Negative colorectal polyp biopsies: the utility of cutting deeper levels.

The objectives of this study were to determine the frequency with which deeper levels reveal a lesion in polyp biopsies where no polyp was found on initial sections and to identify features that predict such occult (histologically unapparent) lesions. All initially negative biopsy specimens were accumulated over an 18-month period. Following standard sections, three to ten levels were cut, 50 µm apart. The presence of any lesion, the level at which it was found, the location, number and size of fragments, number of levels obtained, presence of any lymphoid aggregate, endoscopic size and appearance, and bowel preparation quality were recorded. There were 214 specimens, mean patient age 61.4 years (range 27-86 years). Deeper levels revealed a lesion in 52/214 (24.3 %) cases; 76.9 % were tubular adenomas (TA), 21.2 % were hyperplastic polyps, and one was a leiomyoma. All TAs were negative for high-grade dysplasia and malignancy. The mean level at which TAs were found was 1.85 (range 1-9). Male sex (p = 0.021) and right-sided location (p = 0.0075) were statistically significant predictors of an occult TA. As the presence of an adenoma affects screening, pathologists should consider "pursuing" polyps when initial sections reveal no lesion, after ascertaining the incidence of occult lesions in their own practice.

Activation of protein kinase Cδ leads to increased pancreatic acinar cell dedifferentiation in the absence of MIST1.

Pancreatic ductal adenocarcinoma (PDAC) has a 5 year survival rate post-diagnosis of < 5%. Individuals with chronic pancreatitis (CP) are 20-fold more likely to develop PDAC, making it a significant risk factor for PDAC. While the relationship for the increased susceptibility to PDAC is unknown, loss of the acinar cell phenotype is common to both pathologies. Pancreatic acinar cells can dedifferentiate or trans-differentiate into a number of cell types including duct cells, ß cells, hepatocytes and adipocytes. Knowledge of the molecular pathways that regulate this plasticity should provide insight into PDAC and CP. MIST1 (encoded by Bhlha15 in mice) is a transcription factor required for complete acinar cell maturation. The goal of this study was to examine the plasticity of acinar cells that do not express MIST1 (Mist1(-/-) ). The fate of acinar cells from C57Bl6 or congenic Mist1(-/-) mice expressing an acinar specific, tamoxifen-inducible Cre recombinase mated to Rosa26 reporter LacZ mice (Mist1(CreERT/-) R26r) was determined following culture in a three-dimensional collagen matrix. Mist1(CreERT/-) R26r acini showed increased acinar dedifferentiation, formation of ductal cysts and transient increases in PDX1 expression compared to wild-type acinar cells. Other progenitor cell markers, including Foxa1, Sox9, Sca1 and Hes1, were elevated only in Mist1(-/-) cultures. Analysis of protein kinase C (PKC) isoforms by western blot and immunofluorescence identified increased PKCε accumulation and nuclear localization of PKCδ that correlated with increased duct formation. Treatment with rottlerin, a PKCδ-specific inhibitor, but not the PKCε-specific antagonist εV1-2, reduced acinar dedifferentiation, progenitor gene expression and ductal cyst formation. Immunocytochemistry on CP or PDAC tissue samples showed reduced MIST1 expression combined with increased nuclear PKCδ accumulation. These results suggest that the loss of MIST1 is a common event during PDAC and CP and events that affect MIST1 function and expression may increase susceptibility to these pathologies.

Three dimensional transrectal ultrasound imaging of the prostate: initial experience with an emerging technology.

PURPOSE: A three-dimensional ultrasound system (3-D US) was evaluated for its clinical utility in transrectal prostate imaging, in comparison with the current standard 2-dimensional transrectal ultrasound (TRUS) imaging system. METHODS AND MATERIALS: The computer program developed in our laboratory was coupled with a commercially available ultrasound transducer. Geometric validation and volumetric assessment was performed with "stretched-string" wire models and solution-containing balloons respectively. Anatomic correlation of 3-D TRUS images was performed with cadaveric prostates. Intraprostatic lesion localization by 3D-TRUS was assessed clinically by 2 observers in 11 patients prior to radical prostatectomy and the data compared with those yielded by 2-D TRUS. RESULTS: Geometric assessment by 3D TRUS in comparison with the "between strings in the phantom" model (true dimensions) had an error of up to 1.2%. Volume measurement by 3-D TRUS had an error, compared to the true volume, of 0.9%. The correlation coefficient (r) was 0.99985 for the end-firing probe and 0.978 for side firing. The 3-D images provided accurate representation of the true anatomy in the sagittal, transverse and most uniquely, the coronal plane. Two observers achieved better diagnostic accuracies with intraprostatic abnormalities using 3-D instead of standard 2-D TRUS. The negative predictive value and the specificity were improved. CONCLUSION: 3-D TRUS appears to provided accurate representation of the true anatomy with geometric and volumetric validation. Areas of potential clinical application of 3-D TRUS include treatment monitoring with volume measurements and various intervention and therapeutic procedures for both benign and malignant prostatic disorders.