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Article ; Online: Amelioration of Diabetic Nephropathy Using a Retinoic Acid Receptor

Trasino, Steven E / Tang, Xiao-Han / Shevchuk, Maria M / Choi, Mary E / Gudas, Lorraine J

The Journal of pharmacology and experimental therapeutics

2018 Volume 367, Issue 1, Page(s) 82–94

Abstract: Vitamin A (VA) and its derivatives, known as retinoids, play critical roles in renal development through retinoic acid ... ...

Abstract	Vitamin A (VA) and its derivatives, known as retinoids, play critical roles in renal development through retinoic acid receptor
MeSH term(s)	Actins/metabolism ; Animals ; Benzoates/pharmacology ; Collagen Type IV/metabolism ; Diabetic Nephropathies/drug therapy ; Diabetic Nephropathies/metabolism ; Diet, High-Fat/adverse effects ; Endothelial Cells/drug effects ; Endothelial Cells/metabolism ; Glomerular Basement Membrane/drug effects ; Glomerular Basement Membrane/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Myofibroblasts/drug effects ; Myofibroblasts/metabolism ; Podocytes/drug effects ; Podocytes/metabolism ; Proteinuria/drug therapy ; Proteinuria/metabolism ; Receptors, Retinoic Acid/agonists ; Thiazoles/pharmacology
Chemical Substances	4-(4-(2-(n-butoxy)ethoxy)-5-methylthiazol-2-yl)-2-fluorobenzoic acid ; Actins ; Benzoates ; Collagen Type IV ; Receptors, Retinoic Acid ; Thiazoles ; retinoic acid receptor beta2, mouse
Language	English
Publishing date	2018-07-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3106-9
ISSN	1521-0103 ; 0022-3565
ISSN (online)	1521-0103
ISSN	0022-3565
DOI	10.1124/jpet.118.249375
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Article ; Online: Multiphoton microscopy for rapid histopathological evaluation of kidney tumours.

Jain, Manu / Robinson, Brian D / Aggarwal, Amit / Shevchuk, Maria M / Scherr, Douglas S / Mukherjee, Sushmita

BJU international

2016 Volume 118, Issue 1, Page(s) 118–126

Abstract: Objective: To explore the potential of multiphoton microscopy (MPM) for rapid evaluation and triaging of ex vivo kidney tissue.: Materials and methods: Fresh neoplastic and non-neoplastic tissues from nephrectomy specimens (n = 40) were imaged with ... ...

Abstract	Objective: To explore the potential of multiphoton microscopy (MPM) for rapid evaluation and triaging of ex vivo kidney tissue. Materials and methods: Fresh neoplastic and non-neoplastic tissues from nephrectomy specimens (n = 40) were imaged with MPM and later submitted for routine histopathology. Results: On MPM, normal kidney architecture was evident and clearly distinguishable from tumour. Forty malignant tumours (20 clear-cell renal cell carcinomas [RCCs], 10 papillary RCCs, five chromophobe RCCs and five papillary urothelial carcinomas [UCs], as diagnosed by haematoxylin and eosin staining) were imaged and subtyped as non-papillary and papillary, based on their architecture. Non-papillary tumours were further classified based on their unique cytoplasmic signatures. Clear-cell RCCs had a predominant population of cells with fat droplets in cytoplasm. Chromophobe RCCs had cells with non-fatty/homogeneous cytoplasm and distinct intra-cytoplasmic granules. Papillary RCCs had single-cell-lined papillae with often abundant histiocytes in their core, whereas PUC had multi-layered urothelium-lined papillae. The diagnostic accuracy of tumour subtyping by two independent uropathologists was 95%. Conclusions: We showed that MPM can reliably differentiate neoplastic from non-neoplastic kidney tissue and subtype kidney tumours in fresh, unprocessed tissue, MPM might therefore be useful as a rapid real-time diagnostic tool for the evaluation of kidney biopsies, and surgical margins in partial nephrectomies, to improve overall patient management.
MeSH term(s)	Carcinoma, Renal Cell/pathology ; Humans ; Kidney Neoplasms/pathology ; Microscopy, Fluorescence, Multiphoton ; Time Factors
Language	English
Publishing date	2016-07
Publishing country	England
Document type	Journal Article
ZDB-ID	1462191-5
ISSN	1464-410X ; 1464-4096 ; 1358-8672
ISSN (online)	1464-410X
ISSN	1464-4096 ; 1358-8672
DOI	10.1111/bju.13377
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Article ; Online: In Vivo and Ex Vivo Microscopy: A Business Plan to Justify the Introduction of Similar Emerging Technologies Into Pathology Practice.

