Michael Becich | University of Pittsburgh School of Medicine (original) (raw)

Papers by Michael Becich

Prostate cancer is the second most common cause of cancer deaths and is the most frequently detec... more Prostate cancer is the second most common cause of cancer deaths and is the most frequently detected form of cancer of males in the US. Death rate scan be greatly reduced by early treatment. Consequently, it is important to understand the cause and progression of this disease in order to improve detection and treatment methods. As part of the Cancer

Archives of Pathology & Laboratory Medicine, 2015

Context .- We define the scope and needs within the new discipline of computational pathology, a ... more Context .- We define the scope and needs within the new discipline of computational pathology, a discipline critical to the future of both the practice of pathology and, more broadly, medical practice in general. Objective .- To define the scope and needs of computational pathology. Data Sources .- A meeting was convened in Boston, Massachusetts, in July 2014 prior to the annual Association of Pathology Chairs meeting, and it was attended by a variety of pathologists, including individuals highly invested in pathology informatics as well as chairs of pathology departments. Conclusions .- The meeting made recommendations to promote computational pathology, including clearly defining the field and articulating its value propositions; asserting that the value propositions for health care systems must include means to incorporate robust computational approaches to implement data-driven methods that aid in guiding individual and population health care; leveraging computational pathology as a center for data interpretation in modern health care systems; stating that realizing the value proposition will require working with institutional administrations, other departments, and pathology colleagues; declaring that a robust pipeline should be fostered that trains and develops future computational pathologists, for those with both pathology and nonpathology backgrounds; and deciding that computational pathology should serve as a hub for data-related research in health care systems. The dissemination of these recommendations to pathology and bioinformatics departments should help facilitate the development of computational pathology.

Proceedings / AMIA ... Annual Symposium. AMIA Symposium, 2000

The development of the Multimedia Electronic Medical Record System (MEMRS) offers new opportuniti... more The development of the Multimedia Electronic Medical Record System (MEMRS) offers new opportunities for integrating medical imaging data with text-based clinical data. The effective integration of pathology images into the patient's medical record poses some significant technical and organizational challenges. Before these challenges can be met, it is imperative that we investigate the value and utility of providing these images to clinicians. In this study we examined attitudes towards use of pathology images in Image Engine, a MEMRS under development at the University of Pittsburgh Cancer Institute (UPCI). We conducted semi-structured standardized interviews with a cohort of practicing oncologists, all of whom had significant experience with Image Engine. This study is a first step towards elucidating the potential barriers, uses, and value of anatomic pathology images in the MEMRS.

Cancer research, 1996

The early diagnosis of bladder cancer is central to the effective treatment of the disease. Prese... more The early diagnosis of bladder cancer is central to the effective treatment of the disease. Presently, there are no methods available to easily and specifically identify the presence of bladder cancer cells. The prevailing method for the detection of bladder cancer is the identification of bladder cancer cells by morphological examination of exfoliated cells or biopsy material by a pathologist. A hallmark of the malignant or transformed phenotype is an abnormal nuclear shape, the presence of multiple nucleoli, and altered patterns of chromatin organization. Nuclear structural alterations are so prevalent in cancer cells that they are commonly used as markers of transformation for many types of cancer. Nuclear shape is determined by the nuclear matrix, the dynamic skeleton of the nucleus. The nuclear matrix is the structural component of the nucleus that determines nuclear morphology, organizes the DNA in a three-dimensional fashion that is tissue specific, and has a central role in ...

