Publications by authors named "Kamal S Pohar"

39 Publications

Blue Light Cystoscopy: Indications and Outcomes.

Authors:
Kamal S Pohar

Curr Urol Rep 2020 Apr 4;21(5):19. Epub 2020 Apr 4.

Department of Urology, The Ohio State University, Suite 3000, 915 Olentangy River Rd, Columbus, OH, 43212, USA.

Purpose Of Review: It has been firmly established that hexaminolevulinate-assisted blue light cystoscopy (HAL-BLC) reduces cancer recurrence rates. This review explores the impact of HAL-BLC on other meaningful outcomes in patients with bladder cancer, including disease progression, and earlier detection of disease at the time of surveillance cystoscopy.

Recent Findings: A randomized clinical trial confirmed earlier implementation of HAL-BLC at the time of surveillance cystoscopy increased identification of cancerous lesions, including those of high grade, when compared with white light cystoscopy. In addition, the evidence is evolving that the use of HAL-BLC at the time of endoscopic treatment of high-risk tumors may lead to lower rates of progression to muscle invasion, and this in part may be due to better risk stratification leading to changes in treatment plan. The clinical contexts for the use of HAL-BLC are broader than prior knowledge. It is also becoming more clear that the positive impact of HAL-BLC is likely more than just reducing cancer recurrence rates, and patients would benefit from the technology at many time points in the management and follow-up of their disease.
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http://dx.doi.org/10.1007/s11934-020-0966-5DOI Listing
April 2020

Bladder Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology.

J Natl Compr Canc Netw 2020 03;18(3):329-354

National Comprehensive Cancer Network.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on the clinical presentation and workup of suspected bladder cancer, treatment of non-muscle-invasive urothelial bladder cancer, and treatment of metastatic urothelial bladder cancer because important updates have recently been made to these sections. Some important updates include recommendations for optimal treatment of non-muscle-invasive bladder cancer in the event of a bacillus Calmette-Guérin (BCG) shortage and details about biomarker testing for advanced or metastatic disease. The systemic therapy recommendations for second-line or subsequent therapies have also been revised. Treatment and management of muscle-invasive, nonmetastatic disease is covered in the complete version of the NCCN Guidelines for Bladder Cancer available at NCCN.org. Additional topics covered in the complete version include treatment of nonurothelial histologies and recommendations for nonbladder urinary tract cancers such as upper tract urothelial carcinoma, urothelial carcinoma of the prostate, and primary carcinoma of the urethra.
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http://dx.doi.org/10.6004/jnccn.2020.0011DOI Listing
March 2020

Periodically rotated overlapping parallel lines with enhanced reconstruction acquisition to improve motion-induced artifacts in bladder cancer imaging: Initial findings.

Medicine (Baltimore) 2019 Oct;98(42):e17075

Wright Center of Innovation in Biomedical Imaging, Department of Radiology.

Motion-induced artifacts have been a major drawback in bladder cancer imaging. This study is to evaluate the clinical utility of periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) acquisition in improving motion-induced artifacts in T2-weighted (T2W) magnetic resonance imaging (MRI) of bladder cancer at 3T.Sixteen patient MRI exams were included. Using a Likert scale, 2 radiologists independently scored T2W data without and with PROPELLER in terms of artifact severity and tumor visualization. Statistical analysis was done to assess the image quality improvement by PROPELLER and inter-observer variability.Without PROPELLER, the median scores of artifact severity and tumor visualization were 1.5 and 1.5 for reviewer 1, and 2.0 and 2.0 for reviewer 2. With PROPELLER, the scores increased to 3 and 3.5 for reviewer 1, and 3.5 and 3.5 for reviewer 2. Despite the inter-observer variability (κ scores < 0.2), both reviewers found significant improvement in artifacts and visualization (all P < .001).PROPELLER acquisition significantly improved the image quality of T2W-MRI. These initial findings indicate that this technique should be utilized in clinical MRI of the bladder.
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http://dx.doi.org/10.1097/MD.0000000000017075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824794PMC
October 2019

Systematic Review of Comorbidity and Competing-risks Assessments for Bladder Cancer Patients.

Eur Urol Oncol 2018 Jun 6;1(2):91-100. Epub 2018 Jun 6.

Department of Urology, University of Bern, Bern, Switzerland.

Context: Radical cystectomy continues to be associated with a significant risk of morbidity and all-cause mortality (ACM). Practice pattern data demonstrating underuse of surgery for patients with muscle-invasive and high-risk non-muscle invasive bladder cancer (BC) have been linked to the advanced age and higher comorbidity status of such patients, which suggests that rates of ACM as well as cancer-specific mortality should be incorporated into patient counseling and guideline recommendations.

Objective: To review the literature on risk assessment tools for preoperative comorbidity in BC that may aid in treatment decision-making.

Evidence Acquisition: A systematic search was conducted using Ovid and Medline according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to identify studies between 1970 and 2017 reporting on comorbidity risk assessment (CRA) tools for BC. Prospective and retrospective studies were included.