Wells, Wendy A / Harhen, Michael T / Thrall, Michael J / Shevchuk, Maria M / Tearney, Guillermo J / Hariri, Lida P

Archives of pathology & laboratory medicine

2018 Volume 143, Issue 3, Page(s) 299–304

Abstract: Context.—: Our patients are now demanding value for their medical diagnoses and treatment in terms of optimal costs, quality, and outcomes. The financial justification for the introduction of new emerging technologies that may better meet these needs ... ...

Abstract	Context.—: Our patients are now demanding value for their medical diagnoses and treatment in terms of optimal costs, quality, and outcomes. The financial justification for the introduction of new emerging technologies that may better meet these needs will depend on many factors, even if there is an established reimbursement code. In vivo and ex vivo microscopic technologies (IVM and EVM, respectively) will be used as examples of potentially transforming technologies. Objective.—: To describe the components of a business plan that ensures all of the ramifications of introducing a new technology into pathology practice have been considered. As well as the financial justification, such a plan should include strategic vision and congruence, the advantages and drawbacks of introducing such technology, and how plans for marketing, implementation, and verification can be operationalized. Data sources.—: Unlike many pathologists, administrative directors in clinical laboratories already know the components of a financially sound business plan. In addition to the financial justifications, other considerations of such a plan include expense reductions, multiyear buildups in revenue generation, the replacement of other technologies, improved productivity and workflows, additional space, new capital, retrained personnel, and the impact on other departments. Conclusions.—: Pathologists will learn a business plan format to improve their confidence in making the sound financial justifications needed to consider the introduction of an emerging technology into pathology practice, even when there is initially no obvious revenue stream because formal reimbursement codes have not been established.
MeSH term(s)	Commerce/economics ; Commerce/methods ; Commerce/organization & administration ; Humans ; Microscopy/economics ; Microscopy/methods ; Pathology/economics ; Pathology/methods ; Pathology/organization & administration
Language	English
Publishing date	2018-12-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	194119-7
ISSN	1543-2165 ; 0363-0153 ; 0096-8528 ; 0003-9985
ISSN (online)	1543-2165
ISSN	0363-0153 ; 0096-8528 ; 0003-9985
DOI	10.5858/arpa.2018-0375-RA
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Article: Role of NADH Dehydrogenase (Ubiquinone) 1 Alpha Subcomplex 4-Like 2 in Clear Cell Renal Cell Carcinoma.

Minton, Denise R / Fu, Leiping / Mongan, Nigel P / Shevchuk, Maria M / Nanus, David M / Gudas, Lorraine J

Clinical cancer research : an official journal of the American Association for Cancer Research

2016 Volume 22, Issue 11, Page(s) 2791–2801

Abstract: Purpose: We delineated the functions of the hypoxia-inducible factor-1α (HIF1α) target NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4-like 2 (NDUFA4L2) in clear cell renal cell carcinoma (ccRCC) and characterized NDUFA4L2 as a novel molecular ... ...

Abstract	Purpose: We delineated the functions of the hypoxia-inducible factor-1α (HIF1α) target NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4-like 2 (NDUFA4L2) in clear cell renal cell carcinoma (ccRCC) and characterized NDUFA4L2 as a novel molecular target for ccRCC treatment. Experimental design: We evaluated normal kidney and ccRCC patient microarray and RNAseq data from Oncomine and The Cancer Genome Atlas for NDUFA4L2 mRNA levels and the clinical implications of high NDUFA4L2 expression. In addition, we examined normal kidney and ccRCC patient tissue samples, human ccRCC cell lines, and murine models of ccRCC for NDUFA4L2 mRNA and protein expression. Utilizing short hairpin RNA, we performed NDUFA4L2 knockdown experiments and analyzed the proliferation, clonogenicity, metabolite levels, cell structure, and autophagy in ccRCC cell lines in culture. Results: We found that NDUFA4L2 mRNA and protein are highly expressed in ccRCC samples but undetectable in normal kidney tissue samples, and that NDUFA4L2 mRNA expression correlates with tumor stage and lower overall survival. In addition, we demonstrated that NDUFA4L2 is an HIF1α target in ccRCC and that NDUFA4L2 knockdown has a profound antiproliferative effect, alters metabolic pathways, and causes major stress in cultured RCC cells. Conclusions: Collectively, our data show that NDUFA4L2 is a novel molecular target for ccRCC treatment. Clin Cancer Res; 22(11); 2791-801. ©2016 AACR.
MeSH term(s)	Animals ; Autophagy ; Carcinoma, Renal Cell/enzymology ; Carcinoma, Renal Cell/pathology ; Cell Line, Tumor ; Cell Proliferation ; Electron Transport Complex I/physiology ; Gene Expression ; Gene Knockdown Techniques ; Kidney Neoplasms/enzymology ; Kidney Neoplasms/pathology ; Male ; Metabolic Networks and Pathways ; Mice, Inbred C57BL ; Mice, Transgenic ; Mitochondria/enzymology ; Mitochondria/pathology
Chemical Substances	NDUFA4L2 protein, human ; Electron Transport Complex I (EC 1.6.5.3)
Language	English
Publishing date	2016-01-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-15-1511
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Article ; Online: Activation of HIF2α in kidney proximal tubule cells causes abnormal glycogen deposition but not tumorigenesis.

