Esophagectomy Enhanced Recovery After Surgery Initiative Results in Improved Outcomes.

BACKGROUND: Esophagectomy for esophageal cancer is a procedure with high morbidity and mortality. This study developed a Multidisciplinary Esophagectomy Enhanced Recovery Initiative (MERIT) pathway and analyzed implementation outcomes in a single institution. METHODS: The MERIT pathway was developed as a practice optimization and quality improvement initiative. Patients were studied from November 1, 2021 to June 20, 2022 and were compared with historical control subjects. The Wilcoxon rank sum test and the Fisher exact test were used for statistical analysis. RESULTS: The study compared 238 historical patients (January 17, 2017 to December 30, 2020) with 58 consecutive MERIT patients. There were no significant differences between patient characteristics in the 2 groups. In the MERIT group, 49 (85%) of the patients were male, and their mean age was 65 years (range, 59-71 years). Most cases were performed for esophageal cancer after neoadjuvant therapy. Length of stay improved by 27% from 11 to 8 days (P = .27). There was a 12% (P = .05) atrial arrhythmia rate reduction, as well as a 9% (P = .01) decrease in postoperative ileus. Overall complications were reduced from 54% to 35% (-19%; P = .01). CONCLUSIONS: This study successfully developed and implemented an enhanced recovery after surgery pathway for esophagectomy. In the first year, study investigators were able to reduce overall complications, specifically atrial arrhythmias, and postoperative ileus.

Sublobar Resection, Stereotactic Body Radiation Therapy, and Percutaneous Ablation Provide Comparable Outcomes for Lung Metastasis-Directed Therapy.

BACKGROUND: Prolonged survival of patients with metastatic disease has furthered interest in metastasis-directed therapy (MDT). RESEARCH QUESTION: There is a paucity of data comparing lung MDT modalities. Do outcomes among sublobar resection (SLR), stereotactic body radiation therapy (SBRT), and percutaneous ablation (PA) for lung metastases vary in terms of local control and survival? STUDY DESIGN AND METHODS: Medical records of patients undergoing lung MDT at a single cancer center between January 2015 and December 2020 were reviewed. Overall survival, local progression, and toxicity outcomes were collected. Patient and lesion characteristics were used to generate multivariable models with propensity weighted analysis. RESULTS: Lung MDT courses (644 total: 243 SLR, 274 SBRT, 127 PA) delivered to 511 patients were included with a median follow-up of 22 months. There were 47 local progression events in 45 patients, and 159 patients died. Two-year overall survival and local progression were 80.3% and 63.3%, 83.8% and 9.6%, and 4.1% and 11.7% for SLR, SBRT, and PA, respectively. Lesion size per 1 cm was associated with worse overall survival (hazard ratio, 1.24; P = .003) and LP (hazard ratio, 1.50; P < .001). There was no difference in overall survival by modality. Relative to SLR, there was no difference in risk of local progression with PA; however, SBRT was associated with a decreased risk (hazard ratio, 0.26; P = .023). Rates of severe toxicity were low (2.1%-2.6%) and not different among groups. INTERPRETATION: This study performs a propensity weighted analysis of SLR, SBRT, and PA and shows no impact of lung MDT modality on overall survival. Given excellent local control across MDT options, a multidisciplinary approach is beneficial for patient triage and longitudinal management.

Determinants of Long-term Survival Decades After Esophagectomy for Esophageal Cancer.

