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Objective: Spread through air spaces (STAS) is a new histologic feature of invasion of non-small cell lung cancer that lacks sensitivity and specificity on frozen sections and is associated with higher recurrence and worse survival with sublobar resections. Our objective is to identify preoperative characteristics that are predictive of STAS to guide operative decisions., Methods: From January 2018 through December 2021, 439 cT1-3N0 M0 patients with non-small cell lung cancer and a median age of 68 years, 255 (58%) women, who underwent primary surgery at our institution were included. Patients who received neoadjuvant therapy and whose STAS status was not documented were excluded. Age, sex, smoking status, tumor size, ground-glass opacities, maximum standardized uptake values, and molecular markers on preoperative biopsy were evaluated as preoperative markers. Comparisons between groups were conducted using standardized mean differences and random forest classification was used for prediction modeling., Results: Of the 439 patients, 177 had at least 1 STAS-positive tumor, and 262 had no STAS-positive tumors. Overall, 179 STAS tumors and 293 non-STAS tumors were evaluated. Younger age (50 years or younger), solid tumor, size ≥2 cm, and maximum standardized uptake value ≥2.5 were independently predictive of STAS with prediction probabilities of 50%, 40%, 38%, and 40%, respectively. STAS tumors were more likely to harbor KRAS mutations and be PD-L1 negative., Conclusions: Young age (50 years or younger), larger (≥2 cm) solid tumors, high maximum standardized uptake values, and presence of KRAS mutation, are risk factors for STAS and can be considered for lobectomy. Smoking status and gender are still controversial risk factors for STAS., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: We hypothesized that emergency complications related to asymptomatic paraconduit hernias may occur less often than generally believed. Therefore, we assessed the occurrence and timing of paraconduit hernia diagnosis after esophagectomy, as well as outcomes of these asymptomatic patients managed with a watch-and-wait approach., Methods: From 2006 to 2021, 1214 patients underwent esophagectomy with reconstruction at the Cleveland Clinic. Among these patients, computed tomography scans were reviewed to identify paraconduit hernias. Medical records were reviewed for timing of hernia diagnosis, hernia characteristics, and patient symptoms, complications, and management. During this period, patients with asymptomatic paraconduit hernias were typically managed nonoperatively., Results: Paraconduit hernias were identified in 37 patients. Of these, 31 (84%) had a pre-esophagectomy hiatal hernia. Twenty-one hernias (57%) contained colon, 7 hernias (19%) contained pancreas, and 9 hernias (24%) contained multiple organs. Estimated prevalence of paraconduit hernia was 3.3% at 3 years and 7.7% at 10 years. Seven patients (19%) had symptoms, 4 of whom were repaired electively, with 2 currently awaiting repairs. No patient with a paraconduit hernia experienced an acute complication that required emergency intervention., Conclusions: The risk of paraconduit hernia increases with time, suggesting that long-term symptom surveillance is reasonable. Emergency complications as a result of asymptomatic paraconduit hernias are rare. A small number of patients will experience hernia-related symptoms, sometimes years after hernia diagnosis. Our findings suggest that observation of asymptomatic paraconduit hernias (watch and wait) may be considered, with repair considered electively in patients with persistent symptoms., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Currently, there is no validated patient-reported outcome measure (PROM) applicable to all esophageal diseases. Our objective was to create a psychometrically robust, validated universal esophageal PROM that can also objectively assess patients' quality of life (QoL)., Methods: The pilot PROM constructed based on expert opinions, literature review, and previous unpublished institutional research had 27 items covering 8 domains. It was completed by 30 patients in the outpatient clinic followed by a structured debriefing interview, which allowed for refining the PROM. The final PROM: Cleveland Clinic Esophageal Questionnaire (CEQ) included 34 items across 6 domains (Dysphagia, Eating, Pain, Reflux & Regurgitation, Dyspepsia, Dumping), each accompanied by a corresponding QoL component. Further psychometric assessment of the PROM was conducted by evaluating (1) acceptability, (2) construct validity, (3) reliability, and (4) responsiveness., Results: Five hundred forty-six unique patients (median 63.7 years [54.3-71.7], 53% male [287], 86% White) completed CEQ at >90% completion within 5 minutes. Construct validity was demonstrated by differentiating scores across esophageal cancer (n = 146), achalasia (n = 170), hiatal hernia (n = 160), and other diagnoses (n = 70). Internal reliability (Cronbach alpha 0.83-0.89), and test-retest reliability (intraclass correlation coefficients 0.63-0.85) were strong. Responsiveness was demonstrated through CEQ domains improving for 53 patients who underwent surgery for achalasia or hiatal hernia (Cohen d 0.86-2.59)., Conclusions: We have constructed a psychometrically robust, universal esophageal PROM that allows concise, consistent, objective quantification of symptoms and their effect on the patient. The CEQ is valuable in prognostication and tracking of longitudinal outcomes in both benign and malignant esophageal diseases., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. All rights reserved.)

