Mismatch Repair Status and Surgical Outcomes in Localized Colorectal Cancer: A Nationwide Cohort Study.

Objective: This study examined the association between deficient mismatch repair (dMMR) versus proficient MMR (pMMR) status and overall survival and disease-free survival in patients with localized colorectal cancer.

Background: Several distinctions exist between patients with dMMR and pMMR colorectal cancer. However, the impact on prognosis is yet to be investigated in large-scale cohort studies.

The impact of platelets on the metastatic potential of tumour cells.

In cancer, activation of platelets by tumor cells is critical to disease progression. Development of precise antiplatelet targeting may improve outcomes from anticancer therapy. Alongside a distinct shift in functionality such as pro-metastatic and pro-coagulant properties, platelet production is often accelerated significantly early in carcinogenesis and the cancer-associated thrombocytosis increases the risk of metastasis formation and thromboembolic events.

Introducing Neoadjuvant Immunotherapy for Colorectal Cancer: Advancing the Frontier.

Objective: To give surgeons a review of the current and future use of neoadjuvant immunotherapy in patients with localized colorectal cancer (CRC).

Background: Immunotherapy has revolutionized the standard of care in oncology and improved survival outcomes in several cancers. However, the applicability of immunotherapy is still an ongoing challenge.

Pharmacokinetics, pharmacodynamics, safety, and tolerability of dopamine-receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting.

Introduction: Dopamine (D)-receptor antagonists (RAs) were the first antiemetics used in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV).

Areas Covered: Eight D-RAs, amisulpride, domperidone, droperidol, haloperidol, metoclopramide, metopimazine, olanzapine and prochlorperazine are reviewed focusing on pharmacokinetics, pharmacodynamics, antiemetic effect and side effects.

Expert Opinion: Since the introduction of D-RAs, antiemetics such as corticosteroids, 5-hydroxytryptamine (5-HT)-RAs and neurokinin (NK)-RAs have been developed.

Digitally assessed lymphocyte infiltration in rectal cancer biopsies is associated with pathological response to neoadjuvant therapy.

A frequently used treatment strategy in locally advanced rectal cancer (RC) is neoadjuvant therapy followed by surgery. Patients treated with neoadjuvant therapy achieve varying pathological response, and currently, predicting the degree of response is challenging. This study examined the association between digitally assessed histopathological features in the diagnostic biopsies and pathological response to neoadjuvant therapy, aiming to find potential predictive biomarkers.

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In Denmark, around 4,500 people are diagnosed with colorectal cancer (CRC) annually. This review investigates that while the efficacy of immunotherapy in CRC is still being studied, immunotherapy is currently only indicated in the treatment of mismatch-repair deficient (dMMR) metastatic CRC, which accounts for 10-15% of patients. Recent studies indicate high rates of pathologic response in dMMR CRC treated with pre-operative immunotherapy while large-scale studies on novel immunotherapy combinations are ongoing.

Myocardial injury and long-term oncological outcomes in patients undergoing surgery for colorectal cancer.

Purpose: Myocardial injury after noncardiac surgery (MINS) is associated with increased mortality and postoperative complications. In patients with colorectal cancer (CRC), postoperative complications are a risk factor for cancer recurrence and disease-free survival. This study investigates the association between MINS and long-term oncological outcomes in patients with CRC in an ERAS setting.

The Matrix Reloaded-The Role of the Extracellular Matrix in Cancer.

As the core component of all organs, the extracellular matrix (ECM) is an interlocking macromolecular meshwork of proteins, glycoproteins, and proteoglycans that provides mechanical support to cells and tissues. In cancer, the ECM can be remodelled in response to environmental cues, and it controls a plethora of cellular functions, including metabolism, cell polarity, migration, and proliferation, to sustain and support oncogenesis. The biophysical and biochemical properties of the ECM, such as its structural arrangement and being a reservoir for bioactive molecules, control several intra- and intercellular signalling pathways and induce cytoskeletal changes that alter cell shapes, behaviour, and viability.

Metabolic switch in cancer - Survival of the fittest.

Cell metabolism is characterised by the highly coordinated conversion of nutrients into energy and biomass. In solid cancers, hypoxia, nutrient deficiencies, and tumour vasculature are incompatible with accelerated anabolic growth and require a rewiring of cancer cell metabolism. Driver gene mutations direct malignant cells away from oxidation to maximise energy production and biosynthesis while tumour-secreted factors degrade peripheral tissues to fuel disease progression and initiate metastasis.

Electroporation and Immunotherapy-Unleashing the Abscopal Effect.

The discovery of electroporation in 1968 has led to the development of electrochemotherapy (ECT) and irreversible electroporation (IRE). ECT and IRE have been established as treatments of cutaneous and subcutaneous tumors and locally advanced pancreatic cancer, respectively. Interestingly, the treatment modalities have been shown to elicit immunogenic cell death, which in turn can induce an immune response towards the tumor cells.

Neutrophils and polymorphonuclear myeloid-derived suppressor cells: an emerging battleground in cancer therapy.

