Joshua Melson

Interests

Research

Gastrointestinal cancers, with emphasis on colorectal cancer; Colorectal cancer screening, surveillance, and endoscopic removal of precancerous lesions; Rectal polyposis; Colorectal polyps.

Courses

No activities entered.

Scholarly Contributions

Chapters

• Shapiro, D., Melson, J., & Patil, A. (2013). The Role of Endoscopy in Small Bowel Malignancies. In Gastrointestinal Endoscopy in the Cancer Patient. https://www.wiley.com/en-us/Gastrointestinal+Endoscopy+in+the+Cancer+Patient-p-9780470672464: John Wiley and Sons. doi:10.1002/9781118555651.ch12
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  The role of endoscopy in the management of small bowel cancers is diverse and includes methods for obtaining a tissue diagnosis, staging malignancy, and resection of tumors. In addition, endoscopy allows for management of complications associated with small bowel malignancies, including relief of obstruction and hemostasis. Endoscopic ultrasound is a critical endoscopic technique for the diagnosis and staging of such malignancies and may contribute by defining which lesions are amenable to therapeutic endoscopic resection. Previously, endoscopic techniques were largely limited to the proximal small bowel. However, advancements in endoscopic techniques, including balloon enteroscopy and capsule endoscopy, have enabled endoscopic examination of the entire small bowel. Endoscopic management can be considered as a potential alternative to more invasive surgical approaches for control of bleeding and relief of obstruction in many instances. This edition first published 2013 © 2013 John Wiley & Sons, Limited.