Objective: Minimally invasive Heller myotomy for achalasia is commonly performed laparoscopically, but recently done with robotic assistance. We compare outcomes of the 2 approaches., Methods: From January 2010 to January 2020, 447 patients underwent Heller myotomy with anterior fundoplication (170 with robotic assistance and 277 laparoscopically). End points included short-term and longitudinal esophageal emptying according to timed barium esophagram, symptom relief according to Eckardt score, and time-related reintervention. Normal esophageal morphology, present in 328 patients, was defined as nonsigmoidal with width <5 cm. We performed a propensity score--matched analysis to evaluate outcomes among robotic and laparoscopic groups., Results: Timed barium esophagrams showed complete emptying at 5 minutes in 58% (77/132) of the robotic group and 48% (115/241) of the laparoscopic group in the short term (within 6 months of surgery). In the propensity-matched patients with normal esophageal morphology, the robotic group had a higher longitudinal prevalence of complete emptying of barium at 5 minutes (54% vs 34% at 4 years; P = .05), better intermediate-term Eckardt scores (1.7% vs 10% > 3 at 4 years; P = .0008), and actuarially fewer reinterventions (1.2% vs 11% at 3 years; P = .04)., Conclusions: Both robotically assisted and laparoscopic Heller myotomy had excellent outcomes in patients treated for achalasia. In a matched subgroup of patients with normal esophageal morphology within this heterogeneous disease, the robotic approach might be associated with greater esophageal emptying, palliation of symptoms, and freedom from reintervention in the intermediate term. Long-term analysis would be important to determine if this trend persists., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate differences in presentation, pathology, and outcomes after resection of non-small cell lung cancer (NSCLC) in never-smokers versus ever-smokers., Methods: From January 2006 to July 2016, 172 never-smokers and 1376 ever-smokers with NSCLC underwent pulmonary resection. The 2 cohorts were matched on patient characteristics, histopathological cancer cell type, and pathological stage group using a weighted balancing score, and overall survival and cancer recurrence were compared by pathological stage. Random forests for survival was used to identify granular cancer characteristics with different survival and cancer recurrence importance between groups., Results: In never-smokers, the prevalence of NSCLC was more frequent in women than in men (63% [n = 109] vs 45% [n = 63]). Compared with ever-smokers, never-smokers had less upper-lobe disease (53% [n = 91] vs 62% [n = 855]) and more adenocarcinoma (88% [n = 151] vs 62% [n = 845]). Postoperative complications were similar. Never-smokers had a lower prevalence of non-lung cancer deaths than ever-smokers (13% vs 23% at 5 years; P = .006). Among matched pairs, never-smokers had better overall survival at 5 years in pathological stage I (96% vs 78%), but worse survival in stage II (54% vs 78%). Tumor size, N category, and histopathological cell type were more important drivers of mortality and cancer recurrence in never-smokers than in ever-smokers., Conclusions: NSCLC in never-smokers affects women more than men and presents with different anatomic and histopathological distributions. Matched never-smokers have better or equivalent outcomes than ever-smokers in pathological stage I cancer, but are less likely to survive and to be cured of cancer as tumor burden increases. These findings suggest that there might be unique tumor or host behaviors differentially impacting survival of never- and ever-smoking patients with NSCLC., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: To (1) measure 4 physiologic metrics before esophagectomy, (2) use these in an index to predict composite postoperative outcome after esophagectomy, and (3) compare predictive accuracy of this index to that of the Fried Frailty Index and Modified Frailty Index., Methods: Grip strength (kilograms), 30-second chair sit-stands (number), 6-minute walk distance (meters), and normalized psoas muscle area (cm 2 /m) were measured for 77 consenting patients from January 1, 2018, to April 1, 2019. Imbalanced random forest classification estimated probability of a composite postoperative outcome, which included mortality, respiratory complications, anastomotic leak, delirium, length of stay ≥14 days, discharge to nursing facility, and readmission. G-mean error was used to compare predictive accuracy among indexes., Results: Median grip strength was 38 kg (25th-75th percentiles, 31-44), number