Early Interventional Treatment of High Output Chyle Leak After Esophagectomy is Associated With Improved Survival.

OBJECTIVE: To investigate overall survival and length of stay (LOS) associated with differing management for high output (>1 L over 24 hours) leaks (HOCL) after cancer-related esophagectomy. BACKGROUND: Although infrequent, chyle leak after esophagectomy is an event that can lead to significant perioperative sequelae. Low-volume leaks appear to respond to nonoperative measures, whereas HOCLs often require invasive therapeutic interventions. METHODS: From a prospective single-institution database, we retrospectively reviewed patients treated from 2001 to 2021 who underwent esophagectomy for esophageal cancer. Within that cohort, we focused on a subgroup of patients who manifested a HOCL postoperatively. Clinicopathologic and operative characteristics were collected, including hospital LOS and survival data. RESULTS: A total of 53/2299 patients manifested a HOCL. These were mostly males (77%), with a mean age of 62 years. Of this group, 15 patients received nonoperative management, 15 patients received prompt (<72 hours from diagnosis) interventional management, and 23 received late interventional management. Patients in the late intervention group had longer LOSs compared with early intervention (slope = 9.849, 95% CI: 3.431-16.267). Late intervention (hazard ratio: 4.772, CI: 1.384-16.460) and nonoperative management (hazard ratio: 4.731, CI: 1.294-17.305) were associated with increased mortality compared with early intervention. Patients with early intervention for HOCL had an overall survival similar to patients without chyle leaks in survival analysis. CONCLUSIONS: Patients with HOCL should receive early intervention to possibly reverse the prognostic implications of this potentially detrimental complication.

Octreotide's role in the management of post-esophagectomy chylothorax.

The use of octreotide in managing intrathoracic chyle leak following esophagectomy has gained popularity in the adult population. While the benefits of octreotide have been confirmed in the pediatric population, there remains limited evidence to support its use in the adults post-esophagectomy. Thus, we performed a single-institution cohort study to characterize its efficacy. The study was performed using a prospective, single-center database, from which clinicopathologic characteristics were extracted of patients who had post-esophagectomy chyle leaks. Kaplan-Meier and multivariable Cox regression analyses were performed to investigate the effect of octreotide use on chest tube duration (CTD), hospital length of stay (LOS), and overall survival (OS). In our cohort, 74 patients met inclusion criteria, among whom 27 (36.5%) received octreotide. Kaplan-Meier revealed no significant effect of octreotide on CTD (P = 0.890), LOS (P = 0.740), or OS (P = 0.570). Multivariable Cox regression analyses further corroborated that octreotide had no effect on CTD (HR = 0.62, 95% confidence interval [CI]: 0.32-1.20, P = 0.155), LOS (HR = 0.64, CI: 0.34-1.21, P = 0.168), or OS (1.08, CI: 0.53-2.19, P = 0.833). Octreotide use in adult patients with chyle leak following esophagectomy lacks evidence of association with meaningful clinical outcomes. Level 1 evidence is needed prior to further consideration in this population.

Gender Bias in the Evaluation of Surgical Performance: Results of a Prospective Randomized Trial.

OBJECTIVE: The study aims to determine the influence of trainee gender on assessments of coronary anastomosis performance. SUMMARY OF BACKGROUND DATA: Understanding the impact of gender bias on the evaluation of trainees may enable us to identify and utilize assessment tools that are less susceptible to potential bias. METHODS: Cardiothoracic surgeons were randomized to review the video performance of trainees who were described by either male or female pronouns. All participants viewed the same video of a coronary anastomosis and were asked to grade technique using either a Checklist or Global Rating Scale (GRS). Effect of trainee gender on scores by respondent demographic was evaluated using regression analyses. Inter-rater reliability was assessed using the Cronbach's alpha. RESULTS: 103 cardiothoracic surgeons completed the Checklist (trainee gender: male n=50, female n=53) and 112 completed the GRS (trainee gender: male n=56, female n=56). For the Checklist, male cardiothoracic surgeons who were in practice <10 years ( P = 0.036) and involved in training residents ( P = 0.049) were more likely to score male trainees higher than female trainees. The GRS demonstrated high inter-rater reliability across male and female trainees by years and scope of practice for the respondent (alpha >0.900) when compared to the Checklist assessment tool. CONCLUSIONS: Early career male surgeons may exhibit gender bias against women when evaluating trainee performance of coronary anastomoses. The GRS demonstrates higher interrater reliability and robustness against gender bias in the assessment of technical performance than the Checklist, and such scales should be emphasized in educational evaluations.