Journals/Publications

• Medawar, E., Pohl, H., Rex, D. K., Levenick, J. M., Pleskow, D. K., Khashab, M. A., Moyer, M., Yang, D., Melson, J., Wallace, M. B., Mosko, J. D., Shahidi, N. C., Singh, A., Gavric, A., Djinbachian, R., Gordon, S. R., Ngamruengphong, S., Taunk, P., Barber, J., , Piraka, C., et al. (2026). Adverse events of cold snare compared with hot snare and ablation endoscopic mucosal resection for large colorectal polyps. Endoscopy, 58(2), 163-173.
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  Endoscopic mucosal resection (EMR) techniques for large (≥20 mm) nonpedunculated colorectal polyps (LNPCPs) have expanded with the introduction of ablation and cold EMR. This study assessed adverse events (AEs) for the newer EMR techniques, including cold EMR, compared with hot EMR.We conducted a secondary analysis of four prospective multicenter studies of consecutive patients with LNPCPs undergoing EMR from 2019 to 2024. The primary outcome was serious AEs (SAEs) with cold and hot EMR. Secondary outcomes included SAEs in the hot EMR subgroups (no ablation [hEMR], margin ablation [hEMR-m], margin and base ablation [hEMR-mb]).1762 patients (mean age 65.8; 1890 LNPCPs) were included: 522 cold and 1368 hot EMRs (368 hEMR, 770 hEMR-m, 230 hEMR-mb). SAEs were higher with hot EMR (4.7%, 95%CI 3.6%-5.9%) vs. cold EMR (1.9%, 95%CI 0.9%-3.5%), also for the subgroups of hEMR (6.0%, 95%CI 3.8%-8.9%), hEMR-m (3.9%, 95%CI 2.6%-5.5%), and hEMR-mb (5.2%, 95%CI 2.7%-8.9%). Serious postendoscopic bleeding (PEB) was numerically higher with hot EMR (2.3%, 95%CI 1.6%-3.3%) vs. cold EMR (1.3%, 95%CI 0.5%-2.7%), also for the subgroups of hEMR (3.0%, 95%CI 1.5%-5.3%), hEMR-m (1.9%, 95%CI 1.1%-3.2%), and hEMR-mb (2.6%, 95%CI 1.0%-5.6%). Perforation, intraprocedural and post-procedural, was numerically higher with hot EMR (1.2%, 95%CI 0.7%-2.0%) vs. cold EMR (0.2%, 95%CI 0.0%-1.1%). hEMR-m and hEMR-mb with clipping had lower rates of serious and overall PEB than no clipping.Cold EMR demonstrated lower rates of SAEs, serious PEB, and perforation compared with hot EMR. Perforation and mortality occurred almost exclusively after hot EMR. Hot EMR with margin +/- base ablation did not increase SAEs compared with hot EMR without ablation.
• Medawar, E., Pohl, H., Rex, D. K., Levenick, J. M., Pleskow, D. K., Khashab, M. A., Moyer, M., Yang, D., Melson, J., Wallace, M. B., Mosko, J. D., Shahidi, N. C., Singh, A., Gavric, A., Djinbachian, R., Gordon, S. R., Ngamruengphong, S., Taunk, P., Barber, J., , Piraka, C., et al. (2025). Adverse events of cold snare compared with hot snare and ablation endoscopic mucosal resection for large colorectal polyps. Endoscopy. doi:10.1055/a-2665-0521
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  Background Endoscopic mucosal resection (EMR) techniques for large (≥20mm) nonpedunculated colorectal polyps (LNPCPs) have expanded with the introduction of ablation and cold EMR. This study assessed adverse events (AEs) for the newer EMR techniques, including cold EMR, compared with hot EMR. Methods We conducted a secondary analysis of four prospective multicenter studies of consecutive patients with LNPCPs undergoing EMR from 2019 to 2024. The primary outcome was serious AEs (SAEs) with cold and hot EMR. Secondary outcomes included SAEs in the hot EMR subgroups (no ablation [hEMR], margin ablation [hEMR-m], margin and base ablation [hEMR-mb]). Results 1762 patients (mean age 65.8; 1890 LNPCPs) were included: 522 cold and 1368 hot EMRs (368 hEMR, 770 hEMR-m, 230 hEMR-mb). SAEs were higher with hot EMR (4.7%, 95%CI 3.6%-5.9%) vs. cold EMR (1.9%, 95%CI 0.9%- 3.5%), also for the subgroups of hEMR (6.0%, 95%CI 3.8%- 8.9%), hEMR-m (3.9%, 95%CI 2.6%-5.5%), and hEMR-mb (5.2%, 95%CI 2.7%-8.9%). Serious postendoscopic bleeding (PEB) was numerically higher with hot EMR (2.3%, 95%CI 1.6%-3.3%) vs. cold EMR (1.3%, 95%CI 0.5%-2.7%), also for the subgroups of hEMR (3.0%, 95%CI 1.5%-5.3%), hEMR-m (1.9%, 95%CI 1.1%-3.2%), and hEMR-mb (2.6%, 95%CI 1.0%-5.6%). Perforation, intraprocedural and post-procedural, was numerically higher with hot EMR (1.2%, 95%CI 0.7%-2.0%) vs. cold EMR (0.2%, 95%CI 0.0%-1.1%). hEMRm and hEMR-mb with clipping had lower rates of serious and overall PEB than no clipping. Conclusions Cold EMR demonstrated lower rates of SAEs, serious PEB, and perforation compared with hot EMR. Perforation and mortality occurred almost exclusively after hot EMR. Hot EMR with margin + /- base ablation did not increase SAEs compared with hot EMR without ablation. Background Endoscopic mucosal resection (EMR) techniques for large (≥20mm) nonpedunculated colorectal polyps (LNPCPs) have expanded with the introduction of ablation and cold EMR. This study assessed adverse events (AEs) for the newer EMR techniques, including cold EMR, compared with hot EMR. Methods We conducted a secondary analysis of four prospective multicenter studies of consecutive patients with LNPCPs undergoing EMR from 2019 to 2024. The primary outcome was serious AEs (SAEs) with cold and hot EMR. Secondary outcomes included SAEs in the hot EMR subgroups (no ablation [hEMR], margin ablation [hEMR-m], margin and base ablation [hEMR-mb]). Results 1762 patients (mean age 65.8; 1890 LNPCPs) were included: 522 cold and 1368 hot EMRs (368 hEMR, 770 hEMR-m, 230 hEMR-mb). SAEs were higher with hot EMR (4.7%, 95%CI 3.6%-5.9%) vs. cold EMR (1.9%, 95%CI 0.9%- 3.5%), also for the subgroups of hEMR (6.0%, 95%CI 3.8%- 8.9%), hEMR-m (3.9%, 95%CI 2.6%-5.5%), and hEMR-mb (5.2%, 95%CI 2.7%-8.9%). Serious postendoscopic bleeding (PEB) was numerically higher with hot EMR (2.3%, 95%CI 1.6%-3.3%) vs. cold EMR (1.3%, 95%CI 0.5%-2.7%), also for the subgroups of hEMR (3.0%, 95%CI 1.5%-5.3%), hEMR-m (1.9%, 95%CI 1.1%-3.2%), and hEMR-mb (2.6%, 95%CI 1.0%-5.6%). Perforation, intraprocedural and post-procedural, was numerically higher with hot EMR (1.2%, 95%CI 0.7%-2.0%) vs. cold EMR (0.2%, 95%CI 0.0%-1.1%). hEMRm and hEMR-mb with clipping had lower rates of serious and overall PEB than no clipping. Conclusions Cold EMR demonstrated lower rates of SAEs, serious PEB, and perforation compared with hot EMR. Perforation and mortality occurred almost exclusively after hot EMR. Hot EMR with margin + /- base ablation did not increase SAEs compared with hot EMR without ablation.
• Melson, J. (2025). Application of the Colorectal Cancer (CRC) Screening Guiding Principles for Non-invasive Testing to Multi-target Stool DNA: A Case Study. Digestive diseases and sciences, 70(5), 1676-1682.
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  A significant lack of participation in colorectal cancer (CRC) screening programs in the United States limits the impact of screening to reduce morbidity and mortality. Recently a group of experts in CRC screening defined the Guiding Principles for Noninvasive Testing (GPNIT). GPNIT pathway is intended to serve as a step by step guide for study design to ultimately lead to implementation and integration of a potentially clinically appropriate CRC screening test. Multi-target stool DNA (MT-sDNA) test usage for CRC screening has increased significantly recently in the United States. Here, the key studies in the development of MT-sDNA as an emerging CRC screening test are placed in context of the GPNIT pathway for CRC screening test development. This case study is meant to be instructive for future test development in CRC screening to achieve ultimately clinically relevant future tests and improve the efficacy of CRC screening.
• Amini-Salehi, E., Letafatkar, N., Norouzi, N., Joukar, F., Habibi, A., Javid, M., Sattari, N., Khorasani, M., Farahmand, A., Tavakoli, S., Masoumzadeh, B., Abbaspour, E., Karimzad, S., Ghadiri, A., Maddineni, G., Khosousi, M. J., Faraji, N., Keivanlou, M. H., Mahapatro, A., , Gaskarei, M. A., et al. (2024). Global Prevalence of Nonalcoholic Fatty Liver Disease: An Updated Review Meta-Analysis comprising a Population of 78 million from 38 Countries. Archives of medical research, 55(6), 103043.
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  Nonalcoholic fatty liver disease (NAFLD) is a global health challenge, with a rising rate in line with other metabolic diseases. We aimed to assess the global prevalence of NAFLD in adult and pediatric populations.
• Melson, J. (2024). Colon polyp surveillance - Similar outcomes by size across the histology divide. Endoscopy, 56(Issue 11). doi:10.1055/a-2377-9945
• Melson, J. (2024). Colon polyp surveillance - similar outcomes by size across the histology divide. Endoscopy, 56(11), 828-830.
• Melson, J. (2024). Red dichromatic imaging: going deeper with electronic chromoendoscopy. Gastrointestinal Endoscopy, 100(2). doi:10.1016/j.gie.2024.04.006
• Melson, J. (2024). Red dichromatic imaging: going deeper with electronic chromoendoscopy. Gastrointestinal endoscopy, 100(2), 305-306.
• Bresalier, R. S., Senore, C., Young, G. P., Allison, J., Benamouzig, R., Benton, S., Bossuyt, P. M., Caro, L., Carvalho, B., Chiu, H. M., Coupé, V. M., de Klaver, W., de Klerk, C. M., Dekker, E., Dolwani, S., Fraser, C. G., Grady, W., Guittet, L., Gupta, S., , Halloran, S. P., et al. (2023). An efficient strategy for evaluating new non-invasive screening tests for colorectal cancer: the guiding principles. Gut, 72(10), 1904-1918.
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  New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers.
• Djinbachian, R., Pohl, H., Rex, D. K., Levenick, J. M., Pleskow, D. K., Wallace, M. B., Khashab, M., Singh, A., Melson, J., Yang, D., Gavrić, A., & von Renteln, D. (2023). Thermal ablation after endoscopic mucosal resection of large colorectal polyps: not only the margins, but also the base?. Gut, 73(1), 12-15.
• Rodgers-Fouche, L., Arora, S., Ricker, C., Li, D., Farooqi, M., Balaguer, F., Dominguez-Valentin, M., Guillem, J. G., Kanth, P., Liska, D., Melson, J., Mraz, K. A., Shirts, B. H., Vilar, E., Katona, B. W., & Hodan, R. (2023). Exploring Stakeholders' Perspectives on Implementing Universal Germline Testing for Colorectal Cancer: Findings From a Clinical Practice Survey. JCO precision oncology, 7, e2300440.
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  New guidelines recommend considering germline genetic testing for all patients with colorectal cancer (CRC). However, there is a lack of data on stakeholders' perspectives on the advantages and barriers of implementing universal germline testing (UGT). This study assessed the perspectives of members of the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer (CGA-IGC) regarding the implementation of UGT for patients with CRC, including readiness, logistics, and barriers.
• Van, J., Alsayid, M., Ma, K., Vemulapalli, K., Rex, D., & Melson, J. (2023). Impact of Cold Snare vs Cold Forceps Resection of Diminutive Adenomas on Segmental Incomplete Resection Rate. The American journal of gastroenterology, 118(8), 1410-1418.
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  Polypectomy technique, for diminutive lesion resection, is variable among colonoscopists using either cold snare polypectomy (CSP) or cold forceps polypectomy (CFP). While it is well described that CSP is a preferred technique to resect small lesions, there is little data evaluating the impact resection techniques have on metachronous adenoma burden. The aim of this study was to evaluate the rate of incomplete resection attributable to CSP and CFP of diminutive adenomas.
• Gebrekiristos, M., Melson, J., Jiang, A., & Buckingham, L. (2022). DNA methylation and miRNA expression in colon adenomas compared with matched normal colon mucosa and carcinomas. International journal of experimental pathology, 103(3), 74-82.
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  Dysregulation of DNA methylation patterns and non-coding RNA, including miRNAs, has been implicated in colon cancer, and these changes may occur early in the development of carcinoma. In this study, the role of epigenetics as early changes in colon tumorigenesis was examined through paired sample analysis of patient-matched normal, adenoma and carcinoma samples. Global methylation was assessed by genomic 5-methyl cytosine (5-mC) and long interspersed nuclear element-1 (LINE-1) promoter methylation by pyrosequencing. KRAS mutations were also assessed by pyrosequencing. Expression of miRNA, specifically, two microRNA genes-miR-200a and let-7c-was analysed using RT-qPCR. Differences in global methylation in adenomas were not observed, compared with normal tissue. However, LINE-1 methylation was decreased in adenomas (p = .056) and carcinomas (p = .011) compared with normal tissue. Expressions of miRNA, miR-200a and let-7c were significantly higher in adenomas than normal tissues (p = .008 and p = .045 respectively). Thus the significant changes in LINE-1 methylation and microRNA expression in precancerous lesions support an early role for epigenetic changes in the carcinogenic process. Epigenetic characteristics in adenomas may provide potential diagnostic and prognostic therapeutic targets early in cancer development at the adenoma stage.
• Hamoudah, T., Vemulapalli, K. C., Alsayid, M., Van, J., Ma, K., Jakate, S., Rex, D. K., & Melson, J. (2022). Risk of total metachronous advanced neoplasia in patients with both small tubular adenomas and serrated polyps. Gastrointestinal endoscopy, 96(1), 95-100.
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  The impact of concomitant small serrated polyps (SPs) on the risk of subsequent neoplasia when small tubular adenomas (TAs) are found is uncertain.
• Melson, J. (2022). The pathway to monitoring quality of care for patients with adenomatous oligopolyposis of unknown etiology. Endoscopy, 54(7), 698-699.
• Pannala, R., Krishnan, K., Watson, R. R., Vela, M. F., Abu Dayyeh, B. K., Bhatt, A., Bhutani, M. S., Bucobo, J. C., Chandrasekhara, V., Copland, A. P., Jirapinyo, P., Kumta, N. A., Law, R. J., Maple, J. T., Melson, J., Parsi, M. A., Rahimi, E. F., Saumoy, M., Sethi, A., , Trikudanathan, G., et al. (2022). Devices for esophageal function testing. Gastrointestinal endoscopy, 95(1), 27-29.
• Post, Z., & Melson, J. (2022). Equal Pay for Equal Screening: Impact of Patient and Provider Gender on Reimbursement for Screening Colonoscopy. Digestive Diseases and Sciences, 67(3). doi:10.1007/s10620-021-07083-2
• Alsayid, M., Van, J., Ma, K., & Melson, J. (2021). Segmental metachronous adenoma rate as a metric for monitoring incomplete resection in a colonoscopy screening program. Gastrointestinal Endoscopy, 94(2). doi:10.1016/j.gie.2021.01.046
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  Background and Aims: Polypectomy technique has been shown to vary among colonoscopists, and interval colorectal cancer may result from incomplete resection of an adenoma. Methods to monitor polypectomy quality and the size of polyps resected to monitor have not been well defined. The aim of this study was to compare the rate of metachronous adenoma attributable to incomplete resection in polyps 6 to 9 mm versus polyps 10 to 20 mm. Methods: The segmental metachronous adenoma rate attributable to incomplete resection (SMAR-IR) was calculated by subtracting the rate of metachronous neoplasia (MN) in segments without adenoma from segments with adenoma. The primary outcome of the study was the SMAR-IR in polyps 6 to 9 mm and 10 to 20 mm found on index colonoscopy. Results: Of 337 patients included in the analysis, 146 patients had a tubular adenoma (TA) 10 to 20 mm in size and 191 patients a TA 6 to 9 mm in size as the most advanced lesion. For cases in which an index 10- to 20-mm TA was resected, the SMAR in segments with adenoma was 21.0% and in segments without adenoma 9.6%, so the SMAR-IR was 11.4% (95% confidence interval, 4.5-18.3). For cases in which an index 6- to 9-mm TA was resected, the SMAR in segments with adenoma was 22.0% and in segments without adenoma 8.8%, so the SMAR-IR was 13.2% (95% confidence interval, 7.2-19.4). Among 6 colonoscopists, the SMAR-IR ranged between 7.0% and 15.5% for polyps 6 to 20 mm. Conclusions: MN rates in segments with a TA 10-20 mm and a TA 6-9 mm are higher than the MN rates in segments without index neoplasia. Incomplete resection of neoplasia appears to be a significant risk factor for MN in 6- to 9-mm lesions as well as larger ones.