of sit-stands 11 (10-14), psoas muscle area to height ratio 6.9 cm 2 /m (6.0-8.2), and 6-minute walk distance 407 m (368-451). There was generally weak correlation between these metrics, with the highest between 30-second sit-stands and 6-minute walk distance (r = 0.57). Age, degree of patient-reported exhaustion, and the 4 objective metrics comprised the Esophageal Vitality Index, which had a lower G-mean error of 32% (31-33) than the Fried Frailty Index, 37% (37-38), and the Modified Frailty Index, 48% (47-48)., Conclusions: The Esophageal Vitality Index, an objective, simple assessment consisting of grip strength, 30-second chair sit-stands, 6-minute walk, and psoas muscle area to height ratio outperformed commonly used frailty indexes in predicting postesophagectomy mortality and morbidity. The index provides a robust picture of patients' fitness for surgery beyond the qualitative "eyeball" test., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Use of per oral endoscopic myotomy is increasing for the treatment of achalasia, with potential for rapid recovery and less invasiveness. We report our experience with per oral endoscopic myotomy to better understand how it fits into a modern paradigm of achalasia management., Methods: A total of 152 patients with achalasia underwent per oral endoscopic myotomy from April 2014 to March 2018. Type II achalasia was the most prominent subtype in 69 patients (49%), and 33 patients (21.5%) had a prior Heller myotomy. Postoperative Eckardt scores, integrated relaxation pressure, and timed barium esophagram column height and width at 2 months were compared with preoperative measurements., Results: Per oral endoscopic myotomy was completed in 149 patients (98%). Median operative time was 96 minutes (75 minutes for the last 30 cases), and length of stay was 1 day (interquartile range, 1-2). The most common morbidities were mucosal perforation in 2 patients (1.3%) and bleeding in 3 patients (2.0%), although no nonendoscopic intervention was required. Mortality was zero. Postoperatively, the median Eckardt score decreased from 6 to 0 (P < .001), residual lower esophageal sphincter pressure decreased from 22 mm Hg to 6 mm Hg (P < .001), and timed barium esophagram column height and width at 5 minutes decreased from 8 and 2.5 cm to 1.5 and 0.8 cm (P < .001), respectively. Median time to return to daily activity was 7 days; 49 patients (49.5%) had abnormal acid reflux on 24-hour pH testing postprocedure., Conclusions: Per oral endoscopic myotomy is a safe and effective intervention that provides clear subjective and objective improvement in patients with achalasia. High postprocedure acid reflux raises concern about future sequelae if used in a nonselective fashion., (Copyright © 2018. Published by Elsevier Inc.)

Objectives: Infection is an important cause of morbidity and mortality after lung transplantation. Immunoglobulins are part of both seromucous (IgA) and serum (IgG) infection defense mechanisms. We therefore hypothesized that lower pretransplant IgA levels would be associated with more early post-lung transplant seromucous infections and greater mortality independent of IgG., Methods: From January 2000 to July 2010, 538 patients undergoing primary lung transplantation had pretransplant IgA (n = 429) and IgG (n = 488) measured as a clinical routine. Median IgA was 200 mg·dL -1 (2% < 70 mg·dL -1 , lower limit of normal); median IgG was 970 mg·dL -1 (5% < 600 mg·dL -1 ). Intensive microbiology review was used to categorize infections and their causative organisms within the first posttransplant year., Results: In total, 397 seromucous infections were observed in 247 patients, most bacterial. Although IgA and IgG were moderately correlated (r = 0.5, P < .0001), low pretransplant IgA was a strong risk factor (P = .01) for seromucous infections, but pretransplant IgG was not (P ≥ .6). As pretransplant IgA levels fell below 200 mg·dL -1 , the risk of these posttransplant infections rose nearly linearly. Lower pretransplant levels of IgA were associated with greater posttransplant mortality to end of follow-up (P = .004), but pretransplant IgG was not (P ≥ .3)., Conclusions: Low levels of preoperative IgA, an important immunoglobulin involved in mucosal immunologic defense, but not IgG, are associated with seromucous infections in the year after lung transplantation and increased follow-up mortality. It would appear prudent to identify patients with relative IgA deficiency at listing and to increase vigilance of monitoring for, and prophylaxis against, seromucous infection in this high-risk population., (Copyright © 2018. Published by Elsevier Inc.)