Delayed Surgical Intervention After Chemoradiotherapy in Esophageal Cancer: (DICE) Study.

OBJECTIVE: To determine the impact of delayed surgical intervention following chemoradiotherapy (CRT) on survival from esophageal cancer. BACKGROUND: CRT is a core component of multimodality treatment for locally advanced esophageal cancer. The timing of surgery following CRT may influence the probability of performing an oncological resection and the associated operative morbidity. METHODS: This was an international, multicenter, cohort study, including patients from 17 centers who received CRT followed by surgery between 2010 and 2020. In the main analysis, patients were divided into 4 groups based upon the interval between CRT and surgery (0-50, 51-100, 101-200, and >200 days) to assess the impact upon 90-day mortality and 5-year overall survival. Multivariable logistic and Cox regression provided hazard ratios (HRs) with 95% CIs adjusted for relevant patient, oncological, and pathologic confounding factors. RESULTS: A total of 2867 patients who underwent esophagectomy after CRT were included. After adjustment for relevant confounders, prolonged interval following CRT was associated with an increased 90-day mortality compared with 0 to 50 days (reference): 51 to 100 days (HR=1.54, 95% CI: 1.04-2.29), 101 to 200 days (HR=2.14, 95% CI: 1.37-3.35), and >200 days (HR=3.06, 95% CI: 1.64-5.69). Similarly, a poorer 5-year overall survival was also observed with prolonged interval following CRT compared with 0 to 50 days (reference): 101 to 200 days (HR=1.41, 95% CI: 1.17-1.70), and >200 days (HR=1.64, 95% CI: 1.24-2.17). CONCLUSIONS: Prolonged interval following CRT before esophagectomy is associated with increased 90-day mortality and poorer long-term survival. Further investigation is needed to understand the mechanism that underpins these adverse outcomes observed with a prolonged interval to surgery.

The Role of Surgery in the Treatment of Melanoma Pulmonary Metastases in the Modern Era.

INTRODUCTION: The lung represents a frequent site of spread for metastatic melanoma, which has historically been managed with surgical resection achieving promising outcomes. We hypothesized that the role of surgery in the management of melanoma pulmonary metastases (MPM) is evolving among the development of less invasive diagnostic and novel systemic therapeutic strategies. MATERIALS AND METHODS: A single-center thoracic surgery database was reviewed and patients who underwent surgical resection of MPM between 1998 and 2019 were identified. Demographic, clinicopathologic, and surgical data were collected and analyzed, as were the annual volumes and indications for surgical resection. A Cochran-Armitage test was used to assess the trend in surgical indication. RESULTS: Three hundred and seventy seven surgical procedures for MPM were performed during the years of study in the care of 347 patients. Patients were predominantly male, with a mean age of 59.3 y. The mean number of annual resections was 17 and while this number initially increased from six in 1998 to a peak of 39 cases in 2008, a decline was subsequently observed. Diagnostic resection decreased from 22% in 1998-1999 to 5% at the peak of procedures in 2008-2009 and to 0 in 2018-2019 (P = 0.02). Curative resection increased from 44% in 1998-1999 to 73% in 2008-2009 (P < 0.001) and remained the dominant reason for surgery in later years. CONCLUSIONS: Surgical indications in the management of MPM have transformed in conjunction with systemic modalities, and the volume of resections has decreased in the modern era. Despite innovations in systemic management and shifting goals of operative interventions, surgeons continue to play a vital role in caring for these patients with an advanced disease.

Single Chest Drain Practice Reduces Discharge Opioid Prescriptions in Thoracic Surgery.

