Searched for: in-biosketch:true
person:stefad01
Quantifying Factors Essential to the Integrity of the Esophagogastric Junction During Antireflux Procedures
Stefanova, Dessislava I; Limberg, Jessica N; Ullmann, Timothy M; Liu, Mengyuan; Thiesmeyer, Jessica W; Beninato, Toni; Finnerty, Brendan M; Schnoll-Sussman, Felice H; Katz, Philip O; Fahey, Thomas J; Zarnegar, Rasa
OBJECTIVE:To quantify the contribution of key steps in antireflux surgery on compliance of the EGJ. BACKGROUND:The lower esophageal sphincter and crural diaphragm constitute the intrinsic and extrinsic sphincters of the EGJ, respectively. Interventions to treat reflux attempt to restore the integrity of the EGJ. However, there are limited data on the relative contribution of critical steps during antireflux procedures to the functional integrity of the EGJ. METHODS:Primary antireflux surgery was performed on 100 consecutive patients with pathologic reflux. Intraoperative EGJ measurements including distensibility index (DI), cross-sectional area (CSA), and HPZ length were collected using EndoFLIP. Data was acquired pre-repair, post-diaphragmatic re-approximation with sub-diaphragmatic EGJ relocation, and post-sphincter augmentation. RESULTS:Patients underwent Nissen (45%), Toupet (44%), or LINX (11%). After diaphragmatic re-approximation, DI decreased by a median 0.77 mm2/mm Hg [95%-confidence interval (CI): -0.99, -0.58; P < 0.0001], CSA decreased 16.0 mm2 (95%-CI: -20.0, -8.0; P < 0.0001), whereas HPZ length increased 0.5 cm (95%-CI: 0.5, 1.0; P < 0.0001). After sphincter augmentation, DI decreased 0.14 mm2/mm Hg (95%-CI: -0.30, -0.04; P = 0.0005) and CSA decreased 5.0 mm2 (95%-CI: -10.0, 1.0; P = 0.0.0015), whereas HPZ length increased 0.5 cm (95%-CI: 0.50, 0.54; P < 0.0001). Diaphragmatic re-approximation had a higher percent contribution to distensibility (79% vs 21%), CSA (82% vs 18%), and HPZ (60% vs 40%) than sphincter augmentation. CONCLUSION:Dynamic intraoperative monitoring demonstrates that diaphragmatic re-approximation and sub-diaphragmatic relocation has a greater effect on EGJ compliance than sphincter augmentation. As such, antireflux procedures should address both for optimal improvement of EGJ physiology.
PMID: 32657927
ISSN: 1528-1140
CID: 5872862
Does variability among surgical skills diminish throughout surgical internship? Analysis of a 5-task surgical simulation assessment program starting Day 1
Limberg, Jessica; Karnick, Aleksandrs; Bagautdinov, Iskander; Aveson, Victoria; Stefanova, Dessislava; Symer, Matthew M; Fehling, David; Fahey, Thomas J
BACKGROUND:Simulation assessments are not yet standardized among surgical programs. We instituted a 5-task simulation program to assess surgical technical skills longitudinally during internship. METHODS:First-year residents completed 5 simulation tasks: suturing, knot-tying, vascular anastomosis, and the peg-transfer and the intracorporeal suturing of the Fundamentals of Laparoscopic Skills. Assessments occurred just before residency, mid-year, and at the completion of the intern year. RESULTS:This study involved 19 residents: 8 categorical, 4 urology, 3 interventional radiology, 2 plastics, and 2 non-designated preliminary interns. Mean completion times improved in both the Fundamentals of Laparoscopic Skills peg-transfer (145 ± 50, 111 ± 47, and 95 ± 28 seconds) and suturing (526 ± 92, 392 ± 131, and 351 ± 158 seconds; each P < .001) tasks, and decreased variability was noted in the former. Total scores trended to improve (P = .013). Interns underwent similar training; 95% completed at least 1 core rotation by mid-year. Surgical specialty was associated with total scores during the first knot-tying session, with plastics residents scoring highest; however, all scores progressed toward the group median over time. CONCLUSION/CONCLUSIONS:Technical skills of beginning surgery residents were assessed longitudinally with the institution of a 5-task curriculum. Periodic assessments showed improvement in each task. Furthermore, as residents were exposed to equal surgical training, the variability in resident scores showed the greatest decrease in simpler motor tasks.