Objectives: The value of routine timed barium esophagram (TBE) in longitudinal follow-up of achalasia after Heller myotomy is unknown. We prospectively prescribed a yearly follow-up TBE. Purposes were to characterize esophageal emptying over time after myotomy, identify preoperative TBE measures associated with follow-up TBE, and characterize follow-up TBE over time in relationship to reintervention., Methods: From March 1995 to April 2013, 635 patients underwent Heller myotomy for achalasia; 559 had at least 1 follow-up TBE. Temporal trends of 1335 follow-up TBEs in all nonreintervention and reintervention patients were assessed. Multivariable longitudinal analysis identified preoperative TBE measures associated with follow-up TBE., Results: On average, TBE height and width at 1 and 5 minutes decreased approximately 50% and 60%, respectively, at first postoperative follow-up, and remained stable or slightly decreased for up to 5 years. Wider TBE width at 5 minutes was associated with greater follow-up TBE height and width at 1 minute. Of 118 patients undergoing reintervention, 64 (57%) had only 1 reintervention, with follow-up TBE returning to that of nonreintervention patients. Patients whose follow-up TBE remained abnormal underwent a further reintervention, some normalizing on subsequent TBE, and some not., Conclusions: Follow-up TBE is valuable postmyotomy, particularly if there is substantial esophageal dilatation preoperatively. Follow-up TBE reassures patients with stable or decreasing TBE measures, permitting decreased follow-up intensity. Reintervention should not be considered a myotomy failure, because a successful, single, nonsurgical reintervention often results in long-term successful palliation. More than 1 reintervention requires intensification of TBE follow-up, facilitating treatment planning., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: To (1) assess the continuous distribution of the percentage of residual primary cancer in resection specimens after induction therapy for locally advanced esophageal adenocarcinoma, (2) determine the effects of residual primary cancer on survival after esophagectomy, (3) ascertain interplay between residual primary cancer and classical classifications of response to induction therapy (ypTNM), and (4) identify predictors of residual primary cancer., Methods: From January 2006 to November 2012, 188 patients (78%) underwent accelerated chemoradiotherapy, and 52 patients (22%) underwent chemotherapy alone followed by esophagectomy for adenocarcinoma. Mean age was 61 ± 9.2 years, and 89% were male. Residual primary cancer, assessed as the percentage of residual primary cancer cells in resection specimens, was quantified histologically by a gastrointestinal pathologist. Random Forest technology was used for data analysis., Results: Twenty-five specimens (10%) had no residual primary cancer (ypT0), 79 (33%) had 1% to 25% residual cancer, 91 (38%) had 26% to 75%, and 45 (19%) had >75%. Survival was worse with increasing residual primary cancer, plateauing at 75%. Greater residual primary cancer was associated with worse survival across the spectrum of higher ypTN. Higher ypT, larger number of positive nodes, and use of induction chemotherapy rather than induction chemoradiotherapy were associated with greater residual primary cancer., Conclusions: Less residual primary cancer in response to preoperative therapy is associated with a linear increase in survival after esophagectomy for locally advanced esophageal adenocarcinoma; however, survival is poorer than for resected early-stage cancers. Therefore, for patients with poor prognostic indicators, including higher percentage of residual primary cancer, the role of adjuvant therapy needs to be further examined in an attempt to improve survival., (Copyright © 2016. Published by Elsevier Inc.)