Evidence Synthesis: There are no published randomized control trials comparing CRA tools for BC. Patients undergoing radical cystectomy with combined high-risk comorbidity and performance scores may face up to a sevenfold greater risk of other-cause mortality compared to those with low scores. The Charlson Comorbidity Index is one of the most widely studied indices for 90-d perioperative mortality and overall and cancer-specific survival, with an area under the receiver operating characteristic curve of up to 0.810. Prospective studies of CRA tools for BC have consistently shown that patients with higher comorbidity have worse outcomes. While not specific for BC, comorbidity indices provide useful assessment of competing risks. Competing-risks assessment tools are lacking, with limited studies assessing the impact of these tools on treatment decision-making by patients and providers. We provide the impetus for incorporation of comorbidity risks into practice guidelines when discussing treatment options with patients.

Conclusions: CRA tools should be incorporated into preoperative treatment counseling and the assessment of postoperative outcomes. While retrospective evidence supports the use of CRA tools for BC, further comparative studies evaluating the effectiveness of these tools and identifying the patients most likely to benefit from a treatment according to competing-risks assessment are needed.

Patient Summary: In this review we explored the clinical evidence for comorbidity risk assessment tools in bladder cancer. We found evidence to support incorporation of comorbidity risks into practice guidelines when discussing treatment options with patients.
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http://dx.doi.org/10.1016/j.euo.2018.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6190914PMC
June 2018

NCCN Guidelines Insights: Bladder Cancer, Version 5.2018.

J Natl Compr Canc Netw 2018 09;16(9):1041-1053

The NCCN Clinical Practice Guidelines in Oncology for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer. These NCCN Guidelines Insights discuss important updates to the 2018 version of the guidelines, including implications of the 8th edition of the AJCC Cancer Staging Manual on treatment of muscle-invasive bladder cancer and incorporating newly approved immune checkpoint inhibitor therapies into treatment options for patients with locally advanced or metastatic disease.
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http://dx.doi.org/10.6004/jnccn.2018.0072DOI Listing
September 2018

Quantitative Assessment of Heterogeneity in Bladder Tumor MRI Diffusivity: Can Response be Predicted Prior to Neoadjuvant Chemotherapy?

Bladder Cancer 2017 Oct 27;3(4):237-244. Epub 2017 Oct 27.

Department of Radiology, Wright Center of Innovation in Biomedical Imaging, The Ohio State University, Columbus, OH, USA.

Background: It is a critical unmet need to predict chemosensitivity in muscle-invasive bladder cancer patients who receive neoadjuvant chemotherapy (NAC). Quantification of tumor heterogeneity has been shown to be useful in the assessment of therapeutic response. Apparent diffusion coefficient (ADC) is derived from diffusion weighted MRI (DWI) to quantify the water diffusivity which characterizes micro-cellularity in tumor tissues.

Objective: The aim of this study is to assess if a quantitative measurement of ADC heterogeneity in bladder tumors can be a predictor of therapeutic response to NAC.

Materials And Methods: Twenty patients with pT2 bladder cancer have been included in this study. Patient MRI was performed on a 3T system with DWI prior to NAC. Regions of interest (ROIs) were placed over the whole tumor volume on ADC maps to acquire a data matrix of voxel-wise ADC values for each patient. We performed histogram analysis on each ADC data matrix to calculate uniformity (U) and entropy (E). These quantities were subsequently correlated with the patient's response to chemotherapy. Statistical significance was found with  < 0.05.

Results: Fifteen patients were categorized as responders, and five as non-responders. The data showed that tumors of responders were significantly higher in U ( = 0.01) and lower in E ( < 0.01) than non-responders. This finding indicates that resistant tumors were more heterogeneous in their spatial distribution of ADC values. While this difference in ADC heterogeneity was not always visually recognizable, it could be quantified by the data analytics.

Conclusions: This study demonstrates that the quantitative readout of tumor heterogeneity in micro-cellularity is associated with the patient's defined response to chemotherapy. Quantification of tumor ADC heterogeneity may provide useful information to enable the prediction of chemotherapeutic response prior to the treatment to improve patient outcomes.
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http://dx.doi.org/10.3233/BLC-170110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676757PMC
October 2017

Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology.

J Natl Compr Canc Netw 2017 10;15(10):1240-1267

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on systemic therapy for muscle-invasive urothelial bladder cancer, as substantial revisions were made in the 2017 updates, such as new recommendations for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. The complete version of the NCCN Guidelines for Bladder Cancer addresses additional aspects of the management of bladder cancer, including non-muscle-invasive urothelial bladder cancer and nonurothelial histologies, as well as staging, evaluation, and follow-up.
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http://dx.doi.org/10.6004/jnccn.2017.0156DOI Listing
October 2017

A prospective comparison of UroVysion FISH and urine cytology in bladder cancer detection.

BMC Cancer 2017 04 7;17(1):247. Epub 2017 Apr 7.

Department of Urology, Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.

Background: UroVysion fluorescence in situ hybridization (uFISH) was reported to have superior sensitivity to urine cytology. However uFISH studies are limited by varying definitions of what is considered a positive result, absence of histopathology and small sample size. The aim of our study was to better determine the performance characteristics of uFISH and urine cytology by overcoming some of the deficiencies of the current literature.

Methods: Intraoperative bladder wash cytology and uFISH were collected prospectively on all patients. Strict definitions for positivity of uFISH and cytology were determined before initiating the study. A re-review of false-negative uFISH specimens was performed to analyze potential sources of error. Sixteen bladder tumors embedded in paraffin were analyzed by uFISH and compared with the result in the urine.

