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The Genitourinary Pathology Society Update on Classification of Variant Histologies, T1 Substaging, Molecular Taxonomy, and Immunotherapy and PD-L1 Testing Implications of Urothelial Cancers

Compérat, Eva; Amin, Mahul B; Epstein, Jonathan I; Hansel, Donna E; Paner, Gladell; Al-Ahmadie, Hikmat; True, Larry; Bayder, Dilek; Bivalacqua, Trinity; Brimo, Fadi; Cheng, Liang; Cheville, John; Dalbagni, Guido; Falzarano, Sara; Gordetsky, Jennifer; Guo, Charles; Gupta, Sounak; Hes, Ondrej; Iyer, Gopa; Kaushal, Seema; Kunju, Lakshmi; Magi-Galluzzi, Cristina; Matoso, Andres; McKenney, Jesse; Netto, George J; Osunkoya, Adeboye O; Pan, Chin Chen; Pivovarcikova, Kristina; Raspollini, Maria R; Reis, Henning; Rosenberg, Jonathan; Roupret, Morgan; Shah, Rajal B; Shariat, Shahrokh F; Trpkov, Kiril; Weyerer, Veronika; Zhou, Ming; Reuter, Victor
The Genitourinary Pathology Society (GUPS) undertook a critical review of the recent advances in bladder cancer focusing on important topics of high interest for the practicing surgical pathologist and urologist. This review represents the second of 2 manuscripts ensuing from this effort. Herein, we address the effective reporting of bladder cancer, focusing particularly on newly published data since the last 2016 World Health Organization (WHO) classification. In addition, this review focuses on the importance of reporting bladder cancer with divergent differentiation and variant (subtypes of urothelial carcinoma) histologies and the potential impact on patient care. We provide new recommendations for reporting pT1 staging in diagnostic pathology. Furthermore, we explore molecular evolution and classification, emphasizing aspects that impact the understanding of important concepts relevant to reporting and management of patients.
PMID: 34128484
ISSN: 1533-4031
CID: 4927422

The Genitourinary Pathology Society Update on Classification and Grading of Flat and Papillary Urothelial Neoplasia With New Reporting Recommendations and Approach to Lesions With Mixed and Early Patterns of Neoplasia

Amin, Mahul B; Comperat, Eva; Epstein, Jonathan I; True, Lawrence D; Hansel, Donna; Paner, Gladell P; Al-Ahmadie, Hikmat; Baydar, Dilek; Bivalacqua, Trinity; Brimo, Fadi; Cheng, Liang; Cheville, John; Dalbagni, Guido; Falzarano, Sara; Gordetsky, Jennifer; Guo, Charles C; Gupta, Sounak; Hes, Ondra; Iyer, Gopa; Kaushal, Seema; Kunju, Lakshmi; Magi-Galluzzi, Cristina; Matoso, Andres; Netto, George; Osunkoya, Adeboye O; Pan, Chin Chen; Pivovarcikova, Kristina; Raspollini, Maria R; Reis, Henning; Rosenberg, Jonathan; Roupret, Morgan; Shah, Rajal B; Shariat, Shahrokh; Trpkov, Kiril; Weyerer, Veronika; Zhou, Ming; McKenney, Jesse; Reuter, Victor E
The Genitourinary Pathology Society (GUPS) undertook a critical review of the recent advances in bladder neoplasia with a focus on issues relevant to the practicing surgical pathologist for the understanding and effective reporting of bladder cancer, emphasizing particularly on the newly accumulated evidence post-2016 World Health Organization (WHO) classification. The work is presented in 2 manuscripts. Here, in the first, we revisit the nomenclature and classification system used for grading flat and papillary urothelial lesions centering on clinical relevance, and on dilemmas related to application in routine reporting. As patients of noninvasive bladder cancer frequently undergo cystoscopy and biopsy in their typically prolonged clinical course and for surveillance of disease, we discuss morphologies presented in these scenarios which may not have readily applicable diagnostic terms in the WHO classification. The topic of inverted patterns in urothelial neoplasia, particularly when prominent or exclusive, and beyond inverted papilloma has not been addressed formally in the WHO classification. Herein we provide a through review and suggest guidelines for when and how to report such lesions. In promulgating these GUPS recommendations, we aim to provide clarity on the clinical application of these not so uncommon diagnostically challenging situations encountered in routine practice, while also importantly advocating consistent terminology which would inform future work.
PMID: 34128483
ISSN: 1533-4031
CID: 4929092