Objectives: Symptomatic venous thromboembolism (VTE) after pneumonectomy is associated with poor prognosis. We describe a new care pathway for patients undergoing pneumonectomy in which asymptomatic lower-extremity VTE screening was performed to determine if it increases VTE detection and potentially decreases sequelae., Methods: 112 patients underwent pneumonectomy from 2006 to 2013 at Cleveland Clinic and were enrolled in a care pathway that included VTE prophylaxis and routine, predischarge, lower-extremity VTE screening. These data were contrasted with a previously published cohort of 336 patients (1990-2001) who underwent pneumonectomy without routine VTE screening., Results: 10 of 112 patients (8.9%) had VTE detected by screening before discharge. An additional 4 patients (3.6%) with a negative predischarge screen developed symptomatic VTE within 30 days. Six patients (5.4%) developed VTE after pneumonectomy beyond the first 30 days. Prevalence of in-hospital VTE in the screened cohort was significantly higher than that of the non-screened cohort (3.0%; P = .008). Similarly, VTE within 30 days in the screened cohort (13%) was significantly higher than in the nonscreened cohort (5.0%; P = .007). In both cohorts, a peak was observed approximately 6 days after pneumonectomy and plateaued after 30 days. The presence of a VTE portended worse long-term survival: 66% at 1 year versus 85% for those not developing a VTE., Conclusions: Prevalence of VTE after pneumonectomy is higher than previously thought. The risk of developing a VTE peaks at 6 days after pneumonectomy, and remains increased until 30 days, suggesting a need for additional screening or longer prophylaxis., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Restoring dual blood supply to transplanted lungs by bronchial artery revascularization (BAR) remains controversial. We compared outcomes after lung transplantation performed with and without BAR., Methods: From December 2007 to July 2010, 283 patients underwent transplantation; 187 were 18 years or older, without previous or concomitant cardiac surgery. Of these patients, 27 underwent BAR in a pilot study to test success, safety, effectiveness, and teachability. A propensity score was generated to match BAR patients and 54 routine non-BAR patients. Follow-up was 1.3 ± 0.68 years., Results: BAR was angiographically successful in 26 (96%) of 27 patients. BAR and non-BAR patients had similar skin-to-skin time (P = .07) and postoperative hospital stays (P = .2), but more reoperations for bleeding (P = .002). Tracheostomy was performed in 9 (33%) of 27 BAR and 10 (19%) of 54 non-BAR patients (P = .2, log-rank). One BAR (3.7%) and 4 non-BAR (7.4%) patients required extracorporeal membrane oxygenation (P = .7). Airway ischemia was observed in 1 BAR (3.7%) versus 12 non-BAR (22%) patients (P = .03); anastomotic intervention was required in no BAR versus 8 non-BAR (15%) patients (P = .04). Hospital mortality was 1 of 27 versus 2 of 54 (P = .9). BAR patients had lower early biopsy tissue rejection grades (P = .008) and fewer pulmonary (P < .04) and bloodstream (P < .02) infections. Forced 1-second expiratory volume was similar (P > .2); 3 BAR versus 9 non-BAR patients developed bronchiolitis obliterans syndrome (BOS) (P = .14, log-rank). During follow-up, 4 BAR and 8 non-BAR patients died (P = .6, log-rank)., Conclusions: BAR is safe, with comparable early outcomes. Benefits of BAR include reduced airway ischemia and complications, lower biopsy tissue grades, fewer infections, and delay of BOS. A multicenter study is needed to establish these benefits., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objectives: Intramucosal esophageal cancer treatment is evolving. Less-invasive therapies have emerged, necessitating review of safety, effectiveness, and determinants of long-term outcome after esophagectomy to clarify the role of this traditional, maximally invasive, and potentially harmful therapy., Methods: From January 1983 to January 2011, 164 patients underwent esophagectomy alone for intramucosal adenocarcinoma. Cancers were subdivided by depth of invasion: lamina propria 50 (30%) and muscularis mucosa 114 (70%; inner 42 [26%], middle 16 [10%], and outer 56 [34%]). We assessed complications and esophagectomy-related mortality (safety) and cancer recurrence (effectiveness), and identified determinants of long-term outcomes., Results: Barrett esophagus (P = .005), larger cancers (P < .001), worse histologic grade (P < .001), lymphovascular invasion (P < .001), and overstaging (P = .02) were associated with deeper cancers. One patient had regional lymph node metastases (0.6%). Seventy-five patients (46%) had complications. Seven of 9 deaths within 6 months were esophagectomy related, 6 from respiratory failure. Seven patients had recurrence, all within 4 years. Five-, 