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Biomedical subjects

J S Ross

Publications and source records attributed to J S Ross.

At least 55 records · Page 3Linked to original sources

Pathology residents' use of a Web-based tutorial to improve Gleason grading of prostate carcinoma on needle biopsies.

Little is known about pathology residents' ability to Gleason grade or their ability to learn surgical pathology using Internet-based technology. A free Web-based program (available at www.pathology. jhu.edu/prostate) was developed that consisted of 20 pretutorial images for grading, 24 tutorial images, and the same 20 posttutorial images for Gleason grading. The grading images were selected from cases that had a consensus Gleason grade from 10 uropathology experts. In 2.5 months, 255 residents visited the website, and 151 (59%) completed it. Of those who completed the website, their year in training was known in 85 (56%): 1st year, 25.8%; 2nd year, 20%; 3rd year, 22.3%; 4th year, 14.1%; 5th year, 15.3%; and 6th year, 2.4%. Eighty percent learned Gleason grading in residency versus being self-taught, and 66% were male. In a multivariate analysis, higher pretutorial scores were associated with both their year in training (P = .001) and their hospital size (P = .003). Improvements in grading posttutorial were not related to the residents' year in training. Overall, the website significantly improved grading in 11 of 20 images and had no effect in 9 of 20 images. Improvements were noted in 1 of 1 Gleason score 4; 2 of 7 Gleason score 5 to 6; 2 of 6 Gleason score 7; and 6 of 6 Gleason score above 7 tumors. In summary, a Web-based tutorial improved Gleason grading accuracy by pathology residents to an equal extent regardless of their year in training. It is more difficult to teach residents to grade Gleason scores 5 to 7 tumors, and additional training should be concentrated in this area.

Biopsy, Needle↗

Magnetic resonance imaging of the postoperative spine.

Magnetic resonance (MR) imaging is an excellent technique for evaluating the postoperative spine when the patient has chronic or recurrent symptoms. Potential causes of pain following lumbar surgery include arachnoiditis, stenosis, epidural fibrosis and disc herniations, pseudomeningocele, and infection. The postoperative cervical spine may be complicated by hematoma, canal or foraminal stenosis, disc herniation, and cord abnormality. This article reviews standard imaging protocols, the normal postoperative appearance of the spine, and the characteristic imaging findings for each of the abnormal postoperative conditions.

Diagnosis, Differential↗

MR imaging of intrinsic inflammatory myelopathies.

The neuroimaging evaluation of patients with suspected inflammatory myelopathy is one of the more technically and interpretatively challenging MR examinations. This article reviews several recent MR imaging sequencing developments that have significantly improved spinal cord imaging. The clinical, pathologic, and MR imaging features of several of the more common inflammatory myelopathic-producing diseases also are discussed.

Humans↗

Mismeasurement and the resonance of strong confounders: correlated errors.

Confounding in epidemiology, and the limits of standard methods of control for an imperfectly measured confounder, have been understood for some time. However, most treatments of this problem are based on the assumption that errors of measurement in confounding and confounded variables are independent. This paper considers the situation in which a strong risk factor (confounder) and an inconsequential but suspected risk factor (confounded) are each measured with errors that are correlated; the situation appears especially likely to occur in the field of nutritional epidemiology. Error correlation appears to add little to measurement error as a source of bias in estimating the impact of a strong risk factor: it can add to, diminish, or reverse the bias induced by measurement error in estimating the impact of the inconsequential risk factor. Correlation of measurement errors can add to the difficulty involved in evaluating structures in which confounding and measurement error are present. In its presence, observed correlations among risk factors can be greater than, less than, or even opposite to the true correlations. Interpretation of multivariate epidemiologic structures in which confounding is likely requires evaluation of measurement error structures, including correlations among measurement errors.

Analysis of Variance↗

Telomerase activity in benign and malignant cytologic fluids.

