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Objective The mainstay of treatment for patients with malignant pleural disease is fluid drainage and systemic therapy. A tumor-specific oncolytic virus or T-cell–activating interleukin-2 immunotherapy may provide an opportunity for local control. We previously developed a vaccinia virus–expressing interleukin-2, an oncolytic virus that mediated tumor regression in preclinical peritoneal tumor models with expansion of tumor-infiltrating lymphocytes. We evaluated the antitumor efficacy and immune modulatory effects of vaccinia virus–expressing interleukin-2 in malignant pleural disease. Methods A murine model of malignant pleural disease was established with percutaneous intrapleural deposition of the Lewis lung carcinoma cell line and monitored with bioluminescent imaging. After intrapleural or systemic administration of vaccinia viruses (vaccinia virus yellow fluorescent protein control, vaccinia virus–expressing interleukin-2), systemic anti–programmed cell death-1 antibody, or combination therapy (vaccinia virus–expressing interleukin-2 and anti–programmed cell death-1), tumor mass, immune cell infiltration, T-cell receptor diversity, and survival were assessed. Results Intrapleural vaccinia virus resulted in significant tumor regression compared with phosphate-buffered saline control (P Conclusions Intrapleural vaccinia virus–expressing interleukin-2 reduced tumor burden and enhanced survival in a murine malignant pleural disease model. Increased CD8+ tumor-infiltrating lymphocytes and αβ T-cell receptor diversity are associated with enhanced response. Clinical trials will enable assessment of intrapleural vaccinia virus–expressing interleukin-2 therapy in patients with malignant pleural disease.

[Image: see text] Central Picture Legend: Ethical standards for global health initiatives.

Minimally invasive Heller myotomy for achalasia is commonly performed laparoscopically, but recently done with robotic assistance. We compare outcomes of the 2 approaches.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 widthlt;5 cm. We performed a propensity score--matched analysis to evaluate outcomes among robotic and laparoscopic groups.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% gt; 3 at 4 years; P = .0008), and actuarially fewer reinterventions (1.2% vs 11% at 3 years; P = .04).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.

Objective Lobectomy is a standard treatment for stage I non–small cell lung cancer, but a significant proportion of patients are considered at high risk for complications, including mortality, after lobectomy and might not be candidates. Identifying who is at risk is important and in evolution. The objective of The American Association for Thoracic Surgery Clinical Practice Standards Committee expert panel was to review important considerations and factors in assessing who is at high risk among patients considered for lobectomy. Methods The American Association for Thoracic Surgery Clinical Practice Standards Committee assembled an expert panel that developed an expert consensus document after systematic review of the literature. The expert panel generated a priori a list of important risk factors in the determination of high risk for lobectomy. A survey was administered, and the expert panel was asked to grade the relative importance of each risk factor. Recommendations were developed using discussion and a modified Delphi method. Results The expert panel survey identified the most important factors in the determination of high risk, which included the need for supplemental oxygen because of severe underlying lung disease, low diffusion capacity, the presence of frailty, and the overall assessment of daily activity and functional status. The panel determined that factors, such as age (as a sole factor), were less important in risk assessment. Conclusions Defining who is at high risk for lobectomy for stage I non–small cell lung cancer is challenging, but remains critical. There was impressive strong consensus on identification of important factors and their hierarchical ranking of perceived risk. The panel identified several key factors that can be incorporated in risk assessment. The factors are evolving and as the population ages, factors such as neurocognitive function and frailty become more important. A minimally invasive approach becomes even more critical in this older population to mitigate risk. The determination of risk is a clinical decision and judgement, which should also take into consideration patient perspectives, values, preferences, and quality of life.

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