BACKGROUND: Long-term survival in esophagectomy patients with esophageal cancer is low due to tumor-related characteristics, with few reports of modifiable variables influencing outcome. We identified determinants of overall survival, time to recurrence, and disease-free survival in this patient cohort. METHODS: Adult patients who underwent esophagectomy for primary esophageal cancer from January 5, 2000, through December 30, 2010, at our institution were identified. Univariate Cox models and multivariable logistic regression analyses were used to identify associations between modifiable and unmodifiable patient and clinical variables and outcome of survival for the total cohort and a subgroup with locally advanced disease. RESULTS: We identified 870 patients with esophageal cancer who underwent esophagectomy. The median follow-up time was 15 years, and the 15-year overall survival rate was 25.2%, survival free of recurrence was 57.96%, and disease-free survival was 24.21%. Decreased overall survival was associated with the following unmodifiable variables: older age, male sex, active smoking status, history of coronary artery disease, advanced clinical stage, and tumor location. Decreased overall survival was associated with the following modifiable variables: use of neoadjuvant therapy, advanced pathologic stage, resection margin positivity, surgical reintervention, and blood transfusion requirement. The overall survival probability 6 years after esophagectomy was 0.920 (95% CI, 0.895-0.947), and time-to-recurrence probability was 0.988 (95% CI, 0.976-1.000), with a total of 17 recurrences and 201 deaths. CONCLUSIONS: Once patients survive 5 years, recurrence is rare. Long-term survival can be achieved in high-volume centers adhering to National Comprehensive Cancer Network guidelines using multidisciplinary care teams that is double what has been previously reported in the literature from national databases.

Impact of FDG PET Standardized Uptake Value in Resected Clinical Stage IA Non-Small Cell Lung Cancer.

BACKGROUND: A significant proportion of patients with clinical stage IA non-small cell lung cancer (NSCLC) experience will recurrence and decreased survival after surgery. This study examined the impact of preoperative primary tumor positron emission tomography (PET) scan maximum standardized uptake value (SUVmax) on oncologic outcomes after surgery. METHODS: This was a retrospective review of 251 patients who underwent surgical treatment of clinical stage IA NSCLC at an academic medical center (2005-2014). Patients were classified according to PET SUVmax level (low vs high) for analysis of upstaging, tumor recurrence, and overall survival. RESULTS: Median SUVmax values were higher in squamous cell carcinoma than in adenocarcinoma (median 3.3 vs 7.2; P < .0001). There were 109 (43.4%) patients in the SUVmax low group and 142 (56.6%) in the SUVmax high group. Patients with SUVmax high had larger tumors. SUVmax high was associated with higher rates of nodal upstaging (16.2% vs 4.6% in SUVmax low; P = .004), particularly in N1 nodes. SUVmax high was independently associated with nodal upstaging (adjusted odds ratio, 3.95; 95% CI, 1.36-11.46; P = .011). SUVmax high was associated with time to recurrence (hazard ratio, 1.62; 95% CI, 1.03-2.54; P = .036), but this association was lost on multivariable analysis (hazard ratio, 1.52; 95% CI, 0.91-2.54; P = .106). SUVmax was not associated with overall survival. CONCLUSIONS: Preoperative PET SUVmax level is strongly associated with nodal upstaging, particularly in N1 nodes, in patients with clinical stage IA NSCLC who undergo resection. PET SUVmax should be regarded as a risk factor when considering candidacy for sublobar resections and in future trials involving patients with stage I NSCLC.

Primary esophageal non-Hodgkin's lymphoma: demographics, clinical characteristics, histopathologic types, and survival in 179 patients from the SEER program and systematic review of the literature.

BACKGROUND: The most frequent site for the extranodal appearance of primary non-Hodgkin's lymphomas (NHL) is the gastrointestinal (G.I.) tract. However, primary esophageal lymphoma is extremely rare. The purpose of the present study was to describe and analyze the demographics, clinical characteristics, histopathologic types, and long-term survival of patients with primary esophageal NHL registered in the surveillance, epidemiology, and end results (SEER) database. METHODS: Retrospective cohort study. Individuals with primary esophageal lymphoma (PEL) were identified using the international classification of disease for oncology, third edition histology codes. Patients were excluded if there was no microscopic confirmation of the neoplasm or if the diagnosis was made by autopsy or death certificate. Data on demographics, clinical characteristics, histopathology and survival were analyzed using the Kaplan-Meier method, life table, and cox proportional hazard models. RESULTS: 179 patients were included (68% males, median age 66 years [IQR 46-79]). The overall survival at 1, 5 and 10 years was 65% (95% CI 57.9-72.3%), 49% (95% CI 42.1-57.3%), and 31% (95% CI 24.5-38.6%), respectively. On univariate analyses, individuals with extranodal marginal zone lymphoma (MZL) had a significantly higher overall survival when compared to patients with diffuse large B cell lymphoma (HR 0.29; 95% CI 0.11-0.73. p = 0.008). Furthermore, patients whose cancer was diagnosed after 1997 showed an improved overall survival (HR 0.40; 95% CI 0.26-0.61. p < 0.001) when compared to those diagnosed before 1997. CONCLUSIONS: In this large population-based series, diagnosis after 1997 (year of rituximab approval by the FDA) and MZL subtype were associated with improved survival outcomes in patients with PEL.