10-, and 15-year survivals were 82%, 69%, and 60%, respectively, which were similar to those of a matched general population. Determinants of late mortality were older age (P = .004), poorer lung function (P < .0001), longer cancer (P = .04), postoperative pneumonia (P = .06), cancer recurrence (P < .0001), and second cancers (P < .0001)., Conclusions: Survival after esophagectomy for intramucosal adenocarcinoma is excellent, determined more by patient than cancer characteristics. Patient selection and respiratory function are crucial to minimize harm. Considering the outcome of emerging therapies, esophagectomy should be reserved for patients with a long intramucosal adenocarcinoma or those in whom endoscopic therapies fail or are inappropriate., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: The decline in normalized forced 1-second expiratory volume after lung transplantation is inevitable; however, the effect of this change on survival is unknown. Additionally, the benefit of double versus single lung transplant is debated, particularly because pulmonary function is only slightly better after double lung transplant. Our goal was to determine the effect of the temporal pattern of post-transplant forced 1-second expiratory volume (percentage of predicted) on the risk of death after transplant and the differences in the sensitivity of single and double lung transplant to this relationship., Methods: From February 1990 to January 2008, 622 adults underwent lung transplantation, of whom 315 (51%) received 2 lungs. Of the 509 patients (82%) with available data, 9471 longitudinal evaluations of forced 1-second expiratory volume (percentage of predicted) were analyzed. The temporal pattern was characterized for each patient, and the resulting curve was evaluated as a time-varying covariable function in the survival analysis. Differences in sensitivity of single and double lung transplant were assessed by interaction., Results: Forced 1-second expiratory volume (percentage of predicted) increased from 50% immediately postoperatively to 55% at 1 year after single lung transplant and then gradually declined to 47% by 3 years. Although the pattern was similar after double lung transplant, the corresponding forced 1-second expiratory volume (percentage of predicted) at these points was greater--60%, 75%, and 65%. Lower post-transplant forced 1-second expiratory volume (percentage of predicted) was associated with a substantially increased risk of death after single lung transplant (P < .0001); however, this increase was far less after double lung transplant (P < .0001)., Conclusions: The results of our study have demonstrated the effect of changing lung function after lung transplantation on survival. Survival after single lung transplant proved more sensitive to declining pulmonary function, demonstrating an advantage of the increased pulmonary reserve provided by double lung transplant., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objectives: Submucosal esophageal cancers (pT1b) are considered superficial, implying good survival. However, some are advanced, metastasizing to regional lymph nodes. Interplay of cancer characteristics and lymphatic anatomy may create a watershed, demarcating low-risk from high-risk cancers. Therefore, we characterized submucosal cancers according to depth of invasion and identified those with high likelihood of lymph node metastases and poor survival., Methods: From 1983 to 2010, 120 patients underwent esophagectomy for submucosal cancers at Cleveland Clinic. Correlations were sought among cancer characteristics (location, dimensions, histopathologic cell type, histologic grade, and lymphovascular invasion [LVI]), and their associations with lymph node metastasis were identified by logistic regression. Associations with mortality were identified by Cox regression., Results: As submucosal invasion increased, cancer length (P < .001), width (P < .001), area (P < .001), LVI (P = .007), and grade (P = .05) increased. Invasion of the deep submucosa (P < .001) and LVI (P = .06) predicted lymph node metastases: 45% (23/51) of deep versus 10% (3/29) of middle-third and 7.5% (3/40) of inner-third cancers had lymph node metastases, as did 46% (12/26) with LVI versus 18% (17/94) without. Older age and lymph node metastases predicted worse 5-year survival: 94% for younger pN0 patients, 62% for older pN0 patients, and 36% for pN1-2 patients regardless of age., Conclusions: Submucosal cancer characteristics and lymphatic anatomy create a watershed for regional lymph node metastases in the deep submucosa. This previously unrecognized divide distinguishes superficial submucosal cancers with good survival from deep submucosal cancers with poor survival. Aggressive therapy of more superficial cancers is critical before submucosal invasion