Vani J.A. Konda M.D.

Smith, M. S., B. Cash, V. Konda, A. J. Trindade, S. Gordon, S. DeMeester, V. Joshi, D. Diehl, E. Ganguly, H. Mashimo, S. Singh, B. Jobe, M. McKinley, M. Wallace, Y. Komatsu, S. Thakkar, F. Schnoll-Sussman, R. Sharaiha, M. Kahaleh, P. Tarnasky, H. Wolfsen, R. Hawes, J. Lipham, H. Khara, D. Pleskow, U. Navaneethan, P. Kedia, M. Hasan, A. Sethi, J. Samarasena, U. D. Siddiqui, F. Gress, R. Rodriguez, C. Lee, T. Gonda, I. Waxman, S. Hyder, J. Poneros, K. Sharzehi, J. A. Di Palma, D. V. Sejpal, D. Oh, J. Hagen, R. Rothstein, M. Sawhney, T. Berzin, Z. Malik and K. Chang (2019). “Volumetric laser endomicroscopy and its application to Barrett’s esophagus: results from a 1,000 patient registry.” Dis Esophagus 32(9): 1-8.

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Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett’s esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291.

Snyder, P., K. Dunbar, D. J. Cipher, R. F. Souza, S. J. Spechler and V. J. A. Konda (2019). “Aberrant p53 Immunostaining in Barrett’s Esophagus Predicts Neoplastic Progression: Systematic Review and Meta-Analyses.” Dig Dis Sci 64(5): 1089-1097.

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Risk stratification of patients with Barrett’s esophagus (BE) presently relies on the histopathologic grade of dysplasia found in esophageal biopsies, which is limited by sampling error and inter-pathologist variability. p53 immunostaining of BE biopsies has shown promise as an adjunct tool but is not recommended by American gastroenterology societies, who cite insufficient evidence of its prognostic value. We have conducted a systematic review and meta-analyses to clarify this value. We searched for studies that: (1) used immunohistochemistry to assess p53 expression in esophageal biopsies of BE patients and (2) reported subsequent neoplastic progression. We performed separate meta-analyses of case-control studies and cohort studies. We identified 14 relevant reports describing 8 case-control studies comprising 1435 patients and 7 cohort studies comprising 582 patients. In the case-control study meta-analysis of the risk of neoplasia with aberrant p53 expression, the fixed- and random-effect estimates of average effect size with aberrant p53 expression were OR 3.84, p < .001 (95% CI 2.79-5.27) and OR 5.95, p < .001 (95% CI 2.68-13.22), respectively. In the cohort study meta-analysis, the fixed- and random-effect estimates of average effect size were RR = 17.31, p < .001 (95% CI 9.35-32.08) and RR = 14.25, p < .001 (95% CI 6.76-30.02), respectively. Separate meta-analyses of case-control and cohort studies of BE patients who had baseline biopsies with p53 immunostaining revealed consistent, strong, and significant associations between aberrant p53 immunostaining and progression to high-grade dysplasia or esophageal adenocarcinoma. These findings support the use of p53 immunostaining as an adjunct to routine clinical diagnosis for dysplasia in BE patients.

Smith, M. S., B. Cash, V. Konda, A. J. Trindade, S. Gordon, S. DeMeester, V. Joshi, D. Diehl, E. Ganguly, H. Mashimo, S. Singh, B. Jobe, M. McKinley, M. Wallace, Y. Komatsu, S. Thakkar, F. Schnoll-Sussman, R. Sharaiha, M. Kahaleh, P. Tarnasky, H. Wolfsen, R. Hawes, J. Lipham, H. Khara, D. Pleskow, U. Navaneethan, P. Kedia, M. Hasan, A. Sethi, J. Samarasena, U. D. Siddiqui, F. Gress, R. Rodriguez, C. Lee, T. Gonda, I. Waxman, S. Hyder, J. Poneros, K. Sharzehi, J. A. Di Palma, D. V. Sejpal, D. Oh, J. Hagen, R. Rothstein, M. Sawhney, T. Berzin, Z. Malik and K. Chang (2019). “Volumetric laser endomicroscopy and its application to Barrett’s esophagus: results from a 1,000 patient registry.” Dis Esophagus Apr 30. [Epub ahead of print].