Results: One hundred and twenty-nine specimens were analyzed. Sensitivity was 67% and 69% (p = 0.54); specificity was 72% and 76% (p = 1.0), for uFISH and cytology, respectively. Thirty-two false negative uFISH samples were re-reviewed. Low grade tumors often showed cells with abnormal morphology and patchy DAPI staining but diploid chromosomal counts and a few high grade tumors had tetraploid counts but less than needed to interpret uFISH as positive. uFISH study of the tumors revealed three categories; positive in both tumor and urine (9), negative in both tumor and urine (5) and positive in tumor but negative in urine (2).

Conclusion: In a pathologically-confirmed analysis of bladder washed urine specimens, uFISH does not outperform urine cytology in cancer detection.
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http://dx.doi.org/10.1186/s12885-017-3227-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383950PMC
April 2017

Dosage-dependent copy number gains in E2f1 and E2f3 drive hepatocellular carcinoma.

J Clin Invest 2017 Mar 30;127(3):830-842. Epub 2017 Jan 30.

Disruption of the retinoblastoma (RB) tumor suppressor pathway, either through genetic mutation of upstream regulatory components or mutation of RB1 itself, is believed to be a required event in cancer. However, genetic alterations in the RB-regulated E2F family of transcription factors are infrequent, casting doubt on a direct role for E2Fs in driving cancer. In this work, a mutation analysis of human cancer revealed subtle but impactful copy number gains in E2F1 and E2F3 in hepatocellular carcinoma (HCC). Using a series of loss- and gain-of-function alleles to dial E2F transcriptional output, we have shown that copy number gains in E2f1 or E2f3b resulted in dosage-dependent spontaneous HCC in mice without the involvement of additional organs. Conversely, germ-line loss of E2f1 or E2f3b, but not E2f3a, protected mice against HCC. Combinatorial mapping of chromatin occupancy and transcriptome profiling identified an E2F1- and E2F3B-driven transcriptional program that was associated with development and progression of HCC. These findings demonstrate a direct and cell-autonomous role for E2F activators in human cancer.
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http://dx.doi.org/10.1172/JCI87583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5330731PMC
March 2017

Does the gross prosector impact pT3 subclassification or lymph node counts in bladder cancer?

Hum Pathol 2017 03 16;61:190-198. Epub 2016 Dec 16.

Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. Electronic address:

Gross prosector analysis of perivesicular adipose tumor invasion is the sole differentiator between pT3 substages, and gross evaluation is critical to lymph node identification. Gross prosector impact on pT3 subclassification and lymph node counts in cystectomy specimens resected for bladder cancer has not been previously analyzed. Both pT3 subclassification and total number of lymph nodes removed at radical cystectomy for bladder cancer are considered important components of the pathology report; however, both have controversial prognostic significance. Our objective was to assess the impact of the gross prosector on pT3 substaging and lymph node count. Pathology reports from 560 cystectomy cases performed for primary bladder cancer were reviewed. Educational interventions regarding cystectomy gross prosector documentation were conducted. Gross prosectors did not document the presence or absence of macroscopic perivesicular adipose invasion in 17% of cases. There was a decrease in the frequency of cases lacking documentation after educational intervention (33% to 5%, P<.01). Most pT3 cases lacking documentation were classified as pT3a (75%). The percentage of pT3 cases classified as pT3a decreased after intervention (68% to 35%, P<.01). Overcounting of lymph nodes by gross prosectors was more common than undercounting (22% versus 2%). Pathology residents and prosectors with lower caseloads had more uncounted lymph packets (P<.01). In conclusion, we demonstrated an impact of the gross prosector on pT3 substaging and lymph node counts within bladder cancer resection specimens. This novel variable may confound the relationship of these parameters upon oncologic outcomes and should be incorporated into quality assurance programs.
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http://dx.doi.org/10.1016/j.humpath.2016.12.009DOI Listing
March 2017

NCCN Guidelines Insights: Bladder Cancer, Version 2.2016.

J Natl Compr Canc Netw 2016 10;14(10):1213-1224

From Vanderbilt-Ingram Cancer Center; Moffitt Cancer Center; Huntsman Cancer Institute at the University of Utah; Patient Advocate; Mayo Clinic Cancer Center; Stanford Cancer Institute; Massachusetts General Hospital Cancer Center; University of Colorado Cancer Center; UCSF Helen Diller Family Comprehensive Cancer Center; Fox Chase Cancer Center; Roswell Park Cancer Institute; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Memorial Sloan Kettering Cancer Center; Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute; Duke Cancer Institute; UC San Diego Moores Cancer Center; Dana-Farber/Brigham and Women's Cancer Center; Robert H. Lurie Comprehensive Cancer Center of Northwestern University; Fred & Pamela Buffett Cancer Center; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine; University of Michigan Comprehensive Cancer Center; City of Hope Comprehensive Cancer Center; St. Jude Children's Research Hospital/The University of Tennessee Health Science Center; Yale Cancer Center/Smilow Cancer Hospital; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute; University of Washington/Seattle Cancer Care Alliance; The University of Texas MD Anderson Cancer Center; University of Alabama at Birmingham Comprehensive Cancer Center; and National Comprehensive Cancer Network.

