Explore the vast range of titles available.

BackgroundProgrammed cell death 1 (PD-1) blockade induces tumor regression in patients with advanced esophageal squamous cell carcinoma (ESCC); however, little is known about the efficacy of PD-1 blockade as neoadjuvant therapy in resectable ESCC. We aim to assess the safety and feasibility of using the combination of neoadjuvant PD-1 blockade with chemotherapy in patients with ESCC.MethodsPatients with previously untreated, resectable (stage II or III) ESCC were enrolled. Each patient received two 21-day cycles of neoadjuvant treatment with camrelizumab, nab-paclitaxel, and carboplatin before undergoing surgical resection approximately 6–9 weeks after the first cycle.ResultsBetween January 2020 and September 2020, 37 patients were screened, of whom 23 were enrolled. The neoadjuvant therapeutic regimen had an acceptable side effect profile, and no delays in surgery were observed. Severe (grade 3–4) treatment-related adverse events included neutropenia (9 of 23, 39.1%) and leukopenia (2 of 23, 8.7%). The objective response and disease control rates were 90.5% and 100%, respectively. Twenty patients received surgery, and R0 resection was achieved in all cases. Five (25%) patients had a pathological complete response (PCR) and 10 (50%) patients had a major pathological response. The proportion of patients with a high tumor mutation burden and a high expression of programmed death-ligand 1 (PD-L1) in primary tumor was significantly higher in the PCR group than in the non-PCR group (p=0.044). The number of infiltrating PD-L1+ CD163+ cells was significantly lower in the PCR group than in the non-PCR group after treatment (p=0.017).ConclusionsNeoadjuvant camrelizumab plus carboplatin and nab-paclitaxel had manageable treatment-related adverse effects and induced an objective response in 90.5% of patients, demonstrating its antitumor efficacy in resectable ESCC.Trial registration numberChiCTR2000028900.

The diagnosis and management of tracheobronchial papilloma is challenging due to its rarity, and non-specific presenting symptoms. Small percentage undergoes malignant transformation. Herein, we report an unusual case of tracheal papilloma initially misdiagnosed as chronic obstructive pulmonary disease (COPD) in 36-year-old male with triple Y syndrome. It was successfully treated with local debridement and brachytherapy. To the best of our knowledge, this is the first description of brachytherapy for such a condition.

Retrospective data demonstrates that robotic-assisted thoracoscopic surgery provides many benefits, such as decreased postoperative pain, lower mortality, shorter length of stay, shorter chest tube duration, and reductions in the incidence of common postoperative pulmonary complications, when compared to video-assisted thoracoscopic surgery. Despite the potential benefits of robotic surgery, there are two major barriers against its widespread adoption in thoracic surgery: lack of high-quality prospective data, and the perceived higher cost of it. Therefore, in the face of these barriers, a prospective randomized controlled trial comparing robotic- to video-assisted thoracoscopic surgery is needed. The RAVAL trial is a two-phase, international, multi-centered, blinded, parallel, randomized controlled trial that is comparing robotic- to video-assisted lobectomy for early-stage non-small cell lung cancer that has been enrolling patients since 2016. The RAVAL trial will be conducted in two phases: Phase A will enroll 186 early-stage non-small cell lung cancer patients who are candidates for minimally invasive pulmonary lobectomy; while Phase B will continue to recruit until 592 patients are enrolled. After consent, participants will be randomized in a 1:1 ratio to either robotic- or video-assisted lobectomy, and blinded to the type of surgery they are allocated to. Health-related quality of life questionnaires will be administered at baseline, postoperative day 1, weeks 3, 7, 12, months 6, 12, 18, 24, and years 3, 4, 5. The primary objective of the RAVAL trial is to determine the difference in patient-reported health-related quality of life outcomes between the robotic- and video-assisted lobectomy groups at 12 weeks. Secondary objectives include determining the differences in cost-effectiveness, and in the 5-year survival data between the two arms. The results of the primary objective will be reported once Phase A has completed accrual and the 12-month follow-ups are completed. The results of the secondary objectives will be reported once Phase B has completed accrual and the 5-year follow-ups are completed. If successfully completed, the RAVAL Trial will have studied patient-reported outcomes, cost-effectiveness, and survival of robotic- versus video-assisted lobectomy in a prospective, randomized, blinded fashion in an international setting. ClinicalTrials.gov, NCT02617186. Registered 22-September-2015. https://clinicaltrials.gov/ct2/show/NCT02617186.