Programmed Death Ligand 1 and Immune Cell Infiltrates in Solitary Fibrous Tumors of the Pleura.

BACKGROUND: Approximately 10% to 15% of patients with solitary fibrous tumors of the pleura (SFTP) have recurrence after resection. Many are not candidates for reresection and lack effective treatments. We explored the expression of programmed death ligand 1 (PD-L1) as a biomarker for candidacy for treatment with immune checkpoint inhibitors. METHODS: We reviewed the medical records of 52 patients with primary SFTP and 5 with recurrent SFTP. We performed immunohistochemistry on tumor tissue to determine the expression of PD-L1 and infiltration by cluster of differentiation 8 (CD8)-positive immune cells. RESULTS: Any PD-L1 expression was observed in 11 primary SFTP (21.2%). Overall, PD-L1 expression level was less than 1% in 10 patients (19.2%) and greater than 1% in 1 (1.9%). Tumor infiltration by CD8-positive immune cells was absent or rare in 13 patients (25%), less than 5% in 31 (59.6%), and 5% to 25% in 8 (15.4%). There were no associations between PD-L1 expression or immune cell infiltrates and known risk factors for recurrence or a prognostic risk score classification. Time to recurrence was strongly associated with the risk score classification (P < .001), but it was not associated with PD-L1 expression (P = .296) or immune cell infiltrates (P = .619). In recurrent SFTP, PD-L1 was expressed in 4 of 10 tumors (40%; all <1% expression). There was no correlation in PD-L1 expression between primary and recurrent SFTP samples. CONCLUSIONS: A small subset of SFTP express PD-L1 at low levels (<1%) but exhibit colocalization of CD8-positive immune cells suggesting an inducible expression mechanism. The role of PD-L1 merits exploration in the clinical setting in patients with advanced SFTP when alternative treatments or clinical trials are considered.

Pregnancy-associated idiopathic laryngotracheal stenosis: presentation, management and results of surgical treatment.

OBJECTIVES: Idiopathic laryngotracheal stenosis (ILTS) is an uncommon problem arising mostly in women. In some, it arises during or is exacerbated by pregnancy. Experience with management of patients with this rare association is limited. This study seeks to evaluate the management of patients with pregnancy-associated ILTS and compare outcomes to cases not associated with pregnancy. METHODS: Retrospective review of 15 patients undergoing surgical treatment of pregnancy-associated ILTS from 1971 to 2013. Variables of interest and airway outcomes were compared to patients with non-pregnancy-associated ILTS. RESULTS: Pregnancy-associated ILTS was observed in 15/263 (5.7%) patients. Symptoms developed during their first pregnancy. When compared to non-pregnancy patients, these patients were younger (37 vs 47 years; P = 0.0003), had more prior tracheostomies (26.7% vs 10.9%; P = 0.085) and had more preoperative airway dilatations (86.7% vs 57.7%; P = 0.030). All patients completed pregnancy without complications and ultimately underwent laryngotracheal resection. The expression of hormonal receptors in the surgical specimens was similar in both groups (oestrogen receptors: 100% vs 75% and progesterone receptors: 71.4% vs 72.1%, in pregnancy and non-pregnancy patients, respectively). Airway outcomes were good/excellent in 13 (86.7%) patients with pregnancy-associated ILTS and 225 (90.7%) patients without pregnancy association (P = 0.642), and did not change when adjusting for other risk factors. CONCLUSIONS: Pregnancy-associated ILTS is rare. The pathophysiology is unclear, but appearance of symptoms during pregnancy may suggest hormonal factors. To minimize foetal risk, dilatation during pregnancy followed by laryngotracheal resection after delivery is the preferred treatment. Pregnancy association does not seem to affect outcomes with expected satisfactory results in most patients.

Hyperbaric oxygen therapy in the prevention and management of tracheal and oesophageal anastomotic complications.