Essentials of Anatomic Pathology, 2010

Biomedical informatics has made a deep impact in the overall workflow of the surgical pathology p... more Biomedical informatics has made a deep impact in the overall workflow of the surgical pathology practice and has provided a variety of software tools that accelerate the overall turnaround time, cost effectiveness, and accuracy of information. Laboratory Information System functions as a single comprehensive piece of software managing laboratory workflow, reporting, and billing. Related technologies, such as digital imaging, whole

Human pathology, 2004

As academic pathology departments have become increasingly based in large, regional medical syste... more As academic pathology departments have become increasingly based in large, regional medical systems spread across hundreds of square miles, new methods are needed to tie these increasingly distributed departments together as integrated units. An important part of that integration is the ability to share academic and teaching conferences across long distances. In this article we present an effective, low-cost webcasting system that has evolved at the University of Pittsburgh Medical Center Department of Pathology over the past several years based on inexpensive, widely available software. To date, the system has broadcast and archived more than 400 conferences and currently serves approximately 80 to 100 requests each week. Important factors in the success of the program include the creation of a faculty steering committee to control resources and manage growth, the availability of informatics faculty and support for technical staff, and the decision to operate the service as part of...

Annals of the American Thoracic Society, Jan 8, 2015

Severe deficiency of alpha-1 antitrypsin has a highly variable clinical presentation. The GRADS A... more Severe deficiency of alpha-1 antitrypsin has a highly variable clinical presentation. The GRADS Alpha-1 Study is a prospective, multicenter, cross-sectional, study of adults > age 35 with PiZZ or PiMZ alpha-1 antitrypsin genotypes designed to better understand if microbial factors influence this heterogeneity. Clinical symptoms, pulmonary function testing, computed chest tomography, exercise capacity, and bronchoalveolar lavage (BAL) will be used to define COPD phenotypes that can be studied with an integrated systems biology approach that includes plasma proteomics; mouth, BAL, and stool microbiome and virome analysis; blood miRNA, and blood mononuclear cell RNA and DNA profiling, and relies on global genome, transcriptome, proteome, and metabolome datasets. Matched cohorts of PiZZ participants on or off augmentation therapy, PiMZ participants not on augmentation therapy, and control participants from SPIROMICS who match on FEV1 and age will be compared. The primary analysis wil...

Bmc Bioinformatics, 2004

Background: Microarray studies in cancer compare expression levels between two or more sample gro... more Background: Microarray studies in cancer compare expression levels between two or more sample groups on thousands of genes. Data analysis follows a population-level approach (e.g., comparison of sample means) to identify differentially expressed genes. This leads to the discovery of 'population-level' markers, i.e., genes with the expression patterns A > B and B > A. We introduce the PPST test that identifies genes where a significantly large subset of cases exhibit expression values beyond upper and lower thresholds observed in the control samples.

Background: Shared Pathology Informatics Network (SPIN) is a tissue resource initiative that util... more Background: Shared Pathology Informatics Network (SPIN) is a tissue resource initiative that utilizes clinical reports of the vast amount of paraffin-embedded tissues routinely stored by medical centers. SPIN has an informatics component (sending tissue-related queries to multiple institutions via the internet) and a service component (providing histopathologically annotated tissue specimens for medical research). This paper examines if tissue blocks, identified by localized computer searches at participating institutions, can be retrieved in adequate quantity and quality to support medical researchers.

Background: Claudins are integral membrane proteins that are involved in forming cellular tight j... more Background: Claudins are integral membrane proteins that are involved in forming cellular tight junctions. One member of the claudin family, claudin-3, has been shown to be overexpressed in breast, ovarian, and pancreatic cancer. Here we use immunohistochemistry to evaluate its expression in benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN), normal tissue adjacent to prostatic adenocarcinoma (NAC), primary prostatic adenocarcinoma (PCa), and metastatic prostatic adenocarcinoma (Mets). Methods: Tissue microarrays were immunohistochemically stained for claudin-3, with the staining intensities subsequently quantified and statistically analyzed using a one-way ANOVA with subsequent Tukey tests for multiple comparisons or a nonparametric equivalent. Fifty-three cases of NAC, 17 cases of BPH, 35 cases of PIN, 107 cases of PCa, and 55 cases of Mets were analyzed in the microarrays.

