Using a semi-conductor sequencing-based panel for genotyping of HPV-positive and HPV-negative oropharyngeal cancer: a retrospective pilot study.

OBJECTIVES: The aim of this study was to assess the feasibility of testing actionable mutations in small amounts of formalin-fixed paraffin-embedded material in multiple genes of the receptor tyrosine kinase pathway and to determine the frequency of these mutations in human papillomavirus (HPV)-positive and HPV-negative oropharyngeal cancer (OPC). DESIGN: A retrospective pilot study was performed. SETTING: In OPC, no predictive markers for response to epidermal growth factor receptor inhibition are known. Therefore, identifying predictive biomarkers is of utmost importance, but is often hampered by the small amount of tumour material available. PARTICIPANTS: We included the archival material of 45 OPC, all treated with concomitant chemoradiotherapy between 2003 and 2010. MAIN OUTCOME MEASURES: Besides the HPV status, we assessed mutations using a gene panel that targets 16 genes in the receptor tyrosine kinase pathway and six other genes. The polymerase chain reaction required only 10 ng DNA. RESULTS: In total, 42 of the 45 biopsies have been successfully analysed. In total 20 of 42 samples were HPV-positive and 22 of 42 were HPV-negative. In the receptor tyrosine kinase pathway, mutations in PIK3CA were most frequently identified. A TP53 mutation was identified in one HPV-positive sample and in 13 HPV-negative samples. Additionally, three mutations in three different genes were found. CONCLUSIONS: We evaluated an assay to identify mutations in the receptor tyrosine kinase pathway. As only small amounts of formalin-fixed paraffin-embedded material are sufficient for reliable analysis, this test opens up new possibilities for personalised medicine.

[A man with neutropenic fever]. / Een man met neutropene koorts.

A 43-year-old patient with recurrent acute myeloid leukemia (AML) was treated with high-dose cytarabine. After two weeks of neutropenic fever, multiple cutaneous nodules appeared. Histopathological examination of a skin biopsy showed a mycosis and Fusarium solani was cultured. Despite antimycotic therapy, the patient died due to complications of his AML treatment.

Costs and benefits of a test-and-treat strategy in Helicobacter pylori-infected subjects: a prospective intervention study in general practice.

OBJECTIVE: To identify health outcomes and costs/savings of a Helicobacter pylori test-and-treat strategy in patients using acid suppressants chronically. DESIGN: Prospective intervention study. Patients were tested for H. pylori infection and treated with 14 days of ranitidine bismuth citrate (RBC) 400 mg (b.i.d.) and clarithromycin 500 mg if infected. Cure was determined after six months. SETTING: General practice. PARTICIPANTS: Patients using acid suppressants chronically were identified by a computer search; 184 patients gave written consent and were included. MAIN OUTCOME MEASURES: Serology, symptom questionnaire, medication history, quality of life determination, costs/savings. RESULTS: Out of 184 patients, 85 (46%) had positive serology. A cure rate of 61/80 (76%) was achieved. The intervention group showed significant symptom relief. Benefits were evident in patients with ulcer disease but also in patients with uninvestigated dyspepsia. Quality of life improved for cured patients in the intervention group. No improvements for dyspeptic symptoms or quality of life occurred in the H. pylori-negative group. After six months, significant savings for medication use had occurred in treated patients diagnosed as ulcer disease or non-ulcer dyspepsia. Savings on drug use and doctor visits equalize with costs for tests and antibiotics after nine months. Although less, costs for drugs also decreased significantly in the H. pylori-negative group. Therefore, for the study population, costs and savings are even after 6.5 months. CONCLUSIONS: A test-and-treat strategy for H. pylori, systematically applied at the population level in patients using acid suppressants chronically, results in significant health benefits and economic savings within 1 year of follow-up.