Introduction of routine hepatitis B screening for all patients receiving cancer treatment.

BACKGROUND: Patients with a chronic hepatitis B virus (HBV) infection or patients who have recovered from an HBV infection are at risk for HBV reactivation (HBVr), especially if they need treatment with chemotherapy. International guidelines recommend routine HBV screening for all patients starting with chemotherapy. This study evaluates the implementation of a routine HBV screening protocol. METHODS: A retrospective study was performed between January 2015 and October 2016 at the Medical Centre Slotervaart Amsterdam. All patients with a solid or hematological malignancy starting intravenous chemotherapy were included. In September 2015, a protocol for routine HBV screening was introduced. HBV screening results were evaluated before and after implementation of the screening protocol. RESULTS: In total, 184 patients were included, of which 129 patients were actually screened; 37 of the 70 (53%) patients were screened in the group before implementation of the protocol and 92 of the 114 (81%) after implementation. Before routine HBV screening, 8/37 (21.6%) patients tested anti-HBc positive; after introduction of routine screening, 13/92 (14.1%) patients tested anti-HBc positive. After implementation of the screening protocol, no HBVr occurred. CONCLUSION: Implementation of routine HBV screening in patients starting chemotherapy increases identification of the number of patients identified as at risk for HBVr and contributes to prevention of HBVr. A high prevalence of anti-HBc positive patients was found during routine HBV screening, indicating the importance of screening. Awareness and implementation of routine HBV screening, together with knowledge of existing guidelines is necessary to increase the HBV screening rate in patients treated with chemotherapy.

[Whether or not to use thromboprophylaxis in patients treated with chemotherapy for malignant disease]. / Wel of geen tromboseprofylaxe bij oncologische patiënten gedurende de chemotherapie?

CASE DESCRIPTION: A 55-year-old patient with locally advanced pancreatic carcinoma will start Folfirinox. Should he get thromboprophylaxis? CONSIDERATION: Patients with malignant disease have increased risk of venous thromboembolism (VTE). Several types of malignancy, surgery, chemotherapy and metastasis lead to increased risk. VTE is an underdiagnosed phenomenon and the second cause of death in patients treated with chemotherapy. Therapeutic doses increase the risk of bleeding compared to prophylactic anticoagulant treatment. Even though they are less than perfect, several risk scores are able to identify patients with high risk of VTE. The AVERT and CASSINI trials showed that prophylactic doses of DOACs in cancer patients with high risk of VTE are able to significantly reduce this risk. CONCLUSION: Even though there are many unresolved questions, it seems rational to start thromboprophylaxis in patients with aggressive types of cancer, preferably using DOACs, but low molecular weight heparins are possible as well. Risk scores may be helpful when selecting patients.

Genes associated with venous thromboembolism in colorectal cancer patients.

Essentials The underlying pathophysiological mechanisms behind cancer-associated thrombosis are unknown. We compared expression profiles in tumor cells from patients with and without thrombosis. Tumors from patients with thrombosis showed significant differential gene expression profiles. Patients with thrombosis had a proinflammatory status and increased fibrin levels in the tumor. SUMMARY: Background Venous thromboembolism (VTE) is a frequent complication in patients with cancer, and is associated with significant morbidity and mortality. However, the mechanisms behind cancer-associated thrombosis are still incompletely understood. Objectives To identify novel genes that are associated with VTE in patients with colorectal cancer (CRC). Methods Twelve CRC patients with VTE were age-matched and sex-matched to 12 CRC patients without VTE. Tumor cells were isolated from surgical samples with laser capture microdissection approaches, and mRNA profiles were measured with next-generation RNA sequencing. Results This approach led to the identification of new genes and pathways that might contribute to VTE in CRC patients. Application of ingenuity pathway analysis indicated significant links with inflammation, the methionine degradation pathway, and increased platelet function, which are all key processes in thrombus formation. Tumor samples of patients with VTE had a proinflammatory status and contained higher levels of fibrin and fibrin degradation products than samples of those without VTE. Conclusion This case-control study provides a proof-of-principle that tumor gene expression can discriminate between cancer patients with low and high risks of VTE. These findings may help to further unravel the pathogenesis of cancer-related VTE. The identified genes could potentially be used as candidate biomarkers to select high-risk CRC patients for thromboprophylaxis.

Limitations of screening for occult cancer in patients with idiopathic venous thromboembolism.

