How Much Delay Matters? How Time to Treatment Impacts Overall Survival in Early Stage Lung Cancer.

OBJECTIVES: The aim of this study was to identify drivers of time from diagnosis to treatment (TTT) of surgically resected early stage non-small cell lung cancer (NSCLC) and determine the effect of TTT on post-resection survival. SUMMARY BACKGROUND DATA: Large database studies that lack relevant comorbidity data have identified longer TTT asa driver of worse overall survival. METHODS: From January 1, 2014 to April 1, 2018, 599 patients underwent lung resection for clinical stage I and II NSCLC. Random forest classification, regression, and survival were used to estimate likelihood of TTT = 0 (tissue diagnosis obtained at surgery), >0 (diagnosis obtained pre-resection), and effect of TTT on all-cause mortality. RESULTS: Patients with TTT > 0 (n = 413) had median TTT of 42 days (25-75 th percentile: 27-59 days). Patients with TTT = 0 (n = 186) had smaller tumors and higher percent predicted forced expiratory volume in 1 second (FEV 1 %). Patients with history of stroke, oncology consultation, invasive mediastinal staging, low and high extremes of FEV 1 % had longer TTT. Higher clinical stage, lack of preoperative stress test, anemia, older age, lower FEV1% and diffusion lung capacity, larger tumor size, and longer TTT were the most important predictors of all-cause mortality. One- and 5-year overall survival decreased when TTT was >50 days. CONCLUSIONS: Preoperative physiologic workup and multidisciplinary evaluation were the predominant drivers of longer TTT. Patients with TTT = 0have more favorable presentation and should be considered in TTT analyses for early stage lung cancer populations. The time needed to clinically stage and optimize patients for resection is not deleterious to overall survival until resection is performed after 50 days from diagnosis.

Identifying the barriers to gastric cancer care at safety-net hospitals: A novel comparison of a safety-net hospital to a neighboring quaternary referral academic center in the same healthcare system.

BACKGROUND: The three-delays model describes delays in seeking, reaching, and receiving care for vulnerable populations needing treatment. The dominant delay for patients with gastric adenocarcinoma (GAC) is unknown. We aimed to define patients with GAC who reached and received care at our regional safety-net hospital (Grady Memorial Hospital [GMH]) and our neighboring quaternary referral hospital (Emory University Hospital [EUH]). METHODS: Clinicopathologic data from National Cancer Database (NCDB) participating academic centers were compared with GMH from 2004 to 2014. Outcomes of patients undergoing surgery at GMH were compared to those at EUH. RESULTS: At presentation, compared to NCDB centers (n = 69 662), GMH patients (n = 154) were more often black (85.1 vs 17.2%; P < 0.001), uninsured (30.5 vs 4.7%; P < 0.001), have stage IV disease (43.5 vs 30.1%; P = 0.017), and received no treatment (40.3 vs 18.4%; P < 0.001). When only comparing patients who underwent curative-intent resection at GMH (n = 23) to EUH (n = 137), median overall survival was similar between both groups (GMH: median not reached; EUH: 59.8 mos; P = 0.785). CONCLUSION: Although vulnerable patients with GAC within a safety-net hospital present with later stages of the disease, those who received surgery have acceptable outcomes. Thus, efforts should be made to overcome barriers in seeking care.

Development and validation of a universal esophageal patient-reported outcome measure: The Cleveland Clinic Esophageal Questionnaire (CEQ).

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.

Instructional Video For Hepaticojejunostomy Anastomosis Ensuring Evenly Spaced Sutures.

OBJECTIVE: We demonstrate a surgical technique involving construction of a hepaticojejunostomy (HJ) anastomosis that ensures even spacing between the sutures regardless of the size of the common bile duct. This is demonstrated via a series of illustrations followed by live demonstration of a HJ anastomosis created during a Whipple procedure. VIDEO DESCRIPTION: Overall, this technique results in the creation of a tension-free hepaticojejunostomy anastomosis, that typically does not require stenting, is highly reliable and replicable regardless of the size of the common bile duct. It is also easily reproducible and easy to teach trainees.

Effect of donor smoking and substance use on post-lung transplant outcomes.

OBJECTIVE: The study objective was to determine effects of donor smoking and substance use on primary graft dysfunction, allograft function, and survival after lung transplant. METHODS: From January 2007 to February 2020, 1366 lung transplants from 1291 donors were performed in 1352 recipients at Cleveland Clinic. Donor smoking and substance use history were extracted from the Uniform Donor Risk Assessment Interview and medical records. End points were post-transplant primary graft dysfunction, longitudinal forced expiratory volume in 1 second (% of predicted), and survival. RESULTS: Among lung transplant recipients, 670 (49%) received an organ from a donor smoker, 163 (25%) received an organ from a donor with a 20 pack-year or more history (median pack-years 8), and 702 received an organ from a donor with substance use (51%). There was no association of donor smoking, pack-years, or substance use with primary graft dysfunction (P > .2). Post-transplant forced expiratory volume in 1 second was 74% at 1 year in donor nonsmoker recipients and 70% in donor smoker recipients (P = .0002), confined to double-lung transplant, where forced expiratory volume in 1 second was 77% in donor nonsmoker recipients and 73% in donor smoker recipients. Donor substance use was not associated with allograft function. Donor smoking was associated with 54% non-risk-adjusted 5-year survival versus 59% (P = .09) and greater pack-years with slightly worse risk-adjusted long-term survival (P = .01). Donor substance use was not associated with any outcome (P ≥ 8). CONCLUSIONS: Among well-selected organs, lungs from smokers were associated with non-clinically important worse allograft outcomes without an inflection point for donor smoking pack-years. Substance use was not associated with worse allograft function. Given the paucity of organs, donor smoking or substance use alone should not preclude assessment for lung donation or transplant.