Fu, Leiping / Wang, Gang / Shevchuk, Maria M / Nanus, David M / Gudas, Lorraine J

Cancer research

2013 Volume 73, Issue 9, Page(s) 2916–2925

Abstract: Renal cell carcinoma (RCC) is the most common primary cancer arising from the kidney in adults, with clear cell renal cell carcinoma (ccRCC) representing approximately 75% of all RCCs. Increased expression of the hypoxia-induced factors-1α (HIF1α) and ... ...

Abstract	Renal cell carcinoma (RCC) is the most common primary cancer arising from the kidney in adults, with clear cell renal cell carcinoma (ccRCC) representing approximately 75% of all RCCs. Increased expression of the hypoxia-induced factors-1α (HIF1α) and HIF2α has been suggested as a pivotal step in ccRCC carcinogenesis, but this has not been thoroughly tested. Here, we report that expression of a constitutively activated form of HIF2α (P405A, P530A, and N851A, named as HIF2αM3) in the proximal tubules of mice is not sufficient to promote ccRCC by itself, nor does it enhance HIF1αM3 oncogenesis when coexpressed with constitutively active HIF1αM3. Neoplastic transformation in kidneys was not detected at up to 33 months of age, nor was increased expression of Ki67 (MKI67), γH2AX (H2AFX), or CD70 observed. Furthermore, the genome-wide transcriptome of the transgenic kidneys does not resemble human ccRCC. We conclude that a constitutively active HIF2α is not sufficient to cause neoplastic transformation of proximal tubules, arguing against the idea that HIF2α activation is critical for ccRCC tumorigenesis.
MeSH term(s)	Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Carcinoma, Renal Cell/metabolism ; Cell Proliferation ; Cell Transformation, Neoplastic ; Gene Expression Regulation, Neoplastic ; Glycogen/metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Kidney/metabolism ; Kidney Neoplasms/metabolism ; Kidney Tubules/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mutation
Chemical Substances	Basic Helix-Loop-Helix Transcription Factors ; Hif1a protein, mouse ; Hypoxia-Inducible Factor 1, alpha Subunit ; endothelial PAS domain-containing protein 1 (1B37H0967P) ; Glycogen (9005-79-2)
Language	English
Publishing date	2013-02-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-12-3983
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Article ; Online: In Vivo and Ex Vivo Microscopy: Moving Toward the Integration of Optical Imaging Technologies Into Pathology Practice.

Wells, Wendy A / Thrall, Michael / Sorokina, Anastasia / Fine, Jeffrey / Krishnamurthy, Savitri / Haroon, Attiya / Rao, Babar / Shevchuk, Maria M / Wolfsen, Herbert C / Tearney, Guillermo J / Hariri, Lida P

Archives of pathology & laboratory medicine

2018 Volume 143, Issue 3, Page(s) 288–298

Abstract: The traditional surgical pathology assessment requires tissue to be removed from the patient, then processed, sectioned, stained, and interpreted by a pathologist using a light microscope. Today, an array of alternate optical imaging technologies allow ... ...