These NCCN Guidelines Insights discuss the major recent updates to the NCCN Guidelines for Bladder Cancer based on the review of the evidence in conjunction with the expert opinion of the panel. Recent updates include (1) refining the recommendation of intravesical bacillus Calmette-Guérin, (2) strengthening the recommendations for perioperative systemic chemotherapy, and (3) incorporating immunotherapy into second-line therapy for locally advanced or metastatic disease. These NCCN Guidelines Insights further discuss factors that affect integration of these recommendations into clinical practice.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379654PMC
http://dx.doi.org/10.6004/jnccn.2016.0131DOI Listing
October 2016

Non-invasive quantification of tumour heterogeneity in water diffusivity to differentiate malignant from benign tissues of urinary bladder: a phase I study.

Eur Radiol 2017 May 23;27(5):2146-2152. Epub 2016 Aug 23.

Wright Center of Innovation in Biomedical Imaging, Department of Radiology, The Ohio State University, 395 W. 12th Ave., Room 430, Columbus, OH, 43210, USA.

Objectives: To quantify the heterogeneity of the tumour apparent diffusion coefficient (ADC) using voxel-based analysis to differentiate malignancy from benign wall thickening of the urinary bladder.

Methods: Nineteen patients with histopathological findings of their cystectomy specimen were included. A data set of voxel-based ADC values was acquired for each patient's lesion. Histogram analysis was performed on each data set to calculate uniformity (U) and entropy (E). The k-means clustering of the voxel-wised ADC data set was implemented to measure mean intra-cluster distance (MICD) and largest inter-cluster distance (LICD). Subsequently, U, E, MICD, and LICD for malignant tumours were compared with those for benign lesions using a two-sample t-test.

Results: Eleven patients had pathological confirmation of malignancy and eight with benign wall thickening. Histogram analysis showed that malignant tumours had a significantly higher degree of ADC heterogeneity with lower U (P = 0.016) and higher E (P = 0.005) than benign lesions. In agreement with these findings, k-means clustering of voxel-wise ADC indicated that bladder malignancy presented with significantly higher MICD (P < 0.001) and higher LICD (P = 0.002) than benign wall thickening.

Conclusions: The quantitative assessment of tumour diffusion heterogeneity using voxel-based ADC analysis has the potential to become a non-invasive tool to distinguish malignant from benign tissues of urinary bladder cancer.

Key Points: • Heterogeneity is an intrinsic characteristic of tumoral tissue. • Non-invasive quantification of tumour heterogeneity can provide adjunctive information to improve cancer diagnosis accuracy. • Histogram analysis and k-means clustering can quantify tumour diffusion heterogeneity. • The quantification helps differentiate malignant from benign urinary bladder tissue.
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http://dx.doi.org/10.1007/s00330-016-4549-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613982PMC
May 2017

E2f8 mediates tumor suppression in postnatal liver development.

J Clin Invest 2016 08 25;126(8):2955-69. Epub 2016 Jul 25.

E2F-mediated transcriptional repression of cell cycle-dependent gene expression is critical for the control of cellular proliferation, survival, and development. E2F signaling also interacts with transcriptional programs that are downstream of genetic predictors for cancer development, including hepatocellular carcinoma (HCC). Here, we evaluated the function of the atypical repressor genes E2f7 and E2f8 in adult liver physiology. Using several loss-of-function alleles in mice, we determined that combined deletion of E2f7 and E2f8 in hepatocytes leads to HCC. Temporal-specific ablation strategies revealed that E2f8's tumor suppressor role is critical during the first 2 weeks of life, which correspond to a highly proliferative stage of postnatal liver development. Disruption of E2F8's DNA binding activity phenocopied the effects of an E2f8 null allele and led to HCC. Finally, a profile of chromatin occupancy and gene expression in young and tumor-bearing mice identified a set of shared targets for E2F7 and E2F8 whose increased expression during early postnatal liver development is associated with HCC progression in mice. Increased expression of E2F8-specific target genes was also observed in human liver biopsies from HCC patients compared to healthy patients. In summary, these studies suggest that E2F8-mediated transcriptional repression is a critical tumor suppressor mechanism during postnatal liver development.
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http://dx.doi.org/10.1172/JCI85506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966321PMC
August 2016

Do amount of variant differentiation and mitotic rate in bladder cancer change with neoadjuvant chemotherapy?

Hum Pathol 2015 Sep 4;46(9):1367-75. Epub 2015 Jun 4.

Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210. Electronic address:

Neoadjuvant chemotherapy (NAC) is currently recommended to all candidate patients with muscularis propria-invasive bladder cancer. However, NAC is effective in only a subset of patients, and predictors of response are lacking. Our study aimed to characterize tumoral changes with NAC usage and to identify features at bladder biopsy/transurethral resection (Bx/TUR) that may predict response. A retrospective search was performed to identify patients with bladder cancer that were pT2 at Bx/TUR upon whom a radical cystectomy (RC) was performed from 2007 to 2010. A blinded slide review of the Bx/TUR and RC was conducted. Presence, type, percent of tumor variant morphology, and tumoral mitotic rate were assessed. Ninety RC patients with slides available were identified (46 NAC, 44 non-NAC). In NAC-treated patients, there was a significantly higher percentage of nonurothelial variant differentiation in the RC compared with Bx/TUR, whereas there was no difference in the non-NAC subgroup. Percent variant differentiation at Bx/TUR was not a predictor of response. There was a significant decrease in mitotic rate between Bx/TUR and RC in NAC patients, whereas there was no difference in the non-NAC subgroup, although mitotic rate was not a predictor of response. In conclusion, percent variant differentiation and mitotic rate changed significantly from Bx/TUR to RC with NAC usage, although neither predicted response. Pathologists should be aware that variant differentiation is common in bladder cancer, with increased presence after NAC, in order to improve recognition and documentation of these findings.
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http://dx.doi.org/10.1016/j.humpath.2015.05.020DOI Listing
September 2015