PMID: 31879091
ISSN: 1532-7361
CID: 5140922
Definitive chemoradiotherapy versus neoadjuvant chemoradiotherapy followed by surgery for stage II to III esophageal squamous cell carcinoma
Barbetta, Arianna; Hsu, Meier; Tan, Kay See; Stefanova, Dessislava; Herman, Koby; Adusumilli, Prasad S; Bains, Manjit S; Bott, Matthew J; Isbell, James M; Janjigian, Yelena Y; Ku, Geoffrey Y; Park, Bernard J; Wu, Abraham J; Jones, David R; Molena, Daniela
OBJECTIVE:Definitive chemoradiotherapy (CRT) remains the most commonly used treatment for locally advanced esophageal squamous cell carcinoma (SCC), because of perceptions that esophagectomy offers an unclear survival advantage. We compare recurrence, overall survival (OS), and disease-free survival (DFS) in patients treated with definitive CRT or neoadjuvant CRT followed by surgery (trimodality). METHODS:This was a retrospective cohort study of patients with stage II and III SCC of the middle and distal esophagus in patients who completed CRT. Treatment groups were matched (1:1) on covariates using a propensity score-matching approach. The effect of trimodality treatment, compared with definitive CRT, on OS, DFS, and site-specific recurrence was evaluated as a time-dependent variable and analyzed using Cox regression with a gamma frailty term for matched units. RESULTS:We included 232 patients treated between 2000 and 2016: 124 (53%) with definitive CRT and 108 (47%) with trimodality. Trimodality was used less frequently over time (61% before 2009 and 29% after 2009; P < .0001). After matching, each group contained 56 patients. Median OS and DFS were 3.1 and 1.8 years for trimodality versus 2.3 and 1.0 years for CRT. Surgery was independently associated with improved OS (hazard ratio, 0.57; 95% confidence interval, 0.34-0.97; P = .039) and DFS (hazard ratio, 0.51; 95% confidence interval, 0.32-0.83; P = .007). CONCLUSIONS:CRT followed by surgery might decrease local recurrence and increase DFS and OS in patients with esophageal SCC. Until better tools to select patients with pathological complete response are available, surgery should remain an integral component of the treatment of locally advanced esophageal SCC.
PMID: 29548582
ISSN: 1097-685x
CID: 5873082
Histone variant H2A.Z functions in sister chromatid cohesion in Saccharomyces cerevisiae
Sharma, Upasna; Stefanova, Dessislava; Holmes, Scott G
H2A.Z is a highly conserved variant of histone H2A with well-characterized roles in transcriptional regulation. We previously reported that H2A.Z and Mcd1, a subunit of the cohesin complex, regulate the establishment of transcriptional silencing at telomeres in Saccharomyces cerevisiae and that H2A.Z broadly dissociated from chromatin during the anaphase-to-telophase transition, coincident with the dissociation of Mcd1 from chromosomes and dissolution of cohesion. In this study, we show that depletion of H2A.Z causes precocious loss of sister chromatid cohesion in yeast without loss of Mcd1 from chromosomes. H2A.Z is deposited into chromatin by the SWR1 complex and is subject to acetylation of its four N-terminal tail lysine residues by the NuA4 and SAGA histone acetyltransferase complexes. We found that cells compromised for function of the SWR1 complex were defective in cohesion, as were cells expressing a form of H2A.Z not subject to acetylation. Finally, inactivation of H2A.Z in metaphase-blocked cells led immediately to cohesion defects, suggesting a direct role for H2A.Z in the maintenance of sister chromatid cohesion.
PMCID:3753853
PMID: 23816883
ISSN: 1098-5549
CID: 5873072