• Barlass, U., & Melson, J. (2021). Rev up your engines: a new approach to access the deep small bowel by motorized spiral enteroscopy. Gastrointestinal Endoscopy, 93(6). doi:10.1016/j.gie.2020.12.029
• Chandrasekhara, V., Kumta, N. A., Abu Dayyeh, B. K., Bhutani, M. S., Jirapinyo, P., Krishnan, K., Maple, J. T., Melson, J., Pannala, R., Parsi, M. A., Sethi, A., Trikudanathan, G., Trindade, A. J., & Lichtenstein, D. R. (2021). Endoscopic polypectomy devices. VideoGIE : an official video journal of the American Society for Gastrointestinal Endoscopy, 6(7), 283-293.
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  Video 1Use of submucosal injection prior to en-bloc endoscopic mucosal resection.Video 2Use of a detachable loop ligating device prior to hot snare resection of a pedunculated polyp.
• Jiang, A., Buckingham, L., Bishehsari, F., Sutherland, S., Ma, K., & Melson, J. (2021). Correlation of LINE-1 Hypomethylation with Size and Pathologic Extent of Dysplasia in Colorectal Tubular Adenomas. Clinical and Translational Gastroenterology, 12(6). doi:10.14309/ctg.0000000000000369
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  INTRODUCTION:Conventional adenomas (tubular adenoma [TA] or tubulovillous adenoma) and sessile serrated lesions (SSLs) are neoplastic precancerous lesions frequently detected in patients undergoing average risk screening colonoscopy and polyp surveillance. Metachronous risk stratification of adenomas is currently limited to histologic features and size of polyps. We report long interspersed nucleotide element-1 (LINE-1) methylation levels in SSL in comparison to TA and the impact of TA size and presence of high-grade dysplasia (HGD) on LINE-1 methylation.METHODS:LINE-1 methylation was assessed by pyrosequencing of bisulfite-converted DNA. We compared LINE-1 methylation between TA and SSL, among varying sizes of TA, and between TA with HGD and low-grade dysplasia (LGD).RESULTS:LINE-1 methylation declined with increasing polyp size in TA when comparing those
• Jirapinyo, P., Sethi, A., Abu Dayyeh, B., Bhutani, M., Chandrasekhara, V., Kumta, N., Melson, J., Pannala, R., Rahimi, E., Trikudanathan, G., Maple, J., & Lichtenstein, D. (2021). Devices and techniques for flexible endoscopic management of Zenker's diverticulum (with videos). Gastrointestinal Endoscopy, 94(1). doi:10.1016/j.gie.2021.02.020
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  Background and Aims: Zenker's diverticulum (ZD) has traditionally been treated with open surgery or rigid endoscopy. With the advances in endoscopy, alternative flexible endoscopic treatments have been developed. Methods: This document reviews current endoscopic techniques and devices used to treat ZD. Results: The endoscopic techniques may be categorized as the traditional flexible endoscopic septal division and the more recent submucosal tunneling endoscopic septum division, also known as peroral endoscopic myotomy for ZD. This document also addresses clinical outcomes, safety, and financial considerations. Conclusions: Flexible endoscopic approaches treat symptomatic ZD with results that are favorable compared with traditional open surgical or rigid endoscopic alternatives.
• Krishnan, K., Bhutani, M. S., Aslanian, H. R., Melson, J., Navaneethan, U., Pannala, R., Parsi, M. A., Schulman, A. R., Sethi, A., Sullivan, S., Trikudanathan, G., Trindade, A. J., Watson, R. R., Maple, J. T., & Lichtenstein, D. R. (2021). Enhanced EUS imaging (with videos). Gastrointestinal Endoscopy, 93(Issue 2). doi:10.1016/j.gie.2020.06.075
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  Background and Aims: EUS remains a primary diagnostic tool for the evaluation of pancreaticobiliary disease. Although EUS combined with FNA or biopsy sampling is highly sensitive for the diagnosis of neoplasia within the pancreaticobiliary tract, limitations exist in specific clinical settings such as chronic pancreatitis. Enhanced EUS imaging technologies aim to aid in the detection and diagnosis of lesions that are commonly evaluated with EUS. Methods: We reviewed technologies and methods for enhanced imaging during EUS and applications of these methods. Available data regarding efficacy, safety, and financial considerations are summarized. Results: Enhanced EUS imaging methods include elastography and contrast-enhanced EUS (CE-EUS). Both technologies have been best studied in the setting of pancreatic mass lesions. Robust data indicate that neither technology has adequate specificity to serve as a stand-alone test for pancreatic malignancy. However, there may be a role for improving the targeting of sampling and in the evaluation of peritumoral lymph nodes, inflammatory pancreatic masses, and masses with nondiagnostic FNA or fine-needle biopsy sampling. Further, novel applications of these technologies have been reported in the evaluation of liver fibrosis, pancreatic cysts, and angiogenesis within neoplastic lesions. Conclusions: Elastography and CE-EUS may improve the real-time evaluation of intra- and extraluminal lesions as an adjunct to standard B-mode and Doppler imaging. They are not a replacement for EUS-guided tissue sampling but provide adjunctive diagnostic information in specific clinical situations. The optimal clinical use of these technologies continues to be a focus of ongoing research.
• Melson, J., Trikudanathan, G., Abu Dayyeh, B. K., Bhutani, M. S., Chandrasekhara, V., Jirapinyo, P., Krishnan, K., Kumta, N. A., Pannala, R., Parsi, M. A., Sethi, A., Trindade, A. J., Watson, R. R., Maple, J. T., & Lichtenstein, D. R. (2021). Video capsule endoscopy. Gastrointestinal Endoscopy, 93(Issue 4). doi:10.1016/j.gie.2020.12.001
• Park, E., Barge, W., Kramer, J., Alajati, B., Jakate, S., Cimbaluk, D., Giusto, D., Ritz, E., Bishehsari, F., Lee, S., Singh, S., Losurdo, J., Brown, M., Demeo, M., Abraham, R., Ma, K., & Melson, J. (2021). Interobserver reliability of methods to determine complete resection of adenomas in colonoscopy. Endoscopy, 53(12). doi:10.1055/a-1331-4446
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  Background Forceps margin biopsy and polypectomy specimen margins have both been used to assess for polypectomy resection adequacy. The interobserver reliability of the two methods has not been well described. Methods The interpretability of polypectomy specimens for presence of residual neoplasia at the margin was assessed by two blinded pathologists. Next, the concordance of forceps margin biopsy interpretations between three blinded pathologists was evaluated by calculation of interobserver κ. Results Rates of polypectomy specimen margin interpretability were low: 24/92 (26%) for pathologist A, 28/92 (30.4%) for pathologist B. Concordance of forceps margin biopsy interpretations (n=129) between pathologists was high. Two internal pathologists showed substantial agreement in margin biopsy interpretations (κ 0.779; 95%CL 0.543, 0.912). The concordance remained strong after biopsies were reviewed by a third, external pathologist (κ 0.829; 95%CL 0.658, 0.924). There was complete agreement on 123/129 (95.3%) between all three pathologists for presence of neoplasia. Conclusion The majority of polypectomy specimen margins were uninterpretable by pathologists for presence of residual neoplasia. Forceps margin biopsy shows strong interobserver reliability in adenomatous lesions.
• Tjaden, J., Muller, C., Wideroff, G., Ma, K., Satiya, J., Sussman, D., Yen, E., Kupfer, S., & Melson, J. (2021). Metachronous Advanced Neoplasia on Surveillance Colonoscopy in Patients With Young- vs Older-onset of Colorectal Cancer. Clinical Gastroenterology and Hepatology, 19(9). doi:10.1016/j.cgh.2019.07.034
• Alsayid, M., & Melson, J. (2020). Will magnet-assisted capsule endoscopy become a viable screening tool for Barrett's esophagus and esophageal varices?. Gastrointestinal Endoscopy, 91(4). doi:10.1016/j.gie.2019.12.015
• Ma, K., & Melson, J. (2020). Connecting colonoscopy quality improvement initiatives with reduced rates of interval colorectal cancers. Gastrointestinal Endoscopy, 92(2). doi:10.1016/j.gie.2020.03.3860
• Melson, J. E., Imperiale, T. F., Itzkowitz, S. H., Llor, X., Kochman, M. L., Grady, W. M., Schoen, R. E., Burke, C. A., Shaukat, A., Rabeneck, L., Ladabaum, U., Bresalier, R., Spiegel, B., Yee, J., Wang, T., Lieberman, D., Komanduri, S., Muthusamy, V. R., & Dey, N. (2020). AGA White Paper: Roadmap for the Future of Colorectal Cancer Screening in the United States. Clinical Gastroenterology and Hepatology, 18(Issue 12). doi:10.1016/j.cgh.2020.06.053
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  The American Gastroenterological Association's Center for Gastrointestinal Innovation and Technology convened a consensus conference in December 2018, entitled, “Colorectal Cancer Screening and Surveillance: Role of Emerging Technology and Innovation to Improve Outcomes.” The goal of the conference, which attracted more than 60 experts in screening and related disciplines, including the authors, was to envision a future in which colorectal cancer (CRC) screening and surveillance are optimized, and to identify barriers to achieving that future. This White Paper originates from that meeting and delineates the priorities and steps needed to improve CRC outcomes, with the goal of minimizing CRC morbidity and mortality. A one-size-fits-all approach to CRC screening has not and is unlikely to result in increased screening uptake or desired outcomes owing to barriers stemming from behavioral, cultural, and socioeconomic causes, especially when combined with inefficiencies in deployment of screening technologies. Overcoming these barriers will require the following: efficient utilization of multiple screening modalities to achieve increased uptake; continued development of noninvasive screening tests, with iterative reassessments of how best to integrate new technologies; and improved personal risk assessment to better risk-stratify patients for appropriate screening testing paradigms.
• Musher, B., Melson, J., Amato, G., Chan, D., Hill, M., Khan, I., Kochuparambil, S., Lyons, S., Orsini, J., Pedersen, S., Robb, B., Saltzman, J., Silinsky, J., Gaur, S., Tuck, M., LaPointe, L., & Young, G. (2020). Evaluation of circulating tumor DNA for methylated BCAT1 and IKZF1 to detect recurrence of stage II/Stage III Colorectal Cancer (CRC). Cancer Epidemiology Biomarkers and Prevention, 29(12). doi:10.1158/1055-9965.EPI-20-0574
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  Background: Most recurrences of early-stage colorectal cancer detected with current surveillance measures are widespread and incurable. Circulating tumor DNA (ctDNA) may facilitate earlier diagnosis of recurrent colorectal cancer and improve cancer-related outcomes. Methods: Plasma from patients undergoing standard surveillance after definitive treatment for stage II/III colorectal cancer was assayed with COLVERA and carcinoembryonic antigen (CEA) at a single time point. Results were correlated with radiographic imaging. Assay performance, including sensitivity and specificity for recurrence, were compared. Impact of potentially confounding variables was also explored. Results: 322 patients were included in the final analysis, and 27 recurrences were documented over a median follow-up period of 15 months. Sensitivity for recurrence was 63% [confidence interval (CI), 42.4.80.6] and 48% (CI, 28.7.68.1) for COLVERA and CEA (≥5 ng/mL), respectively (P = 0.046), while specificity was 91.5% (CI, 87.7.94.4) and 96.3% (CI, 93.4.98.1), respectively (P = 0.016). Smoking and age were independent predictors of CEA but not COLVERA positivity. Conclusions: COLVERA was more sensitive but less specific than CEA in detecting recurrent colorectal cancer. Short median follow-up may have been responsible for apparent false positives in COLVERA. Studies with serial sampling and longer follow-up are needed to assess whether earlier detection of colorectal cancer recurrence translates into clinical benefit. Impact: This prospective study showed that COLVERA (a twogene ctDNA assay) was more sensitive for detection of recurrence in a cohort of patients undergoing surveillance after definitive therapy for stages II and III colorectal cancer.
• Pannala, R., Krishnan, K., Melson, J., Parsi, M. A., Schulman, A. R., Sullivan, S., Trikudanathan, G., Trindade, A. J., Watson, R. R., Maple, J. T., & Lichtenstein, D. R. (2020). Artificial intelligence in gastrointestinal endoscopy. VideoGIE, 5(Issue 12). doi:10.1016/j.vgie.2020.08.013
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  Background and Aims: Artificial intelligence (AI)-based applications have transformed several industries and are widely used in various consumer products and services. In medicine, AI is primarily being used for image classification and natural language processing and has great potential to affect image-based specialties such as radiology, pathology, and gastroenterology (GE). This document reviews the reported applications of AI in GE, focusing on endoscopic image analysis. Methods: The MEDLINE database was searched through May 2020 for relevant articles by using key words such as machine learning, deep learning, artificial intelligence, computer-aided diagnosis, convolutional neural networks, GI endoscopy, and endoscopic image analysis. References and citations of the retrieved articles were also evaluated to identify pertinent studies. The manuscript was drafted by 2 authors and reviewed in person by members of the American Society for Gastrointestinal Endoscopy Technology Committee and subsequently by the American Society for Gastrointestinal Endoscopy Governing Board. Results: Deep learning techniques such as convolutional neural networks have been used in several areas of GI endoscopy, including colorectal polyp detection and classification, analysis of endoscopic images for diagnosis of Helicobacter pylori infection, detection and depth assessment of early gastric cancer, dysplasia in Barrett's esophagus, and detection of various abnormalities in wireless capsule endoscopy images. Conclusions: The implementation of AI technologies across multiple GI endoscopic applications has the potential to transform clinical practice favorably and improve the efficiency and accuracy of current diagnostic methods.
• Parsi, M., Jirapinyo, P., Abu Dayyeh, B., Bhutani, M., Chandrasekhara, V., Krishnan, K., Kumta, N., Melson, J., Pannala, R., Trikudanathan, G., Trindade, A., Sethi, A., Watson, R., Maple, J., & Lichtenstein, D. (2020). Techniques and devices for the endoscopic treatment of gastroparesis (with video). Gastrointestinal Endoscopy, 92(3). doi:10.1016/j.gie.2020.03.3857
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  Background and Aims: Gastroparesis is a symptomatic chronic disorder of the stomach characterized by delayed gastric emptying in the absence of mechanical obstruction. Several endoscopic treatment modalities have been described that aim to improve gastric emptying and/or symptoms associated with gastroparesis refractory to dietary and pharmacologic management. Methods: In this report we review devices and techniques for endoscopic treatment of gastroparesis, the evidence regarding their efficacy and safety, and the financial considerations for their use. Results: Endoscopic modalities for treatment of gastroparesis can be broadly categorized into pyloric, nonpyloric, and nutritional therapies. Pyloric therapies such as botulinum toxin injection, stent placement, pyloroplasty, and pyloromyotomy specifically focus on pylorospasm as a therapeutic target. These interventions aim to reduce the pressure gradient across the pyloric sphincter, with a resultant improvement in gastric emptying. Nonpyloric therapies, such as venting gastrostomy and gastric electrical stimulation, are intended to improve symptoms. Nutritional therapies, such as feeding tube placement, aim to provide nutritional support. Conclusions: Several endoscopic interventions have shown utility in improving the quality of life and symptoms of select patients with refractory gastroparesis. Methods to identify which patients are best suited for a specific treatment are not well established. Endoscopic pyloromyotomy is a relatively recent development that may prove to be the preferred pyloric-directed intervention, although additional and longer-term outcomes are needed.