The effect of post-operative adverse events (AEs) on patient outcomes such as length of stay (LOS) and readmissions to hospital is not completely understood. This study examined the severity of AEs from a high-volume thoracic surgery center and its effect on the patient postoperative LOS and readmissions to hospital. This study includes patients who underwent an elective lung resection between September 2018 and January 2020. The AEs were grouped as no AEs, 1 or more minor AEs, and 1 or more major AEs. The effects of the AEs on patient LOS and readmissions were examined using a survival analysis and logistic regression, respectively, while adjusting for the other demographic or clinical variables. Among 488 patients who underwent lung surgery, (Wedge resection [n = 100], Segmentectomy [n = 51], Lobectomy [n = 310], Bilobectomy [n = 10], or Pneumonectomy [n = 17]) for either primary (n = 440) or secondary (n = 48) lung cancers, 179 (36.7%) patients had no AEs, 264 (54.1%) patients had 1 or more minor AEs, and 45 (9.2%) patients had 1 or more major AEs. Overall, the median of LOS was 3 days which varied significantly between AE groups; 2, 4, and 8 days among the no, minor, and major AE groups, respectively. In addition, type of surgery, renal disease (urinary tract infection [UTI], urinary retention, or acute kidney injury), and ASA (American Society of Anesthesiology) score were significant predictors of LOS. Finally, 58 (11.9%) patients were readmitted. Readmission was significantly associated with AE group (P = 0.016). No other variable could significantly predict patient readmission. Overall, postoperative AEs significantly affect the postoperative LOS and readmission rates.

Decellularization efforts must balance the preservation of the extracellular matrix (ECM) components while eliminating the nucleic acid and cellular components. Following effective removal of nucleic acid and cell components, decellularized ECM (dECM) can be solubilized in an acidic environment with the assistance of various enzymes to develop biological scaffolds in different forms, such as sheets, tubular constructs, or three-dimensional (3D) hydrogels. Each organ or tissue that undergoes decellularization requires a distinct and optimized protocol to ensure that nucleic acids are removed, and the ECM components are preserved. The objective of this study was to optimize the decellularization process for dECM isolation from human lung tissues for downstream 2D and 3D cell culture systems. Following protocol optimization and dECM isolation, we performed experiments with a wide range of dECM concentrations to form human lung dECM hydrogels that were physically stable and biologically responsive. The dECM based-hydrogels supported the growth and proliferation of primary human lung fibroblast cells in 3D cultures. The dECM is also amenable to the coating of polyester membranes in Transwell™ Inserts to improve the cell adhesion, proliferation, and barrier function of primary human bronchial epithelial cells in 2D. In conclusion, we present a robust protocol for human lung decellularization, generation of dECM substrate material, and creation of hydrogels that support primary lung cell viability in 2D and 3D culture systems

While randomized controlled trials (RCTs) are regarded as one of the highest forms of clinical research, the robustness of their P values can be difficult to ascertain. Defined as the minimum number of patients in a study arm that would need to be changed from a non-event to event for the findings to lose significance, the Fragility Index is a method for evaluating results from these trials. This study aims to calculate the Fragility Index for trials evaluating perioperative esophagectomy-related interventions to determine the strength of RCTs in this field. MEDLINE and EMBASE were searched for RCTs related to esophagectomy that reported a significant dichotomous outcome. Two reviewers independently screened articles and performed the data extractions with risk of bias assessment. The Fragility Index was calculated using a two-tailed Fisher’s exact test. Bivariate correlation was conducted to evaluate associations between the Fragility Index and study characteristics. 41 RCTs were included, and the median sample size was 80 patients [Interquartile range (IQR) 60–161]. Of the included outcomes, 29 (71%) were primary, and 12 (29%) were secondary. The median Fragility Index was 1 (IQR 1–3), meaning that by changing one patient from a non-event to event, the results would become non-significant. Fragility Index was correlated with P value, number of events, and journal impact factor. The RCTs related to esophagectomy did not prove to be robust, as the significance of their results could be changed by altering the outcome status of a handful of patients in one study arm.

Lung cancer remains the leading cause of cancer death worldwide despite the significant progress made by immune checkpoint inhibitors, including programmed death receptor-1 (PD1)/PD ligand 1 (PDL1)-blockade therapy. PD1/PDL1−blockade has achieved unprecedented tumor regression in some patients with advanced lung cancer. However, the majority of patients fail to respond to PD1/PDL1 inhibitors. The high rate of therapy non-response results from insufficient PDL1 expression on most patients’ tumors and the presence of further immunosuppressive mechanisms in the tumor microenvironment. Here, we sensitize non-responding tumors from patients with lung cancer to PD1-blockade therapy using highly cytotoxic expanded natural killer (NK) cells. We uncover that NK cells expanded from patients with lung cancer dismantle the immunosuppressive tumor microenvironment by maintaining strong antitumor activity against both PDL1+ and PDL1− patient tumors. In the process, through a contact-independent mechanism involving interferon γ, expanded NK cells rescued tumor killing by exhausted endogenous TILs and upregulated the tumor proportion score of PDL1 across patient tumors. In contrast, unexpanded NK cells, which are susceptible to tumor-induced immunosuppression, had no effect on tumor PDL1. As a result, combined treatment of expanded NK cells and PD1-blockade resulted in robust synergistic tumor destruction of initially non-responding patient tumors. Thus, expanded NK cells may overcome the critical roadblocks to extending the prodigious benefits of PD1-blockade therapy to more patients with lung cancer and other tumor types.