Tumor fraction-guided cell-free DNA profiling in metastatic solid tumor patients

Tsui, Dana W Y; Cheng, Michael L; Shady, Maha; Yang, Julie L; Stephens, Dennis; Won, Helen; Srinivasan, Preethi; Huberman, Kety; Meng, Fanli; Jing, Xiaohong; Patel, Juber; Hasan, Maysun; Johnson, Ian; Gedvilaite, Erika; Houck-Loomis, Brian; Socci, Nicholas D; Selcuklu, S Duygu; Seshan, Venkatraman E; Zhang, Hongxin; Chakravarty, Debyani; Zehir, Ahmet; Benayed, Ryma; Arcila, Maria; Ladanyi, Marc; Funt, Samuel A; Feldman, Darren R; Li, Bob T; Razavi, Pedram; Rosenberg, Jonathan; Bajorin, Dean; Iyer, Gopa; Abida, Wassim; Scher, Howard I; Rathkopf, Dana; Viale, Agnes; Berger, Michael F; Solit, David B
BACKGROUND:Cell-free DNA (cfDNA) profiling is increasingly used to guide cancer care, yet mutations are not always identified. The ability to detect somatic mutations in plasma depends on both assay sensitivity and the fraction of circulating DNA in plasma that is tumor-derived (i.e., cfDNA tumor fraction). We hypothesized that cfDNA tumor fraction could inform the interpretation of negative cfDNA results and guide the choice of subsequent assays of greater genomic breadth or depth. METHODS:Plasma samples collected from 118 metastatic cancer patients were analyzed with cf-IMPACT, a modified version of the FDA-authorized MSK-IMPACT tumor test that can detect genomic alterations in 410 cancer-associated genes. Shallow whole genome sequencing (sWGS) was also performed in the same samples to estimate cfDNA tumor fraction based on genome-wide copy number alterations using z-score statistics. Plasma samples with no somatic alterations detected by cf-IMPACT were triaged based on sWGS-estimated tumor fraction for analysis with either a less comprehensive but more sensitive assay (MSK-ACCESS) or broader whole exome sequencing (WES). RESULTS:cfDNA profiling using cf-IMPACT identified somatic mutations in 55/76 (72%) patients for whom MSK-IMPACT tumor profiling data were available. A significantly higher concordance of mutational profiles and tumor mutational burden (TMB) was observed between plasma and tumor profiling for plasma samples with a high tumor fraction (z-score≥5). In the 42 patients from whom tumor data was not available, cf-IMPACT identified mutations in 16/42 (38%). In total, cf-IMPACT analysis of plasma revealed mutations in 71/118 (60%) patients, with clinically actionable alterations identified in 30 (25%), including therapeutic targets of FDA-approved drugs. Of the 47 samples without alterations detected and low tumor fraction (z-score<5), 29 had sufficient material to be re-analyzed using a less comprehensive but more sensitive assay, MSK-ACCESS, which revealed somatic mutations in 14/29 (48%). Conversely, 5 patients without alterations detected by cf-IMPACT and with high tumor fraction (z-score≥5) were analyzed by WES, which identified mutational signatures and alterations in potential oncogenic drivers not covered by the cf-IMPACT panel. Overall, we identified mutations in 90/118 (76%) patients in the entire cohort using the three complementary plasma profiling approaches. CONCLUSIONS:cfDNA tumor fraction can inform the interpretation of negative cfDNA results and guide the selection of subsequent sequencing platforms that are most likely to identify clinically-relevant genomic alterations.
PMCID:8165771
PMID: 34059130
ISSN: 1756-994x
CID: 4895042

The Napoleon: A Pilot Feasibility Study of a Small Endoscopic Ruler for Accurate Polyp Measurement [Meeting Abstract]