occurs., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objectives: Gastroesophageal reflux disease (GERD) is implicated as a risk factor for bronchiolitis obliterans syndrome after lung transplantation, but its effects on acute rejection, early allograft function, and survival are unclear. Therefore, we sought to systematically understand the time-related impact of pretransplant GERD on graft function (spirometry), mortality, and acute rejection early after lung transplantation., Methods: From January 2005 to July 2008, 215 patients underwent lung transplantation; 114 had preoperative pH testing, and 32 (28%) had objective evidence of GERD. Lung function was assessed by forced 1-second expiratory volume (FEV(1); percent of predicted) in 97 patients, mortality by follow-up (median, 2.2 years), and acute rejection by transbronchial biopsy., Results: Pretransplant GERD was associated with decreased FEV(1) early after lung transplantation (P = .01) such that by 18 months, FEV(1) was 70% of predicted in double lung transplant patients with GERD versus 83% among non-GERD patients (P = .05). A similar decrease was observed in single lung transplantation (50% vs 60%, respectively; P = .09). GERD patients had lower survival early after transplant ( P = .02)-75% versus 90%. Presence of GERD did not affect acute rejection (P = .6)., Conclusions: For lung transplant recipients, pretransplant GERD is associated with worse early allograft function and survival, but not increased acute rejection. The compromise in lung function is substantial, such that FEV(1) after double lung transplant in GERD patients approaches that of single lung transplant in non-GERD patients. We advocate thorough testing for GERD before lung transplantation; if identified, aggressive therapy early after transplant, including fundoplication, may prove efficacious., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: The study objective was to evaluate histopathology of the esophagogastric anastomosis after esophagectomy, determine time trends of histologic changes, and identify factors influencing those findings., Methods: A total of 231 patients underwent 468 upper gastrointestinal endoscopies with anastomotic biopsy a median of 3.5 years after esophagectomy. Mean age was 59 ± 12 years, 74% (171) were male, and 96% (222) were white. Seventy-eight percent (179) had esophagectomy for cancer, 13% (30) had chemoradiotherapy, and 13% (30) had prior esophageal surgery. The anastomosis was 20 ± 2.0 cm from the incisors. Anti-reflux medications were used in 59% of patients (276/468) at esophagoscopy. Histopathology was graded as normal (0), consistent with reflux (1), cardia mucosa (2), intestinal metaplasia (3), and dysplasia (4). Repeated-measures nonlinear time-trend analysis and multivariable analyses were used., Results: Grades 0 and 1 were constant, 5% and 92% at 10 years, respectively. Anti-reflux medication, induction therapy, and higher anastomosis were predictive of less grade 1 histopathology. Grades 2 and 3 increased with time: 12% and 33% at 5 years and 4% and 16% at 10 years, respectively. No variable was predictive of grade 2 or 3 (P > .15) except passage of time. No patient's condition progressed to dysplasia or cancer., Conclusions: The esophagogastric anastomosis is subject to gastroesophageal reflux. To minimize histopathologic changes of reflux, the anastomosis should be constructed as high as possible (closer to incisors) and anti-reflux medications prescribed. Surveillance endoscopy, if performed, will document a time-related progression of reflux-related histopathologic changes. However, during surveillance, intestinal metaplasia is uncommon and progression to cancer rare., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: The study objectives were to (1) compare survival after lung transplantation in patients requiring pretransplant mechanical ventilation or extracorporeal membrane oxygenation with that of patients not requiring mechanical support and (2) identify risk factors for mortality., Methods: Data were obtained from the United Network for Organ Sharing for lung transplantation from October 1987 to January 2008. A total of 15,934 primary transplants were performed: 586 in patients on mechanical ventilation and 51 in patients on extracorporeal membrane oxygenation. Differences between nonsupport patients and those on mechanical ventilation or extracorporeal membrane oxygenation support were expressed as 2 propensity scores for use in comparing risk-adjusted survival., Results: Unadjusted survival at 1, 6, 12, and 24 months was 83%, 67%, 62%, and 57% for mechanical ventilation, respectively; 72%, 53%, 50%, and 45% for extracorporeal membrane oxygenation, respectively; and 93%, 85%, 79%, and 70% for unsupported patients, respectively (P < .0001). Recipients on mechanical ventilation were