The role of image guided biopsy targeting in patients with atypical small acinar proliferation.

PURPOSE: Men diagnosed with atypical small acinar proliferation are counseled to undergo early rebiopsy because the risk of prostate cancer is high. However, random rebiopsies may not resample areas of concern. Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy offers an opportunity to accurately target and later retarget specific areas in the prostate. We describe the ability of magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy to detect prostate cancer in areas with an initial diagnosis of atypical small acinar proliferation. MATERIALS AND METHODS: Multiparametric magnetic resonance imaging of the prostate and magnetic resonance imaging/transrectal ultrasound fusion guided biopsy were performed in 1,028 patients from March 2007 to February 2014. Of the men 20 met the stringent study inclusion criteria, which were no prostate cancer history, index biopsy showing at least 1 core of atypical small acinar proliferation with benign glands in all remaining cores and fusion targeted rebiopsy with at least 1 targeted core directly resampling an area of the prostate that previously contained atypical small acinar proliferation. RESULTS: At index biopsy median age of the 20 patients was 60 years (IQR 57-64) and median prostate specific antigen was 5.92 ng/ml (IQR 3.34-7.48). At fusion targeted rebiopsy at a median of 11.6 months 5 of 20 patients (25%, 95% CI 6.02-43.98) were diagnosed with primary Gleason grade 3, low volume prostate cancer. On fusion rebiopsy cores that directly retargeted areas of previous atypical small acinar proliferation detected the highest tumor burden. CONCLUSIONS: When magnetic resonance imaging/transrectal ultrasound fusion guided biopsy detects isolated atypical small acinar proliferation on index biopsy, early rebiopsy is unlikely to detect clinically significant prostate cancer. Cores that retarget areas of previous atypical small acinar proliferation are more effective than random rebiopsy cores.

3D organization and function of the cell: Golgi budding and vesicle biogenesis to docking at the porosome complex.

Insights into the three-dimensional (3D) organization and function of intracellular structures at nanometer resolution, holds the key to our understanding of the molecular underpinnings of cellular structure-function. Besides this fundamental understanding of the cell at the molecular level, such insights hold great promise in identifying the disease processes by their altered molecular profiles, and help determine precise therapeutic treatments. To achieve this objective, previous studies have employed electron microscopy (EM) tomography with reasonable success. However, a major hurdle in the use of EM tomography is the tedious procedures involved in fixing, high-pressure freezing, staining, serial sectioning, imaging, and finally compiling the EM images to obtain a 3D profile of sub-cellular structures. In contrast, the resolution limit of EM tomography is several nanometers, as compared to just a single or even sub-nanometer using the atomic force microscope (AFM). Although AFM has been hugely successful in 3D imaging studies at nanometer resolution and in real time involving isolated live cellular and isolated organelles, it has had limited success in similar studies involving 3D imaging at nm resolution of intracellular structure-function in situ. In the current study, using both AFM and EM on aldehyde-fixed and semi-dry mouse pancreatic acinar cells, new insights on a number of intracellular structure-function relationships and interactions were achieved. Golgi complexes, some exhibiting vesicles in the process of budding were observed, and small vesicles were caught in the act of fusing with larger vesicles, possibly representing either secretory vesicle biogenesis or vesicle refilling following discharge, or both. These results demonstrate the power and scope of the combined engagement of EM and AFM imaging of fixed semi-dry cells, capable of providing a wealth of new information on cellular structure-function and interactions.

Visualization and stereological characterization of individual rat lung acini by high-resolution X-ray tomographic microscopy.

The small trees of gas-exchanging pulmonary airways, which are fed by the most distal purely conducting airways, are called acini and represent the functional gas-exchanging units. The three-dimensional architecture of the acini has a strong influence on ventilation and particle deposition. Due to the difficulty in identifying individual acini on microscopic lung sections, the knowledge about the number of acini and their biological parameters, like volume, surface area, and number of alveoli per acinus, are limited. We developed a method to extract individual acini from lungs imaged by high-resolution synchrotron radiation-based X-ray tomographic microscopy and estimated their volume, surface area, and number of alveoli. Rat acini were isolated by semiautomatically closing the airways at the transition from conducting to gas-exchanging airways. We estimated a mean internal acinar volume of 1.148 mm(3), a mean acinar surface area of 73.9 mm(2), and a mean of 8,470 alveoli/acinus. Assuming that the acini are similarly sized throughout different regions of the lung, we calculated that a rat lung contains 5,470 ± 833 acini. We conclude that our novel approach is well suited for the fast and reliable characterization of a large number of individual acini in healthy, diseased, or transgenic lungs of different species, including humans.