Lower Interobserver Reliability for Nondimensional Intracystic Features Among Abdominal Radiologists for Characterizing Intraductal Papillary Mucinous Neoplasms Using Magnetic Resonance Imaging.

OBJECTIVES: Current guidelines recommend magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP) for risk stratification of intraductal papillary mucinous neoplasms (IPMNs). We assessed the interobserver agreement among radiologists in evaluating and risk stratifying IPMNs. METHODS: This single-center study evaluated 30 patients with IPMNs who had undergone MRI/MRCP, endoscopic ultrasound, and/or surgical resection. Six abdominal radiologists evaluated the MRI/MRCPs to document multiple parameters. The analysis applied Landis and Koch κ interpretation for categorical variables and intraclass correlation coefficient (r) for continuous variables. RESULTS: Radiologists demonstrated almost perfect agreement for location (κ = 0.81, 95% confidence interval [CI], 0.74-0.87), size (r = 0.95; 95% CI, 0.89-0.98), and main pancreatic duct diameter (r = 0.98; 95% CI, 0.96-0.99). Substantial agreement was observed for communication with the main pancreatic duct (κ = 0.66; 95% CI, 0.57-0.75) and classification of IPMN subtype (κ = 0.77; 95% CI, 0.67-0.86). Presence of intracystic nodules (κ = 0.31; 95% CI, 0.21-0.42) and wall thickening (κ = 0.09; 95% CI, -0.01 to 0.18) reached only fair and slight agreement, respectively. CONCLUSIONS: Although MRI/MRCP is excellent in the evaluation of spatial aspects, there is lower reliability for nondimensional characteristics of IPMNs. These data support guideline-recommended complementary evaluation of IPMNs with MRI/MRCP and endoscopic ultrasound.

Quantification of Human Central Adipose Tissue Depots: An Anatomically Matched Comparison Between DXA and MRI.

Excess visceral adipose tissue (VAT) and VAT volume relative to subcutaneous adipose tissue (SAT) are associated with elevated health risks. This study compares fat measurements by dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI). In total, 21 control subjects (Control) and 16 individuals with metabolic syndrome (MetSyn) were scanned by DXA and MRI. The region measured by MRI was matched to the android region defined by DXA, and MRI reproducibility was also evaluated. In addition, liver fat fraction was quantified via MRI and whole-body fat by DXA. VAT measurements are interchangeable between DXA and MRI in the Control (R = 0.946), MetSyn (R = 0.968), and combined cohort (R = 0.983). VAT/SAT ratio did not differ in the Control group (P = .10), but VAT/SAT ratio measured by DXA was significantly higher in the MetSyn group (P < .01) and the combined (P = .03) cohort. Intraobserver (ICC = 0.998) and interobserver (ICC = 0.977) reproducibility of MRI VAT measurements was excellent. Liver fat fraction by MRI was higher (P = .001) in MetSyn (12.4% ± 7.6%) than in controls (2.6% ± 2.2%), as was whole-body fat percentage by DXA (P = .001) between the MetSyn (42.0% ± 8.1%) and Control groups (26.7% ± 6.9%). DXA and MRI VAT are interchangeable when measured over an anatomically matched region of the abdomen, while SAT and VAT/SAT ratio differ between the 2 modalities.

Specificity rescue and affinity maturation of a low-affinity IgM antibody against pro-gastrin-releasing peptide using phage display and DNA shuffling.

The objectives of the present study were to use phage display to rescue the specificity of an IgM antibody and by the use of DNA shuffling to construct a sublibrary from which mutants with higher affinity could be selected. As a test system, a hybridoma cell line producing low-affinity IgM against recombinant pro-gastrin-releasing peptide (ProGRP) was chosen as starting material for construction of a single-chain Fv (scFv) phage library. One clone, pGRP5, demonstrating affinity for the antigen, was selected for the study. Random mutations were introduced into the scFv sequence by DNA shuffling, and mutants with raised affinity were selected by biopanning against recombinant ProGRP. Clones with affinities improved by approximately two orders of magnitude were selected after the first round of DNA shuffling. An additional 8- to 9-fold rise in affinity was demonstrated in mutants after the second round of mutagenesis. Sequence analysis demonstrated changes primarily in the complementarity-determining region (CDR) H1, CDR L1 and CDR H3 as compared to the original clone. Thus, by the use of phage display in combination with DNA shuffling, the specificity of an IgM antibody was rescued and the affinity was raised almost three orders of magnitude.

Rearrangement of squamous cell carcinoma antigen genes--detection of SCCA fusion transcripts.

Squamous cell carcinoma antigen (SCCA), a member of the serine protease inhibitor (serpin) family, is a tumor-associated antigen and a serological marker for squamous cell carcinomas (SCC). Elevated serum levels are correlated with the clinical stage of the disease. Gene cloning has previously revealed two tandemly arrayed genes, SCCA1 and SCCA2. Using RT-PCR, an SCCA1/A2 transcript was identified in 6 out of 8 cell lines and the reciprocal SCCA2/A1 transcript was identified in 6 out of 8 analysed cell lines. Southern blot analysis showed an aberrant band pattern in 3 out of 5 cell lines. The cell lines demonstrating a normal band pattern corresponded to the cell lines where no fusion transcript was detected using PCR. Complex binding studies show that SCCA1/A2 binds to cathepsin G but not to cathepsin L, indicating that the SCCA1/A2 fusion protein has the specificity of SCCA2, but the transcription may be regulated as that of SCCA1. SCCA2/A1 reacts in the opposite way. The clinical relevance of these fusion transcripts is not yet known. Studies using primary tumours are underway to elucidate if these fusion transcripts are tumour specific and if they might be used as a diagnostic and prognostic marker for SCC.