Human Pathology, 2007

This report presents an overview for pathologists of the development and potential applications o... more This report presents an overview for pathologists of the development and potential applications of a novel Web enabled system allowing indexing and retrieval of pathology specimens across multiple institutions. The system was developed through the National Cancer Institute's Shared Pathology Informatics Network program with the goal of creating a prototype system to find existing pathology specimens derived from routine surgical and autopsy procedures ("paraffin blocks") that may be relevant to cancer research. To reach this goal, a number of challenges needed to be met. A central aspect was the development of an informatics system that supported Web-based searching while retaining local control of data. Additional aspects included the development of an eXtensible Markup Language schema, representation of tissue specimen annotation, methods for deidentifying pathology reports, tools for autocoding critical data from these reports using the Unified Medical Language System, and hierarchies of confidentiality and consent that met or exceeded federal requirements. The prototype system supported Web-based querying of millions of pathology reports from 6 participating institutions across the country in a matter of seconds to minutes and the ability of bona fide researchers to identify and potentially to request specific paraffin blocks from the participating institutions. With the addition of associated clinical and outcome information, this system could vastly expand the pool of annotated tissues available for cancer research as well as other diseases.

Lung Cancer International, 2013

The National Mesothelioma Virtual Bank (NMVB), developed six years ago, gathers clinically annota... more The National Mesothelioma Virtual Bank (NMVB), developed six years ago, gathers clinically annotated human mesothelioma specimens for basic and clinical science research. During this period, this resource has greatly increased its collection of specimens by expanding the number of contributing academic health centers including New . Marketing efforts at both national and international annual conferences increase awareness and availability of the mesothelioma specimens at no cost to approved investigators, who query the web-based NMVB database for cumulative and appropriate patient clinicopathological information on the specimens. The data disclosure and specimen distribution protocols are tightly regulated to maintain compliance with participating institutions' IRB and regulatory committee reviews. The NMVB currently has over 1120 annotated cases available for researchers, including paraffin embedded tissues, fresh frozen tissue, tissue microarrays (TMA), blood samples, and genomic DNA. In addition, the resource offers expertise and assistance for collaborative research. Furthermore, in the last six years, the resource has provided hundreds of specimens to the research community. The investigators can request specimens and/or data by submitting a Letter of Intent (LOI) that is evaluated by NMVB research evaluation panel (REP).

The Prostate, 2005

High rates of extracapsular tumor extension have been reported with biopsy perineural invasion (P... more High rates of extracapsular tumor extension have been reported with biopsy perineural invasion (PNI), leading some to advocate routine resection of the ipsilateral neurovascular bundle (NVB) with radical retropubic prostatectomy (RRP) to assure negative surgical margins. The contemporary rates of extracapsular tumor extension (ECE) and margin status associated with biopsy PNI were investigated. The prostate needle biopsies, RRP specimens, and operative reports of 452 consecutive patients undergoing RRP by a single surgeon were reviewed to determine the presence of PNI invasion, presence of ECE, margin status, and preservation of NVB. Patients were excluded from the analysis if they underwent preoperative hormonal ablation or if their original biopsy was not reviewed by the pathologists at our institution. Both univariate and multivariate analyses were performed to determine the effect of PNI on extracapsular extension, the likelihood of performing a bilateral nerve-sparing technique, and the result of a positive surgical margin. In the 402 evaluable cases, based on multivariate models PNI showed only a marginal association with positive surgical margin (+SM) (P = 0.10) and bilateral nerve-sparing (B-NS) (P = 0.07), but was significantly associated with organ confinement (P = 0.03). The odds ratio (OR) of PNI for +SM, although not statistically significant, was 0.36. Although showing a higher level of statistical significance, PNI for OC had an odds ratio of 0.50. Similarly, the odds ratio was 0.54 for B-NS. Although biopsy PNI alone was associated with a higher probability of ECE, it is not predictive of bilateral nerve-sparing technique or a positive surgical margin in an individual patient.