• Schulman, A., Watson, R., Abu Dayyeh, B., Bhutani, M., Chandrasekhara, V., Jirapinyo, P., Krishnan, K., Kumta, N., Melson, J., Pannala, R., Parsi, M., Trikudanathan, G., Trindade, A., Maple, J., & Lichtenstein, D. (2020). Endoscopic devices and techniques for the management of bariatric surgical adverse events (with videos)†. Gastrointestinal Endoscopy, 92(3). doi:10.1016/j.gie.2020.04.002
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  Background and Aims: As the prevalence of obesity continues to rise, increasing numbers of patients undergo bariatric surgery. Management of adverse events of bariatric surgery may be challenging and often requires a multidisciplinary approach. Endoscopic intervention is often the first line of therapy for management of these adverse events. This document reviews technologies and techniques used for endoscopic management of adverse events of bariatric surgery, organized by surgery type. Methods: The MEDLINE database was searched through May 2018 for articles related to endoscopic management of adverse events of bariatric interventions by using relevant keywords such as adverse events related to “gastric bypass,” “sleeve gastrectomy,” “laparoscopic adjustable banding,” and “vertical banded sleeve gastroplasty,” in addition to “endoscopic treatment” and “endoscopic management,” among others. Available data regarding efficacy, safety, and financial considerations are summarized. Results: Common adverse events of bariatric surgery include anastomotic ulcers, luminal stenoses, fistulae/leaks, and inadequate initial weight loss or weight regain. Devices used for endoscopic management of bariatric surgical adverse events include balloon dilators (hydrostatic, pneumatic), mechanical closure devices (clips, endoscopic suturing system, endoscopic plication platform), luminal stents (covered esophageal stents, lumen-apposing metal stents, plastic stents), and thermal therapy (argon plasma coagulation, needle-knives), among others. Available data, composed mainly of case series and retrospective cohort studies, support the primary role of endoscopic management. Multiple procedures and techniques are often required to achieve clinical success, and existing management algorithms are evolving. Conclusions: Endoscopy is a less invasive alternative for management of adverse events of bariatric surgery and for revisional procedures. Endoscopic procedures are frequently performed in the context of multidisciplinary management with bariatric surgeons and interventional radiologists. Treatment algorithms and standards of practice for endoscopic management will continue to be refined as new dedicated technology and data emerge.
• Alcala, A., Burgess, N., Abe, S., Melson, J., & East, J. (2019). Best reviewers 2018 awards. Endoscopy, 51(4). doi:10.1055/a-0861-3356
• Aslanian, H. R., Sethi, A., Bhutani, M. S., Goodman, A. J., Krishnan, K., Lichtenstein, D. R., Melson, J., Navaneethan, U., Pannala, R., Parsi, M. A., Schulman, A. R., Sullivan, S. A., Thosani, N., Trikudanathan, G., Trindade, A. J., Watson, R. R., & Maple, J. T. (2019). ASGE guideline for endoscopic full-thickness resection and submucosal tunnel endoscopic resection. VideoGIE, 4(Issue 8). doi:10.1016/j.vgie.2019.03.010
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  With the development of reliable endoscopic closure techniques and tools, endoscopic full-thickness resection (EFTR) is emerging as a therapeutic option for the treatment of subepithelial tumors and epithelial neoplasia with significant fibrosis. EFTR may be categorized as “exposed” and “nonexposed.” In exposed EFTR, the full-thickness resection is undertaken with a tunneled or nontunneled technique, with subsequent closure of the defect. In nonexposed EFTR, a secure serosa-to-serosa apposition is achieved before full-thickness resection of the isolated lesion. This document reviews current techniques and devices used for EFTR and reviews clinical applications and outcomes.
• Goodman, A. J., Melson, J., Aslanian, H. R., Bhutani, M. S., Krishnan, K., Lichtenstein, D. R., Navaneethan, U., Pannala, R., Parsi, M. A., Schulman, A. R., Sethi, A., Sullivan, S. A., Thosani, N., Trikudanathan, G., Trindade, A. J., Watson, R. R., & Maple, J. T. (2019). Endoscopic simulators. Gastrointestinal Endoscopy, 90(Issue 1). doi:10.1016/j.gie.2018.10.037
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  Background and Aims: Simulation refers to educational tools that allow for repetitive instruction in a nonpatient care environment that is risk-free. In GI endoscopy, simulators include ex vivo animal tissue models, live animal models, mechanical models, and virtual reality (VR) computer simulators. Methods: After a structured search of the peer-reviewed medical literature, this document reviews commercially available GI endoscopy simulation systems and clinical outcomes of simulation in endoscopy. Results: Mechanical simulators and VR simulators are frequently used early in training, whereas ex vivo and in vivo animal models are more commonly used for advanced endoscopy training. Multiple studies and systematic reviews show that simulation-based training appears to provide novice endoscopists with some advantage over untrained peers with regard to endpoints such as independent procedure completion and performance time, among others. Data also suggest that simulation training may accelerate the acquisition of specific technical skills in colonoscopy and upper endoscopy early in training. However, the available literature suggests that the benefits of simulator training appear to attenuate and cease after a finite period. Further studies are needed to determine if meeting competency metrics using simulation will predict actual clinical competency. Conclusions: Simulation training is a promising modality that may aid in endoscopic education. However, for widespread incorporation of simulators into gastroenterology training programs to occur, simulators must show a sustained advantage over traditional mentored teaching in a cost-effective manner. Because most studies evaluating simulation have focused on novice learners, the role of simulation training in helping practicing endoscopists gain proficiency using new techniques and devices should be further explored.
• Parsi, M. A., Schulman, A. R., Aslanian, H. R., Bhutani, M. S., Krishnan, K., Lichtenstein, D. R., Melson, J., Navaneethan, U., Pannala, R., Sethi, A., Trikudanathan, G., Trindade, A. J., Watson, R. R., & Maple, J. T. (2019). Devices for endoscopic hemostasis of nonvariceal GI bleeding (with videos). VideoGIE, 4(Issue 7). doi:10.1016/j.vgie.2019.02.004
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  Background: Endoscopic intervention is often the first line of therapy for GI nonvariceal bleeding. Although some of the devices and techniques used for this purpose have been well studied, others are relatively new, with few available outcomes data. Methods: In this document, we review devices and techniques for endoscopic treatment of nonvariceal GI bleeding, the evidence regarding their efficacy and safety, and financial considerations for their use. Results: Devices used for endoscopic hemostasis in the GI tract can be classified into injection devices (needles), thermal devices (multipolar/bipolar probes, hemostatic forceps, heater probe, argon plasma coagulation, radiofrequency ablation, and cryotherapy), mechanical devices (clips, suturing devices, banding devices, stents), and topical devices (hemostatic sprays). Conclusions: Endoscopic evaluation and treatment remains a cornerstone in the management of nonvariceal upper- and lower-GI bleeding. A variety of devices is available for hemostasis of bleeding lesions in the GI tract. Other than injection therapy, which should not be used as monotherapy, there are few compelling data that strongly favor any one device over another. For endoscopists, the choice of a hemostatic device should depend on the type and location of the bleeding lesion, the availability of equipment and expertise, and the cost of the device.
• Trindade, A. J., Navaneethan, U., Aslanian, H. R., Bhutani, M. S., Krishnan, K., Lichtenstein, D. R., Melson, J., Pannala, R., Parsi, M. A., Schulman, A. R., Sethi, A., Trikudanathan, G., Watson, R. R., & Maple, J. T. (2019). Advances in the diagnosis and surveillance of Barrett's esophagus (with videos). Gastrointestinal Endoscopy, 90(Issue 3). doi:10.1016/j.gie.2019.05.004
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  Background and Aims: Most patients diagnosed with esophageal adenocarcinoma do not carry a known diagnosis of Barrett's esophagus (BE), suggesting that an improved approach to screening may potentially be of benefit. The use of dysplasia as a biomarker and random biopsy protocols for its detection has limitations. In addition, detecting and appropriately classifying dysplasia in patients with known BE can be difficult. Methods: This document reviews several technologies with a recently established or potential role in the diagnosis and/or surveillance of BE as well as risk stratification for progression to esophageal adenocarcinoma. Results: Two technologies were reviewed for imaging or tissue sampling: (1) wide-area transepithelial sampling and (2) volumetric laser endomicroscopy. Four technologies were reviewed for molecular and biomarker technologies for diagnosis and risk stratification: (1) Cytosponge, (2) mutational load, (3) fluorescence in situ hybridization, and (4) immunohistochemistry. Conclusion: Several technologies discussed in this document may improve dysplasia detection in BE in a wide-field manner. Moreover, the addition of different biomarkers may aid in enhanced risk stratification to optimize approaches to surveillance or treatment for patients with BE.
• Vleugels, J., Hassan, C., Senore, C., Cassoni, P., Baron, J., Rex, D., Ponugoti, P., Pellise, M., Parejo, S., Bessa, X., Arnau-Collell, C., Kaminski, M., Bugajski, M., Wieszczy, P., Kuipers, E., Melson, J., Ma, K., Holman, R., Dekker, E., & Pohl, H. (2019). Diminutive Polyps With Advanced Histologic Features Do Not Increase Risk for Metachronous Advanced Colon Neoplasia. Gastroenterology, 156(3). doi:10.1053/j.gastro.2018.10.050
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  Background & Aims: With advances in endoscopic imaging, it is possible to differentiate adenomatous from hyperplastic diminutive (1–5 mm) polyps during endoscopy. With the optical Resect-and-Discard strategy, these polyps are then removed and discarded without histopathology assessment. However, failure to recognize adenomas (vs hyperplastic polyps), or discarding a polyp with advanced histologic features, could result in a patient being considered at low risk for metachronous advanced neoplasia, resulting in an inappropriately long surveillance interval. We collected data from international cohorts of patients undergoing colonoscopy to determine what proportion of patients are high risk because of diminutive polyps advanced histologic features and their risk for metachronous advanced neoplasia. Methods: We collected data from 12 cohorts (in the United States or Europe) of patients undergoing colonoscopy after a positive result from a fecal immunochemical test (FIT cohort, n = 34,221) or undergoing colonoscopies for screening, surveillance, or evaluation of symptoms (colonoscopy cohort, n = 30,123). Patients at high risk for metachronous advanced neoplasia were defined as patients with polyps that had advanced histologic features (cancer, high-grade dysplasia, ≥25% villous features), 3 or more diminutive or small (6–9 mm) nonadvanced adenomas, or an adenoma or sessile serrated lesion ≥10 mm. Using an inverse variance random effects model, we calculated the proportion of diminutive polyps with advanced histologic features; the proportion of patients classified as high risk because their diminutive polyps had advanced histologic features; and the risk of these patients for metachronous advanced neoplasia. Results: In 51,510 diminutive polyps, advanced histologic features were observed in 7.1% of polyps from the FIT cohort and 1.5% polyps from the colonoscopy cohort (P =.044); however, this difference in prevalence did not produce a significant difference in the proportions of patients assigned to high-risk status (0.8% of patients in the FIT cohort and 0.4% of patients in the colonoscopy cohort) (P =.25). The proportions of high-risk patients because of diminutive polyps with advanced histologic features who were found to have metachronous advanced neoplasia (17.6%) did not differ significantly from the proportion of low-risk patients with metachronous advanced neoplasia (14.6%) (relative risk for high-risk categorization, 1.13; 95% confidence interval 0.79–1.61). Conclusion: In a pooled analysis of data from 12 international cohorts of patients undergoing colonoscopy for screening, surveillance, or evaluation of symptoms, we found that diminutive polyps with advanced histologic features do not increase risk for metachronous advanced neoplasia.
• Vutien, P., Shah, R., Ma, K., Saleem, N., & Melson, J. (2019). Utilization of Census Tract-Based Neighborhood Poverty Rates to Predict Non-adherence to Screening Colonoscopy. Digestive Diseases and Sciences, 64(9). doi:10.1007/s10620-019-05585-8
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  Objectives: Efforts to improve colorectal cancer (CRC) screening rates include recognizing predictors of colonoscopy non-adherence and identifying these high-risk patient populations. Past studies have focused on individual-level factors but few have evaluated the influence of neighborhood-level predictors. We sought to assess the effect of census tract-based neighborhood poverty rates on scheduled screening colonoscopy non-adherence. Methods: In this prospective observational cohort study, data from electronic medical records and appointment tracking software were collected in 599 patients scheduled to undergo outpatient CRC screening colonoscopy at two academic endoscopy centers between January 2011 and December 2012. Non-adherence was defined as failure to attend a colonoscopy appointment within 1 year of the date it was electronically scheduled. Neighborhood poverty rate was determined by matching patients’ self-reported home address with their corresponding US census tract. Individual factors including medical comorbidities and prior appointment adherence behavior were also collected. Results: Overall, 17% (65/383) of patients were non-adherent to scheduled colonoscopy at 1-year follow-up. Neighborhood poverty rate was a significant predictor of non-adherence to scheduled screening colonoscopy in multivariate modeling (OR 1.53 per 10% increase in neighborhood poverty rate, 95% CI 1.21–1.95, p < 0.001). By incorporating the neighborhood poverty rate, screening colonoscopy non-adherence was 31% at the highest quartile compared to 14% at the lowest quartile of neighborhood poverty rates (p = 0.006). Conclusions: Census tract-based neighborhood poverty rates can be used to predict non-adherence to scheduled screening colonoscopy. Targeted efforts to increase CRC screening efficiency and completion among patients living in high-poverty geographic regions could reduce screening disparities and improve utilization of endoscopy unit resources.
• Barge, W., Kumar, D., Giusto, D., Kramer, J., Behara, R., Jakate, S., Bishehsari, F., Losurdo, J., Lee, S., Singh, S., & Melson, J. (2018). Alternative approaches to polyp extraction in colonoscopy: a proof of principle study. Gastrointestinal Endoscopy, 88(3). doi:10.1016/j.gie.2018.05.015