Hexaminolevulinate blue-light cystoscopy in non-muscle-invasive bladder cancer: review of the clinical evidence and consensus statement on appropriate use in the USA.

Nat Rev Urol 2014 Oct 23;11(10):589-96. Epub 2014 Sep 23.

University of Chicago, USA.

Hexaminolevulinate (HAL) is a tumour photosensitizer that is used in combination with blue-light cystoscopy (BLC) as an adjunct to white-light cystoscopy (WLC) in the diagnosis and management of non-muscle-invasive bladder cancer (NMIBC). Since being licensed in Europe in 2005, HAL has been used in >200,000 procedures, with consistent evidence that it improves detection compared with WLC alone. Current data support an additional role in the reduction of recurrence of NMIBC. Since the approval of HAL by the FDA in 2010, experience of HAL-BLC in the USA continues to expand. To define areas of need and to identify the benefits of HAL-BLC in clinical practice, a focus group of expert urologists specializing in the management of patients with bladder cancer convened to review the clinical evidence, share their experiences and reach a consensus regarding the optimal use of HAL-BLC in the USA. The focus group concluded that HAL-BLC should be considered for initial assessment of NMIBC, surveillance for recurrent tumours, diagnosis in patients with positive urine cytology but negative WLC findings, and for tumour staging.
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http://dx.doi.org/10.1038/nrurol.2014.245DOI Listing
October 2014

Improving bladder cancer imaging using 3-T functional dynamic contrast-enhanced magnetic resonance imaging.

Invest Radiol 2014 Jun;49(6):390-5

From the *Wright Center of Innovation in Biomedical Imaging, Departments of Radiology, †Urology, ‡Internal Medicine, §Pathology, and ∥Center for Biostatistics, The Ohio State University, Columbus, OH.

Objectives: The objective of this study was to assess the capability of T2-weighted magnetic resonance imaging (T2W-MRI) and the additional diagnostic value of dynamic contrast-enhanced MRI (DCE-MRI) using multitransmit 3 T in the localization of bladder cancer.

Materials And Methods: This prospective study was approved by the local institutional review board. Thirty-six patients were included in the study and provided informed consent. Magnetic resonance imaging scans were performed with T2W-MRI and DCE-MRI on a 3-T multitransmit system. Two observers (with 12 and 25 years of experience) independently interpreted T2W-MRI before DCE-MRI data (maps of pharmacokinetic parameters) to localize bladder tumors. The pathological examination of cystectomy bladder specimens was used as a reference criteria standard. The McNemar test was performed to evaluate the differences in sensitivity, specificity, and accuracy. Scores of κ were calculated to assess interobserver agreement.

Results: The sensitivity, specificity, and accuracy of the localization with T2W-MRI alone were 81% (29/36), 63% (5/8), and 77% (34/44) for observer 1 and 72% (26/36), 63% (5/8), and 70% (31/44) for observer 2. With additional DCE-MRI available, these values were 92% (33/36), 75% (6/8), and 89% (39/44) for observer 1 and 92% (33/36), 63% (5/8), and 86% (38/44) for observer 2. Dynamic contrast-enhanced MRI significantly (P<0.01) improved the sensitivity and accuracy for observer 2. For the 23 patients treated with chemotherapy, DCE-MRI also significantly (P<0.02) improved the sensitivity and accuracy of bladder cancer localization with T2W-MRI alone for observer 2. Scores of κ were 0.63 for T2W-MRI alone and 0.78 for additional DCE-MRI. Of 7 subcentimeter malignant tumors, 4 (57%) were identified on T2W images and 6 (86%) were identified on DCE maps. Of 11 malignant tumors within the bladder wall thickening, 6 (55%) were found on T2W images and 10 (91%) were found on DCE maps.

Conclusions: Compared with conventional T2W-MRI alone, the addition of DCE-MRI improved interobserver agreement as well as the localization of small malignant tumors and those within bladder wall thickening.
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http://dx.doi.org/10.1097/RLI.0000000000000022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326253PMC
June 2014

Challenges in the pathological reporting of urothelial carcinoma involving prostatic transurethral resection specimens within a single institution.

Pathology 2013 12;45(7):664-9

*Department of Pathology, Washington University, St Louis, Missouri †Departments of Pathology ‡Urology, The Ohio State University Medical Center, Columbus, Ohio, USA.

Aim: Primary bladder urothelial carcinoma (UC) may involve the prostate with differing management depending on whether tumour is in situ or invades the prostatic subepithelium or fibromuscular stroma. We aim to understand challenges in reporting UC within prostate transurethral resection (TUR).