BACKGROUND: Telomerase is a ribonucleoprotein that maintains telomeric base pair repeats at the ends of mammalian chromosomes during DNA replication. Telomerase is expressed in various human tumors, some normal tissues, and immortalized cell lines. The assay of telomerase activity has potential as an adjunct for cancer detection in cytologic fluids. METHODS: Twenty-four unfixed cytologic fluids, including 13 ascitic fluids, 7 pleural fluids, 3 pelvic washings, and 1 bronchial washing, were prepared for polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (Oncor, Inc., Gaithersburg, MD). Telomerase activity was determined by PCR. The presence of a ladder of products with 6 base pair increments, separated by polyacrylamide gel electrophoresis and detected by phosphoimaging, was considered a positive result. Results were compared with cytologic evaluation of alcohol fixed, Papanicolaou stained smears. RESULTS: Of the 14 cytologically malignant specimens, 11 (79%) contained detectable telomerase activity. Two cytologically malignant samples could not be evaluated for telomerase activity due to the presence of inhibitory substances of PCR reaction. Of the 10 cytologically negative specimens, 1 (10%) was positive for telomerase activity; this specimen was from a patient with history of both endometrial and lung carcinomas. CONCLUSIONS: Telomerase activity can be detected in malignant cytologic specimens and thus has potential as a diagnostic adjunct in cytopathology.

Adult↗

The prognostic significance of proliferation-associated nucleolar protein p120 expression in prostate adenocarcinoma: a comparison with cyclins A and B1, Ki-67, proliferating cell nuclear antigen, and p34cdc2.

BACKGROUND: In this study, the authors evaluated the prognostic significance of the expression of nucleolar antigen p120, along with other cell proliferation-associated proteins, in prostate adenocarcinomas (PACs) and compared the results with previously reported data on p34cdc2 cyclin-dependent kinase (p34 cdk). METHODS: Archival sections from 132 PACs were immunostained with monoclonal antibodies against p120, cyclin A, cyclin B1, Ki-67, and proliferating cell nuclear antigen (PCNA). The DNA content of each tumor was determined by the Feulgen method using image analysis. The immunohistochemistry (IHC) results were correlated with tumor grade, stage, margin positivity, metastasis, ploidy, and postsurgical disease recurrence. RESULTS: The overall positivity for the various proteins follows: p120, 36%; cyclin A, 35%; cyclin B1, 43%; Ki-67, 46%; and PCNA, 32%. p120 correlated with grade (P = 0.004), stage (P = 0.01), ploidy (P = 0.02), margin positivity (P = 0.03), and metastasis (P = 0.004). Cyclin B1 correlated with ploidy (P = 0.04) and grade (P = 0.05), Ki-67 with grade (P = 0.02) and margins (P = 0.03), and PCNA with grade (P = 0.01). Significant coexpression among these proteins was noted, as was a significant association between the expression of these markers and that previously reported for p34 cdk. In univariate analysis, p120 (P = 0.01), cyclin A (P = 0.01) and p34 cdk (P = 0.002) correlated with disease recurrence. In multivariate analysis of all these proteins, only p34 cdk independently predicted postsurgical recurrence (P = 0.05). CONCLUSIONS: Nucleolar antigen p120 expression appears to be an additional marker of aggressiveness in PACs. The significant coexpression of the various cell cycle regulatory proteins support their collective role in tumor cell proliferation, with p34 cdk positivity being an independent predictor of postsurgical recurrence.

Adenocarcinoma↗

The HER-2/neu oncogene: prognostic factor, predictive factor and target for therapy.

The HER-2/neu oncogene encodes a transmembrane tyrosine kinase receptor with extensive homology to the epidermal growth factor receptor. HER-2/neu has been widely studied in breast cancer. The potential value of HER-2/neu status for the prediction of disease outcome and response to therapy in breast cancer is presented in the light of a series of recently published studies showing a range of impact on the outcome of patients treated with hormonal, cytotoxic and radiation therapies. This review includes the application of serum-based HER-2/neu testing and the use of antibody-based therapies directed against the HER-2/neu protein and their potential to become a new modality for breast cancer treatment.

Breast Neoplasms↗

Can ploidy of prostate carcinoma diagnosed on needle biopsy predict radical prostatectomy stage and grade?

PURPOSE: Deoxyribonucleic acid ploidy correlates with the biological behavior of prostate carcinoma. However, the usefulness of ploidy on needle biopsies that show prostate cancer has not been established to our knowledge. MATERIALS AND METHODS: We retrospectively determined ploidy on needle biopsies of 159 men with prostate carcinoma treated surgically at Johns Hopkins Hospital. Ploidy was determined by image analysis of Feulgen stained slides. Needle ploidy and Gleason score were compared as prognostic tools in the prediction of grade and stage of subsequent prostatectomy. RESULTS: Of the 159 cases 98 (62%) were diploid, 16 (10%) tetraploid and 45 (28%) aneuploid. Of the diploid, tetraploid and aneuploid tumors 69, 50 and 44%, respectively, proved to be organ confined. Tetraploid and aneuploid tumors were grouped for the remaining analysis. Needle ploidy correlated significantly with pathological stage (p = 0.003). However, needle Gleason score correlated even more strongly (p <0.001), and on multivariate analysis ploidy was not further predictive of pathological stage once Gleason score was considered. Needle ploidy and Gleason score were predictive of prostatectomy Gleason score (6 or less versus 7 or greater), and on multivariate analysis ploidy was an independently significant predictor of this parameter (p = 0.04). In 13 cases (8%) there was an important grading discrepancy, in which needle ploidy would have accurately predicted prostatectomy grade. However, in 33 cases (21%) needle and prostatectomy Gleason scores were congruent, and needle ploidy did not accurately predict prostatectomy Gleason score. CONCLUSIONS: With accurate needle Gleason grading, ploidy is not helpful in predicting prostatectomy findings. However, ploidy correlates with prostatectomy stage and grade, and may be useful if accurate Gleason grading is a concern.