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  Background and Aims: A limitation of determination of the completeness of resection in polypectomy is polyp fragmentation. When a polyp fragments, the pathologist cannot determine resection completeness. Alternative approaches to reduce polyp fragmentation include reducing shearing forces on the polyp or removing polyps through the instrument channel. The primary aim of this study was to assess fragmentation of polyps extracted using different approaches from conventional polyp retrieval. Methods: Polyps (5-15 mm) resected by cold snare or cautery by 3 colonoscopists were extracted from the colonoscope using 1 of 4 techniques. Method I was the conventional method of pressing the suction valve button and retrieving the polyp through a trap. Method II involved removing the suction valve, covering the open suction valve cylinder with a finger. Method III used a Roth Net polyp retriever placed through the instrument channel. Method IV involved connecting a polyp trap to suction onto the instrument channel port. Fragmentation was defined as multiple pieces of the specimen in formalin, as grossly described by the pathologist. Alternative approaches (methods II, III, and IV) were all compared with the conventional method (method I). Results: The method I fragmentation rate of polyps was 60.3% (123/204). Method II extraction reduced fragmentation to 43.0% (52/121, P =.003), proving that fragmentation occurs with passage through the suction valve channel. Method III had a lower fragmentation rate of 23.1% (6/26, P
• Hamoudah, T., Ma, K., Esteban, M., Hayat, W., Berger, D., Mahon, B., Jakate, S., & Melson, J. (2018). Patients with small and diminutive proximal hyperplastic polyps have higher rates of synchronous advanced neoplasia compared with patients without serrated lesions. Gastrointestinal Endoscopy, 87(6). doi:10.1016/j.gie.2017.12.028
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  Background and Aims: The association of proximal small and diminutive hyperplastic polyps (HPs) with synchronous advanced neoplasia is not well-defined. However, sessile serrated polyps (SSPs), even when small, are known to portend a risk of synchronous neoplasia. Currently, the U.S. Multi-Society Task Force on Colorectal Cancer does not recommend a change in the surveillance interval when proximal small HPs are detected. We aimed to compare the rates of synchronous advanced neoplasia in a screening colonoscopy cohort of patients with small and then diminutive proximal HPs in comparison, first to a cohort absent any serrated or proximal HPs and then in comparison with a cohort with small proximal SSPs. Methods: Consecutive screening colonoscopies were recorded between 2005 and 2010 at an academic medical center. Patients were divided into 3 mutually exclusive groups. Group 1 consisted of patients with at least 1 HP that was proximal to the sigmoid colon,
• Ma, K., & Melson, J. (2018). Managing the patient with colorectal adenomas found at an early age. Gastrointestinal Endoscopy, 87(3). doi:10.1016/j.gie.2017.07.036
• Ma, K., & Melson, J. (2018). Postcolonoscopy colorectal cancer rates: monitoring and reducing the worst-case scenario. Gastrointestinal Endoscopy, 88(4). doi:10.1016/j.gie.2018.07.006
• Muller, C., Lee, S., Barge, W., Siddique, S., Berera, S., Wideroff, G., Tondon, R., Chang, J., Peterson, M., Stoll, J., Katona, B., Sussman, D., Melson, J., & Kupfer, S. (2018). Low Referral Rate for Genetic Testing in Racially and Ethnically Diverse Patients Despite Universal Colorectal Cancer Screening. Clinical Gastroenterology and Hepatology, 16(12). doi:10.1016/j.cgh.2018.08.038
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  Background & Aims: Guidelines recommend that all colorectal tumors be assessed for mismatch repair deficiency, which could increase identification of patients with Lynch syndrome. This is of particular importance for minority populations, in whom hereditary syndromes are under diagnosed. We compared rates and outcomes of testing all tumor samples (universal testing) collected from a racially and ethnically diverse population for features of Lynch syndrome. Methods: We performed a retrospective analysis of colorectal tumors tested from 2012 through 2016 at 4 academic centers. Tumor samples were collected from 767 patients with colorectal cancer (52% non-Hispanic white [NHW], 26% African American, and 17% Hispanic patients). We assessed rates of tumor testing, recommendations for genetic evaluation, rates of attending a genetic evaluation, and performance of germline testing overall and by race/ethnicity. We performed univariate and multivariate regression analyses. Results: Overall, 92% of colorectal tumors were analyzed for mismatch repair deficiency without significant differences among races/ethnicities. However, minority patients were significantly less likely to be referred for genetic evaluation (21.2% for NHW patients vs 16.9% for African American patients and 10.9% for Hispanic patients; P =.02). Rates of genetic testing were also lower among minority patients (10.7% for NHW patients vs 6.0% for AA patients and 3.1% for Hispanic patients; P
• Tjaden, J., Hause, J., Berger, D., Duveneck, S., Jakate, S., Orkin, B., Hubbard, E., & Melson, J. (2018). Adenoma detection rate metrics in colorectal cancer surveillance colonoscopy. Surgical Endoscopy, 32(7). doi:10.1007/s00464-018-6025-3
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  Background: A target goal for screening adenoma detection rate (S-ADR) of ≥ 25% has been set to define high-quality colonoscopy performance. However, there is no current accepted target goal for ADR in colorectal cancer (CRC) surveillance. This makes quality assessment challenging when physicians perform cancer surveillance colonoscopy but minimal screening procedures. Methods: In this cohort study, consecutive colonoscopies performed at either Rush University Medical Center or Rush Oak Park Hospital by a gastroenterologist or colorectal surgeon in average risk screening population and CRC surveillance population were reviewed retrospectively from 2006 to 2012 and prospectively from 2013 to 2016. ADR in first surveillance colonoscopy following surgical resection of CRC (CRC-ADR) was reported in high-quality detectors (HQD) or low-quality detectors (LQD) based on achievement of 25% ADR in consecutive screening colonoscopy in average risk patients. Pearson’s correlation was used to describe the association between individual S-ADR and CRC-ADR for colonoscopists. Results: There was a very strong positive correlation (r = 0.88, p = 0.002) between ADR in average risk screening and first time CRC surveillance. For HQD as defined by S-ADR ≥ 25% (n = 10 colonoscopists), the CRC-ADR was 37.7% (78/207, SD 8%) which was very similar to their respective S-ADR of 33.4% (816/2440, p = 0.22). For LQD (n = 5 colonoscopists), the CRC-ADR was 20.2% (40/198) which was similar to their respective S-ADR of 20.1% (119/591, p = 0.99). The CRC-ADR was significantly higher for HQD than for LQD (37.7 vs. 20.2%, p < 0.0001). Conclusions: The major finding of this study is a defined CRC-ADR for HQD based on the ability to achieve S-ADR ≥ 25%. S-ADR strongly correlates with CRC-ADR. CRC-ADR is quite similar to the colonoscopists’ respective S-ADR for both HQD and LQD. For colonoscopists who perform limited screening colonoscopies but do perform CRC surveillance colonoscopies, ADR metrics similar to S-ADR to assess quality in colonoscopy could be considered.
• Watson, R. R., Parsi, M. A., Aslanian, H. R., Goodman, A. J., Lichtenstein, D. R., Melson, J., Navaneethan, U., Pannala, R., Sethi, A., Sullivan, S. A., Thosani, N. C., Trikudanathan, G., Trindade, A. J., & Maple, J. T. (2018). Biliary and pancreatic lithotripsy devices. VideoGIE, 3(Issue 11). doi:10.1016/j.vgie.2018.07.010
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  Background and Aims: Lithotripsy is a procedure for fragmentation or destruction of stones to facilitate their removal or passage from the biliary or pancreatic ducts. Although most stones may be removed endoscopically using conventional techniques such as endoscopic sphincterotomy in combination with balloon or basket extraction, lithotripsy may be required for clearance of large, impacted, or irregularly shaped stones. Several modalities have been described, including intracorporeal techniques such as mechanical lithotripsy (ML), electrohydraulic lithotripsy (EHL), and laser lithotripsy, as well as extracorporeal shock-wave lithotripsy (ESWL). Methods: In this document, we review devices and methods for biliary and pancreatic lithotripsy and the evidence regarding efficacy, safety, and financial considerations. Results: Although many difficult stones can be safely removed using ML, endoscopic papillary balloon dilation (EPBD) has emerged as an alternative that may lessen the need for ML and also reduce the rate of adverse events. EHL and laser lithotripsy are effective at ductal clearance when conventional techniques are unsuccessful, although they usually require direct visualization of the stone by the use of cholangiopancreatoscopy and are often limited to referral centers. ESWL is effective but often requires coordination with urologists and the placement of stents or drains with subsequent procedures for extracting stone fragments and, thus, may be associated with increased costs. Conclusions: Several lithotripsy techniques have been described that vary with respect to ease of use, generalizability, and cost. Overall, lithotripsy is a safe and effective treatment for difficult biliary and pancreatic duct stones.
• Jiang, A., Buckingham, L., Barbanera, W., Korang, A., Bishehsari, F., & Melson, J. (2017). Erratum: LINE-1 is preferentially hypomethylated within adenomatous polyps in the presence of synchronous colorectal cancer [Clinical Epigenetics, 9, (2017) (1)] DOI: 10.1186/s13148-017-0325-7. Clinical Epigenetics, 9(1). doi:10.1186/s13148-017-0375-x
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  After publication of the article [1] it was brought to our attention that one of the authors had their name misspelt. The fifth author should be "Faraz Bishehsari".
• Jiang, A., Buckingham, L., Barbanera, W., Korang, A., Bishesari, F., & Melson, J. (2017). LINE-1 is preferentially hypomethylated within adenomatous polyps in the presence of synchronous colorectal cancer. Clinical Epigenetics, 9(1). doi:10.1186/s13148-017-0325-7
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  Background: Conventional tubular adenomas are frequently detected in patients undergoing average risk screening colonoscopy and are over-represented in patients who will develop colorectal cancer (CRC). Whether features of adenomas could serve as predictors of synchronous CRC is not known. Here, we investigate whether global methylation markers, including LINE-1, differ within adenomas in patients with and without synchronous CRC. Methods: Colorectal tubular/tubulovillous adenomatous polyps in the absence (P group, n = 45) and in the presence of synchronous CRC (PC group, n = 32) were identified. Global methylation and demethylation by ELISA for 5-methylcytosine (5-mC) and 5-hydroxymethyl cytosine (5-hmC), respectively, were assessed in polyps and adjacent normal non-neoplastic tissue. LINE-1 hypomethylation was assessed by pyrosequencing of bisulfite-converted DNA as well. Results: Global methylation (5-mC) showed no differences in overall methylation status in the adenomatous polyps in the two groups (5-mC relative to control %, PC group 0.117; P group 0.161, p = 0.148). Global hydroxymethylation 5-hmC was also not significantly different in adenomatous polyps of the PC group than in those of the P group (0.0059 vs 0.0097, p = 0.681). Similarly, global 5-hmC was not different between normal tissues from patients without neoplasia in comparison to those from CRC patients (0.0461 ± 0.080 vs 0.039 ± 0.159, p = 0.215). In contrast, adenomatous polyps of the PC group had lower levels of LINE-1 methylation compared to the adenomas in the P group (53.07 ± 4.5 vs 59.95 ± 5.4, p < 0.001). LINE-1 methylation was also significantly lower in the normal tissue from cancer patients compared to that from patients without any neoplasia (58.07 ± 3.78 vs 71.50 ± 6.47, p < 0.001). Conclusions: LINE-1 hypomethylation of precancerous adenomas correlates with the presence of synchronous CRC. Measurement of DNA hypomethylation levels of colorectal adenomas by LINE-1 could have future implications in approaches to defining CRC risk in screening programs.
• Melson, J., Berger, D., Greenspan, M., Bayoumi, M., & Jakate, S. (2017). Maintaining low non-neoplastic polypectomy rates in high-quality screening colonoscopy. Gastrointestinal Endoscopy, 85(3). doi:10.1016/j.gie.2016.08.029
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  Background and Aims Non-neoplastic polypectomies (NNPs) add pathology and procedural costs but do not reduce cancer risk and should be minimized. We sought to define the minimal non-neoplastic polypectomy rate (NNPR) for those colonoscopists achieving high-quality colorectal cancer screening based on adenoma detection rates (ADRs). Methods NNPRs for colonoscopists achieving high-quality adenoma detection rates were reported to determine minimal NNPR goals. Two approaches to tracking NNPR monitoring were compared: (1) total NNPR, an NNPR inclusive of all non-neoplastic specimens with exclusion of only hyperplastic polyp, sessile serrated polyp, and adenoma; and (2) normal tissue-only NNPR, an NNPR inclusive of those specimens with only normal colonic mucosa or lymphoid follicles. Results For those performing colonoscopy with high-quality ADRs (≥25%), half (6/12) of the colonoscopists had a total NNPR of ≤8.5% and 2 gastroenterologists had a total NNPR of ≤3.4%. The mean total NNPR of the cohort was 8.7% versus the normal tissue only NNPR, which was 7.5% (mean difference of 1.2%, standard deviation ± 0.97). The widest variation between total NNPR versus normal tissue only NNPR for any colonoscopist was 2.9%. The total NNPR ranged between 2.6% and 21.3% among 14 colonoscopists. Conclusions Colonoscopy with a high-quality ADR can be achieved while maintaining a low total NNPR. A total NNPR, inclusive of all non-neoplastic specimens as an alternative to an approach in which all specimens require individual review in order to select out only normal tissue can be considered for monitoring of NNPR.
• Parsi, M. A., Trindade, A. J., Bhutani, M. S., Melson, J., Navaneethan, U., Thosani, N., Trikudanathan, G., Watson, R. R., & Maple, J. T. (2017). Cryotherapy in gastrointestinal endoscopy. VideoGIE, 2(Issue 5). doi:10.1016/j.vgie.2017.01.021
• Trikudanathan, G., Pannala, R., Bhutani, M. S., Melson, J., Navaneethan, U., Parsi, M. A., Thosani, N., Trindade, A. J., Watson, R. R., & Maple, J. T. (2017). EUS-guided portal vein interventions. Gastrointestinal Endoscopy, 85(Issue 5). doi:10.1016/j.gie.2017.02.019
• Chen, H., Liu, H., Zou, H., Chen, R., Dou, Y., Sheng, S., Dai, S., Ai, J., Melson, J., Kittles, R., Pirooznia, M., Liptay, M., Borgia, J., & Deng, Y. (2016). Evaluation of plasma miR-21 and miR-152 as diagnostic biomarkers for common types of human cancers. Journal of Cancer, 7(5). doi:10.7150/jca.12351
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  Stable blood based miRNA species have allowed for the differentiation of patients with various types of cancer. Therefore, specific blood-based miRNA might be considered as a methodology which could be informative of the presence of cancer potentially from multiple distinct organ sites. Recently, miR-21 has been identified as an "oncomir" in various tumors while miR-152 as a tumor suppressor. In this study, we investigated whether circulating miR-21 and miR-152 can be used for early detection of lung cancer (LuCa), colorectal carcinoma (CRC), breast cancer (BrCa) and prostate cancer (PCa), with distinguishing cancer from various benign lesions on these organ sites. We measured the two miRNA levels by using real-time RT-PCR in plasma samples from a total of 204 cancer patients, 159 various benign lesions, and 228 normal subjects. We observed significantly elevated expression of miR-21 and miR-152 in LuCa, CRC, and BrCa when compared with normal controls. We also found upregulation of plasma miR-21 and miR-152 levels in patients with benign lesions of lung and breast, as compared to normal controls, respectively. No significant expression variation of the two miRNAs was observed in PCa or prostatic benign lesions as compared to healthy controls. Receiver operating characteristic (ROC) analyses revealed that miR-21 and/or miR-152 can discriminate LuCa, CRC and BrCa from normal controls. Our results suggest that plasma miR-21 and miR-152 may serve as non-specific noninvasive biomarkers for early screening of LuCa, CRC, and BrCa, but not PCa.
