The Role of Immunotherapy in the Management of Esophageal Cancer in Patients Treated with Neoadjuvant Chemoradiation: An Analysis of the National Cancer Database.

BACKGROUND: The current National Comprehensive Cancer Network advises neoadjuvant chemoradiotherapy followed by surgery for locally advanced cases of esophageal cancer. The role of immunotherapy in this context is under heavy investigation. METHODS: Patients with esophageal adenocarcinoma were identified in the National Cancer Database (NCDB) from 2004 to 2019. Three groups were generated as follows: (a) no immunotherapy, (b) neoadjuvant immunotherapy, and (c) adjuvant immunotherapy. Overall survival was evaluated using the Kaplan-Meier method and Cox proportional hazard analysis, adjusting for previously described risk factors for mortality. RESULTS: Of the total 14,244 patients diagnosed with esophageal adenocarcinoma who received neoadjuvant chemoradiation, 14,065 patients did not receive immunotherapy, 110 received neoadjuvant immunotherapy, and 69 received adjuvant immunotherapy. When adjusting for established risk factors, adjuvant immunotherapy was associated with significantly improved survival compared to no immunotherapy and neoadjuvant immunotherapy during a median follow-up period of 35.2 months. No difference was noted among patients who received no immunotherapy vs. neoadjuvant immunotherapy in the same model. CONCLUSIONS: In this retrospective analysis of the NCDB, receiving adjuvant immunotherapy offered a significant survival advantage compared to no immunotherapy and neoadjuvant immunotherapy in the treatment of esophageal adenocarcinoma. The addition of neoadjuvant immunotherapy to patients treated with neoadjuvant chemoradiation did not improve survival in this cohort. Further studies are warranted to investigate the long-term outcomes of immunotherapy in esophageal cancer.

Estimating the Effects of Cancer Screening in Clinical Practice Settings: The Role of Selective Uptake and Suboptimal Adherence along the Cancer Screening Continuum.

Randomized controlled trials (RCT) are the gold standard in determining efficacy of cancer screening tests. Yet, systematic differences between RCT and the general populations eligible for screening raise concerns about the generalizability and relevance of RCT findings to guide the development and dissemination of cancer screening programs. Observational studies from clinical practice settings have documented selective uptake in screening-i.e., variation across subgroups regarding who is screened and not screened-as well as suboptimal adherence to screening recommendations, including follow-up of positive findings with subsequent imaging studies and diagnostic invasive procedures. When the effectiveness of a screening intervention varies across subgroups, and there is selective uptake and suboptimal adherence to screening in clinical practice relative to that in the RCT, the effects of screening reported in RCTs are not expected to generalize to clinical practice settings. Understanding the impacts of selective uptake and suboptimal adherence on estimates of the effectiveness of cancer screening in clinical practice will generate evidence that can be used to inform future screening recommendations and enhance shared decision-making tools.

Long-term outcomes of robotic versus video-assisted pulmonary lobectomy for non-small cell lung cancer: systematic review and meta-analysis of reconstructed patient data.

Background: Video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracoscopic surgery (RATS) are two viable options in patients undergoing lobectomy for non-small cell lung cancer (NSCLC); however, the debate on which one is superior is unceasing. Methods: PubMed and Scopus databases were queried for studies including patients who underwent either VATS or RATS lobectomy. This meta-analysis is in accordance with the recommendations of the PRISMA statement. Individual patient data on overall survival (OS) and disease-free survival (DFS) were extracted from Kaplan-Meier curves. One- and two-stage survival analyses, and random-effects meta-analyses were conducted. Results: Ten studies met our eligibility criteria, incorporating 1,231 and 814 patients in the VATS and RATS groups, respectively. Patients who underwent VATS had similar OS compared with those who underwent RATS [hazard ratio (HR): 1.05, 95% confidence interval (CI): 0.88-1.27, P=0.538] during a weighted median follow-up of 51.7 months, and this was validated by the two-stage meta-analysis (HR: 1.27, 95% CI: 0.85-1.90, P=0.24, I2=68.50%). Regarding DFS, the two groups also displayed equivalent outcomes (HR: 1.07, 95% CI: 0.92-1.25, P=0.371) and this was once again validated by the two-stage meta-analysis (HR: 1.05, 95% CI: 0.85-1.30, P=0.67, I2=28.27%). Both RATS and VATS had similar postoperative complication rates, prolonged air leak, conversion to thoracotomy and operative times. RATS was found to be superior to VATS in terms of length of hospital stay and number of lymph nodes dissected. Conclusions: In patients undergoing lobectomy for NSCLC, VATS and RATS have equivalent overall and DFS at a median follow-up of 51.7 months.