Methods: A retrospective review from 2007 to 2010 identified prostate TUR performed for primary bladder UC.

Results: 25.1% of cystoprostatectomy patients (60/239) had a prior prostate TUR; 129 patients had a prostate TUR for UC and 50.4% (65/129) were given a neoplastic diagnosis. Prostatic fibromuscular stroma was present in 84.6% of cases, with a comparable rate among surgeons. Diagnostic concordance of UC versus a non-neoplastic diagnosis was 96.7%, with rare cases initially diagnosed as non-neoplastic having in situ UC on review. Of reports with invasive tumour, 19.4% did not specify extent of invasion (e.g., bladder muscularis propria, prostate fibromuscular stroma) and 13.9% had discordant extent of invasion on review. Terminology typically used for bladder (lamina propria/muscularis propria) was found in 23.1% of reports without explicit reference to the bladder or prostate.

Conclusion: This study reveals difficulties in reporting UC within prostatic TUR specimens. We recommend documenting tumour extent and referencing the organ of origin if ambiguous anatomical terms are used.
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http://dx.doi.org/10.1097/PAT.0000000000000009DOI Listing
December 2013

Clinicopathologic characteristics and overall survival in patients with bladder cancer involving the gastrointestinal tract.

Virchows Arch 2013 Dec 4;463(6):811-8. Epub 2013 Oct 4.

Department of Pathology, The Ohio State University Medical Center, 410 W 10th Ave, 401 Doan Hall, Columbus, OH, 43210, USA.

Involvement of the gastrointestinal (GI) tract by bladder cancer is rare and documented in only a few case reports with no prognostic information available. The aim of this study was to clinicopathologically characterize patients with pathologically proven bladder cancer in the GI tract. We reviewed pathology reports from cystectomy patients at our institution from 2006 to 2011, identifying those with GI involvement at or after cystectomy. Overall survival (OS) was analyzed using Kaplan-Meier curves and Cox proportional hazard regression models. Twelve patients had surgical pathology specimens with GI involvement (anus, rectum, colon, and small bowel) at (n = 11) or within 4 months (n = 1) of cystectomy. These patients were noted to be pathologically staged inconsistently. GI involvement was a negative predictor of survival, with a 1.5-year OS of 25 versus 62 % without GI involvement (P < 0.001), similar to our pT4 patients (OS 26 %). In node-negative patients, there was a significantly worse 1.5-year OS with GI involvement compared to those without tumor in the GI tract (P = 0.005). We provide the first case series of patients with bladder cancer in the GI tract. GI involvement is a strong negative predictor of survival and behaves comparable to pT4 patients. However, we recommend that pathologists adhere to the current pT staging guidelines, in which GI involvement is not a criterion, until further research is conducted illustrating if and how it should be incorporated.
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http://dx.doi.org/10.1007/s00428-013-1479-0DOI Listing
December 2013

The anatomic extent and completeness of pelvic lymphadenectomy is what matters.

Authors:
Kamal S Pohar

Curr Opin Urol 2013 Sep;23(5):444-8

The Ohio State University Wexner Medical Center, Columbus, Ohio 43212, USA.

Purpose Of Review: There is an imperative need to improve the cure rates of patients diagnosed with invasive bladder cancer. The lymph node dissection performed at the time of radical cystectomy has an ability to improve locoregional disease control, assign pathologic nodal stage as well as cure some patients with nodal metastases. However, there is a lack of agreement of what constitutes an adequate lymph node dissection at the time of radical cystectomy to optimize oncologic outcomes.

Recent Findings: This review challenges the value of lymph node count as a surrogate for a well performed lymphadenectomy. The review also presents recent articles that add to the body of literature suggesting an extended lymph node dissection cures more patients than lesser anatomic templates of lymphadenectomy, including some patients with common iliac lymph node metastases.

Summary: A meticulous surgical lymphadenectomy adhering to well defined surgical boundaries provides the best opportunity for cure. Ongoing phase III prospective randomized clinical trials will determine the true benefit of extended lymph node dissection.
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http://dx.doi.org/10.1097/MOU.0b013e328363f5f8DOI Listing
September 2013

Penile cancer: Clinical Practice Guidelines in Oncology.

J Natl Compr Canc Netw 2013 May;11(5):594-615

Squamous cell carcinoma of the penis represents approximately 0.5% of all cancers among men in the United States and other developed countries. Although rare, it is associated with significant disfigurement, and only half of the patients survive beyond 5 years. Proper evaluation of both the primary lesion and lymph nodes is critical, because nodal involvement is the most important factor of survival. The NCCN Clinical Practice Guidelines in Oncology for Penile Cancer provide recommendations on the diagnosis and management of this devastating disease based on evidence and expert consensus.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4042432PMC
http://dx.doi.org/10.6004/jnccn.2013.0075DOI Listing
May 2013

Bladder cancer.

J Natl Compr Canc Netw 2013 Apr;11(4):446-75

Vanderbilt-Ingram Cancer Center.