The Journal of Molecular Diagnostics, 2006

The effect of different amplification and labeling methods on DNA microarray expression results h... more The effect of different amplification and labeling methods on DNA microarray expression results has not been previously delineated. To analyze the variation associated with widely accepted T7-based RNA amplification and labeling methods, aliquots of the Stratagene Human Universal Reference RNA were labeled using three eukaryotic target preparation methods followed by uniform replicate array hybridization (Affymetrix U95Av2). Method-dependent variability was observed in the yield and size distribution of labeled products, as well as in the gene expression results. A significant increase in short transcripts, when compared to unamplified mRNA, was observed in methods with long in vitro transcription reactions. Intramethod reproducibility showed correlation coefficients >0.99, whereas intermethod comparisons showed coefficients ranging from 0.94 to 0.98 and a nearly twofold increase in coefficient of variation. Fold amplification for each method positively correlated with the number of genes present. Our experiments uncovered two factors that introduced significant bias in gene expression data: the number of labeled nucleotides, which introduces sequence-dependent bias, and the length of the in vitro transcription reaction, which introduces transcript size-dependent bias. This study provides evidence that variability in expression data may be caused, in part, by differences in amplification and labeling protocols

Neuropediatrics, 1992

A new lethal familial syndrome of unknown etiology is described in two male siblings who died in ... more A new lethal familial syndrome of unknown etiology is described in two male siblings who died in the newborn period. Both had corneal edema and were hypotonic, requiring assisted ventilation at birth. Neuropathological findings included an immature appearance of neocortical neurons, with cortical architecture similar to that normally seen in an infant of 5 months gestational age. Axons and myelin were absent in the cerebral and cerebellar white matter, and also in descending white matter tracts of brainstem and spinal cord. Subacute inflammation was seen in the anterior horns of the spinal cord in both cases, although there was no evidence of inflammation elsewhere in the nervous system. Electron microscopy of endothelial cells from brain, spinal cord and a number of other tissues of the second sibling showed tubuloreticular inclusions (TRIs). There are no known previous reports of similar neuropathology. Future recognition of this condition will be important for genetic counselling.

Molecular Diagnosis, 2000

The Journal of Urology, 1998

cells were situated basally and distributed focally, whereas pS3 positive cells were distributed ... more cells were situated basally and distributed focally, whereas pS3 positive cells were distributed relatively randomly. Heavy staining for bcl-2 was more apparent in well differentiated tumors, whereas p53 expression was more apparent in poorly differentiated tumors. The pathogenesis of these distinct types of malignancy and differences in glandular d-erentiation associated with differential expression of bcl-2 and p53 suggest the possibility of different pathways in malignant transformation according to cell lineage. Such distinctions may conceivably be invoked in designing different approaches to therapy. Michael J. Droller, M.D. The proliferation kinetics of 101 cases of transitional cell carcinoma (TCC) and seven cases of transitional cell carcinoma-in-situ of the bladder were assessed following staining with polyclonal Ki-67 antibody Labeling indices ranged from 49% to 60.2% with a mean value of 22.2% for all cases. A significant association between pKi-67 indices, tumor grade and tumor stage was observed, with significant differences between pKi-67 indices of Grade 1 and 3 tumors and Grade 2 and 3 tumors. Significant differences in labeling indices were also found between superficial (Ta) tumors and both musculoinvasive (T2PT3a) tumors and those infiltrating the penvesical fat (T3b). pKi-67 indices for carcinoma-in-situ were similar to those

The Journal of Urology, 2005

Purpose: Prostate cancer can occur in patients with low screening serum prostate specific antigen... more Purpose: Prostate cancer can occur in patients with low screening serum prostate specific antigen (PSA) values (less than 4.0 ng/ml). It is currently unclear whether these tumors are different from prostate cancer in patients with high PSA levels (greater than 4.0 ng/ml).

The Journal of Urology, 1996

Purpose: To investigate the clonal origin of malignant cells in recurrent superficial bladder can... more Purpose: To investigate the clonal origin of malignant cells in recurrent superficial bladder cancer.