Outcomes Following Lung Transplant for COVID-19-Related Complications in the US.

Importance: The COVID-19 pandemic led to the use of lung transplant as a lifesaving therapy for patients with irreversible lung injury. Limited information is currently available regarding the outcomes associated with this treatment modality. Objective: To describe the outcomes following lung transplant for COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis. Design, Setting, and Participants: In this cohort study, lung transplant recipient and donor characteristics and outcomes following lung transplant for COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis were extracted from the US United Network for Organ Sharing database from March 2020 to August 2022 with a median (IQR) follow-up period of 186 (64-359) days in the acute respiratory distress syndrome group and 181 (40-350) days in the pulmonary fibrosis group. Overall survival was calculated using the Kaplan-Meier method. Cox proportional regression models were used to examine the association of certain variables with overall survival. Exposures: Lung transplant following COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis. Main Outcomes and Measures: Overall survival and graft failure rates. Results: Among 385 included patients undergoing lung transplant, 195 had COVID-19-related acute respiratory distress syndrome (142 male [72.8%]; median [IQR] age, 46 [38-54] years; median [IQR] allocation score, 88.3 [80.5-91.1]) and 190 had COVID-19-related pulmonary fibrosis (150 male [78.9%]; median [IQR] age, 54 [45-62]; median [IQR] allocation score, 78.5 [47.7-88.3]). There were 16 instances of acute rejection (8.7%) in the acute respiratory distress syndrome group and 15 (8.6%) in the pulmonary fibrosis group. The 1-, 6-, and 12- month overall survival rates were 0.99 (95% CI, 0.96-0.99), 0.95 (95% CI, 0.91-0.98), and 0.88 (95% CI, 0.80-0.94) for the acute respiratory distress syndrome cohort and 0.96 (95% CI, 0.92-0.98), 0.92 (95% CI, 0.86-0.96), and 0.84 (95% CI, 0.74-0.90) for the pulmonary fibrosis cohort. Freedom from graft failure rates were 0.98 (95% CI, 0.96-0.99), 0.95 (95% CI, 0.90-0.97), and 0.88 (95% CI, 0.79-0.93) in the 1-, 6-, and 12-month follow-up periods in the acute respiratory distress cohort and 0.96 (95% CI, 0.92-0.98), 0.93 (95% CI, 0.87-0.96), and 0.85 (95% CI, 0.74-0.91) in the pulmonary fibrosis cohort, respectively. Receiving a graft from a donor with a heavy and prolonged history of smoking was associated with worse overall survival in the acute respiratory distress syndrome cohort, whereas the characteristics associated with worse overall survival in the pulmonary fibrosis cohort included female recipient, male donor, and high recipient body mass index. Conclusions and Relevance: In this study, outcomes following lung transplant were similar in patients with irreversible respiratory failure due to COVID-19 and those with other pretransplant etiologies.

Cancer-related Fatigue in Lung Cancer: A Research Agenda: An Official American Thoracic Society Research Statement.