Aged↗

MR evaluation of epidural fibrosis: proposed grading system with intra- and inter-observer variability.

The purpose of this study is to present a grading system for the Magnetic Resonance (MR) appearance of epidural fibrosis, and to present the inter- and intra-observer variability of the system. The study population was from a randomized, double blind, controlled multicenter clinical trial evaluating the safety and effectiveness of ADCON-L anti-adhesion barrier gel, in preventing epidural fibrosis and dural adhesions following single-level unilateral laminectomy/discectomy for lumbar disc herniations. MRI of the lumbar spine was obtained, without and with gadolinium enhancement, pre-operatively and at six months post-operatively. Patients having extensive epidural scar have been shown to be 3.2 times more likely to experience recurrent radicular pain than those patients with less extensive epidural scarring. New agents have appeared in the marketplace and in clinical trials that may be used intra-operatively to modulate the presence or absence of epidural scar tissue. Given these factors, the need to accurately describe the location and amount of epidural scar tissue has assumed more pressing importance. Two readers, blinded to clinical findings and to the other reader, independently evaluated the MR examinations in 50 post-operative lumbar spine surgery patients using the previously defined categorization of epidural scar for five levels in each patient, four quadrants per level. In addition, 114 examinations were separately evaluated by the same reader for evaluation of intra-observer variability. For the purposes of epidural fibrosis identification, only the axial T1-weighted images with and without contrast were utilized. The amount of epidural fibrosis was graded on a scale of 0-4 for each quadrant at each imaging slice encompassing the operative level: 0 = no/trace scar; 1 = > 0% and < or = 25% of quadrant filled with scar; 2 = > 25% and < or = 50% of quadrant filled with scar; 3 = > 50% and < or = 75% of quadrant filled with scar; 4 = > 75% and < or = 100% of quadrant filled with scar. Each reader evaluated a total of 1000 epidural quadrants for the inter-observer assessment. The estimated kw index is 0.68 with 95% confidence interval (CI) of [0.64, 0.71]; this is substantial agreement. There were a total of 2,280 quadrants evaluated overall for the intra-observer assessment. The estimated kw index is 0.94 with 95% CI of [0.93, 0.95]; this is almost perfect agreement. Substantial intra-observer and near perfect inter-observer agreement was achieved for evaluation of epidural scar using a relatively simple, semi-quantitative approach to the T1-weighted axial MR images. A standard grading system for epidural scar is proposed.

Cicatrix↗

HER-2/neu oncogene amplification by fluorescence in situ hybridization in epithelial tumors of the ovary.

HER-2/neu gene amplification and protein overexpression have been associated with prognosis in breast, lung and prostate cancers but have not been extensively studied in ovarian carcinoma. For the study, we selected 5-micron-thick, formalin-fixed, paraffin-embedded tissue sections from 74 cases of ovarian epithelial tumors of low malignant potential and ovarian carcinoma. Tumors were graded and staged and evaluated for amplification of the HER-2/neu gene by fluorescence in situ hybridization. HER-2/neu amplifications was present in 3 of 13 serous, mucinous, and endometrioid epithelial tumors of low malignant potential and in 40 of 61 epithelial carcinomas. In the carcinoma group, amplification did not correlate with stage, grade, or tumor type. Mean follow-up was 31 months; 1 patient with a low malignant potential tumor and 32 patients with carcinomas died of disease. On univariate and multivariate analysis, survival correlated with stage of disease but not with HER-2/neu amplification. HER-2/neu amplification by fluorescence in situ hybridization can be performed on tissue sections of ovarian neoplasms; amplification is uncommon in ovarian tumors of low malignant potential, but is present in 66% of ovarian epithelial carcinomas. HER-2/neu amplification did not predict outcome in ovarian epithelial neoplasia but may have an important role in tumor development.