Prostate cancer is the second most common cause of cancer deaths and is the most frequently detec... more Prostate cancer is the second most common cause of cancer deaths and is the most frequently detected form of cancer of males in the US. Death rate scan be greatly reduced by early treatment. Consequently, it is important to understand the cause and progression of this disease in order to improve detection and treatment methods. As part of the Cancer

Archives of Pathology & Laboratory Medicine, 2015

Context .- We define the scope and needs within the new discipline of computational pathology, a ... more Context .- We define the scope and needs within the new discipline of computational pathology, a discipline critical to the future of both the practice of pathology and, more broadly, medical practice in general. Objective .- To define the scope and needs of computational pathology. Data Sources .- A meeting was convened in Boston, Massachusetts, in July 2014 prior to the annual Association of Pathology Chairs meeting, and it was attended by a variety of pathologists, including individuals highly invested in pathology informatics as well as chairs of pathology departments. Conclusions .- The meeting made recommendations to promote computational pathology, including clearly defining the field and articulating its value propositions; asserting that the value propositions for health care systems must include means to incorporate robust computational approaches to implement data-driven methods that aid in guiding individual and population health care; leveraging computational pathology as a center for data interpretation in modern health care systems; stating that realizing the value proposition will require working with institutional administrations, other departments, and pathology colleagues; declaring that a robust pipeline should be fostered that trains and develops future computational pathologists, for those with both pathology and nonpathology backgrounds; and deciding that computational pathology should serve as a hub for data-related research in health care systems. The dissemination of these recommendations to pathology and bioinformatics departments should help facilitate the development of computational pathology.

Proceedings / AMIA ... Annual Symposium. AMIA Symposium, 2000

The development of the Multimedia Electronic Medical Record System (MEMRS) offers new opportuniti... more The development of the Multimedia Electronic Medical Record System (MEMRS) offers new opportunities for integrating medical imaging data with text-based clinical data. The effective integration of pathology images into the patient's medical record poses some significant technical and organizational challenges. Before these challenges can be met, it is imperative that we investigate the value and utility of providing these images to clinicians. In this study we examined attitudes towards use of pathology images in Image Engine, a MEMRS under development at the University of Pittsburgh Cancer Institute (UPCI). We conducted semi-structured standardized interviews with a cohort of practicing oncologists, all of whom had significant experience with Image Engine. This study is a first step towards elucidating the potential barriers, uses, and value of anatomic pathology images in the MEMRS.

Cancer research, 1996

The early diagnosis of bladder cancer is central to the effective treatment of the disease. Prese... more The early diagnosis of bladder cancer is central to the effective treatment of the disease. Presently, there are no methods available to easily and specifically identify the presence of bladder cancer cells. The prevailing method for the detection of bladder cancer is the identification of bladder cancer cells by morphological examination of exfoliated cells or biopsy material by a pathologist. A hallmark of the malignant or transformed phenotype is an abnormal nuclear shape, the presence of multiple nucleoli, and altered patterns of chromatin organization. Nuclear structural alterations are so prevalent in cancer cells that they are commonly used as markers of transformation for many types of cancer. Nuclear shape is determined by the nuclear matrix, the dynamic skeleton of the nucleus. The nuclear matrix is the structural component of the nucleus that determines nuclear morphology, organizes the DNA in a three-dimensional fashion that is tissue specific, and has a central role in ...