Background: Fatigue is the most common symptom among cancer survivors. Cancer-related fatigue (CRF) may occur at any point in the cancer care continuum. Multiple factors contribute to CRF development and severity, including cancer type, treatments, presence of other symptoms, comorbidities, and medication side effects. Clinically, increasing physical activity, enhancing sleep quality, and recognizing sleep disorders are integral to managing CRF. Unfortunately, CRF is infrequently recognized, evaluated, or treated in lung cancer survivors despite more frequent and severe symptoms than in other cancers. Therefore, increased awareness and understanding of CRF are needed to improve health-related quality of life in lung cancer survivors. Objectives: 1) To identify and prioritize knowledge and research gaps and 2) to develop and prioritize research questions to evaluate mechanistic, diagnostic, and therapeutic approaches to CRF among lung cancer survivors. Methods: We convened a multidisciplinary panel to review the available literature on CRF, focusing on the impacts of physical activity, rehabilitation, and sleep disturbances in lung cancer. We used a three-round modified Delphi process to prioritize research questions. Results: This statement identifies knowledge gaps in the 1) detection and diagnostic evaluation of CRF in lung cancer survivors; 2) timing, goals, and implementation of physical activity and rehabilitation; and 3) evaluation and treatment of sleep disturbances and disorders to reduce CRF. Finally, we present the panel's initial 32 research questions and seven final prioritized questions. Conclusions: This statement offers a prioritized research agenda to 1) advance clinical and research efforts and 2) increase awareness of CRF in lung cancer survivors.

US Prison Policies on Organ Donation for Individuals Who Are Incarcerated.

This cross-sectional study collects data on US prison policies concerning organ donation by incarcerated individuals.

Transthoracic fundoplication using the Belsey Mark IV technique versus Nissen fundoplication: A systematic review and meta-analysis.

BACKGROUND: Nissen fundoplication is considered the cornerstone surgical treatment for hiatal hernia repair. Belsey Mark IV (BMIV) transthoracic fundoplication is an alternative approach that is rarely utilized in today's minimally invasive era. This study aims to summarize the safety and efficacy of BMIV and to compare it with Nissen fundoplication. METHODS: We searched MEDLINE, Scopus, and Cochrane Library databases for single arm and comparative studies published by March 31st, 2022, according to PRISMA statement. Inverse-variance weights were used to estimate the proportion of patients experiencing the studied outcome and random-effects meta-analyses were performed. RESULTS: 17 studies were identified, incorporating 2136 and 638 patients that underwent Belsey Mark IV or Nissen fundoplication, respectively. A total of 13.8% (95% CI: 9.6-18.6) of the patients that underwent fundoplication with the BMIV technique had non-resolution of their symptoms and 3.5% (95% CI: 2.0-5.4) required a reoperation. Overall, 14.8% (95% CI: 9.5-20.1) of the BMIV arm patients experienced post-operative complications, 5.0% (95% CI: 2.0-9.0) experienced chronic postoperative pain and 6.9% (95% CI: 3.1-11.9) had a hernia recurrence. No statistically significant difference was observed between Belsey Mark IV and Nissen fundoplication in terms of post-interventional non-resolution of symptoms (odds ratio [OR]: 1.49 [95% Confidence Interval (95%CI):0.6-4.0]; p = 0.42), post-operative complications (OR:0.83, 95%CI: 0.5-1.5, p = 0.54) and in-hospital mortality (OR:0.69, 95%CI: 0.13-3.80, p = 0.67). Belsey Mark IV arm had significantly lower reoperation rates compared to Nissen arm (OR:0.28, 95%CI: 0.1-0.7, p = 0.01). CONCLUSIONS: BMIV fundoplication is a safe and effective but technically challenging. The BMIV technique may offer benefits to patients compared to the laparoscopic Nissen fundoplication. These benefits, however, are challenged by the increased morbidity of a thoracotomy.

ACR Appropriateness Criteria® Staging and Follow-Up of Esophageal Cancer.

This document provides recommendations regarding the role of imaging in the staging and follow-up of esophageal cancer. For initial clinical staging, locoregional extent and nodal disease are typically assessed with esophagogastroduodenoscopy and esophageal ultrasound. FDG-PET/CT or CT of the chest and abdomen is usually appropriate for use in initial clinical staging as they provide additional information regarding distant nodal and metastatic disease. The detection of metastatic disease is critical in the initial evaluation of patients with esophageal cancer because it will direct patients to a treatment pathway centered on palliative radiation rather than surgery. For imaging during treatment, particularly neoadjuvant chemotherapy, FDG-PET/CT is usually appropriate, because some studies have found that it can provide information regarding primary lesion response, but more importantly it can be used to detect metastases that have developed since the induction of treatment. For patients who have completed treatment, FDG-PET/CT or CT of the chest and abdomen is usually appropriate for evaluating the presence and extent of metastases in patients with no suspected or known recurrence and in those with a suspected or known recurrence. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Receipt of Recommended Follow-up Care After a Positive Lung Cancer Screening Examination.

