Immune checkpoint inhibitor-associated myocarditis : Case reports and a review of the literature.

Immune checkpoint inhibitors (ICIs) are increasingly recognised to effectuate long-lasting therapeutic responses in solid tumours. However, ICI therapy can also result in various immune-related adverse events, such as ICI-associated myocarditis, a rare but serious complication. The clinical spectrum is wide and includes asymptomatic patients and patients with fulminant heart failure, making it challenging to diagnose this condition. Furthermore, the optimal diagnostic algorithm and treatment of ICI-associated myocarditis is unknown. In this review, we describe two cases on both ends of the spectrum and discuss the challenges in recognising, diagnosing and treating ICI-associated myocarditis.

Defective differentiation of myeloid and plasmacytoid dendritic cells in advanced cancer patients is not normalized by tyrosine kinase inhibition of the vascular endothelial growth factor receptor.

Tumor-derived vascular endothelial growth factor (VEGF) has previously been identified as a causative factor in the disturbed differentiation of myeloid dendritic cells (DC) in advanced cancer patients. Here, we investigated the potential of vascular endothelial growth factor receptor (VEGFR) tyrosine kinase (TK) inhibition to overcome this defective DC differentiation. To this end, peripheral blood DC (PBDC) precursor and subset frequencies were measured in 13 patients with advanced cancer before and after treatment with AZD2171, a TK inhibitor (TKI) of VEGFR, coadministered with gefitinib, and an epidermal growth factor receptor (EGFR) TKI. Of note, not only myeloid DC but also plasmacytoid DC frequencies were significantly reduced in the blood of the cancer patients prior to treatment, as compared to healthy controls. Moreover, besides an accumulated population of immature myeloid cells (ImC), a population of myeloid suppressor cells (MSC) was significantly increased. Upon systemic VEGFR TK inhibition, DC frequencies did not increase, whereas the rate of circulating MSC showed a slight, but not significant, decrease. In conclusion, TK inhibition of VEGFR with AZD2171 does not restore the defective PBDC differentiation observed in advanced cancer patients.

A patient with a VEGF and endostatin producing gastrointestinal autonomic nerve tumour.

Tumour associated neovascularisation has been characterised as chaotic and insufficient. This report details the results of the analysis of angiogenic factors in tumour cyst fluid, pleural fluid, and blood from a patient with a gastrointestinal autonomic nerve tumour. The tumour produced vascular endothelial growth factor and endostatin in large quantities, which may explain the dysfunctional angiogenesis and tendency to bleeding seen in this tumour type.

[New oncological treatment principle with imatinib]. / Nieuw oncologisch behandelprincipe met imatinib.

One of the undoubted major breakthroughs in the recent treatment of cancer is imatinib, a tyrosine-kinase inhibitor of the bcr-abl fusion protein, the stem-cell factor receptor c-kit (KIT) and the platelet-derived growth-factor receptor. The successes obtained with imatinib in the treatment of chronic myeloid leukaemia (CML), gastrointestinal stroma-cell tumours (GIST), and dermatofibrosarcoma protuberans, demonstrate that targeted therapy with a rationally designed, small, synthetic molecule can be highly successful. However, experience so far with imatinib in KIT-positive tumours indicates that imatinib seems only to be effective in those tumours with a gain-of-function mutation in c-kit. There are arguments in favour of investigating a combined therapy of imatinib and classical chemotherapy.

Potential role of platelets in endothelial damage observed during treatment with cisplatin, gemcitabine, and the angiogenesis inhibitor SU5416.

PURPOSE: An increased incidence of thromboembolic events was observed during treatment with cisplatin-gemcitabine plus SU5416 (CG+SU5416), a tyrosine kinase inhibitor targeting the vascular endothelial growth factor (VEGF) receptor-1 and -2. Nine thromboembolic events occurred in eight of 19 patients. We performed an analysis of parameters of the coagulation cascade and vessel wall activation. MATERIALS AND METHODS: Markers for thrombin generation and endothelial cell activation were measured in three patients treated with CG+SU5416, two of whom developed a thromboembolic event. The results were compared with measurements in six patients treated with CG alone, and in 17 patients treated with SU5416 alone. RESULTS: During cycles 1 and 2 of treatment with CG+SU5416, a significant cycle-dependent activation of both the coagulation cascade and endothelial cells occurred, whereas platelet counts decreased. Change in platelet number had a significant negative predictive effect on soluble (s)-E-selectin levels. Significant activation of the coagulation cascade only was observed in the patients treated with CG alone, whereas in patients treated with SU5416 alone, significant endothelial cell activation was observed. CONCLUSION: We hypothesize that endothelial cells deprived of VEGF after exposure to SU5416 became activated and more susceptible to damage during treatment with CG+SU5416, which was aggravated by a transient decrease in platelets, which are, among other things, carriers of VEGF. These results suggests that VEGF, in addition to being a permeability, proliferation, and migration factor, also is a maintenance and protection factor for endothelial cells, and that platelets may have a role in maintaining vascular integrity.