Endoscopic pyloromyotomy is feasible and effective in improving post-lung transplant gastroparesis.

OBJECTIVES: Gastroparesis is a debilitating and difficult to manage problem that has been reported in 20% to 90% of lung and heart-lung transplant recipients. The primary objective was to evaluate the safety and clinical effectiveness of per-oral endoscopic pyloromyotomy in relieving gastroparesis after lung transplant. Secondary objectives evaluated the effect of per-oral endoscopic pyloromyotomy on gastroesophageal reflux and allograft function. METHODS: Fifty-two lung transplant recipients underwent per-oral endoscopic pyloromyotomy for refractory gastroparesis. Gastroparesis was assessed by a pre-per-oral endoscopic pyloromyotomy and post-per-oral endoscopic pyloromyotomy radionuclide gastric emptying test and Gastroparesis Cardinal Symptom Index. Secondary outcomes included 90-day complications, gastroesophageal reflux as measured by pH testing, and longitudinal spirometry measurements. RESULTS: Median time from lung transplant to per-oral endoscopic pyloromyotomy was 10.5 months. Twenty-eight patients had prior pyloric botulinum injection with either no improvement or relapse of symptoms. Post-per-oral endoscopic pyloromyotomy gastric emptying tests were available for 32 patients and showed a decrease in median gastric retention at 4 hours from 63.5% pre-per-oral endoscopic pyloromyotomy to 5.5% post-per-oral endoscopic pyloromyotomy (P < .0001). Complete normalization of gastric emptying time was noted in 19 patients. Gastroparesis Cardinal Symptom Index score significantly improved after per-oral endoscopic pyloromyotomy (median, 23-3.5; P < .0001). Post-per-oral endoscopic pyloromyotomy pH testing showed improved or stable DeMeester score in all patients except 1. Graft function (forced expiratory volume in 1 second) remained stable 1 year after per-oral endoscopic pyloromyotomy. CONCLUSIONS: The improvements in symptom score and radionuclide imaging observed in this uncontrolled study suggest that per-oral endoscopic pyloromyotomy is an effective strategy in the lung transplant population and can be performed with minimal morbidity.

Looking beyond the eyeball test: A novel vitality index to predict recovery after esophagectomy.

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 (cm2/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 cm2/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.

Signet Ring Cell Histology Confers Worse Overall Survival in Treated Esophageal Adenocarcinoma.

BACKGROUND: Signet ring cell (SRC) histology is regarded as a poor prognostic indicator for esophageal cancer. The objectives of this study were to understand the clinical presentation and stage-specific survival outcomes of patients with SRC and nonsignet adenocarcinoma (AC). METHODS: From 2004 to 2016, 140,324 patients were diagnosed with esophageal and gastroesophageal junction cancers in the National Cancer Database. Demographics, tumor variables, and treatment were studied. Overall survival was shown by the Kaplan-Meier method, and random survival forest identified important predictors. RESULTS: SRC patients (N = 3825) comprised roughly 3% of esophageal cancers per year. SRC patients were less likely to present at early stage disease (cStage I: 10.2% vs 17.8% for AC; P < .001) and more likely to have pathologic upstaging (28% vs 16%, P < .001) and less pathologic downstaging after neoadjuvant therapy (36% vs 48%, P < .001). More SRC patients had positive margins after resection (15% vs 6.0%, P < .001). In a stage-matched comparison median survival for SRC patients was worse than for AC patients (cStage I: 60 vs 113 months; cStage II: 31 vs 40 months; cStage III: 22 vs 30 months). Clinical tumor and nodal stage, chemotherapy sequence, and age were important predictors of survival. CONCLUSIONS: SRC patients had worse survival than their AC counterparts. Worse biology and higher rates of incomplete resection in SRC should steer patients away from undergoing limited resection, such as endoscopic submucosal dissection, even when identified at very early stages. In future esophageal cancer staging iterations, separating SRC from AC appears to be indicated because of their different clinical behavior and response to therapy.

Natural History of Pleural Complications After Lung Transplantation.