Bladder cancer is the fourth most common cancer in the United States. Urothelial carcinoma that originates from the urinary bladder is the most common subtype. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) provide recommendations on the diagnosis and management of non-muscle-invasive and muscle-invasive urothelial carcinoma of the bladder. This version of the guidelines provides extensive reorganization and updates on the principles of chemotherapy management.
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http://dx.doi.org/10.6004/jnccn.2013.0059DOI Listing
April 2013

Retrospective analysis of survival in muscle-invasive bladder cancer: impact of pT classification, node status, lymphovascular invasion, and neoadjuvant chemotherapy.

Virchows Arch 2012 Oct 23;461(4):467-74. Epub 2012 Aug 23.

Department of Pathology, The Ohio State University Medical Center, Columbus, OH 43210, USA.

A range of studies have analyzed prognostic factors in bladder cancer. However, prior cohorts have included heterogeneous pT classification at biopsy and others were derived from large, multi-institutional clinical trials over the span of many years. Our objective was to analyze prognostic factors in a recent radical cystectomy (RC) cohort at a single institution and evaluate outcomes based on current practice patterns. A retrospective analysis of overall survival (OS) was conducted on 180 RC patients with biopsy proven pT2 disease between 2007-2010. Increasing pT classification was a negative predictor of survival. pT was grouped into three categories with pT0/a/is/1/2a surviving longer than pT2b/3a/3b, and pT4 having the worst prognosis. Subclassifying pT2 and pT3 showed no statistically significant difference in survival. Lymphovascular invasion (LVI) and node positivity correlated with decreased OS. Patients treated with neoadjuvant chemotherapy (NAC) had a higher incidence of pT0, yet pN1+ was more common and NAC was not associated with improved OS. This investigation provides reference OS values for patients with pathologically diagnosed muscle-invasive bladder cancer based on current medical guidelines outside the context of a clinical trial. pT4 was the strongest negative predictor of survival, followed by pN1+, the group pT2b/3a/3b, and presence of LVI. NAC patients were noted to have a higher frequency of low pT classification, yet more frequent node positivity, suggesting that pT classification in NAC patients may not accurately reflect remaining tumor burden.
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http://dx.doi.org/10.1007/s00428-012-1249-4DOI Listing
October 2012

Urinary bladder chondroma.

Virchows Arch 2012 Apr 7;460(4):437-8. Epub 2012 Mar 7.

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http://dx.doi.org/10.1007/s00428-012-1218-yDOI Listing
April 2012

Quality of lymphadenectomy is equivalent with robotic and open cystectomy using an extended template.

J Urol 2012 Apr 15;187(4):1200-4. Epub 2012 Feb 15.

Department of Urology, Ohio State University Medical Center and James Cancer Hospital, Columbus, Ohio 43210, USA.

Purpose: Extended lymph node dissection for bladder cancer provides better staging, cancerous node removal and potentially survival. Minimally invasive techniques have been criticized about the ability to adequately perform extended lymph node dissection. We compared the extended lymph node dissection quality of robotic and open cystectomy by assessing node yield and positivity.

Materials And Methods: We compared extended lymph node dissection in 120 open and 35 robotic cystectomy cases. Extended lymph node dissection included skeletonization of structures in each nodal group below the aortic bifurcation (common iliac, external iliac, obturator, hypogastric and presacral nodes). Nodes were processed identically but submitted as 1 or 2 packets for robotic cases and as 10 or more packets for open surgery cases.

Results: The mean±SD node count in the open group was 36.9±14.8 (range 11 to 87) and in the robotic group the mean yield was 37.5±13.2 (range 18 to 64). Only 12 of 120 open (10%) and 2 of 35 robotic (6%) cases had fewer than 20 nodes. A total of 36 open (30%) and 12 robotic (34%) cases were node positive. Open extended lymph node dissection identified 80% and 90% confidence of accurate staging as pN0 when obtaining 23 and 27 nodes, respectively. A node count of 23 or 27 was achieved in 87% and 77% of open cases, and in 91% and 83% of robotic cases, respectively. Of patients with open surgery 36% received neoadjuvant chemotherapy compared to 31% of those with robotic surgery.

Conclusions: No difference was identified in the lymph node yield or the positive node rate when comparing open and robotic extended lymph node dissection. Local recurrence and survival data are needed to confirm whether the 2 techniques are oncologically equivalent.
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http://dx.doi.org/10.1016/j.juro.2011.11.092DOI Listing
April 2012

Prostate-specific antigen response after definitive radiotherapy for Skene's gland adenocarcinoma resembling prostate adenocarcinoma.

Urol Oncol 2012 Sep 25;30(5):602-6. Epub 2010 Sep 25.

Department of Radiation Oncology, James Cancer Hospital, Columbus, OH 43210, USA.

Objectives: To assess prostate-specific antigen response after definitive radiotherapy in a patient with localized Skene's gland adenocarcinoma resembling prostate adenocarcinoma.

Materials And Methods: A 71-year-old patient was evaluated for a 2 year history of painless hematuria and found to have a localized Skene's gland adenocarcinoma resembling prostate adenocarcinoma with a pre-therapy PSA of 54.52 ng/ul. She elected to undergo definitive radiotherapy holding radical surgery for salvage. She received 73.8 Gy of intensity modulated radiotherapy in 41 fractions. Serum PSA, imaging, and cystoscopy were followed at 6 month intervals for 2.5 years.

Results: The PSA decreased to 0.65 ng/ul 32 months after treatment, her clinical symptoms resolved, and on imaging and exam she has no evidence of residual disease. The PSA half life was 6.16 months (r(2) = 0.97).