INTRODUCTION: Chest drains are placed following pulmonary resection to promote lung re-expansion. The superiority of two chest drains at preventing postoperative complications has not been established, and practice remains largely dictated by surgeon preference. We sought to compare patient outcomes based on number of chest drains used. METHODS: This is a retrospective analysis including patients undergoing lobectomies and segmentectomies between March 2016 and April 2020. Patients were categorized based on number of chest drains placed and were matched 1:1 using the nearest neighbor (greedy) technique. Our primary outcome was opioid prescriptions at discharge (in morphine equivalent daily dose [MEDD]). Associations were tested using multilevel mixed-effects regression to account for variability between surgeons. RESULTS: A total of 1,094 patients met inclusion criteria. Single chest drain was used in 922 patients, whereas 172 had two chest tubes. After matching, there were 111 patients in each group. In multilevel mixed-effects logistic regression, patients treated with a single chest drain received fewer opioid prescriptions (ß: -194 MEDD, 95% confidence interval [CI]: -302 to -86 MEDD, p < 0.01), were more likely to be opioid-free at hospital discharge (odds ratio [OR] = 2.11, 95% CI: 1.08-4.12, p = 0.03), and had lower readmission rates within 30 days (OR = 0.33, 95% CI: 0.13-0.84, p = 0.02). Single chest drain practice did not affect the risk of pulmonary complications and there was no statistically significant difference in length of hospital stay (3 days [interquartile range: 2-5] vs. 4 days [3-6], p = 0.08). CONCLUSION: Single chest drain practice in lobectomies and segmentectomies was associated with less opioid prescription requirement without any increase in complications.

Simultaneous versus staged resections for bilateral pulmonary metastases.

BACKGROUND: For patients with bilateral pulmonary metastases, staged resections have historically been the preferred surgical intervention. During the spring of 2020, the COVID-19 pandemic made patient travel to the hospital challenging and necessitated reduction in operative volume so that resources could be conserved. We report our experience with synchronous bilateral metastasectomies for the treatment of disease in both lungs. METHODS: Patients with bilateral pulmonary metastases who underwent simultaneous bilateral resections were compared with a cohort of patients who underwent staged resections. We used nearest-neighbor propensity score (1:1) matching to adjust for confounders. Perioperative outcomes were compared between groups using paired statistical analysis techniques. RESULTS: Between 1998 and 2020, 36 patients underwent bilateral simultaneous metastasectomies. We matched 31 pairs of patients. The length of stay was significantly shorter in patients undergoing simultaneous resection (median 3 vs. 8 days, p < .001) and operative time was shorter (156 vs. 235.5 min, p < .001) when compared to the sum of both procedures in the staged group. The groups did not significantly differ with regard to postoperative complications. CONCLUSION: In a carefully selected patient population, simultaneous bilateral metastasectomy is a safe option. A single procedure confers benefits for both the patient as well as the hospital resource system.

Treatment and Clinical Outcomes of Patients with Teratoma with Somatic-Type Malignant Transformation: An International Collaboration.

PURPOSE: We assessed prognostic factors, treatments and outcomes in patients with teratoma with malignant transformation, a rare occurrence among germ cell tumors. MATERIALS AND METHODS: Data on patients diagnosed with teratoma with malignant transformation between June 1981 and August 2014 were collected across 5 referral centers. Chemotherapy was dichotomized as based on germ cell tumor or teratoma with malignant transformation. Cox analyses were done to evaluate prognostic factors of overall survival, the primary end point. Each factor was evaluated in a univariable model. Forward stepwise selection was used to construct an optimal model. RESULTS: Among 320 patients the tumor primary site was gonadal in 287 (89.7%), retroperitoneal in 17 (5.3%) and mediastinal in 16 (5%). Teratoma with malignant transformation and germ cell tumor were diagnosed concurrently in 130 patients (40.6%). A total of 49 patients (16.8%) initially presented with clinical stage I. The remaining patients were at good (123 or 42.3%), intermediate (42 or 14.4%) and poor (77 or 26.5%) risk for metastasis according to IGCCCG (International Germ Cell Cancer Collaborative Group). First line chemotherapy was given for germ cell tumor in 159 patients (49.7%), chemotherapy for teratoma with malignant transformation was performed in 14 (4.4%) and only surgery was done in 147 (45.9%). Median followup was 25.1 months (IQR 5.4-63.8). Five-year overall survival was 83.4% (95% CI 61.3 to 93.5) in patients with clinical stage I and it was also worse than expected in those with metastasis. On multivariable analyses nonprimitive neuroectodermal tumor histology (overall p = 0.004), gonadal primary tumor (p = 0.005) and fewer prior chemotherapy regimens (p <0.001) were independent predictors of better overall survival. Chemotherapy was not independently prognostic. CONCLUSIONS: Less heavily pretreated teratoma with malignant transformation with a gonadal primary tumor and nonprimitive neuroectodermal tumor histology appears to be associated with longer overall survival. Generally, teratoma with malignant transformation had a worse prognosis than germ cell tumor. Uncertainties persist regarding optimal chemotherapy.

