Clinical T2 N0 M0 Esophageal Cancer: Identifying Predictive Factors of Upstaging.

BACKGROUND: Inaccuracy of clinical staging renders management of clinical T2 N0 M0 (cT2 N0 M0) esophageal cancer difficult. When an underlying advanced-stage disease is understaged to cT2 N0 M0, patients miss the opportunity to gain the potential benefits of neoadjuvant therapy. This study aimed to identify preoperative factors that predict underlying advanced-stage esophageal cancer. METHODS: From 2000 to 2020, 1579 patients with esophageal cancer underwent esophagectomy. Sixty patients who underwent upfront surgery for cT2 N0 M0 esophageal cancer were included in this study. The median age was 62.5 years, and 78% (n = 47) of these patients were male. Radiologic, clinical, and endoscopic factors were evaluated as preoperative markers. The Fisher exact and the Wilcoxon rank sum tests were used for categoric and continuous variables, respectively. Random forest classification was used to identify preoperative factors for predicting upstaging and downstaging. RESULTS: Of the 60 patients, 8 (13%) were found to have pathologic T2 N0 M0 esophageal cancer. Sixteen (27%) patients had cancer that was pathologically downstaged, and 36 (60%) had upstaged disease. Seven (19%) patients had upstaged cancer on the basis of the pathologic T stage, 14 (39%) had upstaging on the basis of the pathologic N stage, and 15 (42%) had upstaging on the basis of both T and N stages. Dysphagia (P = .003) and tumor maximum standardized uptake value (P = .048) were predictors of upstaging, with a combined predictive value of up to 75%. CONCLUSIONS: The presence of dysphagia and of high maximum standardized uptake value (≥5) of the tumor is predictive of more advanced underlying disease for patients with cT2 N0 M0 esophageal cancer, and these patients should be considered for neoadjuvant therapy.

Thoracoabdominal Esophagectomy: Then and Now.

BACKGROUND: Open approaches for esophagectomy are often still useful; of these, left thoracoabdominal esophagectomy (TAE) is poorly understood and often criticized. Hence, we examined TAE's worldwide utilization, survival, and present-day use and outcomes at our institution compared with contemporary national averages. METHODS: The Worldwide Esophageal Cancer Collaboration database includes 8854 patients who underwent esophagectomy for cancer between 2005 and 2014, a period when TAE was our center's most common approach. Two propensity score-matched models were constructed: worldwide TAE vs worldwide non-TAE (751 matched pairs); and our high-volume center TAE vs worldwide non-TAE (273 matched pairs). All-cause mortality was compared between matched groups. Institutional TAE data from 2017 to 2021 were assessed for present-day use and outcomes. RESULTS: Worldwide, propensity score-matched patients undergoing TAE had a median of 20 lymph nodes resected vs 17 after non-TAE (P < .0001). Five-year survival was 34% for worldwide TAE vs 42% for worldwide non-TAE groups (P = .04). Three-year matched survival was 52% for high-volume TAE compared with 54% for worldwide non-TAE groups (P = .1). From 2017 to 2021 at our institution, 90 (26%) of 346 esophagectomies were performed by TAE. Pneumonia developed in 5 patients (5.6%), with 88 patients (98%) alive at 30 days, comparable to contemporary averages of The Society of Thoracic Surgeons. CONCLUSIONS: When it is performed as the primary approach in high volumes, TAE can have comparable outcomes to non-TAE with low morbidity. At present, we find that TAE is most useful in patients with truncal obesity, prior abdominal operations, and locally advanced cardia tumors with potential for variable extent of resection.

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.

The Value of Fundoplication in the Treatment of Type I Achalasia.

BACKGROUND: Type I achalasia comprises 20% of achalasia and has nearly absent esophageal motor activity. Concerns that fundoplication decreases the effectiveness of Heller myotomy in these patients has increased adoption of peroral endoscopic myotomy (POEM). Hence, we compared outcomes after Heller myotomy with Dor fundoplication vs POEM. METHODS: From 2005 to 2020, 150 patients with type I achalasia underwent primary surgical myotomy (117 Heller myotomy, 33 POEM). Patient demographics, prior treatments, timed barium esophagrams, Eckardt scores, and reinterventions were assessed between the 2 groups. Median follow-up was 5 years for Heller myotomy and 2.5 years for POEM. RESULTS: The Heller myotomy group was younger, had fewer comorbidities, and lower body mass index vs POEM. Risk-adjusted models demonstrated clinical success (Eckardt ≤3) in 83% of Heller myotomies and 87% of POEMs at 3 years; longitudinal complete timed barium esophagram emptying and reintervention were also similar. An abnormal pH test result was documented in 10% (6 of 60) after Heller myotomy and in 45% (10 of 22) after POEM (P < .001). CONCLUSIONS: Despite nearly absent esophageal contractility, Heller myotomy with Dor fundoplication and POEM result in similar long-term symptom relief, esophageal emptying, and occurrence of reintervention in patients with type I achalasia. There is decreased esophageal acid exposure with the addition of a fundoplication, without compromised esophageal drainage, allaying fears of a detrimental effect of a fundoplication. Hence, choice of procedure may be personalized based on patient characteristics and esophageal morphology and not solely on manometric subtype.

Paraconduit hernia following esophagectomy: Is it safe to watch and wait?

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.

Preoperative predictors of spread through air spaces in lung cancer.

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.

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.

Adjuvant Therapy After Neoadjuvant Therapy for Esophageal Cancer: Who Needs It?

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.