• Desai, V., Sussman, D., Greenspan, M., Dayanand, S., Ollington, K., Patel, S., Li, H., & Melson, J. (2016). Most Premature Surveillance Colonoscopy Is Not Attributable to Bowel Preparation or New Clinical Indications. Digestive Diseases and Sciences, 61(9). doi:10.1007/s10620-016-4177-3
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  Background and Aims: Surveillance colonoscopy frequently occurs prior to recommended intervals. Studies delineating the reasons why premature surveillance occurs are limited. We sought to define the frequency in which premature surveillance colonoscopy occurs in the setting of an inadequate bowel preparation or with a provided patient clinical indication versus when premature surveillance colonoscopy occurs without any provided discernible rationale in the setting of adequate bowel preparation. Methods: A retrospective cross-sectional cohort study of 700 patients undergoing colonoscopy for an indication of “surveillance of polyps” from 2008 to 2014 at two tertiary-care referral centers was carried out. Patients were deemed either “adherent” or “premature” based on US Multi-Society Task Force guideline intervals for surveillance colonoscopy. A documented decision-making rationale for premature surveillance was determined through review of the electronic medical record with assessment of clinical notes and endoscopy order and report. Results: Premature surveillance occurred in 43.0 % (n = 301) of all surveillance colonoscopies performed. Among the premature cases, rationale was attributed to inadequate bowel preparation in 17.3 % (n = 52) and due to a new clinical indication in 21.6 % (n = 65). Most commonly, in 61.1 % (n = 184) of premature cases, no rationale was documented for the early colonoscopy. Conclusions: Documented decision-making rationale for premature surveillance colonoscopy is usually absent in premature cases with inadequate bowel preparation and new clinical indications explaining only a minority of the occurrences.
• Greenspan, M., & Melson, J. (2016). Seeking the Cecum: Assessing Metrics in Fellow Procedural Training. Digestive Diseases and Sciences, 61(11). doi:10.1007/s10620-016-4300-5
• Melson, J., Ma, K., Arshad, S., Greenspan, M., Kaminsky, T., Melvani, V., Bishehsari, F., Mahon, B., & Jakate, S. (2016). Presence of small sessile serrated polyps increases rate of advanced neoplasia upon surveillance compared with isolated low-risk tubular adenomas. Gastrointestinal Endoscopy, 84(2). doi:10.1016/j.gie.2016.01.064
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  Background and Aims The U.S. Multi-Society Task Force (USMSTF) stratifies patients with sessile serrated polyps (SSPs) without cytologic dysplasia of
• Shobar, R., Velineni, S., Keshavarzian, A., Swanson, G., DeMeo, M., Melson, J., Losurdo, J., Engen, P., Sun, Y., Koenig, L., & Mutlu, E. (2016). The effects of bowel preparation on microbiota-related metrics differ in health and in inflammatory bowel disease and for the mucosal and luminal microbiota compartments. Clinical and Translational Gastroenterology, 7(2). doi:10.1038/ctg.2015.54
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  OBJECTIVES: Bowel preparations (BPs) taken before colonoscopy may introduce a confounding effect on the results of gastrointestinal microbiota studies. This study aimed to determine the effect of bowel preparation on the mucosa-Associated and luminal colonic microbiota in healthy subjects (HC) and inflammatory bowel disease (IBD) patients. METHODS: Biopsy samples (n=36) and fecal samples (n=30) were collected from 10 HC and 8 IBD subjects pre-and post-BP. 16S rRNA gene was pyrosequenced using 454 Titanium protocols. We compared the differences between the pre-and post-BP samples (i.e., comparisons-Across-bowel-prep); we examined the effect of BP on the expected separation of the mucosal vs.The luminal compartments (i.e., comparisons-Across-compartments). Last, we compared the baseline differences between the HC vs. IBD groups (a secondary analysis), and examined whether the differences between the HC vs. IBD changed after BP. RESULTS: In comparisons-Across-bowel-prep, the Shannon s index (SI) decreased only in the biopsy samples of IBD subjects post-BP (P=0.025) and phylogenetic diversity-whole tree (PD-WT) metric decreased in biopsy samples of HC subjects post-BP (P=0.021). In secondary comparisons, the subtle differences between the fecal samples of the HC vs. IBD groups, in terms of evenness and the SI, were not apparent post-BP. In terms of β-diversity, in comparisons-Across-bowel-prep, the proportion of shared operational taxonomic units (OTUs) in pre-and post-BP samples was low (∼30%) and unweighted Unifrac distances between pre-and post-BP specimens ranged from 0.52 to 0.66. HC biopsies were affected more than IBD biopsies with BP (P=0.004). In comparisons-Across-compartments, the proportion of shared OTUs between biopsy and fecal samples increased and Unifrac distances decreased post-BP in IBD subjects, reducing the differences between the mucosal and luminal compartments of the gut microbiota. Interindividual differences in Unifrac distances were preserved even with BP effects, although the effects were greater on weighted Unifrac distances. Bacteroidetes and its subtypes increased post-BP in both the luminal and mucosal compartments. CONCLUSIONS: Bowel preparations affect the composition and diversity of the fecal and luminal microbiota in the short term, introducing potential bias into experiments examining the gut microbiota. The magnitude of the effect of BP is not greater than that of interindividual variation. Both the luminal and mucosal compartments of the gut microbiota get affected, and samples from controls and IBD subjects may get affected differently. Studies of the colonic microbiota should take into account the direction and the magnitude of the change introduced by BP during the design stage of the experiments, and consider sample sizes so that potential bias is minimized.
• Greenspan, M., Chehl, N., Shawron, K., Barnes, L., Li, H., Avery, E., Sims, S., Losurdo, J., Mobarhan, S., & Melson, J. (2015). Patient Non-adherence and Cancellations Are Higher for Screening Colonoscopy Compared with Surveillance Colonoscopy. Digestive Diseases and Sciences, 60(10). doi:10.1007/s10620-015-3664-2
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  Background: A significant proportion of the eligible population is non-adherent to colonoscopy for colorectal cancer (CRC) screening. Aims: To define the demographic and clinical variables associated with non-adherence and multiple cancellations to scheduled colonoscopy within 1 year in a CRC screening and adenomatous polyp surveillance population. Methods: This was an observational cohort study of 617 consecutive patients scheduled to undergo colonoscopy at an outpatient academic tertiary care center for CRC screening or adenomatous polyp surveillance from January 2012 to September 2012. Results: Overall, 551 patients (89.3 %) were adherent and 66 (10.7 %) were non-adherent to scheduled colonoscopy at 1 year. The relative risk for non-adherence was 5.42 [95 % confidence interval (CI) 2.74–10.75] in patients undergoing colonoscopy for screening compared to those for surveillance (16.7 vs. 3.5 % non-adherence, respectively, P < 0.001). An indication of screening in comparison with surveillance was associated with non-adherence [odds ratio (OR) 12.69, 95 % CI 4.18–38.51] and multiple cancellations (OR 2.33, 95 % CI 1.27–4.31) by multiple regression analysis. Conclusions: Patients undergoing colonoscopy for CRC screening are significantly less likely to attend their scheduled procedure within a year and have more procedure cancellations than those undergoing surveillance colonoscopy.
• Ma, K., Nayak, S., Li, H., Evans, K., Francescatti, A., Brand, M., Orkin, B., Hill, M., Cameron, J., Mobarhan, S., Favuzza, J., & Melson, J. (2015). Radiographic staging practices of newly diagnosed colorectal cancer vary according to medical specialty. Gastrointestinal Endoscopy, 82(3). doi:10.1016/j.gie.2015.01.039
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  Background Since 2008, multiple guidelines have endorsed incorporation of chest CT in the radiographic staging assessment of newly diagnosed colorectal cancer (CRC). Radiographic staging practices performed after CRC is detected have not been studied. Objective To evaluate radiographic staging practices for newly diagnosed CRC between gastroenterologists versus non-gastroenterologists. Design Observational cohort study. Setting Single, tertiary-care referral center. Patients Patients newly diagnosed with a T1 or higher stage CRC at time of colonoscopy between 2008 and 2013. Interventions Radiographic staging. Main Outcome Measurements Radiographic preoperative staging examinations ordered by gastroenterologists in comparison to those ordered by non-gastroenterology specialists. Results This study included 277 patients with CRC newly diagnosed by colonoscopy. There were 141 total ordering physicians (68 gastroenterologists and 73 non-gastroenterologists). The majority of preoperative radiographic staging was performed by gastroenterologists (59.2% of patients, n = 164). Colorectal surgeons managed staging in 28.7% of patients (n = 47). Gastroenterologists were more likely to omit a staging chest CT than were non-gastroenterologists (64.6% vs 46.9%; P
• Melson, J., Desai, V., Greenspan, M., Yau, S., Abdalla, M., Dhanekula, R., Mobarhan, S., Shapiro, D., Losurdo, J., & Jakate, S. (2015). Negative surveillance endoscopy occurs frequently in patients with short-segment non-dysplastic Barrett's esophagus. Diseases of the Esophagus, 28(7). doi:10.1111/dote.12250
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  Surveillance endoscopy of non-dysplastic Barrett's esophagus (NDBE) that fails to detect intestinal metaplasia (IM), or negative surveillance, is known to occur in clinical practice, although the frequency and possible outcomes in a large cohort in clinical practice is not well described. The goals of this study were to define frequency in which negative surveillance occurs and endoscopic outcomes in a screening cohort of short segment NDBE. A retrospective cohort (n = 184) of patients newly diagnosed with short segment NDBE at an outpatient academic tertiary care center between 2003 and 2011 were reviewed. Only those with one or more surveillance endoscopies were included to define a frequency of negative surveillance. Included patients were further assessed if they had two or more surveillance endoscopies and were classified into groups as sampling error or negative IM on consecutive surveillances based on the results of their surveillance endoscopies. The frequency of a negative surveillance endoscopy in all short-segment NDBE patients was 19.66% (92 endoscopic exams were negative for IM of 468 total surveillance exams). A negative surveillance endoscopy occurred in 40.76% (n = 75) patients. Sampling error occurred in 44.12% and negative IM on consecutive surveillance endoscopies in 55.88% of those with ≥2 surveillance endoscopies and an initially negative surveillance exam. The frequency of negative IM on consecutive surveillances was 19.00% of all patients who had two surveillance endoscopies. When the index diagnostic Barrett's esophagus segment length was
• Abdalla, M., Dhanekula, R., Greenspan, M., Mobarhan, S., Patil, A., Jakate, S., Giusto, D., Silva, R., Li, H., & Melson, J. (2014). Dysplasia detection rate of confirmatory EGD in nondysplastic Barrett's esophagus. Diseases of the Esophagus, 27(6). doi:10.1111/j.1442-2050.2012.01431.x
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  Summary: Current guidelines for endoscopic surveillance of Barrett's esophagus (BE) recommend that patients with newly diagnosed BE undergo confirmatory esophagogastroduodenoscopy (EGD) to exclude the presence of dysplasia. The extent to which confirmatory endoscopy alters management and detects missed dysplasia in newly diagnosed BE has not been reported. The frequency with which confirmatory endoscopy changed surveillance management in patients with newly diagnosed BE was assessed. A two center cohort analysis was conducted on patients newly diagnosed with BE. The rate of dysplasia on confirmatory endoscopy for patients who had nondysplastic BE was obtained. Demographic and endoscopic variables were assessed for association with dysplasia detection using Firth logistic regression model. Out of the 146 patients newly diagnosed with BE and initially determined to be without dysplasia, 12 had dysplasia on the confirmatory second EGD (8.2%). Eleven of 12 cases with dysplasia on confirmatory endoscopy had long-segment BE (LSBE). Among all the LSBE cases in our cohort, 11 had newly diagnosed dysplasia on confirmatory EGD, 29.7% (11/37). The average number of biopsies obtained from the 11 LSBE cases with dysplasia was comparable with the rest of the LSBE cases without dysplasia (6.73 and 5.42, respectively, P-value 0.205). The rate of dysplasia detection in short-segment BE (SSBE) was much lower, 0.95% (1 out of 105). There were no cases of high-grade dysplasia (HGD) or cancer detected in any SSBE case. HGD was detected on confirmatory EGD in two cases, both were LSBE. Segment length was the only statistically significant factor to predict the presence of dysplasia on confirmatory endoscopy (odds ratio 9.158, P. 0.008). Confirmatory EGD in newly diagnosed LSBE had significant rate of dysplasia detection (29.7%) in this cohort. Among patients with SSBE, there was a low rate of dysplasia detection with confirmatory EGD, less than 1% of cases. No additional cases of HGD or esophageal carcinoma in SSBE cases were detected. This suggests that the yield of confirmatory EGD is greater in patients with LSBE. © 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.
• Melson, J., Li, Y., Cassinotti, E., Melnikov, A., Boni, L., Ai, J., Greenspan, M., Mobarhan, S., Levenson, V., & Deng, Y. (2014). Commonality and differences of methylation signatures in the plasma of patients with pancreatic cancer and colorectal cancer. International Journal of Cancer, 134(11). doi:10.1002/ijc.28593
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  Profiling of DNA methylation status of specific genes is a way to screen for colorectal cancer (CRC) and pancreatic cancer (PC) in blood. The commonality of methylation status of cancer-related tumor suppressor genes between CRC and PC is largely unknown. Methylation status of 56 cancer-related genes was compared in plasma of patients in the following cohorts: CRC, PC and healthy controls. Cross validation determined the best model by area under ROC curve (AUC) to differentiate cancer methylation profiles from controls. Optimal preferential gene methylation signatures were derived to differentiate either cancer (CRC or PC) from controls. For CRC alone, a three gene signature (CYCD2, HIC and VHL) had an AUC 0.9310, sensitivity (Sens) = 0.826, specificity (Spec) = 0.9383. For PC alone, an optimal signature consisted of five genes (VHL, MYF3, TMS, GPC3 and SRBC), AUC 0.848; Sens = 0.807, Spec = 0.666. Combined PC and CRC signature or "combined cancer signature" was derived to differentiate either CRC and PC from controls (MDR1, SRBC, VHL, MUC2, RB1, SYK and GPC3) AUC = 0.8177, Sens = 0.6316 Spec = 0.840. In a validation cohort, N = 10 CRC patients, the optimal CRC signature (CYCD2, HIC and VHL) had AUC 0.900. In all derived signatures (CRC, PC and combined cancer signature) the optimal panel used preferential VHL methylation. In conclusion, CRC and PC differ in specific genes methylated in plasma other than VHL. Preferential methylation of VHL is shared in the optimal signature for CRC alone, PC alone and combined PC and CRC. Future investigations may identify additional methylation markers informative for the presence of both CRC and PC. What's new The potential use of the methylation status of cancer-related genes as a biomarker for plasma-based screening is an area of investigation for both pancreatic and colorectal cancer. While there is evidence that pancreatic and colorectal cancer may share methylation markers - which might enable concomitant and non-invasive screening - how similar their methylation profiles is remains unknown. Here, the authors defined the best methylation signature for both pancreatic and colorectal cancer and identified VHL as a shared optimal marker. The findings suggest that the methylation status of genes may be utilized as a potential source of information on both types of tumors. © 2013 UICC.