Disparities in early-stage lung cancer outcomes at minority-serving hospitals compared with nonminority serving hospitals.

OBJECTIVES: Disparities in cancer care are omnipresent and originate from a multilevel set of barriers. Our objectives were to describe the likelihood of undergoing surgery for early-stage non-small cell lung cancer at minority-serving hospitals (MSHs), and evaluate the association of race/ethnicity with resection based on MSH status. METHODS: A retrospective study using the National Cancer Database (2008-2016) was conducted including patients with clinical stage I non-small cell lung cancer. MSHs were defined as hospitals in the top decile of providing care to Hispanic or African American patients. The primary outcome evaluated was receipt of definitive surgery at MSHs vs non-MSHs. Outcomes related to race/ethnicity stratified by hospital type were also investigated. RESULTS: A total of 142,580 patients were identified from 1192 hospitals (120 MSHs and 1072 non-MSHs). Most patients (85% [n = 121,240]) were non-Hispanic White, followed by African American (9% [n = 12,772]), and Hispanic (3%, [n= 3749]). MSHs cared for 7.4% (n = 10,491) of the patients included. In adjusted analyses, patients treated at MSHs were resected less often than those at non-MSHs (odds ratio, 0.87; 95% CI, 0.76-1.00; P = .0495). African American patients were less likely to receive surgery in the overall analysis (P < .01), and at MSHs specifically (P < .01), compared with non-Hispanic White patients. Hispanic patients had similar rates of resection in the overall analysis (P = .11); however, at MSHs, they underwent surgery more often compared with non-Hispanic White patients (P = .02). Resected patients at MSHs had similar overall survival (median, 91.7 months; 95% CI, 86.6-96.8 months) compared with those resected at non-MSHs (median, 85.7 months; 95% CI, 84.5-86.8 months). CONCLUSIONS: Patients with early-stage non-small cell lung cancer underwent resection less often at MSHs compared with non-MSHs. Disparities related to underutilization of surgery for African American patients continue to persist, regardless of hospital type.

Endobronchial ultrasound: A novel screening test for pulmonary hypertension prior to major pulmonary surgery.

Objectives: Pulmonary hypertension (PH) is an important physiologic variable in the assessment of patients undergoing major thoracic operations but all too often neglected because of the need for right heart catheterization (RHC) due to the inaccuracy of transthoracic echocardiography. Patients with lung cancer often require endobronchial ultrasound (EBUS) as part of the staging of the cancer. We sought to investigate whether EBUS can be used to screen these patients for PH. Methods: Patients undergoing a major thoracic operation requiring EBUS for staging were included prospectively in the study. All patients had also a RHC (gold standard). We aimed to compare the pulmonary artery pressure measurements by EBUS with the RHC values. Results: A total of 20 patients were enrolled in the study. The prevalence of abnormal pulmonary artery pressure was 65% based on RHC. All patients underwent measurement of the pulmonary vascular acceleration time (PVAT) by EBUS with no adverse events. Linear regression analysis comparing PVAT and RHC showed a correlation (r = -0.059, -0.010 to -0.018, P = .007). A receiver operator characteristic curve (area under the curve = 0.736) was used to find the optimal PVAT threshold (140 milliseconds) to predict PH; this was used to calculate a positive and negative likelihood ratio following a positive diagnosis of 2.154 and 0.538, respectively. Conclusions: EBUS interrogation of pulmonary artery hemodynamic is safe and feasible. EBUS may be used as a screening test for PH in high-risk individuals.