BACKGROUND: Despite advances in lung transplantation, 5-year survival remains at 56%. Although the focus has been on chronic lung allograft dysfunction and infection, pleural complications in some may contribute to adverse outcomes. Therefore, we determined (1) the prevalence of, and risk factors for, pleural complications after lung transplantation and (2) their association with allograft function and mortality. METHODS: From 2006 to 2017, 1039 adults underwent primary lung transplantation at Cleveland Clinic in Cleveland, Ohio. Multivariable analyses were performed in the multiphase mixed longitudinal and hazard function domains to identify risk factors associated with allograft function and survival. RESULTS: A total of 468 patients (45%) had pleural complications, including pleural effusion in 271 (26%), pneumothorax in 152 (15%), hemothorax in 128 (12%), empyema in 47 (5%), and chylothorax in 9 (1%). Risk factors for pleural complications within the first 3 months included higher recipient-to-donor weight ratio, lower recipient albumin, and recipient-to-donor race mismatch; risk factors extending beyond 3 months included older age, hypertension, smoking history, lower lung allocation score, and donor death from anoxia. Cardiopulmonary bypass and previous thoracic interventions were not risk factors in patients with pleural effusions who were treated with thoracentesis only, and forced expiratory volume in 1 second improved after drainage; however, repeat percutaneous or surgical interventions did not impart a similar benefit. Pleural complications were associated with worse survival. CONCLUSIONS: Pleural complications are common after lung transplantation and are associated with worse allograft function and survival. These complications are likely secondary to other underlying clinical problems. Malnourishment and size mismatch are modifiable risk factors.

Pleural space management after lung transplant: Early and late outcomes of pleural decortication.

BACKGROUND: Pleural complications after lung transplant may restrict allograft expansion, requiring decortication. However, its extent, indications, risk factors, and effect on allograft function and survival are unclear. METHODS: From January 2006 to January 2017, 1,039 patients underwent primary lung transplant and 468 had pleural complications, 77 (16%) of whom underwent 84 surgical decortications for pleural space management. Multivariable time-related analysis was performed to identify risk factors for decortication. Mixed-effect longitudinal modeling was used to assess allograft function before and after decortication. RESULTS: Cumulative number of decortications per 100 transplants was 1.8, 7.8, and 8.8 at 1 month, 1 year, and 3 years after transplant, respectively. Indications for the 84 decortications were complex effusion in 47 (56%), fibrothorax in 17 (20%), empyema in 11 (13%), and hemothorax in 9 (11%). Thoracoscopic operations were performed in 52 (62%) and full lung re-expansion was achieved in 76 (90%). Complications occurred after 30 (36%) decortications, with 15 pulmonary complications (18%), including 2 patients requiring extracorporeal support due to worsening function. Ten reinterventions occurred via thoracentesis (2), tube thoracostomy (1), and reoperation (7). In-hospital and 30-day mortality was 5.2% (n = 4/77). Forced expiratory volume in 1 second increased from 50% to 60% within the first year after decortication, followed by a slow decline to 55% at 5 years. Postdecortication survival was 87%, 68%, and 48% at 1, 3, and 5 years, respectively. CONCLUSIONS: Despite high risk of reoperative surgery, decortication after lung transplant allows salvage of pleural space and graft function with a reasonable morbidity profile.

Thymic Malignancy-Updates in Staging and Management.

Thymomas are relatively indolent tumors that present with locally advanced disease in 30% of the patients. Thymic carcinoma is a more aggressive histology with shorter disease-free and overall survival. Early-stage tumors are managed best with complete resection. Multimodal therapy is the standard of care for locally advanced tumors and neoadjuvant therapy may help improve respectability. Stage and complete resection are the strongest prognostic factors for long-term survival. Based on early experience, targeted and immunotherapies have shown limited promise in advanced disease.

Urgently listed lung transplant patients have outcomes similar to those of electively listed patients.

OBJECTIVES: To (1) determine outcomes after urgent listing compared with elective listing for lung transplant and (2) compare in-hospital morbidity and mortality, survival, and allograft function in these 2 groups. METHODS: From January 2006 to September 2017, 201 patients were urgently and 1423 electively listed. Among urgently listed patients, 130 subsequently underwent primary lung transplant as did 995 electively listed patients. Competing-risks analysis for death and transplant after listing and weighted balancing score matching (76 pairs) were used to compare in-hospital morbidity and survival. Mixed-effect longitudinal modeling was used to compare allograft function to 8 years post-transplant. RESULTS: At 1 month, mortality was 26% in urgently listed patients, and 58% were transplanted. Risk factors for death included older age, higher bilirubin, and transfer from an outside hospital. At transplantation, urgently listed transplant patients were younger (53 ± 13 vs 55 ± 12 years), had more ventilator and extracorporeal membrane oxygenation support (32/25% vs 20/2.0%), more restrictive lung disease (95/73% vs 509/51%), and a higher lung allocation score (82 ± 13 vs 47 ± 17). In-hospital morbidity and mortality, time-related survival, and longitudinal allograft function were similar between matched groups. CONCLUSIONS: Urgent listing more often than not leads to transplantation. Although urgently listed patients are sicker overall, after transplant their perioperative morbidity and mortality, overall survival, and allograft function are similar to those of electively listed patients. Appropriate patient selection and aggressive supportive care allow urgently listed lung transplant patients to achieve these similar post-transplant outcomes.