Pochapin, M B; Khan, A; Rosenberg, J; Chang, S; Li, X; Goldberg, J; Ghiasian, G; Sharma, B; Knotts, R M; Poppers, D M
INTRODUCTION: Multi-society recommendations state, "Given the importance of polyp size for informing surveillance intervals, documentation of a polyp > 10 mm within a report should be accompanied by an endoscopic photo of the polyp with comparison to an open snare or open biopsy forceps".1 We evaluate the feasibility of the Napoleon, an endoscopically-deployed small ruler to more accurately measure and document the size of colon polyps.
METHOD(S): The Micro-Tech Endoscopic Gauge (Non-FDA approved) named Napoleon, a catheter with a 15 mm ruler calibrated in 1 mm intervals with demarcations every 5 MM, was advanced through the biopsy channel of a colonoscope and positioned adjacent to a polyp to accurately measure polyp size (Image 1). Polyps sizes were first assessed visually and then measured using the Napoleon. Patients included were 50 to 85 years of age and undergoing screening or surveillance colonoscopy. Napoleon placement, extension/retraction, and photograph acquisition were evaluated on a 1-s10 scale (1 = Easy, 10 = Difficult).
RESULT(S): 23 patients were evaluated by 6 physicians. A total of 36 polyps were found. Each score represents the average of several polyps if more than one polyp was identified per patient (Table 1). The most polyps found in any patient was 3. Each polyp size was placed into 1 of 3 categories (Table 2): 1-5 mm (Diminutive), 6-9 mm (Small) and $ 10 mm (Large). 30 of the 36 total polyps (83%) were diminutive. 3 polyps were downgraded into the next smaller size category after measurement with the Napoleon - specifically, 1 polyp (33%) dropped from small to diminutive size and 2 polyps (67%) dropped from large to small size.
CONCLUSION(S): Prior studies on polyp size have shown that visual assessment is inaccurate.2 This study demonstrates the ease and feasibility of the Napoleon as an endoscopic measuring device. The majority of polyps found were diminutive (1-5 mm) and explains why there is such a minute difference noted in the weighted mean polyp size (0.28 mm). Of the 3 polyps that were visually assessed to be $ 10 mm, 2 of those polyps (67%) were measured to be < 10 mm, changing recommended surveillance from 3 years to 7-10 years.1 Further studies utilizing an endoscopic measuring tool such as the Napoleon are needed to evaluate the effect of accurate polyp measurement on our clinical management, training, and colonoscopy surveillance intervals
EMBASE:633657603
ISSN: 1572-0241
CID: 4718812

Metastatic Cutaneous Squamous Cell Carcinoma of the Colon Presenting as Transfusion-Dependent Hematochezia [Case Report]

Dornblaser, David; Hajdu, Cristina; Rosenberg, Jonathan; Gurvits, Grigoriy
Squamous cell carcinoma (SCC) of the colon is an exceedingly rare clinical diagnosis with few cases reported in the literature. We report a case of a 61-year-old man with a medical history of cutaneous SCC of the penis who presented with hematochezia and was found to have metastatic SCC to the distal transverse colon. To our knowledge, this is the first case of colonic SCC presenting as a metastatic disease from a primary penile site.
PMCID:7145165
PMID: 32309497
ISSN: 2326-3253
CID: 4402062

Colonic irrigation as a non-oral, same-day bowel preparation for colonoscopy: Efficacy, safety, and patient satisfaction [Meeting Abstract]

Smukalla, S M; Liang, P S; Khan, A; Hudesman, D P; Rosenberg, J; Esterow, J; Lucak, B; Pochapin, M B
Introduction: Colonoscopy is the most commonly used test for colorectal cancer screening in the US, but patients often find the oral bowel preparation difficult, inconvenient, or intolerable. Suboptimal bowel prep occurs in 20-24% of colonoscopies, leading to inadequate examinations that necessitate additional procedures. Colonic irrigation is an FDA-approved method of colon cleansing using a warm water lavage, but few studies have evaluated it as preparation for colonoscopy. The purpose of this study is to evaluate colonic irrigation as an alternative to oral bowel prep in patients undergoing screening/ surveillance colonoscopy. Methods: We conducted a single-center, single-arm feasibility study using the Hydro-San Plus system. Patients followed a low-residue diet and took 2 doses of polyethylene glycol the day before the procedure. Colonoscopy was performed immediately following colonic irrigation. Boston Bowel Prep Scale (BBPS) and adverse events were recorded. A telephone questionnaire was administered within 7 days of the procedure. Results: Of the 21 patients enrolled, 48% had at a medical risk factor for poor prep (Table 1). Eighteen patients completed irrigation, of whom 12 (67%) had an adequate bowel prep, defined as BBPS>1 in all segments (Table 2). Two irrigations were not completed due to minor adverse events (discomfort from speculum insertion and rectal abrasion) and 1 was aborted for mechanical repair. There were no major adverse events. Patients with no risk factors for poor prep were 4 times more likely to have an adequate prep, although this was not statistically significant (P=0.14). Half of the patients felt that irrigation was easy (47%) and comfortable (53%), while most felt it was tolerable (71%) and convenient (82%). Among participants who had previous a colonoscopy with oral prep, the majority felt that irrigation was easier (85%), more tolerable (77%), and more convenient (85%) than oral prep. 82% of respondents said they would ask for irrigation again and only 12% said they would refuse if it were offered. Conclusion: Colonic irrigation is a safe and moderately efficacious alternative to oral bowel prep for screening/surveillance colonoscopy. A more potent oral pre-prep, especially for patients with risk factors for poor prep, may improve efficacy. Importantly, patient satisfaction with colonic irrigation appears to be higher than with oral bowel prep. (Table Presented)
EMBASE:620839252
ISSN: 1572-0241
CID: 2968232