Importance: Maximizing benefits of lung cancer screening requires timely follow-up after a positive screening test. The American College of Radiology (ACR) Lung CT Screening Reporting and Data System (Lung-RADS) recommends testing and follow-up timing based on the screening result. Objective: To determine rates of and factors associated with recommended follow-up after a positive lung cancer screening examination by Lung-RADS category. Design, Setting, and Participants: This prospective cohort study of lung cancer screening examinations performed from January 1, 2015, through July 31, 2020, with follow-up through July 31, 2021, was conducted at 5 academic and community lung cancer screening sites in North Carolina. Participants included 685 adults with a positive screening examination, Lung-RADS categories 3, 4A, 4B, or 4X. Statistical analysis was performed from December 2020 to March 2022. Exposures: Individual age, race, sex, smoking exposure, year of lung cancer screening examination, chronic obstructive pulmonary disease, body mass index, referring clinician specialty, rural or urban residence. Main Outcomes and Measures: Adherence, defined as receipt of recommended follow-up test or procedure after the positive screen per ACR Lung-RADS timeframes: 6 months for Lung-RADS 3 and 3 months for Lung-RADS 4A. For Lung-RADS 4B or 4X, adherence was defined as follow-up care within 4 weeks, as ACR Lung-RADS does not specify a timeframe. Results: Among the 685 individuals included in this study who underwent lung cancer screening with low-dose computed tomography, 416 (60.7%) were aged at least 65 years, 123 (18.0%) were Black, 562 (82.0%) were White, and 352 (51.4%) were male. Overall adherence to recommended follow-up was 42.6% (292 of 685) and varied by Lung-RADS category: Lung-RADS 3 = 30.0% (109 of 363), Lung-RADS 4A = 49.5% (96 of 194), Lung-RADS 4B or 4X = 68.0% (87 of 128). Extending the follow-up time increased adherence: Lung-RADS 3 = 68.6% (249 of 363) within 9 months, Lung-RADS 4A = 77.3% (150 of 194) within 5 months, and Lung-RADS 4B or 4X = 80.5% (103 of 128) within 62 days. For Lung-RADS 3, recommended follow-up was less likely among those currently smoking vs those who quit (adjusted odds ratio [aOR], 0.48; 95% CI, 0.29-0.78). In Lung-RADS 4A, recommended follow-up was less likely in Black individuals vs White individuals (aOR, 0.35; 95% CI, 0.15-0.86). For Lung-RADS 4B or 4X, recommended follow-up was more likely in female individuals vs male individuals (aOR, 2.82; 95% CI, 1.09-7.28) and less likely in those currently smoking vs those who quit (aOR, 0.31; 95% CI, 0.12-0.80). Conclusions and Relevance: In this cohort study, adherence to recommended follow-up after a positive screening examination was low but improved among nodules with a higher suspicion of cancer and after extending the follow-up timeline. However, the association of extending the follow-up time of screen-detected nodules with outcomes at the population level, outside of a clinical trial, is unknown. These findings suggest that studies to understand why recommended follow-up is lower in Black individuals, male individuals, and individuals currently smoking are needed to develop strategies to improve adherence.

Pulmonary complications observed in patients with infective endocarditis with and without injection drug use: An analysis of the National Inpatient Sample.