OBJECTIVES: Failure of anastomotic healing is a morbid complication after airway or oesophageal surgery. Hyperbaric oxygen therapy (HBOT) has been used extensively in the management of complex wound-healing problems. We demonstrate the use of HBOT to rescue at-risk anastomoses or manage anastomotic failures in thoracic surgery. METHODS: Retrospective review of 25 patients who received HBOT as part of the management of tracheal or oesophageal anastomotic problems during 2007-2018. HBOT was delivered at 2 atm with 100% oxygen in 90-min sessions. RESULTS: Twenty-three patients underwent airway resection and reconstruction while 2 patients underwent oesophagectomy. There were 16 (70%) laryngotracheal and 7 (30%) tracheal resections. Necrosis at the airway anastomosis was found in 13 (57%) patients, partial dehiscence in 2 (9%) patients and both in 6 (26%) patients. HBOT was prophylactic in 2 (9%) patients. Patients received a median of 9.5 HBOT sessions (interquartile range 5-19 sessions) over a median course of 8 days. The airway anastomosis healed in 20 of 23 (87%) patients. Overall, a satisfactory long-term airway outcome was achieved in 19 (83%) patients; 4 patients failed and required reoperation (2 tracheostomies and 1 T-tube). HBOT was used in 2 patients after oesophagectomy to manage focal necrosis or ischaemia at the anastomosis, with success in 1 patient. Complications from HBOT were infrequent and mild (e.g. ear discomfort). CONCLUSIONS: HBOT should be considered as an adjunct in the management of anastomotic problems after airway surgery. It may also play a role after oesophagectomy. Possible mechanisms of action are rapid granulation, early re-epithelialization and angiogenesis.

Impact of Radial Margin Status After Esophagectomy for Adenocarcinoma.

INTRODUCTION: The clinical impact of a positive radial margin after esophagectomy for cancer has not been clearly  identified. The goal of this study was to identify risk factors for a positive radial margin and determine the impact on recurrence and survival. METHODS: Retrospective review of 196 patients with pathological T3 N0-3 esophageal adenocarcinoma undergoing esophagectomy between 2002 and 2017. Mortality data was extracted from Electronic Medical Records and Social Security Death Index. RESULTS: Mean age was 63.7 ± 11.4 years, and there were 166 (84.7%) men. Neoadjuvant therapy was given in 141(71.9%) patients. We identified 29(14.8%) patients with a positive radial margin. Factors significantly associated with a positive radial margin include not receiving neoadjuvant therapy and presence of lymphatic, vascular, or perineural invasion. Overall, there were 94(48%) recurrences during a mean follow-up of 24.7 months. Involvement of the radial margin was not significantly associated with recurrence-free survival (HR 1.24, CI 95% 0.73-2.12, p = 0.425). Overall survival for the entire cohort was 41.6% and 28.9% at 3 and 5 years, respectively. Involvement of the radial margin did not have a significant impact on overall survival (HR 1.23, CI 95% 0.68-2.22, p = 0.493). CONCLUSIONS: The likelihood of encountering a positive margin is associated with lack of neoadjuvant treatment and the presence of lymphatic, vascular, or perineural invasion in the esophagectomy specimen. An involved radial margin after esophagectomy for locally advanced cancer was not associated with tumor recurrence or overall survival in our cohort, and other factors such as lymph node involvement are stronger in determining outcome.

Programmed death ligand 1 and CD8+ immune cell infiltrates in resected primary tracheal malignant neoplasms.

