Research Spotlight

Weiss, E., F. Saner, S. K. Asrani, G. Biancofiore, A. Blasi, J. Lerut, F. Durand, J. Fernandez, J. Y. Findlay, C. Fondevila, C. Francoz, T. Gustot, S. Jaber, C. Karvellas, K. Kronish, W. Laleman, P. F. Laterre, E. Levesque, S. M. Mandell, M. McPhail, P. Muiesan, J. C. Olson, K. Olthoff, A. D. Pinna, T. Reiberger, K. Reyntjens, F. Saliba, O. Scatton, K. J. Simpson, O. Soubrane, R. M. Subramanian, F. Tacke, D. Tomescu, V. Xia, G. Wagener and C. Paugam-Burtz (2020). “When Is a Critically Ill Cirrhotic Patient Too Sick to Transplant? Development of Consensus Criteria by a Multidisciplinary Panel of 35 International Experts.” Transplantation. Jun 15. [Epub ahead of print].

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BACKGROUND: Critically ill cirrhotic patients are increasingly transplanted, but there is no consensus about futile liver transplantation (LT).Therefore, the decision to delay or deny LT is often extensively debated. These debates arise from different opinions of futility among transplant team members. This study aims to achieve a multinational and multidisciplinary consensus on the definition of futility in LT and to develop well-articulated criteria for not proceeding with LT due to futility. METHODS: Thirty-five international experts from anesthesiology/intensive care, hepatology and transplant surgery were surveyed using the Delphi method. More than 70% of similar answers to a question were necessary to define agreement. RESULTS: The panel recommended patient and graft survival at 1 year after LT to define futility. Severe frailty, and persistent fever or less than 72 hours of appropriate antimicrobial therapy in case of ongoing sepsis were considered reasons to delay LT. A simple assessment of the number of organs failing was considered the most appropriate way to decide whether LT should be delayed or denied, with respiratory, circulatory and metabolic failures having the most influence in this decision. The thresholds of severity of organ failures contraindicating LT for which a consensus was achieved were a PaO2/FiO2 ratio<150 mmHg, a norepinephrine dose >1μg/kg/min and a serum lactate level >9 mmol/l. CONCLUSION: Our expert panel provides a consensus on the definition of futile LT and on specific criteria for postponing or denying LT. A framework that may facilitate the decision if a patient is too sick for transplant is presented.

Mehta, R. S., S. G. Holtan, T. Wang, M. T. Hemmer, S. R. Spellman, M. Arora, D. R. Couriel, A. M. Alousi, J. Pidala, H. Abdel-Azim, V. Agrawal, I. Ahmed, A. S. Al-Homsi, M. Aljurf, J. H. Antin, M. Askar, J. J. Auletta, V. R. Bhatt, L. Chee, S. Chhabra, A. Daly, Z. DeFilipp, J. Gajewski, R. P. Gale, U. Gergis, P. Hematti, G. C. Hildebrandt, W. J. Hogan, Y. Inamoto, R. Martino, N. S. Majhail, D. I. Marks, T. Nishihori, R. F. Olsson, A. Pawarode, M. A. Diaz, T. Prestidge, H. G. Rangarajan, O. Ringden, A. Saad, B. N. Savani, H. Schoemans, S. Seo, K. R. Schultz, M. Solh, T. Spitzer, J. Storek, T. Teshima, L. F. Verdonck, B. Wirk, J. A. Yared, J. Y. Cahn and D. J. Weisdorf (2020). “Composite GRFS and CRFS Outcomes After Adult Alternative Donor HCT.” J Clin Oncol 38(18): 2062-2076.