BACKGROUND: The impact of cardiovascular and neurologic complications on infective endocarditis (IE) are well studied, yet the prevalence and significance of pulmonary complications in IE is not defined. To better characterize the multifaceted nature of IE management, we aimed to describe the occurrence and significance of pulmonary complications in IE, including among persons with IE related to drug use. METHODS: Hospitalizations of adult (≥18 years old) patients diagnosed with IE were identified in the 2016 National Inpatient Sample using ICD-10 codes. Multivariable logistic and linear regression were used to compare IE patient outcomes between those with and without pulmonary complications and to identify predictors of pulmonary complications. Interaction terms were used to assess the impact of drug-use IE (DU-IE) and pulmonary complications on inpatient outcomes. RESULTS: In 2016, there were an estimated 88,995 hospitalizations of patients diagnosed with IE. Of these hospitalizations,15,490 (17%) were drug-use related. Drug-use IE (DU-IE) had the highest odds of pulmonary complications (OR 2.97, 95% CI 2.50, 3.45). At least one pulmonary complication was identified in 6,580 (7%) of IE patients. DU-IE hospitalizations were more likely to have a diagnosis of pyothorax (3% vs. 1%, p<0.001), lung abscess (3% vs. <1%, p<0.001), and septic pulmonary embolism (27% vs. 2%, p<0.001). Pulmonary complications were associated with longer average lengths of stay (CIE 7.22 days 95% CI 6.11, 8.32), higher hospital charges (CIE 78.51 thousand dollars 95% CI 57.44, 99.57), more frequent post-discharge transfers (acute care: OR 1.37, 95% CI 1.09, 1.71; long-term care: OR 2.19, 95% CI 1.83, 2.61), and increased odds of inpatient mortality (OR 1.81 95% CI 1.39, 2.35). CONCLUSION AND RELEVANCE: IE with pulmonary complications is associated with worse outcomes. Patients with DU-IE have a particularly high prevalence of pulmonary complications that may require timely thoracic surgical intervention, likely owing to right-sided valve involvement. More research is needed to determine optimal management strategies for complications to improve patient outcomes.

Enhanced recovery after thoracic surgery: Systematic review and meta-analysis.

ERATS decreased length of stay, postoperative complications, and readmission.

Thoracic Enhanced Recovery After Surgery: Single Academic Center Observations After Implementation.

BACKGROUND: Enhanced recovery after surgery (ERAS) is an evidence-based, multidisciplinary perioperative care model shown to reduce complications and hospital length of stay (LOS). While some thoracic ERAS studies were inconclusive, others demonstrated that ERAS improves patient outcomes after lung resections and provides more cost-effective care. We aimed to investigate the effects of preliminary implementation of an ERAS protocol, in comparison with conventional care, on lung resection outcomes at a single academic institution. METHODS: In this observational study, adult patients undergoing lung resections during the pre-ERAS (April 2014 to September 2015) and post-ERAS (January 2016 to May 2017) periods were identified. Relevant demographic, preoperative, anesthesia, and surgical variables were collected. Pre-ERAS and post-ERAS cohorts were compared in terms of hospital LOS, postoperative complications, and 30-day outcomes. RESULTS: We identified 264 patients, half in each cohort. Pre-ERAS and post-ERAS groups were similar with respect to age, race, and comorbidities. There were no significant differences in LOS, complications, 30-day readmission and mortality rates, or patient-reported outcomes. Of the patients with prolonged LOS, 31% had pulmonary complications, almost half of which were prolonged air leaks. ERAS adherence rate was approximately 60%. CONCLUSIONS: In the first year of implementation, median LOS, complications, and 30-day outcomes did not differ significantly between the pre-ERAS and post-ERAS groups. Prolonged air leaks commonly led to prolonged LOS; therefore, thoracic ERAS protocols could include interventions to reduce air leak and consideration for discharging patients with chest tubes placed to Heimlich valves. Buy-in and adherence to a new protocol are necessary for implementation to be effective.

Trends and Outcomes in Minimally Invasive Surgery for Locally Advanced Non-Small-Cell Lung Cancer With N2 Disease.

