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Objective: Based on current practice guidelines, we hypothesized that most patients with esophageal cancer, particularly those with locally advanced cancer, would benefit from adjuvant therapy after esophagectomy versus esophagectomy alone. We sought to obtain a granular estimate of patient-level risk-adjusted survival for each therapeutic option by cancer histopathology and stage., Background: Although esophagectomy alone is now an uncommon therapy for treating locally advanced esophageal cancer, the value of adjuvant therapy after esophagectomy is unknown., Methods: From 1970 to 2014, 22,123 consecutive patients from 33 centers on 6 continents (Worldwide Esophageal Cancer Collaboration) were diagnosed with biopsy-proven adenocarcinoma (n = 7526) or squamous cell carcinoma (n = 5625), of whom 10,873 received esophagectomy alone and 2278 additional adjuvant therapy. Random forests for survival and virtual-twin analyses were performed for all-cause mortality., Results: For adenocarcinoma, adjuvant therapy was beneficial only in pT4NanyM0 cancers (6-8 month survival benefit) and in pTanyN3M0 cancers (4-8 month benefit); a survival decrement was observed in pT1-3N0M0 cancers, with no effect on TanyN1-2M0 cancers. In squamous cell carcinoma, there was a 4 to 21 month survival benefit for pT3-4N0M0 cancers and a 4 to 15 month survival benefit for pT2-4N1-3M0 cancers., Conclusions: Adjuvant therapy after esophagectomy appears to benefit most patients with node-positive squamous cell carcinoma, but for adenocarcinoma, its value is limited to deep cancers and to those with substantial nodal burden. Future studies of the role of adjuvant therapies should treat these 2 cancers differently, with guidelines reflecting the histopathologic-appropriate survival value of adjuvant therapy., Competing Interests: Disclosure: The authors declare that they have nothing to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: We hypothesized that, on average, patients do not benefit from additional adjuvant therapy after neoadjuvant therapy for locally advanced esophageal cancer, although subsets of patients might. Therefore, we sought to identify profiles of patients predicted to receive the most survival benefit or greatest detriment from adding adjuvant therapy., Background: Although neoadjuvant therapy has become the treatment of choice for locally advanced esophageal cancer, the value of adding adjuvant therapy is unknown., Methods: From 1970 to 2014, 22,123 patients were treated for esophageal cancer at 33 centers on 6 continents (Worldwide Esophageal Cancer Collaboration), of whom 7731 with adenocarcinoma or squamous cell carcinoma received neoadjuvant therapy; 1348 received additional adjuvant therapy. Random forests for survival and virtual-twin analyses were performed for all-cause mortality., Results: Patients received a small survival benefit from adjuvant therapy (3.2±10 months over the subsequent 10 years for adenocarcinoma, 1.8±11 for squamous cell carcinoma). Consistent benefit occurred in ypT3-4 patients without nodal involvement and those with ypN2-3 disease. The small subset of patients receiving most benefit had high nodal burden, ypT4, and positive margins. Patients with ypT1-2N0 cancers had either no benefit or a detriment in survival., Conclusions: Adjuvant therapy after neoadjuvant therapy has value primarily for patients with more advanced esophageal cancer. Because the benefit is often small, patients considering adjuvant therapy should be counseled on benefits versus morbidity. In addition, given that the overall benefit was meaningful in a small number of patients, emerging modalities such as immunotherapy may hold more promise in the adjuvant setting., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this study was to assess the effect on survival of extent of lymphadenectomy during esophagectomy for patients undergoing multimodality (neoadjuvant) therapy for adenocarcinoma of the esophagus and esophagogastric junction using Worldwide Esophageal Cancer Collaboration data., Summary Background Data: Previous worldwide data demonstrated that optimum lymphadenectomy during esophagectomy alone for esophageal cancer provides accurate staging and maximum survival. However, for patients undergoing neoadjuvant therapy for locally advanced adenocarcinoma, its value is unclear, leading to wide practice variability., Methods: A total of 3859 patients with adenocarcinoma of the esophagus or esophagogastric junction received neoadjuvant therapy. The endpoint was all-cause mortality, reported as gain or loss of lifetime within 10 years. Lifetime predicted for each regional lymph node resected used quantile survival random forest methodology., Results: Across all post-neoadjuvant ypTNM cancer categories, some degree of lymphadenectomy was associated with longer lifetime, but in a nonlinear fashion. For patients with ypN0 cancers, there was a modest gain in lifetime up to 25 lymph nodes resected and an incremental loss in lifetime as >25 were resected. For patients with ypN+ cancers, there was a robust gain in lifetime up to 30 lymph nodes resected and then an incremental loss in lifetime., Conclusions: Worldwide data for adenocarcinoma of the esophagus and esophagogastric junction demonstrate that lymphadenectomy during esophagectomy is a valuable component of neoadjuvant therapy. Survival is maximized when an optimum range of nodes is resected., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Reports of early failure of the Trifecta externally wrapped, bovine pericardial aortic valve prosthesis (Abbott Laboratories, Abbott Park, IL) raise concerns about its durability. This study evaluated the hemodynamic performance and explant of Trifecta valves compared with the PERIMOUNT bovine pericardial prosthesis (Edwards Lifesciences, Irvine, CA)., Methods: From October 2007 to July 2017, 2305 patients received a Trifecta bioprosthesis during aortic valve replacement at Cleveland Clinic. Trends in postoperative valve hemodynamics were assessed from 4971 transthoracic echocardiograms and valve explants by systemic follow-up. To compare outcomes, 2298 patients receiving a Trifecta valve were 1:1 propensity matched from 17,281 patients receiving a PERIMOUNT bioprosthesis., Results: Mean age at implant was 69 years in both matched groups. Compared with PERIMOUNT valves, early transvalvular mean gradient of Trifecta valves was lower (11 vs 15 mm Hg at 1 year, P < .001); however, its longitudinal rate of rise was greater (P < .001), resulting in 5-year mean gradients of 17 vs 16 mm Hg, and more patients experienced severe aortic regurgitation (2.4% vs 0.81%; P < .001). At 5 years, 35 Trifecta valves had been explanted vs 14 PERIMOUNT valves; freedom from explant at 1, 3, and 5 years was 98.9%, 98.0%, and 95.9%, respectively, for the Trifecta group vs 99.3%, 99.0%, and 98.7% for the PERIMOUNT group (P < .001)., Conclusions: Compared with an older-generation internally mounted bovine pericardial valve, the Trifecta externally wrapped bioprosthesis exhibits superior early hemodynamic performance, but has a rapid increase in transvalvular gradient and more aortic regurgitation, with lower freedom from explant at 5 years. These findings raise concern regarding long-term Trifecta durability despite favorable early hemodynamics., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