Abstract	The traditional surgical pathology assessment requires tissue to be removed from the patient, then processed, sectioned, stained, and interpreted by a pathologist using a light microscope. Today, an array of alternate optical imaging technologies allow tissue to be viewed at high resolution, in real time, without the need for processing, fixation, freezing, or staining. Optical imaging can be done in living patients without tissue removal, termed in vivo microscopy, or also in freshly excised tissue, termed ex vivo microscopy. Both in vivo and ex vivo microscopy have tremendous potential for clinical impact in a wide variety of applications. However, in order for these technologies to enter mainstream clinical care, an expert will be required to assess and interpret the imaging data. The optical images generated from these imaging techniques are often similar to the light microscopic images that pathologists already have expertise in interpreting. Other clinical specialists do not have this same expertise in microscopy, therefore, pathologists are a logical choice to step into the developing role of microscopic imaging expert. Here, we review the emerging technologies of in vivo and ex vivo microscopy in terms of the technical aspects and potential clinical applications. We also discuss why pathologists are essential to the successful clinical adoption of such technologies and the educational resources available to help them step into this emerging role.
MeSH term(s)	Aged ; Diagnostic Imaging/methods ; Female ; Humans ; Image Interpretation, Computer-Assisted/methods ; Male ; Microscopy/methods ; Middle Aged ; Optical Imaging/methods ; Pathology, Surgical/methods
Language	English
Publishing date	2018-12-10
Publishing country	United States
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	194119-7
ISSN	1543-2165 ; 0363-0153 ; 0096-8528 ; 0003-9985
ISSN (online)	1543-2165
ISSN	0363-0153 ; 0096-8528 ; 0003-9985
DOI	10.5858/arpa.2018-0298-RA
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Article ; Online: Multiphoton microscopy: a potential intraoperative tool for the detection of carcinoma in situ in human bladder.

Jain, Manu / Robinson, Brian D / Shevchuk, Maria M / Aggarwal, Amit / Salamoon, Bekheit / Dubin, Justin M / Scherr, Douglas S / Mukherjee, Sushmita

Archives of pathology & laboratory medicine

2015 Volume 139, Issue 6, Page(s) 796–804

Abstract: Context: Urothelial carcinoma in situ (CIS) is a precursor of invasive bladder cancer, which if left untreated, will likely progress to more aggressive disease. Approximately 50% of CIS lesions are missed on routine cystoscopy owing to their flat ... ...

Abstract	Context: Urothelial carcinoma in situ (CIS) is a precursor of invasive bladder cancer, which if left untreated, will likely progress to more aggressive disease. Approximately 50% of CIS lesions are missed on routine cystoscopy owing to their flat architecture. Furthermore, many benign but abnormal-appearing areas may be biopsied owing to lack of cellular resolution of cystoscopes. Multiphoton microscopy (MPM) is an optical imaging technique that generates subcellular-resolution three-dimensional images from unfixed tissue without using exogenous dyes. Objective: To assess the diagnostic potential of MPM in identifying and differentiating benign from malignant flat bladder lesions, especially CIS. Design: Seventy-eight specimens (benign = 46, CIS = 23, invasive = 9, as diagnosed on histopathology) were obtained from flat bladder mucosa via transurethral resection of bladder, cold cup biopsy, or cystectomy, imaged fresh with a commercial benchtop MPM, and submitted for routine histopathology. Multiphoton microscopy and hematoxylin-eosin diagnoses were compared. Results: In 77 of 78 specimens (99%), accurate MPM diagnoses (benign/malignant) were given on the basis of their architectural and cytologic features (nuclear to cytoplasmic ratio, pleomorphism, polarity/organization of urothelial layers, etc). The sensitivity and specificity were 97% and 100%, respectively, with positive (malignant) and negative (benign) predictive values of 100% and 98%, respectively. The interobserver agreement, κ, was 0.93. Conclusions: Our study demonstrates the capability of MPM to identify and differentiate benign from malignant flat bladder lesions, especially CIS. With the advent of MPM endoscopes, we foresee their potential as a biopsy guidance tool for early detection and treatment of CIS, thus reducing the rate of biopsies with benign diagnoses and their associated complications.
MeSH term(s)	Adult ; Carcinoma in Situ/diagnosis ; Carcinoma, Transitional Cell/diagnosis ; Cohort Studies ; Female ; Histocytochemistry ; Humans ; Male ; Microscopy, Fluorescence, Multiphoton/methods ; Monitoring, Intraoperative/instrumentation ; Reproducibility of Results ; Sensitivity and Specificity ; Single-Blind Method ; Urinary Bladder/pathology ; Urinary Bladder Neoplasms/diagnosis
Language	English
Publishing date	2015-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	194119-7
ISSN	1543-2165 ; 0363-0153 ; 0096-8528 ; 0003-9985
ISSN (online)	1543-2165
ISSN	0363-0153 ; 0096-8528 ; 0003-9985
DOI	10.5858/arpa.2014-0076-OA
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Article ; Online: Proliferative extensor tenosynovitis of the wrist in the absence of rheumatoid arthritis.