Analysis of coagulation cascade and endothelial cell activation during inhibition of vascular endothelial growth factor/vascular endothelial growth factor receptor pathway in cancer patients.

OBJECTIVE: The angiogenesis inhibitor SU5416 is a potent inhibitor of vascular endothelial growth factor (VEGF) receptor-1 and -2. VEGF may be involved in hemostasis by altering the hemostatic properties of endothelial cells. We analyzed the effects of SU5416 on the coagulation cascade and the vessel wall in patients with advanced cancer. METHODS AND RESULTS: Markers for thrombin generation, activation of the protein C pathway, fibrinolysis, and endothelial cell activation were measured in patients with renal cell carcinoma, soft tissue sarcoma, or melanoma on days 0, 14, and 28 of treatment with SU5416. Three of 17 sampled patients developed a thromboembolic event in the fifth week of treatment. Markers for thrombin generation and fibrinolysis did not show significant changes. We observed a significant increase in endogenous thrombin potential and of parameters reflecting endothelial cell activation (von Willebrand antigen, soluble tissue factor, and soluble E-selectin) in all patients (P< or =0.001). In patients experiencing a thromboembolic event, endogenous thrombin potential, soluble tissue factor, and soluble E-selectin increased to a significantly greater extent (P=0.029, P=0.021, and P=0.007, respectively). CONCLUSIONS: VEGF is not only a permeability, proliferation, and migration factor, but it is also a maintenance and protection factor for endothelial cells.

Effect of providing cancer patients with the audiotaped initial consultation on satisfaction, recall, and quality of life: a randomized, double-blind study.

PURPOSE: By means of a randomized double-blind study, the effect of providing taped initial consultations on cancer patients' satisfaction, recall, and quality of life was investigated. PATIENTS AND METHODS: Consecutive cancer patients referred to either the gynecology or medical oncology outpatient clinic were eligible. Initial consultations were audiotaped. Patients were either provided with the tape (experimental group) or not (control group). Baseline variables included sociodemographics, preferences for information, coping styles, and clinical characteristics. Follow-up (after 1 week and 3 months) variables included attitudes toward the intervention, satisfaction, recall, and quality of life. Assessments took place through mailed questionnaires and telephone interviews. RESULTS: Two hundred one patients were included (response, 71%), 105 in the experimental group and 96 in the control group. Most patients (75%) listened to the tape, the majority of which (73%) listened with others. Almost all patients, both in the experimental group (96%) and control group (98%) were positive about the intervention. Expectations were confirmed; patients provided with the tape were more satisfied (P <.05) and recalled more information (P <.01) than patients without the tape. The intervention did not have an effect on quality of life. An interaction effect was found between the intervention and patients' age on satisfaction with the taped consultation (P <.01) and recall of diagnostic information (P <.01); access to tapes seems more helpful in enhancing satisfaction in younger patients and recall of diagnostic information in older patients. CONCLUSION: Cancer patients and their families value the taped initial consultation. This intervention enhances their satisfaction and improves their recall of information. Tapes seem more helpful in enhancing satisfaction in younger patients and recall of diagnostic information in older patients.

Mondor's disease as first thrombotic event in hereditary protein C deficiency and anticardiolipin antibodies.

A 45-year-old Caucasian woman presented with superficial thrombophlebitis of the right arm and right anterior thoracic wall after bilateral breast surgery followed by spontaneous left anterior thoracic vein thrombophlebitis 3 months later. Besides breast surgery and use of oral contraceptives, hereditary protein C deficiency and anticardiolipin antibodies were found as causes for this bilateral Mondor's disease.

Non-islet-cell tumour induced hypoglycaemia: a case report and review of literature.

A 54-year-old man presented with a poorly differentiated adenocarcinoma of the rectum with multiple metastases to the liver. During hospitalization the patient developed periods of hypoglycaemia due to production of "big" IGF-II by the tumour. Possible pathophysiological mechanisms of non-islet-cell tumour-induced hypoglycaemia are discussed.