Implementation of a novel peer review academy by Surgery and the Association of Women Surgeons.

BACKGROUND: A novel Peer Review Academy was developed as a collaborative effort between the Association of Women Surgeons and the journal Surgery to provide formal training in peer review. We aimed to describe the outcomes of this initiative using a mixed methods approach. METHODS: We developed a year-long curriculum with monthly online didactic sessions. Women surgical trainee mentees were paired 1:1 with rotating women surgical faculty mentors for 3 formal peer review opportunities. We analyzed pre-course and post-course surveys to evaluate mentee perceptions of the academy and assessed changes in mentee review quality over time with blinded scoring of unedited reviews. Semi-structured interviews were conducted upon course completion. RESULTS: Ten women surgical faculty mentors and 10 women surgical trainees from across the United States and Canada successfully completed the Peer Review Academy. There were improvements in the mentees' confidence for all domains of peer review evaluated, including overall confidence in peer review, study novelty, study design, analytic approach, and review formatting (all, P ≤ .02). The mean score of peer review quality increased over time (59.2 ± 10.8 vs 76.5 ± 9.4; P = .02). In semi-structured interviews, important elements were emphasized across the Innovation, Implementation Process, and Individuals Domains, including the values of (1) a comprehensive approach to formal peer review education; (2) mentoring relationships between women faculty and resident surgeons; and (3) increasing diversity in the scientific peer review process. CONCLUSION: Our novel Peer Review Academy was feasible on a national scale, resulting in significant qualitative and quantitative improvements in women surgical trainee skillsets, and has the potential to grow and diversify the existing peer review pool.

Surgical outcomes after chemotherapy plus nivolumab and chemotherapy plus nivolumab and ipilimumab in patients with non-small cell lung cancer.

OBJECTIVE: Chemotherapy plus nivolumab is the standard of care neoadjuvant treatment for patients with resectable stage IB to IIIA non-small cell lung cancer. The influence of dual checkpoint blockade with chemotherapy on surgical outcomes remains unknown. We aimed to determine operative complexity and perioperative outcomes associated with neoadjuvant chemotherapy and nivolumab with or without ipilimumab. METHODS: A total of 44 patients with stage IB (≥4 cm) to IIIA non-small cell lung cancer were treated on sequential platform arms of the NEOSTAR trial. A total of 22 patients were treated with nivolumab + chemotherapy, and 22 patients were treated with ipilimumab + nivolumab + chemotherapy. The safety of surgical resection after neoadjuvant therapy was estimated using 30-day complication rates. Operative reports and surgeons' narratives were evaluated to determine procedural complexity and operative conduct. RESULTS: All 22 of 22 patients (100%) treated with nivolumab + chemotherapy underwent surgical resection: 20 R0 (90.9%), 17 (77.3%) lobectomies, 1 wedge resection, 2 segmentectomies, and 2 pneumonectomies. The majority, 21 of 22 (95%), were performed by thoracotomy. A total of 13 of 22 (59.1%) were rated as challenging resections. A total of 4 of 22 patients (18.2%) experienced grade 3 or greater Clavien-Dindo complication. A total of 20 of 22 patients (90.9%) treated with ipilimumab + nivolumab + chemotherapy underwent surgical resection: 19 R0 (95%), 18 (90%) lobectomies, 1 pneumonectomy, and 1 segmentectomy. A total of 16 of 20 (80%) resections were performed via thoracotomy, 3 of 20 (15%) via robotics, and 1 of 20 (5%) via thoracoscopy. A total of 9 of 20 (45%) resections were considered challenging. A total of 4 of 20 patients (20%) experienced grade 3 or greater Clavien-Dindo complication. CONCLUSIONS: Surgical resections are feasible and safe, with high rates of R0 after neoadjuvant chemotherapy and nivolumab with or without ipilimumab. Overall, approximately half of cases (22/42, 52.3%) were considered to be more challenging than a standard lobectomy.

Outcomes after thymectomy in non-thymomatous myasthenia gravis.