Cooper, H John / Shevchuk, Maria M / Li, Xiaosong / Yang, S Steven

The Journal of hand surgery

2009 Volume 34, Issue 10, Page(s) 1827–1831

Abstract: Purpose: Proliferative tenosynovitis in the fourth extensor compartment is common in patients with rheumatoid arthritis. It may also occur in the absence of rheumatoid arthritis; the purpose of this study is to describe this clinical condition in a ... ...

Abstract	Purpose: Proliferative tenosynovitis in the fourth extensor compartment is common in patients with rheumatoid arthritis. It may also occur in the absence of rheumatoid arthritis; the purpose of this study is to describe this clinical condition in a series of patients, to report the results of surgical intervention, and to compare histological findings to those typically seen in rheumatoid tenosynovitis. Methods: This study presents a retrospective case series of 11 patients who do not have rheumatoid arthritis, who had proliferative tenosynovitis of the fourth extensor compartment treated surgically. Relevant features of the clinical presentation, physical examination, radiographic findings, and results of attempts at conservative treatment are described. Surgical pathology specimens were reviewed by a single pathologist to define common histological features and to compare the histology to that which is classically seen in rheumatoid tenosynovitis. Results: All patients presented with a painful wrist mass over the fourth extensor compartment. Characteristic in physical examination was severe limitation of active wrist extension with the fingers extended, with improvement when the fingers were flexed into a fist. After tenosynovectomy, wrist extension and grip strength improved. Examination of the surgical pathology specimens revealed a spectrum of pathological findings generally consistent with traumatic tenosynovitis, but a few specimens had rheumatoid-like features. Conclusions: A review of this case series of patients with tenosynovitis but without rheumatoid arthritis demonstrates a distinct clinical condition of exuberant proliferative extensor tenosynovitis blocking proximal tendon excursion, thereby causing pain and limited active wrist extension, as well as a less distinct histological condition with a constellation of findings generally resembling traumatic tenosynovitis. In this group of patients, surgical tenosynovectomy generally yields excellent results. Type of study/level of evidence: Therapeutic IV.
MeSH term(s)	Adult ; Aged ; Arthritis, Rheumatoid/pathology ; Arthritis, Rheumatoid/surgery ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Hand Strength/physiology ; Humans ; Male ; Middle Aged ; Postoperative Complications/physiopathology ; Range of Motion, Articular/physiology ; Retrospective Studies ; Synovectomy ; Synovial Membrane/pathology ; Tendon Entrapment/diagnosis ; Tendon Entrapment/pathology ; Tendon Entrapment/surgery ; Wrist/pathology ; Wrist/surgery
Language	English
Publishing date	2009-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	605716-0
ISSN	1531-6564 ; 0363-5023
ISSN (online)	1531-6564
ISSN	0363-5023
DOI	10.1016/j.jhsa.2009.08.006
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Article ; Online: Generation of a mouse model of Von Hippel-Lindau kidney disease leading to renal cancers by expression of a constitutively active mutant of HIF1α.

Fu, Leiping / Wang, Gang / Shevchuk, Maria M / Nanus, David M / Gudas, Lorraine J

Cancer research

2011 Volume 71, Issue 21, Page(s) 6848–6856

Abstract: Renal cancers are highly aggressive and clinically challenging, but a transgenic mouse model to promote pathologic studies and therapeutic advances has yet to be established. Here, we report the generation of a transgenic mouse model of von Hippel-Lindau ...