A comparative study of robotic and laparoscopic approaches to Heller myotomy.

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.

Select octogenarians with stage IIIa non-small cell lung cancer can benefit from trimodality therapy.

Objectives: Currently, more than 36% of patients diagnosed with lung cancer are 75 years of age or older. Management of stage IIIA cancer is variable, especially for octogenarians who might not be offered surgery because of questionable benefit. In this study we investigated the outcomes of definitive chemoradiotherapy (CR) and trimodality therapy (TM) management (CR and surgery) for clinical stage IIIA non-small cell lung cancer (NSCLC) in patients 80 years of age or older. Methods: The National Cancer Data Base was queried for stage IIIA NSCLC in patients 80 years of age or older between 2004 and 2015. Patients were divided according to treatment type: definitive CR and TM. Patient demographic characteristics, facility type, Charlson-Deyo score, final tumor pathology, and survival data were extracted. Univariate analysis was performed, followed by 3:1 propensity matching to analyze overall survival differences. Unadjusted and adjusted Kaplan-Meier survival analyses were performed. Results: From the database, 6048 CR and 190 TM octogenarians were identified. Patients in the TM group were younger (82 years old [TM] vs 83 years old [CR]; P < .0001), more likely to be treated at an academic/research institution (36% [TM] vs 26% [CR]; P = .003), had greater proportion of adenocarcinoma (52% [TM] vs 34% [CR]; P < .001), and a smaller tumor size (38 mm [TM] vs 33 mm [CR]; P = .025). After 3:1 matching, the 5-year overall survival for the TM group was 29% (95% CI, 22%-38%) versus 15% (95% CI, 11%-20%) for the CR group. Conclusions: Selected elderly patients with stage IIIa NSCLC can benefit from an aggressive TM approach.

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.

Repair, Reconstruct, or Divert: Fate of the Perforated Esophagus.

OBJECTIVES: The aim of this study was to determine differences in esophageal perforation populations undergoing different advanced interventions for perforated esophagus and identify predictors of treatment outcomes. SUMMARY BACKGROUND DATA: Contained esophageal perforation can often be managed expectantly, but uncontained perforation is uniformly fatal without invasive intervention. Treatment options for the latter range from simple endoscopic control through advanced intervention. Clinical presentation varies greatly and directs which intervention is most appropriate. METHODS: From 1996 to 2017, 335 patients were treated for esophageal perforation, and 166 for advanced interventions: 74 primary repair with tissue flap (repair), 26 esophagectomy and gastric pull-up (resection), and 66 esophagectomy and immediate diversion with planned delayed reconstruction (resection-diversion). Patient characteristics, clinical presentation, operative outcomes, and survival were abstracted. Pittsburgh Severity Scores (PSS) were retrospectively calculated. Random survival forest analysis was performed for 90-day mortality and competing risks for reconstruction after resection-diversion. RESULTS: Repair and resection patients had lower PSS than resection-diversion patients (3 vs 3 vs 6, respectively). Ninety-day mortality for repair, resection, and resection-diversion was 11% vs 7.7% vs 23%, and 5-year survival was 71% vs 63% vs 47%. Risk of death after resection-diversion was highest within 1 year, but 52% of patients had reconstruction of the upper alimentary tract within 2 years. CONCLUSIONS: Several advanced interventions exist for critically ill patients with uncontained esophageal perforation. Repair and organ preservation are always preferred; however, patients at extremes of illness might best be treated with resection-diversion, with the understanding that the competing risk of death may preclude eventual reconstruction.

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.

Value of Lymphadenectomy in Patients Receiving Neoadjuvant Therapy for Esophageal Adenocarcinoma.

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.

Non-small cell lung cancer in never- and ever-smokers: Is it the same disease?

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.

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.

Intercostal Blocks with Liposomal Bupivacaine in Thoracic Surgery: A Retrospective Cohort Study.

OBJECTIVE: Assess the efficacy of adding liposomal bupivacaine (LB) to bupivacaine-containing intercostal nerve blocks (ICNBs) to improve analgesia and decrease opioid consumption and hospital length of stay compared with bupivacaine-only ICNBs. DESIGN: This retrospective, observational investigation compared pain intensity scores and cumulative opioid consumption within the first 72 postoperative hours in patients who received ICNBs with bupivacaine plus LB (LB group) versus bupivacaine only (control group) after minimally invasive anatomic pulmonary resection. LB was tested for noninferiority on pain scores and opioid consumption. If LB was noninferior, superiority of LB was tested on both outcomes. SETTING: Academic tertiary care medical center. PARTICIPANTS: Adult patients undergoing minimally invasive anatomic pulmonary resection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For the secondary analysis, hospital length of stay was compared through the Cox regression model. Of 396 patients, 178 (45%) received LB and 218 (55%) did not. The mean (standard deviation) pain score was three (one) in the LB group and three (one) in the control group, with a difference of -0.10 (97.5% confidence interval [-0.39 to 0.18]; p = 0.41). The mean (standard deviation) cumulative opioid consumption (intravenous morphine equivalents) was 198 (208) mg in the LB group and 195 (162) mg in the control group. Treatment effect in opioid consumption was estimated at a ratio of geometric mean of 0.94 (97.5% confidence interval [0.74-1.20]; p = 0.56). Pain control and opioid consumption were noninferior with LB but not superior. Hospital discharge was not different between groups. CONCLUSIONS: LB with bupivacaine in ICNBs did not demonstrate superior postoperative analgesia or affect the rate of hospital discharge.