Adenocarcinoma↗

Prognostic significance of p34cdc2 cyclin-dependent kinase and MIB1 overexpression, and HER-2/neu gene amplification detected by fluorescence in situ hybridization in breast cancer.

The HER-2/neu oncogene, localized to chromosome 17q, shares substantial homology with the epidermal growth factor receptor. HER-2/neu gene amplification and protein overexpression have been associated with poor prognosis in breast cancer. Formalin-fixed paraffin-embedded primary invasive breast cancer tissues from 135 women were tested for HER-2/neu gene amplification by automated fluorescence in situ hybridization (FISH) using a sequence probe. The tumors also were evaluated by immunohistochemistry for proliferation markers Ki 67 (MIB1) and p34cdc2 cyclin-dependent kinase. Patients were followed up for a mean of 61 months. There were 70 node-negative and 65 node-positive cases. Ki 67 and p34cdc2 proliferation marker overexpression, HER-2/neu oncogene amplification, large tumor size, high tumor grade, advanced tumor stage, positive lymph node status, and distant metastasis at the time of diagnosis predicted disease-related death in combined node-negative and node-positive breast cancer. HER-2/neu gene amplification, tumor stage, lymph node metastasis, tumor grade, and distant metastasis at the time of diagnosis independently predicted disease outcome. HER-2/neu amplification detected by FISH also predicted disease-related death independent of lymph node status, tumor grade, and distant metastasis in breast cancer patients who received adjuvant therapy.

Adult↗

Needle biopsy DNA ploidy status predicts grade shifting in prostate cancer.

DNA ploidy analysis of prostate needle biopsy specimens was performed to determine whether ploidy status could predict tumor grade shifting at radical prostatectomy. The paired needle biopsy and radical prostatectomy specimens from 111 randomly selected men with prostate cancer were obtained from the surgical pathology files of the Albany Medical Center Hospital. The original tumor grades were assigned by a staff of 12 surgical pathologists according to the Gleason system. Tumors with original Gleason scores < or = 6 were classified as low grade, and tumors with scores of > or = 7 were considered high grade. DNA ploidy analysis was performed on the needle biopsy specimens using the CAS 200 image analyzer (Becton Dickinson Immunocytometry Systems, Mountain View, CA, USA) on Feulgen stained 5-microm tissue sections. There were 88 diploid and 23 nondiploid cases. Thirty-eight of 111 (34%) of cases had grade shifting from needle biopsy to radical prostatectomy specimens. Of 89 low-grade needle biopsy cases, 28 (31%) were upgraded at radical prostatectomy. Of 22 high-grade needle biopsy cases, 10 (45%) were downgraded to low grade at radical prostatectomy. Of the 28 low-grade needle biopsy specimens that were upgraded at radical prostatectomy, 19 (68%) featured an aneuploid histogram and 9 (32%) were diploid. Nineteen of 28 (68%) of aneuploid low-grade tumors on needle biopsy became high-grade at radical prostatectomy. Nine of 10 (90%) diploid high-grade tumors at needle biopsy became low-grade at radical prostatectomy. Of the 38 cases in which ploidy and grade were incongruous, 28 (74%) had grade shifting. In a multivariate regression analysis, a high-grade Gleason score on radical prostatectomy specimens correlated significantly with needle biopsy ploidy (p = 0.0001) but not with needle biopsy grade (p = 0.15). The sensitivity of the needle biopsy grade in the detection of high-grade tumors on radical prostatectomy was 30%, and the specificity was 86%. The sensitivity of ploidy status in the prediction of high grade at radical prostatectomy was 78%, and the specificity was 96%. With a prostate-specific antigen (PSA) level of >0.4 ng/ml as the indicator of post-radical prostatectomy disease recurrence on a subset of 106 patients, on univariate analysis, disease recurrence was predicted by needle biopsy ploidy (p = 0.001) and radical prostatectomy grade (p = 0.04) but not by needle biopsy grade (p = 0.39). On multivariate analysis, needle biopsy DNA ploidy status independently predicted disease recurrence (p = 0.002), whereas needle biopsy and prostatectomy grade did not. These results indicate that DNA ploidy analysis of needle biopsy specimens of prostate cancer predicts grade shifting, that it is a more sensitive and specific indicator of final tumor grade at radical prostatectomy than is the original needle biopsy grade, and that ploidy status independently predicts postoperative disease recurrence.

Adult↗