Abstract	Renal cancers are highly aggressive and clinically challenging, but a transgenic mouse model to promote pathologic studies and therapeutic advances has yet to be established. Here, we report the generation of a transgenic mouse model of von Hippel-Lindau (VHL) renal cancer termed the TRACK model (transgenic model of cancer of the kidney). TRACK mice specifically express a mutated, constitutively active HIF1α in kidney proximal tubule (PT) cells. Kidney histologies displayed by TRACK mice are highly similar to histologies seen in patients with VHL disease, including areas of distorted tubular structure, cells with clear cytoplasm and increased glycogen and lipid deposition, multiple renal cysts, and early onset of clear cell renal cell carcinoma (ccRCC). Distorted tubules in TRACK mice exhibit higher levels of CA-IX, Glut1, and VEGF than tubules in nontransgenic control mice. Furthermore, these tubules exhibit increased numbers of endothelial cells, increased cell proliferation, and increased expression of the human ccRCC marker CD70(TNFSF7). Moreover, PT cells in kidney tubules from TRACK mice exhibit increased genomic instability, as monitored by elevated levels of γH2AX. Our findings establish that activated HIF1α in murine kidney PT cells is sufficient to promote cell proliferation, angiogenesis, genomic instability, and other phenotypic alterations characteristic of human VHL kidney disease, establishing the TRACK mouse as a valid preclinical model of human renal cell carcinoma.
MeSH term(s)	Amino Acid Substitution ; Animals ; Biomarkers, Tumor/biosynthesis ; Carcinoma, Renal Cell/genetics ; Carcinoma, Renal Cell/pathology ; Cell Division ; Cell Hypoxia ; Disease Models, Animal ; Genomic Instability/genetics ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/chemistry ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Hypoxia-Inducible Factor 1, alpha Subunit/physiology ; Kidney Diseases, Cystic/genetics ; Kidney Diseases, Cystic/pathology ; Kidney Neoplasms/genetics ; Kidney Neoplasms/pathology ; Kidney Tubules, Proximal/metabolism ; Kidney Tubules, Proximal/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mutagenesis, Site-Directed ; Neovascularization, Pathologic/genetics ; Neovascularization, Pathologic/pathology ; Promoter Regions, Genetic ; Recombinant Fusion Proteins/physiology ; Structure-Activity Relationship ; Up-Regulation/genetics ; gamma-Glutamyltransferase/genetics ; von Hippel-Lindau Disease/genetics ; von Hippel-Lindau Disease/pathology
Chemical Substances	Biomarkers, Tumor ; Hypoxia-Inducible Factor 1, alpha Subunit ; Recombinant Fusion Proteins ; gamma-Glutamyltransferase (EC 2.3.2.2)
Language	English
Publishing date	2011-09-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-11-1745
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Article ; Online: Predictive models for worsening prognosis in potential candidates for active surveillance of presumed low-risk prostate cancer.

Sooriakumaran, Prasanna / Srivastava, Abhishek / Christos, Paul / Grover, Sonal / Shevchuk, Maria / Tewari, Ashutosh

International urology and nephrology

2011 Volume 44, Issue 2, Page(s) 459–470

Abstract: Purpose: Low-risk prostate cancer patients clinically eligible for active surveillance can also be managed surgically. We evaluated the pathologic outcomes for this cohort that was treated by radical prostatectomy and devised nomograms to predict ... ...

Abstract	Purpose: Low-risk prostate cancer patients clinically eligible for active surveillance can also be managed surgically. We evaluated the pathologic outcomes for this cohort that was treated by radical prostatectomy and devised nomograms to predict patients at risk of upgrading and/or upstaging. Materials and methods: Seven hundred and fifty patients treated by radical prostatectomy from Jan 2005 to the present fulfilled conventional active surveillance criteria and formed the study cohort. Preoperative data on standard clinicopathologic parameters were available. The radical prostatectomy specimens were graded and staged, and any upgrading to Gleason sum >6 or upstaging to ≥pT3 ('worsening prognosis') were noted. Multivariable logistic regression models were used to develop predictive nomograms. Results: Of the 750 patients, 303 (40.4%) patients were either upgraded or upstaged. Multivariable analysis found that preoperative PSA, number of positive cores, and prostate volume were significantly predictive of worsening prognosis and formed the nomogram criteria. Conclusions: Of patients deemed eligible for active surveillance based on conventional criteria, 40.4% have worse prognostic factors after radical prostatectomy. Current active surveillance criteria may be too relaxed, and the use of nomograms which we have devised, may aid in counseling primary prostate cancer patients considering active surveillance as their therapy of choice.
MeSH term(s)	Biopsy, Needle ; Disease Progression ; Humans ; Incidence ; Male ; Middle Aged ; Neoplasm Grading/methods ; Neoplasm Grading/standards ; Nomograms ; Patient Selection ; Population Surveillance ; Predictive Value of Tests ; Prognosis ; Prostatectomy ; Prostatic Neoplasms/epidemiology ; Prostatic Neoplasms/pathology ; Prostatic Neoplasms/surgery ; Retrospective Studies ; Risk Factors ; United States/epidemiology
Language	English
Publishing date	2011-06-26
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	204048-7
ISSN	1573-2584 ; 0301-1623 ; 0042-1162
ISSN (online)	1573-2584
ISSN	0301-1623 ; 0042-1162
DOI	10.1007/s11255-011-0020-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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