Survival of patients with deficient mismatch repair metastatic colorectal cancer in the pre-immunotherapy era.

Background: Metastatic colorectal cancer patients with deficient mismatch repair (dMMR mCRC) benefit from immunotherapy. Interpretation of the single-arm immunotherapy trials is complicated by insignificant survival data during systemic non-immunotherapy. We present survival data on a large, comprehensive cohort of dMMR mCRC patients, treated with or without systemic non-immunotherapy.

Diagnostic accuracy of contrast-enhanced diffusion-weighted MRI for liver metastases of pancreatic cancer: towards adequate staging and follow-up of pancreatic cancer - DIA-PANC study: study protocol for an international, multicenter, diagnostic trial.

Background: At the time of surgery, approximately 10-20% of the patients with pancreatic cancer are considered unresectable because of unexpected liver metastasis, peritoneal carcinomatosis or locally advanced disease. This leads to futile surgical treatment with all the associated morbidity, mortality and costs. More than 50% of all liver metastases develop in the first six months postoperatively.

Intravenous lidocaine affects oxaliplatin pharmacokinetics in simultaneous infusion.

Background: Oxaliplatin is a chemotherapeutic agent used to treat malignancies of the gastrointestinal tract. Neuropathy is a frequent dose-limiting side-effect of oxaliplatin therapy, without preventive or curative strategies. Concomitant administration of intravenous lidocaine could be a promising treatment.

Loss of skeletal muscle index and survival in patients with metastatic colorectal cancer: Secondary analysis of the phase 3 CAIRO3 trial.

Background: Low skeletal muscle index (SMI) in metastatic colorectal cancer (mCRC) patients is associated with poor outcomes. The prognostic impact of SMI changes during consecutive palliative systemic treatments is unknown.

Methods: This is a retrospective analysis of the phase 3 CAIRO3 study.

Neoadjuvant Chemotherapy for Locally Advanced T4 Colon Cancer: A Nationwide Propensity-Score Matched Cohort Analysis.

Introduction: Neoadjuvant chemotherapy (CT) for locally advanced colon cancer (LACC) could potentially lead to tumor shrinkage, eradication of micrometastases, and prevention of tumor cell shedding during surgery. This retrospective study investigates the surgical and oncological outcomes of preoperative CT for LACC.

Methods: Using the Netherlands Cancer Registry, data of patients with stage II or III colon cancer, diagnosed between 2008 and 2016 was collected.

RAS and BRAF mutations in cell-free DNA are predictive for outcome of cetuximab monotherapy in patients with tissue-tested RAS wild-type advanced colorectal cancer.

In metastatic colorectal cancer, RAS and BRAF mutations cause resistance to anti-EGFR therapies, such as cetuximab. Heterogeneity in RAS and BRAF mutations might explain nonresponse in a subset of patients receiving cetuximab. Analyzing mutations in plasma-derived circulating tumor DNA (ctDNA) could provide a more comprehensive overview of the mutational landscape as compared to analyses of primary and/or metastatic tumor tissue.

Perioperative systemic therapy and cytoreductive surgery with HIPEC versus upfront cytoreductive surgery with HIPEC alone for isolated resectable colorectal peritoneal metastases: protocol of a multicentre, open-label, parallel-group, phase II-III, randomised, superiority study (CAIRO6).

Background: Upfront cytoreductive surgery with HIPEC (CRS-HIPEC) is the standard treatment for isolated resectable colorectal peritoneal metastases (PM) in the Netherlands. This study investigates whether addition of perioperative systemic therapy to CRS-HIPEC improves oncological outcomes.

Methods: This open-label, parallel-group, phase II-III, randomised, superiority study is performed in nine Dutch tertiary referral centres.

Simple surface EMG recording as a noninvasive screening method for the detection of acute oxaliplatin-induced neurotoxicity: a feasibility pilot study.

Objectives: Oxaliplatin-induced neurotoxicity can be a dose-limiting side effect to effective chemotherapy. Acute hyperexcitability causes cold-evoked sensory and motor symptoms, which resemble neuromyotonia. An accessible and non-invasive technique for early detection could help select patients for potential treatments.