Essentials of Anatomic Pathology, 2010

Biomedical informatics has made a deep impact in the overall workflow of the surgical pathology p... more Biomedical informatics has made a deep impact in the overall workflow of the surgical pathology practice and has provided a variety of software tools that accelerate the overall turnaround time, cost effectiveness, and accuracy of information. Laboratory Information System functions as a single comprehensive piece of software managing laboratory workflow, reporting, and billing. Related technologies, such as digital imaging, whole

Human pathology, 2004

As academic pathology departments have become increasingly based in large, regional medical syste... more As academic pathology departments have become increasingly based in large, regional medical systems spread across hundreds of square miles, new methods are needed to tie these increasingly distributed departments together as integrated units. An important part of that integration is the ability to share academic and teaching conferences across long distances. In this article we present an effective, low-cost webcasting system that has evolved at the University of Pittsburgh Medical Center Department of Pathology over the past several years based on inexpensive, widely available software. To date, the system has broadcast and archived more than 400 conferences and currently serves approximately 80 to 100 requests each week. Important factors in the success of the program include the creation of a faculty steering committee to control resources and manage growth, the availability of informatics faculty and support for technical staff, and the decision to operate the service as part of...

Annals of the American Thoracic Society, Jan 8, 2015

Severe deficiency of alpha-1 antitrypsin has a highly variable clinical presentation. The GRADS A... more Severe deficiency of alpha-1 antitrypsin has a highly variable clinical presentation. The GRADS Alpha-1 Study is a prospective, multicenter, cross-sectional, study of adults > age 35 with PiZZ or PiMZ alpha-1 antitrypsin genotypes designed to better understand if microbial factors influence this heterogeneity. Clinical symptoms, pulmonary function testing, computed chest tomography, exercise capacity, and bronchoalveolar lavage (BAL) will be used to define COPD phenotypes that can be studied with an integrated systems biology approach that includes plasma proteomics; mouth, BAL, and stool microbiome and virome analysis; blood miRNA, and blood mononuclear cell RNA and DNA profiling, and relies on global genome, transcriptome, proteome, and metabolome datasets. Matched cohorts of PiZZ participants on or off augmentation therapy, PiMZ participants not on augmentation therapy, and control participants from SPIROMICS who match on FEV1 and age will be compared. The primary analysis wil...

Bmc Bioinformatics, 2004

Background: Microarray studies in cancer compare expression levels between two or more sample gro... more Background: Microarray studies in cancer compare expression levels between two or more sample groups on thousands of genes. Data analysis follows a population-level approach (e.g., comparison of sample means) to identify differentially expressed genes. This leads to the discovery of 'population-level' markers, i.e., genes with the expression patterns A > B and B > A. We introduce the PPST test that identifies genes where a significantly large subset of cases exhibit expression values beyond upper and lower thresholds observed in the control samples.

Background: Shared Pathology Informatics Network (SPIN) is a tissue resource initiative that util... more Background: Shared Pathology Informatics Network (SPIN) is a tissue resource initiative that utilizes clinical reports of the vast amount of paraffin-embedded tissues routinely stored by medical centers. SPIN has an informatics component (sending tissue-related queries to multiple institutions via the internet) and a service component (providing histopathologically annotated tissue specimens for medical research). This paper examines if tissue blocks, identified by localized computer searches at participating institutions, can be retrieved in adequate quantity and quality to support medical researchers.

Background: Claudins are integral membrane proteins that are involved in forming cellular tight j... more Background: Claudins are integral membrane proteins that are involved in forming cellular tight junctions. One member of the claudin family, claudin-3, has been shown to be overexpressed in breast, ovarian, and pancreatic cancer. Here we use immunohistochemistry to evaluate its expression in benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN), normal tissue adjacent to prostatic adenocarcinoma (NAC), primary prostatic adenocarcinoma (PCa), and metastatic prostatic adenocarcinoma (Mets). Methods: Tissue microarrays were immunohistochemically stained for claudin-3, with the staining intensities subsequently quantified and statistically analyzed using a one-way ANOVA with subsequent Tukey tests for multiple comparisons or a nonparametric equivalent. Fifty-three cases of NAC, 17 cases of BPH, 35 cases of PIN, 107 cases of PCa, and 55 cases of Mets were analyzed in the microarrays.