Background: Guidelines by the myasthenia gravis (MG) Foundation of America suggest patients aged 18 to 50 years with non-thymomatous myasthenia gravis (NTMG) benefit from thymectomy. Our objective was to investigate utilization of thymectomy in NTMG patients outside the confines of a clinical trial. Methods: From the Optum de-identified Clinformatics Data Mart Claims Database (2007 to 2021), we identified patients diagnosed with MG between 18-50 years old. We then selected patients who received a thymectomy within 12 months of MG diagnosis. Outcomes included use of steroids, non-steroidal immunosuppressive agents (NSIS), and rescue therapy (plasmapheresis or intravenous immunoglobulin), as well as NTMG-related emergency department (ED) visits and hospital admissions. These outcomes were compared in the 6-months before and after thymectomy. Results: A total of 1,298 patients met our inclusion criteria, of whom 45 (3.47%) received a thymectomy, performed via minimally invasive surgery in 53.3% of cases (n=24). In comparing the pre- to post-operative period, we noted that steroid use increased (53.33% to 66.67%, P=0.034), NSIS use remained stable, and use of rescue therapy decreased (44.44% to 24.44%, P=0.007). Costs associated with steroid and NSIS use remained stable. However, the mean costs of rescue therapy decreased (from $13,243.98 to $8,486.26, P=0.035). Hospital admissions and ED visits related to NTMG remained stable. There were 2 readmissions within 90 days (4.44%) associated with thymectomy. Conclusions: Patients with NTMG undergoing thymectomy experienced less need for rescue therapy following resection, albeit with increased rates of steroid prescriptions. Thymectomy is infrequently performed in this patient population despite acceptable postsurgical outcomes.

Tumor thickness in mesothelioma predicts differential response to neoadjuvant therapy and survival.

OBJECTIVE: Neoadjuvant systemic therapy in resectable malignant pleural mesothelioma remains controversial and demonstrates variable responses. We sought to evaluate tumor thickness as a predictor of response to neoadjuvant therapy and as a prognostic marker for overall survival. METHODS: Data from patients who underwent neoadjuvant therapy followed by cytoreductive surgery from 2002 to 2019 were reviewed. Baseline and postneoadjuvant therapy tumor thickness were measured on computed tomography. Radiological tumor response was categorized as progressive disease (≥20% increase), partial response (≥30% decrease), or stable disease (in between). Tumor response outcomes were modeled using logistic regression and multinomial regression models. Overall survival was evaluated based on tumor thickness and tumor response. RESULTS: Of the 143 patients reviewed, 36 (25%) had progressive disease, 54 (38%) had stable disease, and 56 (39%) had partial response. The baseline tumor thickness of the progressive disease group (36 mm) was lower than in both stable disease and partial response groups (both 63 mm; P < .001). Both logistic regression and multinomial regression analyses demonstrated that thicker baseline tumor thickness was associated with decreased probability of progressive disease and increased probability of partial response. In a multivariable Cox model, thicker postneoadjuvant therapy tumor thickness was associated with worse overall survival (hazard ratio, 1.01, 95% confidence interval, 1.00-1.01, P = .008). The same trend was observed for thicker baseline tumor thickness (hazard ratio, 1.02, 95% confidence interval, 1.01-1.04, P = .008), and the risk was decreased in tumors with partial response (hazard ratio, 0.98, 95% confidence interval, 0.96-0.100, P = .014). CONCLUSIONS: We present the first study demonstrating the relationship between baseline tumor thickness and differential radiographic response to neoadjuvant therapy and survival. Further studies are needed to validate tumor thickness as both a prognostic and predictive biomarker.

Surgical Approach and Persistent Opioid Use in Medicare Patients Undergoing Lung Cancer Resection.