Improving preoperative detection of synchronous liver metastases in pancreatic cancer with combined contrast-enhanced and diffusion-weighted MRI.

Purpose: To explore the value of gadolinium-enhanced MRI combined with diffusion-weighted MRI (Gd-enhanced MRI with DWI) in addition to contrast-enhanced CT (CECT) for detection of synchronous liver metastases for potentially resectable pancreatic cancer.

Methods: By means of a retrospective cohort study we included patients with potentially resectable pancreatic cancer on CECT, who underwent Gd-enhanced MRI with DWI between January 2012 and December 2016. A single observer evaluated MRI and CT and was blinded to imaging, pathology, and surgery reports.

Group medical consultations (GMCs) and tablet-based online support group sessions in the follow-up of breast cancer: A multicenter randomized controlled trial.

Objective: Group medical consultations (GMCs) provide individual medical visits in the presence of ≤7 peer-patients. In the follow-up of breast cancer, we evaluated the efficacy of a new type of blended care My-GMC, a GMC combined with a tablet-based online app, consisting of three online support group sessions (SGS) and additional information.

Methods: This randomized controlled trial compared the effect of My-GMC (n = 59) with one individual medical visit (n = 50) (care as usual).

Dietary Intake of Magnesium or Calcium and Chemotherapy-Induced Peripheral Neuropathy in Colorectal Cancer Patients.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and severe side-effect in colorectal cancer (CRC) patients. This study assessed the association between habitual dietary intake of magnesium or calcium and prevalence and severity of chronic CIPN in CRC patients receiving adjuvant chemotherapy. For this prospective cohort study, 196 CRC patients were considered.

Intravenous Lidocaine: Old-School Drug, New Purpose-Reduction of Intractable Pain in Patients with Chemotherapy Induced Peripheral Neuropathy.

Treatment of intractable pain due to chemotherapy induced peripheral neuropathy (CIPN) is a challenge. Intravenous (iv) lidocaine has shown to be a treatment option for neuropathic pain of different etiologies. Lidocaine (1.

The in vitro mechanisms and in vivo efficacy of intravenous lidocaine on the neuroinflammatory response in acute and chronic pain.

Introduction: The neuroinflammatory response plays a key role in several pain syndromes. Intravenous (iv) lidocaine is beneficial in acute and chronic pain. This review delineates the current literature concerning in vitro mechanisms and in vivo efficacy of iv lidocaine on the neuroinflammatory response in acute and chronic pain.

Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial.

Background: The peritoneum is the second most common site of recurrence in colorectal cancer. Early detection of peritoneal carcinomatosis (PC) by imaging is difficult. Patients eventually presenting with clinically apparent PC have a poor prognosis.

Neo-adjuvant chemotherapy followed by surgery versus surgery alone in high-risk patients with resectable colorectal liver metastases: the CHARISMA randomized multicenter clinical trial.

Background: Efforts to improve the outcome of liver surgery by combining curative resection with chemotherapy have failed to demonstrate definite overall survival benefit. This may partly be due to the fact that these studies often involve strict inclusion criteria. Consequently, patients with a high risk profile as characterized by Fong's Clinical Risk Score (CRS) are often underrepresented in these studies.

Colorectal signet-ring cell carcinoma: benefit from adjuvant chemotherapy but a poor prognostic factor.

Colorectal signet-ring cell carcinoma (SRCC) has been associated with poor survival compared with mucinous adenocarcinoma (MC) and the more common adenocarcinoma (AC). Efficacy of adjuvant chemotherapy in SRCC has never been assessed. This study analyzes the prognostic impact of SRCC and determines whether colonic SRCC patients benefit from adjuvant chemotherapy equally compared with MC and AC patients.

Prognosis and value of adjuvant chemotherapy in stage III mucinous colorectal carcinoma.

Background: Colorectal mucinous adenocarcinoma (MC) has been associated with impaired prognosis compared with nonmucinous adenocarcinoma (NMC). Response to palliative chemotherapy is poor in metastatic disease, but the benefit of adjuvant chemotherapeutic treatment has never been assessed in large patient groups. This study analyses overall survival and efficacy of adjuvant chemotherapy in terms of survival in patients following radical resection for MC.