• Xicola, R., Gagnon, M., Clark, J., Carroll, T., Gao, W., Fernandez, C., Mijic, D., Rawson, J., Janoski, A., Pusatcioglu, C., Rajaram, P., Gluskin, A., Regan, M., Chaudhry, V., Abcarian, H., Blumetti, J., Cintron, J., Melson, J., Xie, H., , Guzman, G., et al. (2014). Excess of proximal microsatellite-stable colorectal cancer in african americans from a multiethnic study. Clinical Cancer Research, 20(18). doi:10.1158/1078-0432.ccr-14-0353
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  Purpose: African Americans (AA) have the highest incidence of colorectal cancer compared with other U.S. populations and more proximal colorectal cancers. The objective is to elucidate the basis of these cancer disparities. Experimental design: Of note, 566 AA and 328 non-Hispanic White (NHW) colorectal cancers were ascertained in five Chicago hospitals. Clinical and exposure data were collected. Microsatellite instability (MSI) and BRAF (V600E) and KRAS mutations were tested. Statistical significance of categorical variables was tested by the Fisher exact test or logistic regression and age by the Mann-Whitney U test. Results: Over a 10-year period, the median age at diagnosis significantly decreased for both AAs (68-61; P < 0.01) andNHWs(64.5- 62; P= 0.04); more AA patients were diagnosed before age 50 thanNHWs(22% vs. 15%; P = 0.01). AAs had more proximal colorectal cancer than NHWs (49.5% vs. 33.7%; P < 0.01), but overall frequencies of MSI, BRAF and KRAS mutations were not different nor were they different by location in the colon. Proximal colorectal cancers often presented with lymphocytic infiltrate (P < 0.01) and were diagnosed at older ages (P = 0.02). Smoking, drinking, and obesity were less common in this group, but results were not statistically significant. Conclusions: Patients with colorectal cancer have gotten progressively younger. The excess of colorectal cancer in AAs predominantly consists of more proximal, microsatellite stable tumors, commonly presenting lymphocytic infiltrate and less often associated with toxic exposures or a higher BMI. Younger AAs had more distal colorectal cancers than older ones. These data suggest two different mechanisms driving younger age and proximal location of colorectal cancers in AAs.
• Eichenseer, P., Dhanekula, R., Jakate, S., Mobarhan, S., & Melson, J. (2013). Endoscopic mis-sizing of polyps changes colorectal cancer surveillance recommendations. Diseases of the Colon and Rectum, 56(3). doi:10.1097/dcr.0b013e31826dd138
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  BACKGROUND: Adenomatous polyps greater than 1 cm are defined as advanced adenomas. Inaccurate size estimation can lead to inappropriate surveillance recommendations of colorectal adenomas. OBJECTIVE: The aim of this study was to determine the impact of endoscopic polyp mis-sizing on colorectal cancer surveillance recommendations. DESIGN: This is a prospective study. SETTING: This study was conducted in a gastroenterology practice at a US academic medical center. PATIENTS: Patients undergoing colorectal cancer screening and surveillance colonoscopies from 2010 to 2011 were included. MAIN OUTCOME MEASUREMENTS: Endoscopic size estimates of polyps 10 to 25 mm were compared with postfixation histopathologic polyp measurements for 15 different gastroenterologists. Only adenomatous polyps removed in entirety by snare polypectomy were included in the analysis. Size variation was defined as (endoscopic estimate - histopathologic size)/(histopathologic size). Clinical mis-sizing was defined as a size variation of >33%. The mean size variation, the percentage of clinical mis-sizing, and the percentage of inappropriate surveillance recommendation due to size variation >33% were reported per endoscopist. RESULTS: Included for analysis were 4990 procedures from 15 gastroenterologists. A total of 230 polyps from 200 patients met inclusion criteria. The average age was 62.6 years (SD 10.1), and 52% were men. The mean size variation between the endoscopic polyp size estimation and the histopathologic polyp was 73.6% (range of mean size variation, 13%-127%). 62.6% (range, 0%-91%) of included polyps had clinical mis-sizing. Of included polypectomies, 35.2% (range, 0%-67%) resulted in an inappropriate surveillance recommendation due to clinical mis-sizing even after considering histology and synchronous polyps. LIMITATIONS: This was a single-center study. CONCLUSIONS: There is marked variation in endoscopists' ability to accurately size adenomatous polyps. Some endoscopists rarely mis-size adenomas, and their surveillance recommendations are appropriate in regard to sizing. However, other endoscopists inaccurately size adenomas, and this leads to inappropriate surveillance of colorectal polyps. In this study, approximately 1 of 3 included polypectomies yielded inappropriate surveillance recommendations because of clinical mis-sizing. © The ASCRS 2013.
• Greenspan, M., Rajan, K., Baig, A., Beck, T., Mobarhan, S., & Melson, J. (2013). Advanced adenoma detection rate is independent of nonadvanced adenoma detection rate. American Journal of Gastroenterology, 108(8). doi:10.1038/ajg.2013.149
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  Objectives: Adenoma detection rate (ADR) is the accepted rate marker in colonoscopy quality. Advanced adenomas detected at index colonoscopy, while less frequent than nonadvanced adenomas, carry greater risk for future advanced neoplasia during surveillance colonoscopy. This study aimed to determine the effect of the colonoscopist and other factors on advanced ADR and to define the correlation of advanced and nonadvanced ADRs among colonoscopists.Methods: An observational study of a cohort of patients undergoing first-time colorectal cancer screening colonoscopy was conducted. Patient characteristics and colonoscopic findings were collected. Adenoma, advanced adenoma, and nonadvanced ADRs were calculated. Logistic regression was used to determine variable effects on advanced adenoma detection, and Spearman's rank-order correlation was used to evaluate the relationship between advanced and nonadvanced ADRs.Results: A total of 1,944 patients had first-time screening colonoscopies by 14 colonoscopists. All colonoscopists had adequate (>20%) ADRs. The variability in the colonoscopist ranges of detection was 22.22 to 44.66% for adenomas and 2.00 to 18.18% for advanced adenomas. Logistic regression showed that increasing patient age (odds ratio (OR) 1.16 per 5-year increase, 95% confidence interval (CI) 1.05-1.28, P=0.008) and male gender (OR 2.15, 95% CI 1.51-3.06, P
• Khan, M., Keshavarzian, A., Gounaris, E., Melson, J., Cheon, E., Blatner, N., Chen, Z., Tsai, F., Lee, G., Ryu, H., Barrett, T., Bentrem, D., Beckhove, P., & Khazaie, K. (2013). PI3K/AKT signaling is essential for communication between tissue-infiltrating mast cells, macrophages, and epithelial cells in colitis-induced cancer. Clinical Cancer Research, 19(9). doi:10.1158/1078-0432.ccr-12-2623
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  Purpose: To understand signaling pathways that shape inflamed tissue and predispose to cancer is critical for effective prevention and therapy for chronic inflammatory diseases. We have explored phosphoinositide 3-kinase (PI3K) activity in human inflammatory bowel diseases and mouse colitis models. Experimental Design: We conducted immunostaining of phosphorylated AKT (pAKT) and unbiased high-throughput image acquisition and quantitative analysis of samples of noninflamed normal colon, colitis, dysplasia, and colorectal cancer. Mechanistic insights were gained from ex vivo studies of cell interactions, the piroxicam/IL-10-/- mouse model of progressive colitis, and use of the PI3K inhibitor LY294002. Results: Progressive increase in densities of pAKT-positive tumor-associated macrophages (TAM) and increase in densities of mast cells in the colonic submucosa were noted with colitis and progression to dysplasia and cancer. Mast cells recruited macrophages in ex vivo migration assays, and both mast cells and TAMs promoted invasion of cancer cells. Pretreatment of mast cells with LY294002 blocked recruitment of TAMs. LY294002 inhibited mast cell and TAM-mediated tumor invasion, and in mice, blocked stromal PI3K, colitis, and cancer. Conclusion: The PI3K/AKT pathway is active in cells infiltrating inflamed human colon tissue. This pathway sustains the recruitment of inflammatory cells through a positive feedback loop. The PI3K/AKT pathway is essential for tumor invasion and the malignant features of the piroxicam/IL-10-/- mouse model. LY294002 targets the PI3K pathway and hinders progressive colitis. These findings indicate that colitis and progression to cancer are dependent on stromal PI3K and sensitive to treatment with LY294002. ©2013 AACR.
• Cassinotti, E., Melson, J., Liggett, T., Melnikov, A., Yi, Q., Replogle, C., Mobarhan, S., Boni, L., Segato, S., & Levenson, V. (2012). DNA methylation patterns in blood of patients with colorectal cancer and adenomatous colorectal polyps. International Journal of Cancer, 131(5). doi:10.1002/ijc.26484
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  Colorectal cancer (CRC) screening rates are currently suboptimal. Blood-based screening could improve rates of earlier detection for CRC and adenomatous colorectal polyps. In this study, we evaluated the feasibility of plasma-based detection of early CRC and adenomatous polyps using array-mediated analysis methylation profiling of 56 genes implicated in carcinogenesis. Methylation of 56 genes in patients with Stages I and II CRC (N = 30) and those with adenomatous polyps (N = 30) were compared with individuals who underwent colonoscopy and were found to have neither adenomatous changes nor CRC. Composite biomarkers were developed for adenomatous polyps and CRC, and their sensitivity and specificity was estimated using five-fold cross validation. Six promoters (CYCD2, HIC1, PAX 5, RASSF1A, RB1 and SRBC) were selected for the biomarker, which differentiated CRC patients and controls with 84% sensitivity and 68% specificity. Three promoters (HIC1, MDG1 and RASSF1A) were selected for the biomarker, which differentiated patients with adenomatous polyps and controls with sensitivity of 55% and specificity of 65%. Methylation profiling of plasma DNA can detect early CRC with significant accuracy and shows promise as a methodology to develop biomarkers for CRC screening. © 2011 UICC.
• Melson, J., Giusto, D., Kwasny, M., Eichenseer, P., Jakate, S., & Keshavarzian, A. (2010). Histopathology predictors of medically refractory ulcerative colitis. Diseases of the Colon and Rectum, 53(9). doi:10.1007/dcr.0b013e3181e751df
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  PURPOSE: The ability of ulcerative colitis histology to predict medically refractory disease was evaluated. AMETHODS: Twenty patients who underwent colectomy for medically refractory disease were compared with 48 medically managed patients. All patients were followed up for > 6 months. The study design was a retrospective longitudinal observational chart review to determine whether specific histologic parameters were predictive of a later colectomy for medically refractory disease. RESULTS: On initial biopsy, medically refractory patients were more likely to have severe cryptitis, 75% vs 49%; lymphoid follicles, 78% vs 48%; and erosions, 35% vs 11%. There was no significant difference in the prevalence of crypt abscesses, mucin depletion, crypt distortion, or mucosal ulceration between medically refractory and medically managed patients. Active inflammation on endoscopy was not statistically different between groups (P = .192). In a recursive partition model, the strongest predictors of future colectomy were age dependent. Among older patients (>38 y), severe cryptitis was the strongest determinant of refractory disease. Only 1 of 21 (5%) of the patients who initially did not have severe cryptitis progressed to colectomy. In younger patients (
• Melson, J., Jakate, S., Fung, H., Arai, S., & Keshavarzian, A. (2007). Crypt loss is a marker of clinical severity of acute gastrointestinal graft-versus-host disease. American Journal of Hematology, 82(10). doi:10.1002/ajh.20976
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  Background: Crypt loss is a histological finding in acute gastrointestinal Graft-Versus-Host Disease (GI-GvHD) of undefined clinical significance. Methods: Colonic crypt loss was graded in twenty-three patients treated for GI-GvHD following stem cell transplantation and then correlated with clinical parameters of disease severity and mortality. Results: Crypt loss was present in 17/23 cases, and in 11/23 cases crypt loss was deemed severe by the presence of contiguous areas of crypt loss. Nine of 11 patients with severe crypt loss had daily stool volumes in excess of 1000 ml/day, while only 3/12 of those with minimal or no crypt loss had this level of severe diarrhea. All 11 patients with severe crypt loss had a pathologic appearance at endoscopy and 10/11 had steroid refractory disease. Diarrhea resolved in only 3/9 patients with severe crypt loss. Five out of 10 patients (50%) with severe crypt loss expired within 15 months of diagnosis. All five deaths were attributable to the progression of GvHD itself or infection in the presence of continued GI-GvHD. Conversely, only 1 of 12 patients (8%) with mild or no crypt loss had a death attributable to GvHD or infection. Conclusions: This study shows that severe colonic crypt loss predicts severe clinical GI-GvHD that is more likely to be refractory to steroid treatment. In addition, crypt loss severity appears associated with higher mortality related to GvHD. Crypt loss can serve as a tool to predict clinically severe GI-GvHD. © 2007 Wiley-Liss, Inc.
• Quander, C., Morris, M., Melson, J., Bienias, J., & Evans, D. (2005). Prevalence of and factors associated with fecal incontinence in a large community study of older individuals. American Journal of Gastroenterology, 100(4). doi:10.1111/j.1572-0241.2005.30511.x
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  OBJECTIVES: In this study, we describe the prevalence of fecal incontinence by race, age, sex, the presence of major chronic conditions of stroke and diabetes, and the use of certain psychoactive medications. METHODS: Study subjects are participants in the Chicago Health and Aging Project, a study of older Chicago residents of a geographically defined area. In the period 1993-1996, interviewers conducted a door-to-door census that identified 6,099 individuals who participated in in-home interviews. The interviews included a wide range of questions regarding demographics, medical history, and medication use. The question used to determine the presence of fecal incontinence was: "In the past few months have you ever lost control of your bowels when you didn't want to?" RESULTS: Fecal incontinence was seen in 585 of 6,099 survey responders yielding an overall prevalence of 9.6%. The prevalence of fecal incontinence was strongly associated with age across all demographic groups. We did not observe significant differences in the prevalence for males and females once we adjusted for age. However, the increase in prevalence with age was significantly greater among Blacks than Whites. The use of psychoactive medications was found to be associated with significantly higher odds of fecal incontinence. Diabetes and stroke were associated with a higher prevalence of fecal incontinence. CONCLUSIONS: These cross-sectional analyses offer promising evidence that this common condition is correlated with the presence of certain conditions (e.g., stroke and diabetes) and use of certain psychoactive medications. © 2005 by Am. Coll. of Gastroenterology. Published by Blackwell Publishing.