Difficult populations : dysphagia/partial SBOs/ICDs/Pediatrics

Chapter by: Gross, Seth A; Dikman, Andrew; Rosenberg, Jonathan
in: Capsule endoscopy : a guide to becoming an efficient and effective reader by Hass, David J (Ed)
Cham, Switzerland : Springer, 2017
pp. 35-47
ISBN: 3319491717
CID: 3426332

Endoscopy plays an important preoperative role in bariatric surgery

Sharaf, Ravi N; Weinshel, Elizabeth H; Bini, Edmund J; Rosenberg, Jonathan; Sherman, Alex; Ren, Christine J
BACKGROUND: The role of upper endoscopy (EGD) in obese patients prior to bariatric surgery is controversial. The aim of this study was to evaluate the diagnostic yield and cost of routine EGD before bariatric surgery. METHODS: The medical records of consecutive obese patients who underwent EGD prior to bariatric surgery between May 2000 and September 2002 were reviewed. Two experienced endoscopists reviewed all EGD reports, and findings were divided into 4 groups based on predetermined criteria: group 0 (normal study), group 1 (abnormal findings that neither changed the surgical approach nor postponed surgery), group 2 (abnormal findings that changed the surgical approach or postponed surgery), and group 3 (results that were an absolute contraindication to surgery). Clinically important findings included lesions in groups 2 and 3. The cost of EGD (430.72 US dollars) was estimated using the endoscopist fee under Medicare reimbursement. RESULTS: During the 28-month study period, 195 patients were evaluated by EGD prior to bariatric surgery. One or more lesions were identified in 89.7% of patients, with 61.5% having a clinically important finding. The prevalence of endoscopic findings using the classification system above was as follows: group 0 (10.3%), group 1 (28.2%), group 2 (61.5%), and group 3 (0.0%). Overall, the most common lesions identified were hiatal hernia (40.0%), gastritis (28.7%), esophagitis (9.2%), gastric ulcer (3.6%), Barrett's esophagus (3.1%), and esophageal ulcer (3.1%). The cost of performing routine endoscopy on all patients prior to bariatric surgery was 699.92 US dollars per clinically important lesion detected. CONCLUSIONS: Routine upper endoscopy before bariatric surgery has a high diagnostic yield and has a low cost per clinically important lesion detected
PMID: 15603653
ISSN: 0960-8923
CID: 49346

Radiologic assessment of the upper gastrointestinal tract: does it play an important preoperative role in bariatric surgery?

Sharaf, Ravi N; Weinshel, Elizabeth H; Bini, Edmund J; Rosenberg, Jonathan; Ren, Christine J
BACKGROUND: The role of upper GI series (UGIS) before bariatric surgery is controversial. The aim of this study was to evaluate the diagnostic yield and cost of routine UGIS prior to bariatric surgery. METHODS: The medical records of consecutive obese patients who underwent UGIS before bariatric surgery between April 2001 and October 2002 were reviewed. UGIS reports were reviewed by 2 experienced gastroenterologists, and the findings were divided into 4 groups based on predetermined criteria: group 0 (normal study), group 1 (abnormal findings that neither changed the surgical approach nor postponed surgery), group 2 (abnormal findings that changed the surgical approach or postponed surgery), and group 3 (results which were an absolute contraindication to surgery). Clinically important findings included lesions in groups 2 and 3. The cost of an upper GI series (154.80 USD) was estimated from the published 2002 New York State Medicare reimbursement schedule. RESULTS: During the 18-month study period, 171 patients were evaluated by UGIS prior to bariatric surgery. One or more lesions were identified in 48.0% of patients, with only 5.3% having clinically important findings. The prevalence of radiologic findings using the classification system above was as follows: group 0 (52.0%), group 1 (42.7%), group 2 (5.3%), and group 3 (0.0%). The most common findings identified were esophageal reflux (21.6%) and hiatal hernias (18.7%). The cost of performing routine UGIS on all patients before bariatric surgery was 2,941.20 USD per clinically important finding detected. CONCLUSIONS: Routine preoperative upper GI series before bariatric surgery had a low diagnostic yield, rarely revealing pathology that changed the surgical approach or postponed surgery
PMID: 15072649
ISSN: 0960-8923
CID: 42670

Endoscopy plays an important role in determining bariatric surgical approach [Meeting Abstract]

Sharaf, RN; Weinshel, EH; Bini, EJ; Rosenberg, J; Sherman, A; Ren, CJ
ISI:000182696600163
ISSN: 0016-5107
CID: 108241