Phase I pharmacokinetic and pharmacodynamic study of the oral protein kinase C beta-inhibitor enzastaurin in combination with gemcitabine and cisplatin in patients with advanced cancer.

Purpose: Enzastaurin targets the protein kinase C and phosphatidylinositol 3-kinase/AKT pathways to reduce tumor angiogenesis and cell proliferation and to induce cell death. A phase I trial was conducted to evaluate the feasibility of combining enzastaurin with gemcitabine and cisplatin.

Experimental Design: Patients with advanced cancer received a 14-day lead-in treatment with oral enzastaurin followed by subsequent 21-day cycles of daily enzastaurin, gemcitabine on days 1 and 8, and cisplatin on day 1.

A phase I, randomized, open-label, parallel-cohort, dose-finding study of elacridar (GF120918) and oral topotecan in cancer patients.

Purpose: Breast cancer resistance protein (ABCG2) substantially limits the oral bioavailability of topotecan. Coadministration with elacridar, an inhibitor of breast cancer resistance protein-mediated drug transport, increases the bioavailability of topotecan. The aim of this study was to establish the lowest effective dose of elacridar to obtain maximum oral bioavailability of topotecan and to determine the optimal schedule of coadministration of oral topotecan and elacridar.

Phase I clinical evaluation of weekly administration of the novel vascular-targeting agent, ZD6126, in patients with solid tumors.

Purpose: ZD6126 is a novel vascular-targeting agent that induces selective effects on the morphology of endothelial cells by disrupting the tubulin cytoskeleton. This leads to cell detachment and tumor vessel congestion, resulting in extensive central necrosis in a range of tumor xenograft models. Results from a phase I dose-escalation study of ZD6126 are reported.

[The clinical perspective of angiogenesis inhibitors].

An important development in the treatment of cancer is the recognition that the tumour's microenvironment, notably its vasculature, may be an attractive target for therapy. In the eighties of the last century, the concept of angiogenesis (the formation of new blood vessels from existing vasculature) was developed. Angiogenesis is the driving force behind tumour growth and metastasis.

CD4 antibody treatment in patients with active Crohn's disease: a phase 1 dose finding study.

Background: T cells play an important part in Crohn's disease. Immunomodulating therapies that target T cell activation may have clinical effects in Crohn's disease.

Aim: To investigate the toxicity and potential efficacy of anti-CD4 monoclonal antibody therapy in patients with Crohn's disease.

Inflammatory bowel disease is associated with increased mucosal levels of bactericidal/permeability-increasing protein.

Background & Aims: Clinical sepsis seldom accompanies inflammatory bowel disease. The aim of this study was to measure colonic mucosal levels of the neutrophil product bactericidal/permeability-increasing protein (BPI), which kills gram-negative bacteria in addition to inactivating endotoxin.

Methods: Enzyme-linked immunosorbent assay and immunohistochemistry for BPI were performed on homogenates and tissue secretions of biopsy specimens from patients with ulcerative colitis (n=11) and Crohn's disease (n=5) and from normal controls (n=5).

Mechanisms underlying neutrophil adhesion to apical epithelial membranes.

Crypt abscesses allow prolonged apposition of activated neutrophils to the epithelial surface of the colon. Adhesion of neutrophils to both the vascular endothelium and basolateral epithelial membrane share common effector molecules but are distinct processes. This study aimed to define the mechanisms that effect adhesion, independent of transmigration, to the apical epithelium.

Anti-CD4 Therapy Decreases Epithelial Expression of HLA-DR Molecules in Patients with Crohn's Disease.

: Mucosal cells from patients with Crohn's disease regularly express HLA-class II antigens, which are thought to be induced by cytokines, in particular interferon gamma, that are secreted by activated T-cells. Abberant MHC-class II expression by epithelial cells may play a role in diseases characterized by T-cell activation. Activated CD4-positive T-cells are present in the lamina propria of patients with Crohn's disease.