maf promoted tumor-infiltrating γδT-cells exhaustion via the upregulation of inhibitory receptors.

What's new?

Alterations to circulating white blood cell counts have been associated with colorectal cancer, but whether these changes have causal effects remains unexplored. Using multivariable Mendelian randomisation, the authors assessed the independent causal effects of white blood cell counts by cell subtype by adjusting for shared genetic architecture. In parallel, they ran the largest longitudinal cohort study to explore causal effects between white blood cell counts and colorectal cancer using UK Biobank data. The evidence suggests that elevated eosinophil and lymphocyte counts may have a protective effect against colorectal cancer, adding new insights into colorectal cancer pathogenesis.

What's new?

Early-onset colorectal cancer is on the rise worldwide, possibly driven by exposure to risk factors in childhood. Long-term or recurrent use of antibiotics, for instance, could cause long-lasting changes in the gut microbiota that lead to cancer susceptibility. Here, the authors investigated the association between antibiotics use and cancer risk, both overall and according to certain genetic factors. They found that long-term or recurrent antibiotic use increased the risk of early-onset CRC and adenomas, with a stronger effect in people with a particular variant of the gut microbiota regulatory gene, Fucosyltransferase 2 (FUT2).

What's new?

Recent advancements in colorectal cancer (CRC) management have reduced the risk of late recurrence and metachronous CRC 5–10 years after curative surgery for non-metastatic CRC—a timeframe with no surveillance according to current guidelines. Despite more patients are cancer-free survivors at the 5-year mark, late events remain uncommon. Our study does not support extending current surveillance protocols, as late recurrence or metachronous CRC don't impact more patients than late second non-CRC primary cancers.

What's new?

A variety of patterns in metastasis can occur in RAS wildtype metastatic colorectal cancer (mCRC). Heterogeneity in metastatic spread, however, challenges prognostic evaluation for patients with these tumors. Here, the prognostic and therapeutic significance of different metastatic patterns in RAS wildtype mCRC was investigated in patients on maintenance therapy with 5-fluorouracil/folinic acid, with or without panitumumab. In patients who presented with liver-limited disease, spread to one additional organ had limited impact on survival. Survival was less favorable for metastasis to multiple organs. Maintenance therapy involving panitumumab had greater effect in RAS wildtype mCRC patients with multiple organ metastasis.

What's new?

Patients with metastatic colorectal cancer (mCRC) who are taking EGFR inhibitors often find their cancers develop resistance. In this article, the authors investigated whether rechallenge with EGFR inhibitors in refractory mCRC patients could improve outcomes. They report results from VELO, the first prospective randomized trial testing to show that adding the EGFR inhibitor panitumumab to trifluridine/tiparicil as third-line treatment improved progression-free survival in mCRC with wild-type RAS. Patients in the control arm who later received fourth-line treatment also had better PFS with panitumumab than with other therapies. These results support the rechallenge approach with EGFR inhibitors for refractory mCRC.

The aim of this study was to assess the quality and content of short videos Douyin and TikTok for educational role on early screening of rectal cancer. We found that in terms of quality score and content score, the Chinese videos on Douyin exhibit superiority over the English and Japanese videos on TikTok.

The association between colonoscope intubation time and adenoma detection is unclear. The current study demonstrated that prolonged cecal intubation time significantly decreased the number of detected adenomas. Cecal intubation time may be an important quality indicator for colonoscopy.

This study indicates that the neoadjuvant rectal (NAR) score predicts disease-free survival (DFS) and overall survival (OS) for locally advanced rectal cancer (LARC) patients treated with long-course chemoradiotherapy followed by radical surgery. NAR-based nomograms have the potential to be used in clinical practice.

Schema flow chart of the study. The analysis included multi-omics data from transcriptomic, genomic, and whole slide images of more than 2500 colorectal cancer (CRC) patients. Senescence subtypes were established by unsupervised clustering, and multi-omics data were utilized to further analyze the biological characteristics, tumor microenvironment, mutational landscape, and drug sensitivity of the senescence subtypes. Finally, the senescence scoring system senescore was developed and its clinical prognosis and therapeutic efficacy were validated in multiple CRC cohorts.

We conducted a multicenter, prospective clinical study which recruited 4,245 high-risk CRC individuals to evaluate the clinical performance of the multitarget fecal immunochemical and stool DNA (FIT-sDNA) test for CRC screening. We found that the FIT-sDNA test detected more colorectal advanced neoplasia than FIT. It indicated that in areas with limited colonoscopy resources, the FIT-sDNA test could be a promising further risk triaging modality to select patients for colonoscopy in CRC screening.

GPAT3 is responsible for G3P converting to LPA. It is the first step in TG synthesis and LD production. Oxa induces GPAT3 overexpression and LDs accumulation, which confers chemoresistance to CRC cells. Chemoresistant cells present a more malignant phenotype and suppress the cell killing effect of CD8+T cells, resulting in immune evasion and tumor recurrence

Nanobodies (Nbs) are the variable domain of heavy-chain antibodies derived from the blood of camelids or sharks. In this review, we summarize recent advances in the discovery and production of novel nanobodies, and their use in detection and diagnosis platforms.

Melatonin's role in cancer treatment and nanotechnological developments for efficient delivery of the drug to the targeted sites. Natural sources of MLT, its physiological functions and mechanism of action is explained in detail along with targeted sites in humans for the easy delivery of the MLT administered via nanostructured materials.

The research of cancer metabolism heterogeneity seeks to identify common metabolic pathways and processes that are shared across different types of cancer, mainly including specimen collection, data generation, and data analysis. This approach can avoid tumor heterogeneity and present a comprehensive metabolic panorama of tumors, thus helping to identify metabolic targets relevant to multiple cancer types and search for more sensitive markers to develop more broadly effective therapies.

Oridonin, a natural diterpenoid, exhibits broad-spectrum anticancer effects by targeting multiple oncogenic proteins mainly via Michael addition between its unsaturated ketone and the cysteines in the target proteins. Thus, oridonin and its derivatives hold the potential to be developed as multitargeting anticancer drugs.

We develop lipid-coated poly(lactide-co-glycolide) nanoparticles coloaded with indocyanine green and Gasdermin E expressing plasmid DNA (GSDME-pDNA) to possess the spatiotemporal controllability of target gene expression induced by a heat-inducible mHSP70 promoter. Oxaliplatin is administered to activate caspase-3 to cleave GSDME to cause pyroptosis, which promotes the release of damage-associated molecular patterns molecules and causes an immunogenic inflammatory response and attendant strong antitumor effect.

The activation of several critical signalling pathways cooperatively stimulates the cellular and molecular characteristics of cancer stem cells (CSCs). This is characterized by features like stemness, self-renewal, recurrence, and therapy resistance. Treatments are usually based on either blocking or dysregulating the signalling pathways, thereby inducing CSC death in several cases.