Full text of this article.

Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett’s esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291.

Snyder, P., K. Dunbar, D. J. Cipher, R. F. Souza, S. J. Spechler and V. J. A. Konda (2019). “Aberrant p53 Immunostaining in Barrett’s Esophagus Predicts Neoplastic Progression: Systematic Review and Meta-Analyses.” Dig Dis Sci Mar 26. [Epub ahead of print].

Full text of this article.

Risk stratification of patients with Barrett’s esophagus (BE) presently relies on the histopathologic grade of dysplasia found in esophageal biopsies, which is limited by sampling error and inter-pathologist variability. p53 immunostaining of BE biopsies has shown promise as an adjunct tool but is not recommended by American gastroenterology societies, who cite insufficient evidence of its prognostic value. We have conducted a systematic review and meta-analyses to clarify this value. We searched for studies that: (1) used immunohistochemistry to assess p53 expression in esophageal biopsies of BE patients and (2) reported subsequent neoplastic progression. We performed separate meta-analyses of case-control studies and cohort studies. We identified 14 relevant reports describing 8 case-control studies comprising 1435 patients and 7 cohort studies comprising 582 patients. In the case-control study meta-analysis of the risk of neoplasia with aberrant p53 expression, the fixed- and random-effect estimates of average effect size with aberrant p53 expression were OR 3.84, p < .001 (95% CI 2.79-5.27) and OR 5.95, p < .001 (95% CI 2.68-13.22), respectively. In the cohort study meta-analysis, the fixed- and random-effect estimates of average effect size were RR = 17.31, p < .001 (95% CI 9.35-32.08) and RR = 14.25, p < .001 (95% CI 6.76-30.02), respectively. Separate meta-analyses of case-control and cohort studies of BE patients who had baseline biopsies with p53 immunostaining revealed consistent, strong, and significant associations between aberrant p53 immunostaining and progression to high-grade dysplasia or esophageal adenocarcinoma. These findings support the use of p53 immunostaining as an adjunct to routine clinical diagnosis for dysplasia in BE patients.

Kobashigawa, J., D. Dadhania, S. Bhorade, D. Adey, J. Berger, G. Bhat, M. Budev, A. Duarte-Rojo, M. Dunn, S. Hall, M. N. Harhay, K. L. Johansen, S. Joseph, C. C. Kennedy, E. Kransdorf, K. L. Lentine, R. J. Lynch, M. McAdams-DeMarco, S. Nagai, M. Olymbios, J. Patel, S. Pinney, J. Schaenman, D. L. Segev, P. Shah, L. G. Singer, J. P. Singer, C. Sonnenday, P. Tandon, E. Tapper, S. G. Tullius, M. Wilson, M. Zamora and J. C. Lai (2019). “Report from the American Society of Transplantation on frailty in solid organ transplantation.” Am J Transplant 19(4): 984-994.

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A consensus conference on frailty in kidney, liver, heart, and lung transplantation sponsored by the American Society of Transplantation (AST) and endorsed by the American Society of Nephrology (ASN), the American Society of Transplant Surgeons (ASTS), and the Canadian Society of Transplantation (CST) took place on February 11, 2018 in Phoenix, Arizona. Input from the transplant community through scheduled conference calls enabled wide discussion of current concepts in frailty, exploration of best practices for frailty risk assessment of transplant candidates and for management after transplant, and development of ideas for future research. A current understanding of frailty was compiled by each of the solid organ groups and is presented in this paper. Frailty is a common entity in patients with end-stage organ disease who are awaiting organ transplantation, and affects mortality on the waitlist and in the posttransplant period. The optimal methods by which frailty should be measured in each organ group are yet to be determined, but studies are underway. Interventions to reverse frailty vary among organ groups and appear promising. This conference achieved its intent to highlight the importance of frailty in organ transplantation and to plant the seeds for further discussion and research in this field.