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PURPOSE: There is no consensus on the best choice of an alternative donor (umbilical cord blood [UCB], haploidentical, one-antigen mismatched [7/8]-bone marrow [BM], or 7/8-peripheral blood [PB]) for hematopoietic cell transplantation (HCT) for patients lacking an HLA-matched related or unrelated donor. METHODS: We report composite end points of graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) and chronic GVHD (cGVHD)-free relapse-free survival (CRFS) in 2,198 patients who underwent UCB (n = 838), haploidentical (n = 159), 7/8-BM (n = 241), or 7/8-PB (n = 960) HCT. All groups were divided by myeloablative conditioning (MAC) intensity or reduced intensity conditioning (RIC), except haploidentical group in which most received RIC. To account for multiple testing, P < .0071 in multivariable analysis and P < .00025 in direct pairwise comparisons were considered statistically significant. RESULTS: In multivariable analysis, haploidentical group had the best GRFS, CRFS, and overall survival (OS). In the direct pairwise comparison of other groups, among those who received MAC, there was no difference in GRFS or CRFS among UCB, 7/8-BM, and 7/8-PB with serotherapy (alemtuzumab or antithymocyte globulin) groups. In contrast, the 7/8-PB without serotherapy group had significantly inferior GRFS, higher cGVHD, and a trend toward worse CRFS (hazard ratio [HR], 1.38; 95% CI, 1.13 to 1.69; P = .002) than the 7/8-BM group and higher cGVHD and trend toward inferior CRFS (HR, 1.36; 95% CI, 1.14 to 1.63; P = .0006) than the UCB group. Among patients with RIC, all groups had significantly inferior GRFS and CRFS compared with the haploidentical group. CONCLUSION: Recognizing the limitations of a registry retrospective analysis and the possibility of center selection bias in choosing donors, our data support the use of UCB, 7/8-BM, or 7/8-PB (with serotherapy) grafts for patients undergoing MAC HCT and haploidentical grafts for patients undergoing RIC HCT. The haploidentical group had the best GRFS, CRFS, and OS of all groups.

Kavesh, M., M. Martinez and J. R. Asirvatham (2020). “Pleomorphic lobular carcinoma in situ composed of signet ring cells mimicking cribriform ductal carcinoma in situ.” Breast J Jun 26. [Epub ahead of print.].

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Pleomorphic signet ring LCIS is unusual and may mimic DCIS. In DCIS with true cribriform architecture, punched out lumina with cellular polarization would be observed rather than a low‐magnification impression of cribriforming due to numerous cells with signet ring morphology as seen in this case. LCIS may be distinguished from other diagnostic entities by negative E‐cadherin IHC, an intact surrounding myoepithelial layer highlighted by p63 or SMMHC, absence of intraluminal basement membrane‐like material, and lack of true lumina. The invasive component of the tumor in this case furthermore demonstrated both tubular and classic lobular patterns of infiltration, consistent with a tubulolobular variant of invasive lobular carcinoma. [No abstract; excerpt from article.].

Emmett, M. (2020). “Metabolic Alkalosis: A Brief Pathophysiologic Review.” Clin J Am Soc Nephrol Jun 25;CJN.16041219. [Epub ahead of print.].

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Metabolic alkalosis is a very commonly encountered acid-base disorder that may be generated by a variety of exogenous and/or endogenous, pathophysiologic mechanisms. Multiple mechanisms are also responsible for the persistence, or maintenance, of metabolic alkalosis. Understanding these generation and maintenance mechanisms helps direct appropriate intervention and correction of this disorder. The framework utilized in this review is based on the ECF volume-centered approach popularized by Donald Seldin and Floyd Rector in the 1970s. Although many subsequent scientific discoveries have advanced our understanding of the pathophysiology of metabolic alkalosis, that framework continues to be a valuable and relatively straightforward diagnostic and therapeutic model.

Fleshman, J. W. (2020). “How to Develop a Leadership Training Program.” Clin Colon Rectal Surg 33(4): 204-211.

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Leadership training is an essential component of faculty development and resident training. Characteristics of leaders include growth mindset, curiosity, humility, selflessness, intrinsic motivation, hunger to achieve, insight, collaboration, harmony, introversion and analytical approach (inherited) and emotional intelligence, empathy, flexibility, adaptability, conflict management, resilience, interpersonal skills, and judgment (learned). Training for each of these characteristics will enhance the leadership abilities of the surgical department.