Proceedings Publications

• Dey, N., Kochman, M., Komanduri, S., Melson, J., & Muthusamy, V. (2020). Report from the AGA Center for GI Innovation and Technology's Consensus Conference: Envisioning Next-Generation Paradigms in Colorectal Cancer Screening and Surveillance. In AGA 2020 Summit on Colorectal Cancer, 158.

Presentations

• Melson, J. (2024, April).

  “Colorectal Cancer Screening"

  . Tucson Medical Center (TMC) Grand Rounds Presentation. Tucson, AZ: Tucson Medical Center (TMC).
• Melson, J. (2024, August).

  Meet a CPC Scientist Seminar Series

  . STEP-UP. Virtual/Tucson, AZ.
• Melson, J. (2024, September).

  “Genetic Screening and High-Risk Surveillance Programs for Pancreatic Cancer”

  . Hepato-Pancreato-Biliary (HPB) Symposium Presentation, University of Arizona. Tucson, AZ.

Poster Presentations

• Witten, B., Cheong, S. H., Rodden, D., Alvarez, R. A., Aggarwal, A., & Melson, J. (2024, May). Metachronous Advanced Neoplasia Rates in Patients with Isolated Sessile Serrated Lesions (SSlS) Versus those With SSlS with Concomitant Small Tubular Adenomas.. Oral presentation: Digestive Disease Week 2024. Washington, DC.
• Melson, J., Chambers, S. K., schmanski, a., maynard, l., lee, s., alvarez, r., alameri, a., & trieu, r. (2023). Frequency and determinants of missed colonoscopy surveillance in Lynch Syndrome patients in a Screening program with a procedural recall system (ABSTRACT/POSTER). Collaborative Group of Americas on Inherited Gastrointestinal Cancer (CGA-IGC). Las Vegas, NV.