Neutrophils are central mediators of innate and adaptive immunity and first responders to tissue damage. Although vital to our health, their activation, function, and resolution are critical to preventing chronic inflammation that may contribute to carcinogenesis. Cancers are associated with the expansion of the neutrophil compartment with an escalation in the number of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) in the peripheral circulation and tumor microenvironment.

Tumor-Infiltrating Lymphocytes as Biomarkers of Treatment Response and Long-Term Survival in Patients with Rectal Cancer: A Systematic Review and Meta-Analysis.

Neoadjuvant chemoradiotherapy (NCRT) is indicated in locally advanced rectal cancer (LARC) to downstage tumors before surgery. Watchful waiting may be a treatment option to avoid surgery in patients, obtaining a complete clinical response. However, biomarkers predictive of treatment response and long-term prognosis are lacking.

Myocardial Injury After Colorectal Cancer Surgery and Postoperative 90-Day Mortality and Morbidity: A Retrospective Cohort Study.

Background: Myocardial injury after noncardiac surgery is a strong predictor of 30-day mortality and morbidity.

Objective: The purpose of this study was to examine the incidence of myocardial injury in patients undergoing colorectal cancer surgery in an enhanced recovery after surgery protocol and its association with 90-day mortality and morbidity.

Design: This is a retrospective cohort study.

Natural Killer Cells in Cancer and Cancer Immunotherapy.

The detection and killing of neoplastic cells require coordination of a variety of antitumor effector cells. Natural killer (NK) cells of the innate immune system are at the forefront of the body's defense systems and evidence suggests that the infiltration and cytotoxicity of NK cells in the cancer tissue influence treatment efficacy and survival. As powerful effectors in the anticancer immune response, NK cells rapidly recognize and kill transformed cells with little reactivity against healthy self-tissues, which highlights their potential role in cancer immunotherapy.

Cancer-Associated Fibroblasts and Tumor-Associated Macrophages in Cancer and Cancer Immunotherapy.

Our understanding of the tumor microenvironment (TME), including the interplay between tumor cells, stromal cells, immune cells, and extracellular matrix components, is mandatory for the innovation of new therapeutic approaches in cancer. The cell-cell communication within the TME plays a pivotal role in the evolution and progression of cancer. Cancer-associated fibroblasts (CAF) and tumor-associated macrophages (TAM) are major cell populations in the stroma of all solid tumors and often exert protumorigenic functions; however, the origin and precise functions of CAF and TAM are still incompletely understood.

Cytotoxic CD8 T cells in cancer and cancer immunotherapy.

The functions of, and interactions between, the innate and adaptive immune systems are vital for anticancer immunity. Cytotoxic T cells expressing cell-surface CD8 are the most powerful effectors in the anticancer immune response and form the backbone of current successful cancer immunotherapies. Immune-checkpoint inhibitors are designed to target immune-inhibitory receptors that function to regulate the immune response, whereas adoptive cell-transfer therapies use CD8 T cells with genetically modified receptors-chimaeric antigen receptors-to specify and enhance CD8 T-cell functionality.

The prognostic value of tumour-infiltrating lymphocytes in pancreatic cancer: a systematic review and meta-analysis.

Importance: Tumour-infiltrating lymphocytes (TILs) have previously been found to influence patient prognosis in other gastrointestinal cancers, for instance in colorectal cancer. An immunosuppressive phenotype often characterizes pancreatic cancer with a low degree of immune cell infiltration. Cytotoxic CD8 T cell infiltration in tumours is found to be the best predictive variable for response to immune checkpoint inhibitor therapy, emphasizing the importance of investigating TILs in pancreatic cancer, especially focussing on CD8 T cells.

Long-Term Outcomes after Use of Perioperative Glucocorticoids in Patients Undergoing Cancer Surgery: A Systematic Review and Meta-Analysis.

The surgical stress response can accelerate clinical metastasis formation. Perioperative glucocorticoids might modulate this response and the metastatic process. We aimed to describe associations between perioperative glucocorticoids and long-term outcomes after cancer surgery.

Premetastatic niches, exosomes and circulating tumor cells: Early mechanisms of tumor dissemination and the relation to surgery.

The physiological stress response to surgery promotes wound healing and functional recovery and includes the activation of neural, inflammatory and proangiogenic signaling pathways. Paradoxically, the same pathways also promote metastatic spread and growth of residual cancer. Human and animal studies show that cancer surgery can increase survival, migration and proliferation of residual tumor cells.

The Intestinotrophic Effects of Glucagon-Like Peptide-2 in Relation to Intestinal Neoplasia.

Context: Glucagon-like peptide-2 (GLP-2) is a gastrointestinal hormone with intestinotrophic and antiapoptotic effects. The hormone's therapeutic potential in intestinal diseases and relation to intestinal neoplasia has raised great interest among researchers. This article reviews and discusses published experimental and clinical studies concerning the growth-stimulating and antiapoptotic effects of GLP-2 in relation to intestinal neoplasia.