BACKGROUND: Robotic and video-assisted thoracoscopic surgery (VATS) approaches for lung resection are associated with decreased inpatient opioid use compared with open surgery. Whether these approaches affect outpatient persistent opioid use remains unknown. METHODS: Non-small cell lung cancer patients aged 66 years or more who underwent lung resection between 2008 and 2017 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Persistent opioid use was defined as filling an opioid prescription 3 to 6 months after lung resection. Adjusted analyses were performed to evaluate surgical approach and persistent opioid use. RESULTS: We identified 19,673 patients: 7479 (38%) underwent open surgery, 10,388 (52.8%) VATS, and 1806 (9.2%) robotic surgery. Persistent opioid use was 38% in the entire cohort, including 27% of opioid naïve patients, and highest after open surgery (42.5%), followed by VATS (35.3%) and robotic (33.1%, P < .001). In multivariable analyses, robotic (odds ratio 0.84; 95% CI, 0.72-0.98; P = .028) and VATS (odds ratio 0.87; 95% CI, 0.79-0.95; P = .003) approaches were both associated with decreased persistent opioid use compared with open surgery in opioid naïve patients. At 12 months, patients resected using a robotic approach had the lowest oral morphine equivalent per month compared with VATS (133 vs 160, P < .001) and open surgery (133 vs 200, P < .001). Among chronic opioid patients, surgical approach was not associated with postoperative opioid use. CONCLUSIONS: Persistent opioid use after lung resection is common. Both robotic and VATS approaches were associated with decreased persistent opioid use compared with open surgery among opioid naïve patients. Whether a robotic approach yields additional long-term advantages over VATS warrants further investigation.

Radiographic response to neoadjuvant therapy in pleural mesothelioma should serve as a guide for patient selection for cytoreductive operations.

Background: Malignant pleural mesothelioma (MPM) is associated with poor prognosis despite advances in multimodal therapeutic strategies. While patients with resectable disease may benefit from added survival with oncologic resection, patient selection for mesothelioma operations often relies on both objective and subjective evaluation metrics. We sought to evaluate factors associated with improved overall survival (OS) in patients with mesothelioma who underwent macroscopic complete resection (MCR). Methods: Patients with MPM who received neoadjuvant therapy and underwent MCR were identified in a prospectively maintained departmental database. Clinicopathologic, blood-based, and radiographic variables were collected and included in a Cox regression analysis (CRA). Response to neoadjuvant therapy was characterized by a change in tumor thickness from pretherapy to preoperative scans using the modified RECIST criteria. Results: In this study, 99 patients met the inclusion criteria. The median age of the included patients was 64.7 years, who were predominantly men, had smoking and asbestos exposure, and who received neoadjuvant therapy. The median change in tumor thickness following neoadjuvant therapy was -16.5% (interquartile range of -49.7% to +14.2%). CRA demonstrated reduced OS associated with non-epithelioid histology [hazard ratio (HR): 3.06, 95% confidence interval (CI): 1.62-5.78, p < 0.001] and a response to neoadjuvant therapy inferior to the median (HR: 2.70, CI: 1.55-4.72, p < 0.001). Patients who responded poorly (below median) to neoadjuvant therapy had lower median survival (15.8 months compared to 38.2 months, p < 0.001). Conclusion: Poor response to neoadjuvant therapy in patients with MPM is associated with poor outcomes even following maximum surgical cytoreduction and should warrant a patient-centered discussion regarding goals of care and may therefore help guide further therapeutic decisions.

Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial.

Neoadjuvant ipilimumab + nivolumab (Ipi+Nivo) and nivolumab + chemotherapy (Nivo+CT) induce greater pathologic response rates than CT alone in patients with operable non-small cell lung cancer (NSCLC). The impact of adding ipilimumab to neoadjuvant Nivo+CT is unknown. Here we report the results and correlates of two arms of the phase 2 platform NEOSTAR trial testing neoadjuvant Nivo+CT and Ipi+Nivo+CT with major pathologic response (MPR) as the primary endpoint. MPR rates were 32.1% (7/22, 80% confidence interval (CI) 18.7-43.1%) in the Nivo+CT arm and 50% (11/22, 80% CI 34.6-61.1%) in the Ipi+Nivo+CT arm; the primary endpoint was met in both arms. In patients without known tumor EGFR/ALK alterations, MPR rates were 41.2% (7/17) and 62.5% (10/16) in the Nivo+CT and Ipi+Nivo+CT groups, respectively. No new safety signals were observed in either arm. Single-cell sequencing and multi-platform immune profiling (exploratory endpoints) underscored immune cell populations and phenotypes, including effector memory CD8+ T, B and myeloid cells and markers of tertiary lymphoid structures, that were preferentially increased in the Ipi+Nivo+CT cohort. Baseline fecal microbiota in patients with MPR were enriched with beneficial taxa, such as Akkermansia, and displayed reduced abundance of pro-inflammatory and pathogenic microbes. Neoadjuvant Ipi+Nivo+CT enhances pathologic responses and warrants further study in operable NSCLC. (ClinicalTrials.gov registration: NCT03158129 .).