Conclusions: For this rare tumor we show that PSA is a reliable marker for disease response and also show that definitive radiotherapy can be an option for organ and functional preservation in patients with localized disease. Cases of periurethral adenocarcinomas should be pathologically screened to assess if they are of Skene's gland origin, as our results suggest a radiotherapy treatment paradigm may be appropriate management in a select subgroup of women with periurethral adenocarcinoma.
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http://dx.doi.org/10.1016/j.urolonc.2010.06.015DOI Listing
September 2012

How do commonly performed lymphadenectomy templates influence bladder cancer nodal stage?

J Urol 2010 Feb 14;183(2):499-503. Epub 2009 Dec 14.

Department of Urology, Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, USA.

Purpose: Determining pathological nodal stage in patients with bladder cancer is important for prognosis. We determined how the extent of lymphadenectomy and the lymph node count influence accurate nodal staging.

Materials And Methods: The study included 120 patients who underwent at least extended lymphadenectomy at radical cystectomy. Different anatomical templates for lymphadenectomy were evaluated for nodal staging accuracy. The cumulative percent was plotted to determine a lymph node count that confidently identified node positive cases.

Results: The mean +/- SD total lymph node count in the study population was 36.9 +/- 14.8 at extended lymphadenectomy. Of the patients 36 (30%) had lymph node metastasis, including 14 (39%) with metastasis involving the common iliac and/or presacral lymph nodes. Limited, standard and extended lymphadenectomy accurately identified 75%, 88.9% and 100% of node positive cases, respectively. Removing 23 and 27 lymph nodes provided 80% and 90% confidence, respectively, that a case was accurately staged as pN0. No patient had lymph node metastasis above the aortic bifurcation without nodal metastasis below the aortic bifurcation and none had a change in pN stage by extending lymphadenectomy above the aortic bifurcation.

Conclusions: To accurately identify node positive and negative cases, and correctly assign pN stage in node positive cases it is necessary to perform extended lymphadenectomy. Identifying at least 23 to 27 lymph nodes on final pathological evaluation provides a high level of confidence that a case is correctly staged as node positive or negative.
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http://dx.doi.org/10.1016/j.juro.2009.09.080DOI Listing
February 2010

Management of the residual post-chemotherapy retroperitoneal mass in germ cell tumors.

Ther Adv Urol 2009 Oct;1(4):199-207

Department of Urology, Ohio State University Medical Center, 456 West 10th Ave, Columbus, Ohio, OH 43210, USA.

The management of the residual mass in the retroperitoneum following induction chemotherapy for metastatic testicular cancer has evolved over the past three decades. A multidisciplinary approach involving cisplatin-based chemotherapy and postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) has increased long-term survival rates above 80%. Advances into the appropriate patient selection and timing of surgery have lowered morbidity while improving oncologic outcomes. However, areas of controversy still exist within the field. Management of the small residual mass, predictors of the histology of the residual mass, the extent of PC-RPLND, the role of PC-RPLND in the setting of elevated serum tumor markers, and the role of positron-emission tomography are all topics of ongoing research and debate. We will discuss these issues and review the current guidelines for the management of the residual postchemotherapy retroperitoneal mass in this review.
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http://dx.doi.org/10.1177/1756287209350315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126061PMC
October 2009

How close are we to establishing standards of lymphadenectomy for invasive bladder cancer?

Ther Adv Urol 2009 Aug;1(3):167-74

The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.

Radical cystectomy and lymphadenectomy is an accepted standard of care for muscle-invasive bladder cancer. Although the absolute limits of lymphadenectomy have not been standardized a growing body of evidence supports an improvement in nodal staging and survival from an extended lymphadenectomy. The benefit has been reported for both node negative and node positive patients. This review focuses on lymph node mapping, factors that influence total lymph node count and the optimal number of lymph nodes that should be removed at lymphadenectomy.
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http://dx.doi.org/10.1177/1756287209346832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126060PMC
August 2009

Ras-MAPK pathway as a therapeutic target in cancer--emphasis on bladder cancer.

Recent Pat Anticancer Drug Discov 2009 Jun;4(2):125-36

Department of Urology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.

The Ras-MAPK pathway is important to orchestrating a cell's response to external and internal stimuli. This pathway is commonly dysregulated in cancer, including bladder cancer. Multiple components of this complex pathway have been identified as potential targets for drug development. After initial preclinical studies many drugs targeting the Ras-MAPK pathway are being studied in phase II clinical trials for advanced bladder cancer either alone or in combination with other chemotherapeutic agents. Drugs presently in clinical trials inhibit the tyrosine kinases, including FGFR, EGFR, ERBB2, and PDGF, either through small molecule tyrosine kinase, dual kinase or farnesyltransferase inhibitors. Recent drug patents targeting the Ras-MAPK pathway in cancer are becoming more selective with the potential for improved therapeutic response and better toxicity as compared to the more universal MAPK pathway inhibitors. In the present review we summarize the importance of the Ras-MAPK pathway in cancer with a focus on bladder cancer and discuss current drugs and recent patents (2004-2008) that target this important pathway in bladder cancer.
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http://dx.doi.org/10.2174/157489209788452812DOI Listing
June 2009