Nonhypervascular pancreatic neuroendocrine tumors: Spectrum of MDCT imaging findings and differentiation from pancreatic ductal adenocarcinoma.

PURPOSE: The purpose of our study was to determine contrast-enhanced MDCT features to differentiate nonhypervascular pancreatic neuroendocrine tumors (PNETs) from pancreatic ductal adenocarcinomas (PDACs). METHODS: and materials: We included 74 patients with PNETs and 80 patients with PDACs who underwent preoperative MDCT. Two radiologists evaluated the morphologic characteristic and enhancement patterns of the tumors. Quantitative and qualitative analysis was performed, including evaluation of tumor size, homogeneity, contrast enhancement pattern, presence of pancreatic duct dilatation and tumor invasion to the adjacent vessels and peripancreatic infiltration. Tumor-to-pancreas enhancement ratio was defined as the Hounsfield units (HU) value of the tumor divided by the HU value of the pancreas. the first group was hypervascular PNETs showing hyperenhancement on arterial phase images and nonhypervascular PNETs, showing iso- or hypoenhancement on arterial phase images. After that, two radiologists estimated the possibilities of PNET or PDAC were for nonhypervascular PNETs. RESULTS: On the basis of arterial enhancement, 43 PNETs were hypervascular and 31 were nonhypervascular. When compared to PDAC, nonhypervascular PNETs more frequently had well-defined tumor margins, intratumoral cystic components, calcifications and blood vessels and less frequently had main pancreatic duct dilatation, peripancreatic infiltration and vascular invasion (p < 0.01 for all). Nonhypervascular PNETs had higher tumor-to-pancreas enhancement ratio in venous phase (1.02 vs. 0.78, p = 0.012). Nonhypervascular PNETs more often had portal-venous hyperenhancement or persistent isoenhancement, while PDAC more often had persistent hypoenhancement or gradual delayed enhancement (p < 0.001). The absence of pancreatic duct dilatation and portal-venous hyperenhancement or persistent isoenhancement were the independent predictors for nonhypervascular PNETs. (The most accurate MDCT-findings to predict nonhypervascular PNET were the absence of pancreatic duct dilatation and peripancreatic infiltration (79% and 92% accuracy), portal-venous phase hyperenhancement or persistent isoenhancement (77%), the presence of intratumoral blood vessels (77%) and relative enhancement intensity in venous phase >0.9 (76%). Using these criteria, the area under curve for differentiation of PNET from PDAC was 0.906-0.846. CONCLUSION: Combined assessment of the enhancement and morphologic characteristics can improve the differentiation between nonhypervascular PNETs and PDAC at contrast-enhanced MDCT.

TPMT genetic variations in populations of the Russian Federation.

BACKGROUND: Polymorphisms that reduce the activity of thiopurine S-methyltransferase (TPMT) cause adverse reactions to conventional doses of thiopurines, routinely used for antileukemic and immunosuppressive treatment. There are more than 20 variant alleles of TPMT that cause decreased enzymatic activity. We studied the most common variant alleles of TPMT and their frequency distribution in a large cohort of multiracial residents in the Russian Federation and compared their frequencies in children with and without malignancy to determine whether TPMT gene abnormality is associated with hematologic malignancy. PROCEDURE: The TPMT biochip was used to detect 6 TPMT single nucleotide polymorphisms (SNPs) corresponding to 7 TPMT-deficiency alleles (TPMT*2, TPMT*3A, TPMT*3B, TPMT*3C, TPMT*3D, TPMT*7, and TPMT*8). We analyzed allele frequencies in the whole cohort, the childhood cancer group, and the non-cancer group. We also characterized disease features and outcome according to the presence of TPMT SNPs in children with acute lymphoblastic leukemia (ALL). RESULTS: Fifty-five (5.5%) study participants overall had heterozygous TPMT genotypes (1 variant and 1 wild-type allele): TPMT*1/*3A (n = 45; 4.5%), TPMT*1/*3C (n = 8; 0.8%), and TPMT*1/*2 (n = 2; 0.2%). TPMT SNPs were more frequent in children with hematologic malignancy than in other participants (7.5% vs. 4.0%, P = 0.02). We found no significant association between TPMT SNPs and ALL treatment outcome (median follow-up, 31.3 months). CONCLUSIONS: TPMT*3A is the most prevalent variant allele in the Russian Federation. The estimated frequency of variant alleles in the study cohort (5.5%) was similar to that observed in the White populations in the U.S. and Eastern Europe.

Rapid genotyping of common deficient thiopurine S-methyltransferase alleles using the DNA-microchip technique.

Thiopurine drugs are metabolized, in part, by S-methylation catalyzed by thiopurine S-methyltransferase (TPMT). Patients with very low or undetectable TPMT activity are at high risk of severe, potentially fatal hematopoietic toxicity when they are treated with standard doses of thiopurines. As human TPMT activity is controlled by a common genetic polymorphism, it is an excellent candidate for the clinical application of pharmacogenetics. Here, we report a new molecular approach developed to detect point mutations in the TPMT gene that cause the loss of TPMT activity. A fluorescently labeled amplified DNA is hybridized with oligonucleotide DNA probes immobilized in gel pads on a biochip. The specially designed TPMT biochip can recognize six point mutations in the TPMT gene and seven corresponding alleles associated with TPMT deficiency: TPMT*2; TPMT*3A, TPMT*3B, TPMT*3C, TPMT*3D, TPMT*7, and TPMT*8. The effectiveness of the protocol was tested by genotyping 58 samples of known genotype. The results showed 100% concordance between the biochip-based approach and the established PCR protocol. The genotyping procedure is fast, reliable and can be used for rapid screening of inactivating mutations in the TPMT gene. The study also provides the first data on the frequency of common TPMT variant alleles in the Russian population, based on a biochip analysis of 700 samples. TPMT gene mutations were identified in 44 subjects; genotype *1/*3A was most frequent.