Background The Venous Thromboembolism Prophylaxis (VTE-PRO) randomized trial is a pilot study evaluating the impact of extended-duration prophylaxis on venous thromboembolic events in patients undergoing lung cancer resection. Enrolled VTE-PRO participants self-inject either low-molecular weight heparin or a saline placebo for 30 days postoperatively. Study outcomes include feasibility, incidence of venous thromboembolism, and venous thromboembolism-related morbidity and mortality. Initial analyses demonstrated low rates of accrual and retention for the VTE-PRO pilot. Therefore, the purpose of the current study was to develop a knowledge translation intervention to improve VTE-PRO pilot trial accrual and retention. Methods Eligible participants were surveyed to identify the barriers to VTE-PRO participation. The Theoretical Domains Framework was used to categorize these barriers. Barriers were mapped to the capabilities, opportunities, and behavior (COM-B) behavioral change wheel to identify potential interventions to support trial accrual and retention. The resulting knowledge translation intervention was titled Inform, Remind, Involve and Support to improve Accrual and Retention (IRIS-AR). Key informant interviews with patients were held to refine and confirm the validity of identified barriers and perceived acceptability of the proposed IRIS-AR intervention. Institutional Review Board approval was granted for this study. Results The resulting intervention included: information booklets and counseling sessions to identify unique participant challenges to trial participation (Inform); daily reminders to administer injections (Remind); involvement of family/caregivers in study processes (Involve); and leverage of an existing home-care nursing program to provide injection support when needed (Support). Twenty-six key informant participants were interviewed. The most common barriers to trial participation included lack of social support and fear of needle injection. Participants generally supported use of information booklets, involvement of family/caregivers, and support by a home-care nursing program; however, not all supported the use of daily reminders. Conclusion Developed using theory and integrated knowledge translation, the IRIS-AR presents a patient-centered intervention that leverages existing programs to promote trial engagement. The proposed strategy can likely be adapted to improve compliance with other patient-directed interventions. Trial registration ClinicalTrials.gov, NCT02334007 . Registered on 8 January 2015.

Background The optimal analgesia method in video-assisted thoracoscopic surgery (VATS) remains controversial. Intercostal nerve blockade (ICNB) is limited by its duration of action. The erector spinae plane (ESP) block has the potential to provide satisfactory analgesia for VATS; however, the effectiveness of continuous ESP versus surgeon-performed ICNB has not been investigated. The objectives of this study were to establish feasibility of patient recruitment and follow-up before undertaking a fully powered randomized controlled trial (RCT); and, secondarily, to compare opioid usage, pain control, and sensory blockade. Methods This feasibility RCT was undertaken at St Joseph’s Hospital, Hamilton, Ontario, Canada, and included 24 patients (>18 years) having elective VATS with at least one overnight stay. Exclusion criteria were patient refusal, body mass index >40 kg/m 2 , contraindications to neuraxial analgesia techniques as per the American Society of Regional Anesthesia and Pain guidelines, known allergy to local anesthetics, language or comprehension barriers, procedures with a higher chance of open surgery, and regular opioid use for ≥3 months preoperatively. Patients underwent either continuous ESP ( n =12) or surgeon-performed ICNB ( n =12). All patients received routine intraoperative anesthesia care and multimodal analgesia. Feasibility criteria were recruitment rate of two patients/week and full follow-up in all patients in-hospital. We compared opioid consumption, postoperative pain scores (0–10 numerical rating scale), adverse events, patient satisfaction, and distribution of sensory blockade as clinical outcomes (secondary). Results Feasibility of primary outcomes was successfully demonstrated. Five patients had an epidural in anticipation of open surgery. Mean opioid consumption as equivalent morphine units was less in the ESP group over the first 24 h (mean difference, 1.63 [95% CI –1.20 to 4.45]) and 48 h (mean difference, 2.34 [95% CI –1.93 to 6.61]). There were no differences in adverse effects. Conclusions A fully powered RCT is feasible with modifications. Our results also suggest that continuous ESP is safe and can decrease opioid needs. However, it is important to consider procedures to improve compliance to protocol and adherence to assigned interventions. Trial registration Clinicaltrials.gov identifier: NCT03176667 . Registered June 5, 2017.

Unilateral absence of the pulmonary artery (UAPA) represents a rare condition that is often associated with cardiac congenital abnormalities but can also be relatively asymptomatic and indolent. There is a lack of consensus regarding the management of UAPA. However, in the setting of associated complications and ongoing infection, pulmonary resection is advocated. Although rare, the association between UAPA and bronchogenic carcinoma has been previously reported in seven published cases. In the majority of these, anatomic lung resection (most commonly with pneumonectomy) was curative. We present the first reported case of ipsilateral metastatic non-small-cell lung cancer- (NSCLC-) associated UAPA in a 47-year-old patient with ventilator-dependent hypoxic respiratory failure and bronchorrhea, who had been lost to follow-up for 8 years. Initial investigations did not yield evidence of malignancy, and confirmation of metastatic disease was made intraoperatively at the time of thoracotomy. The findings demonstrated evidence of diffuse metastatic pleural disease with lymphangitic carcinomatosis and superimposed infection. The patient was palliated and passed away shortly thereafter. In the setting of UAPA, clinicians should have a high index of suspicion for the possibility of malignancy, and if proven, they should consider early resection following appropriate staging.