Human Pathology, 2007

This report presents an overview for pathologists of the development and potential applications o... more This report presents an overview for pathologists of the development and potential applications of a novel Web enabled system allowing indexing and retrieval of pathology specimens across multiple institutions. The system was developed through the National Cancer Institute's Shared Pathology Informatics Network program with the goal of creating a prototype system to find existing pathology specimens derived from routine surgical and autopsy procedures ("paraffin blocks") that may be relevant to cancer research. To reach this goal, a number of challenges needed to be met. A central aspect was the development of an informatics system that supported Web-based searching while retaining local control of data. Additional aspects included the development of an eXtensible Markup Language schema, representation of tissue specimen annotation, methods for deidentifying pathology reports, tools for autocoding critical data from these reports using the Unified Medical Language System, and hierarchies of confidentiality and consent that met or exceeded federal requirements. The prototype system supported Web-based querying of millions of pathology reports from 6 participating institutions across the country in a matter of seconds to minutes and the ability of bona fide researchers to identify and potentially to request specific paraffin blocks from the participating institutions. With the addition of associated clinical and outcome information, this system could vastly expand the pool of annotated tissues available for cancer research as well as other diseases.

Lung Cancer International, 2013

The National Mesothelioma Virtual Bank (NMVB), developed six years ago, gathers clinically annota... more The National Mesothelioma Virtual Bank (NMVB), developed six years ago, gathers clinically annotated human mesothelioma specimens for basic and clinical science research. During this period, this resource has greatly increased its collection of specimens by expanding the number of contributing academic health centers including New . Marketing efforts at both national and international annual conferences increase awareness and availability of the mesothelioma specimens at no cost to approved investigators, who query the web-based NMVB database for cumulative and appropriate patient clinicopathological information on the specimens. The data disclosure and specimen distribution protocols are tightly regulated to maintain compliance with participating institutions' IRB and regulatory committee reviews. The NMVB currently has over 1120 annotated cases available for researchers, including paraffin embedded tissues, fresh frozen tissue, tissue microarrays (TMA), blood samples, and genomic DNA. In addition, the resource offers expertise and assistance for collaborative research. Furthermore, in the last six years, the resource has provided hundreds of specimens to the research community. The investigators can request specimens and/or data by submitting a Letter of Intent (LOI) that is evaluated by NMVB research evaluation panel (REP).

The Prostate, 2005

High rates of extracapsular tumor extension have been reported with biopsy perineural invasion (P... more High rates of extracapsular tumor extension have been reported with biopsy perineural invasion (PNI), leading some to advocate routine resection of the ipsilateral neurovascular bundle (NVB) with radical retropubic prostatectomy (RRP) to assure negative surgical margins. The contemporary rates of extracapsular tumor extension (ECE) and margin status associated with biopsy PNI were investigated. The prostate needle biopsies, RRP specimens, and operative reports of 452 consecutive patients undergoing RRP by a single surgeon were reviewed to determine the presence of PNI invasion, presence of ECE, margin status, and preservation of NVB. Patients were excluded from the analysis if they underwent preoperative hormonal ablation or if their original biopsy was not reviewed by the pathologists at our institution. Both univariate and multivariate analyses were performed to determine the effect of PNI on extracapsular extension, the likelihood of performing a bilateral nerve-sparing technique, and the result of a positive surgical margin. In the 402 evaluable cases, based on multivariate models PNI showed only a marginal association with positive surgical margin (+SM) (P = 0.10) and bilateral nerve-sparing (B-NS) (P = 0.07), but was significantly associated with organ confinement (P = 0.03). The odds ratio (OR) of PNI for +SM, although not statistically significant, was 0.36. Although showing a higher level of statistical significance, PNI for OC had an odds ratio of 0.50. Similarly, the odds ratio was 0.54 for B-NS. Although biopsy PNI alone was associated with a higher probability of ECE, it is not predictive of bilateral nerve-sparing technique or a positive surgical margin in an individual patient.

