An analysis of the utilisation of chemoprophylaxis against Pneumocystis jirovecii pneumonia in patients with malignancy receiving corticosteroid therapy at a cancer hospital

Pneumocystis jirovecii pneumonia (PCP) is associated with high mortality in immunocompromised patients without human immunodeficiency virus infection. However, chemoprophylaxis is highly effective. In patients with solid tumours or haematologic malignancy, several risk factors for developing PCP have been identified, predominantly corticosteroid therapy. The aims of this study were to identify the potentially preventable cases of PCP in patients receiving corticosteroid therapy at a tertiary care cancer centre and to estimate the frequency of utilisation of chemoprophylaxis in these patients. Two retrospective reviews were performed. Over a 10-year period, 14 cases of PCP were identified: no cases were attributable to failed chemoprophylaxis, drug allergy or intolerance. During a 6-month period, 73 patients received high-dose corticosteroid therapy (⩾25 mg prednisolone or ⩾4 mg dexamethasone daily) for ⩾4 weeks. Of these, 22 (30%) had haematologic malignancy, and 51 (70%) had solid tumours. Fewer patients with solid tumours received prophylaxis compared to patients with haematologic malignancy (3.9 vs 63.6%, P<0.0001). Guidelines for PCP chemoprophylaxis in patients with haematologic malignancy or solid tumours who receive corticosteroid therapy are proposed. Successful primary prevention of PCP in this population will require a multifaceted approach targeting the suboptimal prescribing patterns for chemoprophylaxis

Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21.

Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology

Molecular biology of neuroendocrine tumors

Professional as well as patient-oriented societies have contributed significantly to the development of understanding and management of patients with neuroendocrine tumors. The European Neuroendocrine Tumor Society (ENETS) has been an icebreaker for the development of guidelines and classification systems for these heterogeneous tumors and has been followed by other international societies such as the North American Neuroendocrine Tumor Society (NANETS), Asia Pacific Neuroendocrine Tumour Society (AP-NET), and Latin American Neuroendocrine Tumor Society (LANETS). All international societies have contributed to (specific) guidelines with specific twists for their own region. The development of an accreditation system for centers of excellence by the ENETS has significantly improved the management of patients with neuroendocrine tumors. Patient organization societies have been very important support groups for the professional societies and also significantly contributed to the increased knowledge about these diseases among patients with NETs. Further development of collaboration between the different societies will be of clear benefit to patients with neuroendocrine tumors and contribute to development of new diagnostic and therapeutic procedures. \ua9 Springer-Verlag Berlin Heidelberg 2015