BACKGROUND: Idiopathic venous thrombosis (IVT) is associated with occult malignancy in 10% of patients. The Trousseau study investigated whether extensive screening using abdominal and chest computed tomography (CT) scans and mammography in women would decrease mortality, compared with limited screening. Here, the costs and test characteristics of these screening strategies are presented, including true- and false-positive findings, sensitivity and specificity. METHODS: All investigations performed because of a suspicion of malignancy in the limited or extensive screening groups were collected. Costs were calculated using Dutch healthcare tariffs. RESULTS: A total of 342 and 288 patients with IVT were included in the extensive and the limited screening group, respectively. The prevalences of malignancy and mortality were comparable between these two groups, as were the abnormal findings during routine screening. In 30% of the extensively screened patients, the CT scans or mammography showed abnormalities necessitating further diagnostic work-up; this yielded six malignancies and resulted in a positive predictive value of 6.6%, sensitivity of 33% and specificity of 70%. Mean costs per patient were €165.17 for the routine and €530.92 for the extensive screening. CONCLUSION: Screening using CT scans and mammography results in extra costs due to the high percentage of false-positive findings for which a further diagnostic work-up is indicated.

Is extensive screening for cancer in idiopathic venous thromboembolism warranted?

BACKGROUND: Patients with a first episode of idiopathic venous thromboembolism (IVTE) have an estimated 10% incidence of cancer within 12 months after diagnosis. However, the utility of screening for cancer in this population is controversial. METHODS: In this prospective concurrently controlled cohort study, limited and extensive cancer screening strategies were compared. All 630 patients underwent baseline screening consisting of history, physical examination, basic laboratory tests and chest X-ray. In the extensive screening group abdominal and chest CT scan and mammography were added. Outcomes were incidence and curability of cancer, and cancer-related and overall mortality. RESULTS: In 12 of the 342 (3.5%) patients in the extensive screening group malignancy was diagnosed at baseline compared with 2.4% (seven of 288 patients) in the limited screening group. Extensive screening detected six additional cancers (2.0%; 95% CI, 0.74-4.3), of which three were potentially curable. During a median 2.5 years of follow-up, cancer was diagnosed in 3.7% and 5.0% in the extensive and limited screening groups, respectively. In the extensive screening group 26 patients (7.6%) died compared with 24 (8.3%) in the limited screening group; adjusted hazard ratio 1.22 (95% CI, 0.69-2.22). Of these deaths 17 (5.0%) in the extensive screening group and 8 (2.8%) in the limited screening group were cancer related; adjusted hazard ratio 1.79 (95% CI, 0.74-4.35). CONCLUSIONS: The low yield of extensive screening and lack of survival benefit do not support routine screening for cancer with abdominal and chest CT scan and mammography in patients with a first episode of IVTE.

Screening for cancer in patients with idiopathic venous thromboembolism: the clinical practice.

The reported incidence of concomitant cancer in patients with idiopathic venous thromboembolism (IVTE) varies between 4 and 24%, while the mean incidence of cancer within 3 years thereafter approximates 9%. Baseline investigations of patients with IVTE have been recommended. We evaluated the clinical practice regarding the screening of these patients according to these recommendations in two teaching hospitals. Medical history and physical examination were done reasonably exhaustively, except for investigations of the urogenital tract. Laboratory and imaging investigations were performed incompletely in a substantial proportion of the patients. The clinical evaluation regarding cancer, performed in patients with IVTE, could be improved. The implementation of a protocol should be considered.

Survival after massive ecstasy overdose.

INTRODUCTION: The toxicity profile of the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is well known. This designer drug is usually taken at "house parties" and may cause severe complications, sometimes leading to death, even when taken in relatively small units (1 or 2 tablets). Up to now, only a few cases of survival after ingestion of an overdose of Ecstasy have been described. In most cases the users developed hyperthermia, disseminated intravascular coagulation, rhabdomyolysis, and renal failure. CASE REPORT: We describe a man who, after ingesting 50 tablets of Ecstasy (in combination with oxazepam and alcohol) at home, recovered within 2 days. Presenting features were unconsciousness, apnea, and convulsions. It is suggested that in most cases severe 3,4-methylenedioxymethamphetamine toxicity results from an interaction between direct pharmacological effects of the drug and the prevailing environmental conditions (high ambient temperature, dancing in trance, little fluid intake).

Combined dapsone and clofazimine intoxication.

We report clinical findings and pharmacokinetic data regarding a combined dapsone and clofazimine intoxication in a man, who ingested 50 tablets of dapsone (100 mg) 20 capsules of clofazimine (100 mg) and two tablets of rifampicin (600 mg). Oral administration of activated charcoal (50 grams) and sodium sulphate (20 grams) after gastric lavage resulted in an elimination half-life in plasma of 11.1 and 10.8 h for dapsone and its main metabolite, monoacetyldapsone, respectively. A rapid initial decrease of the plasma concentration of clofazimine was observed after gastric lavage and administration of activated charcoal and sodium sulphate. 15 h after this treatment, clofazimine plasma levels remained relatively constant. Dapsone-induced methaemoglobinaemia (48% at admission) was treated successfully with methylene blue.