To address uncertainty of whether clinical stage groupings (cTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for clinically staged patients from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 22,123 clinically staged patients, 8,156 had squamous cell carcinoma, 13,814 adenocarcinoma, 116 adenosquamous carcinoma, and 37 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (18.5-25 mg/kg 2 , 47%), little weight loss (2.4 ± 7.8 kg), 0-1 ECOG performance status (67%), and history of smoking (67%). Cancers were cT1 (12%), cT2 (22%), cT3 (56%), cN0 (44%), cM0 (95%), and cG2-G3 (89%); most involved the distal esophagus (73%). Non-risk-adjusted survival for squamous cell carcinoma was not distinctive for early cT or cN; for adenocarcinoma, it was distinctive for early versus advanced cT and for cN0 versus cN+. Patients with early cancers had worse survival and those with advanced cancers better survival than expected from equivalent pathologic categories based on prior WECC pathologic data. Thus, clinical and pathologic categories do not share prognostic implications. This makes clinically based treatment decisions difficult and pre-treatment prognostication inaccurate. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient characteristics, cancer categories, and treatment characteristics and should direct 9th edition data collection., (© 2016 International Society for Diseases of the Esophagus.)

To address uncertainty of whether pathologic stage groupings after neoadjuvant therapy (ypTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for pathologically staged cancers after neoadjuvant therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 7,773 pathologically staged neoadjuvant patients, 2,045 had squamous cell carcinoma, 5,686 adenocarcinoma, 31 adenosquamous carcinoma, and 11 undifferentiated carcinoma. Patients were older (61 years) men (83%) with normal (40%) or overweight (35%) body mass index, 0-1 Eastern Cooperative Oncology Group performance status (96%), and a history of smoking (69%). Cancers were ypT0 (20%), ypT1 (13%), ypT2 (18%), ypT3 (44%), ypN0 (55%), ypM0 (94%), and G2-G3 (72%); most involved the distal esophagus (80%). Non-risk-adjusted survival for yp categories was unequally depressed, more for earlier categories than later, compared with equivalent categories from prior WECC data for esophagectomy-alone patients. Thus, survival of patients with ypT0-2N0M0 cancers was intermediate and similar regardless of ypT; survival for ypN+ cancers was poor. Because prognoses for ypTNM and pTNM categories are dissimilar, prognostication should be based on separate ypTNM categories and groupings. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics and should direct 9th edition data collection., (© 2016 International Society for Diseases of the Esophagus.)

We report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for patients with pathologically staged cancer of the esophagus and esophagogastric junction after resection or ablation with no preoperative therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted de-identified data using standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 13,300 patients, 5,631 had squamous cell carcinoma, 7,558 adenocarcinoma, 85 adenosquamous carcinoma, and 26 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (51%), little weight loss (1.8 kg), 0-2 ECOG performance status (83%), and a history of smoking (70%). Cancers were pT1 (24%), pT2 (15%), pT3 (50%), pN0 (52%), pM0 (93%), and pG2-G3 (78%); most involved distal esophagus (71%). Non-risk-adjusted survival for both squamous cell carcinoma and adenocarcinoma was monotonic and distinctive across pTNM. Survival was more distinctive for adenocarcinoma than squamous cell carcinoma when pT was ordered by pN. Survival for pTis-1 adenocarcinoma was better than for squamous cell carcinoma, although monotonic and distinctive for both. WECC pathologic staging data is improved over that of the 7th edition, with more patients studied and patient and cancer variables collected. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics, and should direct 9th edition data collection. However, the role of pure pathologic staging as the principal point of reference for esophageal cancer staging is waning., (© 2016 International Society for Diseases of the Esophagus.)