Few studies examine outcomes by surgical approach in non-small-cell lung cancer (NSCLC) with N2 disease. We examined time trends in surgical approach and outcomes among patients undergoing minimally invasive (MIS, robotic and video-assisted thoracoscopic surgery [VATS]) vs open lobectomy in this patient population. We performed a retrospective analysis of patients from the National Cancer Database diagnosed with clinical Stage IIIA-N2 NSCLC from 2010 to 2016. We examined the yearly proportion of MIS vs open resections. Multivariable regression was used to assess the association of surgical approach with length of stay, unplanned readmissions, 30-day and 90-day mortality. Multivariable Cox proportional hazards modeling was used to assess the association of surgical approach with 5-year overall mortality. We identified 5741 patients who underwent lobectomy for Stage IIIA-N2 NSCLC (459 robotic, 1403 VATS, 3879 open). From 2010 to 2016, the proportion of minimally invasive procedures increased from 20% to 45%. MIS patients, on average, stayed 1 day less in the hospital (95% confidence interval [CI] 0.7, 1.5) and had lower odds of 90-day (odds ratio [OR] 0.74; 95% CI 0.54, 0.99) and 5-year mortality (OR 0.82; 95% CI 0.75, 0.91), compared to open resections. There was no difference in odds of readmission by surgical approach (OR 0.97; 95% CI 0.71, 1.33). Among MIS procedures, robotic resections had lower odds of 90-day mortality (OR 0.42; 95% CI 0.18, 0.97) than VATS. Among patients undergoing lobectomy for locally advanced N2 NSCLC robotic and VATS techniques appear safe and effective compared to open surgery and may offer short- and long-term advantages.

Does routine uniportal thoracoscopy during rib fixation identify more injuries and impact outcomes?

BACKGROUND: Flail chest and severely displaced rib fractures due to blunt trauma can be associated with intrathoracic injuries. At our institution, two thoracic surgeons perform all surgical stabilization of rib fractures (SSRF): one performs routine uniportal thoracoscopy (R-VATS) at the time of SSRF and the other for only select cases (S-VATS). In this pilot study, we hypothesized that R-VATS at the time of SSRF identifies and addresses intrathoracic injuries not seen on imaging and may impact patient outcomes. METHODS: A retrospective review of all patients who underwent SSRF from 2013-2019 at our institution was performed for severely displaced rib fractures or flail chest. Data collected included demographics, imaging results, treatment strategy, and operative findings. RESULTS: Ninety-nine patients underwent SSRF. Uniportal thoracoscopy was performed on 69% of these patients. When thoracoscopy was performed, 31 additional injuries were identified. R-VATS identified 23 additional intrathoracic findings at time of thoracoscopy not seen on CT scan compared to 8 findings in the S-VATS group (P=0.367). At 3 months follow-up, one empyema and one diaphragmatic hernia required reoperation-neither of which underwent thoracoscopy at time of SSRF. There were no differences in LOS, operative times, and overall mortality between the SSRF/thoracoscopy and SSRF only groups. CONCLUSIONS: R-VATS at the time of SSRF did not identify a statistically significant greater number of occult intrathoracic injuries compared to S-VATS. R-VATS was not associated with increased operative time, LOS, and mortality. Further study is needed to determine if there is benefit to R-VATS in patients meeting requirements for rib fracture repair.

Lung Cancer Surgical Regionalization Disproportionately Worsens Travel Distance for Rural Patients.

PURPOSE: Major cancer surgeries have regionalized to fewer and higher-volume hospitals, with the goal of improving the quality of surgical care. However, regionalization may have negative effects on geographic access to care. We hypothesize that lung cancer patients have been traveling further for surgery over time as regionalization has occurred, and this increased travel has primarily impacted rural patients. METHODS: A North Carolina all-payer state discharge database was used to capture discharges from 2005 to 2015 for patients undergoing lung cancer resection. Changes in patterns of care over time in high-volume centers (HVC) were examined. Adjusted patient straight-line travel distance was estimated over time and stratified by rural-urban location. FINDINGS: The number of hospitals performing lung cancer resections decreased from 49 to 31 over the study period (P = .0006), and the proportion of patients receiving care at HVC increased from 23% to 44% (P < .0001). Rural patient travel distance increased over time by 8.5 miles (95% CI: 0.56-17.10, P = .048), from 45.1 to 53.6 miles. There was no change in urban patient travel distance. The difference in adjusted travel distance between rural and urban patients nearly doubled from 2005 to 2015 (9.6 to 17.9 miles,P < .0001). CONCLUSION: In North Carolina, lung cancer surgical regionalization occurred over the study period and was accompanied by increases in travel distance for rural patients only. Further work is needed to determine the effects of greater travel distance on patterns of cancer care for rural patients.