Current Surgical Indications for Non-Small-Cell Lung Cancer.

With recent strides made within the field of thoracic oncology, the management of NSCLC is evolving rapidly. Careful patient selection and timing of multi-modality therapy to permit the optimization of therapeutic benefit must be pursued. While chemotherapy and radiotherapy continue to have a role in the management of lung cancer, surgical therapy remains an essential component of lung cancer treatment in early, locally and regionally advanced, as well as in selected, cases of metastatic disease. Recent and most impactful advances in the treatment of lung cancer relate to the advent of immunotherapy and targeted therapy, molecular profiling, and predictive biomarker discovery. Many of these systemic therapies are a part of the standard of care in metastatic NSCLC, and their indications are expanding towards surgically operable lung cancer to improve survival outcomes. Numerous completed and ongoing clinical trials in the surgically operable NSCLC speak to the interest and importance of the multi-modality therapy even in earlier stages of NSCLC. In this review, we focus on the current standard of care indications for surgical therapy in stage I-IV NSCLC as well as on the anticipated future direction of multi-disciplinary lung cancer therapy.

Informed Consent for Placebo-Controlled Trials: Do Ethics and Science Conflict?

The use of a placebo has been considered the best method for controlling bias in a prospective randomized clinical trial and provides the most rigorous test of treatment efficacy for evaluating a medical therapy. Placebos commonly produce clinically important effects particularly in studies where the primary outcomes are subjective. Yet the potential beneficial or harmful effects of placebos are often not addressed in designing a clinical trial, calculating the sample size, seeking consent, or interpreting clinical trial results. In this manuscript, we use an actual study to indicate three approaches that might be considered in seeking informed consent for placebo-controlled trials, and we explore the fundamental ethical and scientific complexities involved with each.

Intraoperative challenges after induction therapy for non-small cell lung cancer: Effect of nodal disease on technical complexity.

Objectives: Neoadjuvant therapy has been theorized to increase complexity of non-small cell lung cancer resections; however, specific factors that contribute to intraoperative challenges after induction therapy have not been well described. We aimed to characterize the effect of nodal involvement and nodal treatment response on surgical complexity after neoadjuvant therapy. Methods: We identified patients treated with neoadjuvant therapy followed by anatomic lung resection for cN + non-small cell lung cancer between 2010 and 2020. Patients were categorized according to clinical N1 versus N2 disease. To evaluate the effect of nodal response to therapy, thoracic radiologists measured clinically suspected and pathologically involved lymph nodes before and after induction therapy. Operative reports were reviewed to identify technical challenges specifically related to nodal disease. Categorical outcomes were compared using Fisher exact test. Results: One hundred twenty-four patients met inclusion criteria, among whom 107 (86.3%) were treated with neoadjuvant chemotherapy, whereas chemoradiation (n = 8) and targeted therapy (n = 9) were less common. In cases with N1 disease, 8/38 (21.0%) required proximal pulmonary arterial control, whereas this was necessary in only 2/88 (2.3%) of N2 cases (P = .001). Likewise, sleeve resection and arterioplasty were needed more frequently during resection of N1 disease (7/38, 18.4%) versus N2 disease (0/88, P < .001). Increased nodal response to therapy was associated with greater likelihood of requiring change in vascular approach (P = .011). Conclusions: After induction therapy, N1 disease was associated with greater need for complex surgical maneuvers than N2 disease. Likewise, substantial treatment response was associated with increased intraoperative technical challenges. Recognizing such factors enables surgical teams to engage in appropriate operative planning to ensure patient safety.