younger, had lower forced vital capacity, and had diagnoses other than emphysema. Recipients on extracorporeal membrane oxygenation were also younger, had higher body mass index, and had diagnoses other than cystic fibrosis/bronchiectasis. Once these variables, transplant year, and propensity for mechanical support were accounted for, survival remained worse after lung transplantation for patients on mechanical ventilation and extracorporeal membrane oxygenation., Conclusion: Although survival after lung transplantation is markedly worse when preoperative mechanical support is necessary, it is not dismal. Thus, additional risk factors for mortality should be considered when selecting patients for lung transplantation to maximize survival. Reduced survival for this high-risk population raises the important issue of balancing maximal individual patient survival against benefit to the maximum number of patients., (Copyright 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: The impact of size matching between donor and recipient is unclear in lung transplantation. Therefore, we determined the relation of donor lung size to 1) posttransplant survival and 2) pulmonary function as measured by forced expiratory volume in 1 second., Methods: From 1990 to 2006, 469 adults underwent lung transplantation with lungs from donors aged 7 to 70 years. Donor and recipient total lung capacities were calculated using established formulae (predicted total lung capacity), and actual recipient lung size was measured in the pulmonary function laboratory. Disparity between donor and recipient lung size was expressed as a ratio of donor predicted total lung capacity to recipient predicted total lung capacity-the predicted total lung capacity ratio-and predicted donor total lung capacity to actual recipient total lung capacity-the actual total lung capacity ratio. Survival was measured by multiphase hazard methodology and repeated measures of National Health and Nutrition Examination Survey-normalized forced expiratory volume in 1 second analyzed by temporal decomposition., Results: Predicted total lung capacity ratio and actual total lung capacity ratio ranged widely, from 0.55 to 1.59 and 0.52 to 4.20, respectively. Overall survival was unaffected by predicted total lung capacity ratio (P = .3) or actual total lung capacity ratio (P = .5). Patients with emphysema and an actual total lung capacity ratio of 0.67 or less or 1.03 or greater had higher predicted mortality (P = .01). During the first posttransplant year, forced expiratory volume in 1 second increased and then gradually declined. Predicted total lung capacity ratio and actual total lung capacity ratio had a small impact on forced expiratory volume in 1 second, primarily in the late phase after transplant in a disease-specific manner., Conclusion: Size matching between donor and recipient using predicted total lung capacity ratio and actual total lung capacity ratio is an effective technique. Wide discrepancies in lung sizing do not affect overall posttransplant survival or pulmonary function. Therefore, a greater degree of lung size mismatch can likely be accepted, thereby improving patients' odds of undergoing transplantation.

Objective: We compared 1) survival after lung transplantation of recipients of donation after cardiac death (DCD) versus brain death donor organs in the United States and 2) recipient characteristics., Methods: Data were obtained from the United Network for Organ Sharing for lung transplantation from October 1987 to May 2007. Follow-up after DCD lung transplantation extended to 8.6 years, median 1 year. Differences among recipients of DCD versus brain death donor organs were expressed as a propensity score for use in comparing risk-adjusted survival., Results: A total of 14,939 transplants were performed, 36 with DCD organs (9 single, 27 double). Among the 36 patients, 3 have died after 1 day, 11 days, and 1.5 years. Unadjusted survival at 1, 6, 12, and 24 months was 94%, 94%, 94%, and 87%, respectively, for DCD donors versus 92%, 84%, 78%, and 69%, respectively, for brain death donors (P = .04). DCD recipients were more likely to undergo double lung transplantation and have diabetes, lower forced 1-second expiratory volume, and longer cold ischemic times. Once these were accounted for and propensity adjusted, survival was still better for DCD recipients, although the P value equals .06., Conclusion: Concern about organ quality and ischemia-reperfusion injury has limited the application of lung DCD. However, DCD as practiced in the United States results in survival at least equivalent to that after brain death donation. It also demonstrates selection bias, particularly in performing double lung transplantation, making generalization regarding survival difficult. Nevertheless, the data support the expanded use of DCD.