The Journal of Molecular Diagnostics, 2006

The effect of different amplification and labeling methods on DNA microarray expression results h... more The effect of different amplification and labeling methods on DNA microarray expression results has not been previously delineated. To analyze the variation associated with widely accepted T7-based RNA amplification and labeling methods, aliquots of the Stratagene Human Universal Reference RNA were labeled using three eukaryotic target preparation methods followed by uniform replicate array hybridization (Affymetrix U95Av2). Method-dependent variability was observed in the yield and size distribution of labeled products, as well as in the gene expression results. A significant increase in short transcripts, when compared to unamplified mRNA, was observed in methods with long in vitro transcription reactions. Intramethod reproducibility showed correlation coefficients >0.99, whereas intermethod comparisons showed coefficients ranging from 0.94 to 0.98 and a nearly twofold increase in coefficient of variation. Fold amplification for each method positively correlated with the number of genes present. Our experiments uncovered two factors that introduced significant bias in gene expression data: the number of labeled nucleotides, which introduces sequence-dependent bias, and the length of the in vitro transcription reaction, which introduces transcript size-dependent bias. This study provides evidence that variability in expression data may be caused, in part, by differences in amplification and labeling protocols

Neuropediatrics, 1992

A new lethal familial syndrome of unknown etiology is described in two male siblings who died in ... more A new lethal familial syndrome of unknown etiology is described in two male siblings who died in the newborn period. Both had corneal edema and were hypotonic, requiring assisted ventilation at birth. Neuropathological findings included an immature appearance of neocortical neurons, with cortical architecture similar to that normally seen in an infant of 5 months gestational age. Axons and myelin were absent in the cerebral and cerebellar white matter, and also in descending white matter tracts of brainstem and spinal cord. Subacute inflammation was seen in the anterior horns of the spinal cord in both cases, although there was no evidence of inflammation elsewhere in the nervous system. Electron microscopy of endothelial cells from brain, spinal cord and a number of other tissues of the second sibling showed tubuloreticular inclusions (TRIs). There are no known previous reports of similar neuropathology. Future recognition of this condition will be important for genetic counselling.

Molecular Diagnosis, 2000

The Journal of Urology, 1998

cells were situated basally and distributed focally, whereas pS3 positive cells were distributed ... more cells were situated basally and distributed focally, whereas pS3 positive cells were distributed relatively randomly. Heavy staining for bcl-2 was more apparent in well differentiated tumors, whereas p53 expression was more apparent in poorly differentiated tumors. The pathogenesis of these distinct types of malignancy and differences in glandular d-erentiation associated with differential expression of bcl-2 and p53 suggest the possibility of different pathways in malignant transformation according to cell lineage. Such distinctions may conceivably be invoked in designing different approaches to therapy. Michael J. Droller, M.D. The proliferation kinetics of 101 cases of transitional cell carcinoma (TCC) and seven cases of transitional cell carcinoma-in-situ of the bladder were assessed following staining with polyclonal Ki-67 antibody Labeling indices ranged from 49% to 60.2% with a mean value of 22.2% for all cases. A significant association between pKi-67 indices, tumor grade and tumor stage was observed, with significant differences between pKi-67 indices of Grade 1 and 3 tumors and Grade 2 and 3 tumors. Significant differences in labeling indices were also found between superficial (Ta) tumors and both musculoinvasive (T2PT3a) tumors and those infiltrating the penvesical fat (T3b). pKi-67 indices for carcinoma-in-situ were similar to those

The Journal of Urology, 2005

Purpose: Prostate cancer can occur in patients with low screening serum prostate specific antigen... more Purpose: Prostate cancer can occur in patients with low screening serum prostate specific antigen (PSA) values (less than 4.0 ng/ml). It is currently unclear whether these tumors are different from prostate cancer in patients with high PSA levels (greater than 4.0 ng/ml).

The Journal of Urology, 1996

Purpose: To investigate the clonal origin of malignant cells in recurrent superficial bladder can... more Purpose: To investigate the clonal origin of malignant cells in recurrent superficial bladder cancer.