OBJECTIVES: Many patients with primary malignant tracheal neoplasms are not surgical candidates nor do they experience residual or recurrent disease after surgery and may benefit from alternative therapies. This study explores the expression of programmed death ligand 1 (PD-L1) in patients with primary tracheal malignancy as a biomarker for candidacy for treatment with immune checkpoint inhibitors. METHODS: We conducted a retrospective review of the medical records of 23 patients with resected primary tracheal malignant tumours from 2010 to 2016. Paraffin-embedded blocks of tumour tissue were evaluated immunohistochemically to determine the expression of PD-L1 and infiltration by CD8+ immune cells. RESULTS: We identified 14 (61%) adenoid cystic carcinomas, 4 (17%) squamous cell carcinomas (SCC), 4 (17%) mucoepidermoid carcinomas and 1 adenosquamous carcinoma. PD-L1 expression was observed in 3 (75%) cases of SCC and 1 (100%) case of adenosquamous carcinoma, but it was absent in cases of adenoid cystic carcinomas and mucoepidermoid carcinomas. PD-L1 expression was significantly higher in tumours with a SCC component than in salivary-type tumours (P = 0.001). The presence of CD8+ immune cells in the tumour or peritumoural stroma was significantly higher in cases of tracheal tumours with a SCC component than in salivary-type tumours. CONCLUSIONS: Salivary-type primary malignant tracheal tumours do not significantly express PD-L1. In contrast, most primary tracheal tumours with a SCC component show membranous expression of PD-L1 and larger numbers of infiltrating CD8+ immune cells. PD-L1 expression may serve as a biomarker in patients with primary tracheal squamous cell malignant neoplasms when the patients are being considered for alternative treatments and inclusion in clinical trials. IRB APPROVAL: Protocol No. 2017P000415 (22 March 2017).

Prevention and management of complications following tracheal resections-lessons learned at the Massachusetts General Hospital.

Tracheal surgery has developed and evolved over the last 50 years, becoming an integral part of the clinical practice of modern thoracic surgeons. Today, surgeons can safely and effectively operate on most patients suffering from post-intubation tracheal stenosis, tracheal tumors and other pathologies that result in an abnormal shape and function of the central airways. The Massachusetts General Hospital (MGH) in Boston witnessed first-hand the birth and growth of tracheal surgery under Dr. Hermes Grillo, becoming a reference center and accumulating one of the largest institutional experiences in the world. This vast experience of the management of patients with tracheal pathologies has allowed our group at MGH to refine the care of these patients, including their judicious preoperative evaluation, meticulous surgical treatment, and dedicated postoperative care. However, this experience has also provided valuable lessons on the potential complications that can arise after tracheal surgery. Here, we attempt to accumulate our institutional knowledge and experience to provide a summary of the key aspects to prevent complications following tracheal resections. Unfortunately, complications can occur despite strict adherence to the core principles of tracheal surgery, and therefore, we also highlight our institutional experience with the early recognition and management of the most common and dreaded complications.

Extraanatomic Bypass of a Complex Adult Coarctation.

Complex adult coarctations associated with arch hypoplasia and aneurysms require a range of surgical approaches depending upon anatomy. Extraanatomic bypass is an important strategy that enables the surgeon to avoid the risks of extensive dissection/mobilization. Extraanatomic bypass can be accomplished from the ascending to lower descending thoracic aorta via an intrapericardial route lateral to the right atrium and posterior to the inferior vena cava; however, this approach incompletely addresses post-stenotic aneurysmal disease. In the case of complex coarctation with aneurysm, we prefer an alternate approach to exclude the aneurysm, routing the bypass graft anterior to the phrenic nerve to the upper descending thoracic aorta.

Pseudoaneurysm of the left main coronary artery: A complication of orbital atherectomy.

Plaque modification devices are used to treat heavily calcified coronary artery lesions during percutaneous coronary artery interventions. As these devices have unique risk profiles, clinicians need to be aware of potential complications associated with their use. A case of a contained rupture (i.e., pseudoaneurysm) of the proximal left main coronary artery following orbital atherectomy is presented. This lesion was managed with coronary artery bypass grafting and oversewing of the left main coronary artery ostium. This case illustrates that lesion location and configuration may influence tracking of these devices, as well as the actual site of tissue ablation. This case underscores the importance of concurrent imaging during treatment and concern for potential unintended consequences of atherectomy.

Surgical Management of Esophageal Epiphrenic Diverticula: A Transthoracic Approach Over Four Decades.

BACKGROUND: Epiphrenic esophageal diverticula are infrequent. Although surgical treatment is generally recommended, technique varies widely and optimal management remains controversial. This study evaluated a single-institution experience for surgical treatment of epiphrenic diverticula. METHODS: A retrospective review was made of medical records of 31 patients undergoing surgical treatment for epiphrenic diverticula from 1974 to 2016. RESULTS: There were 17 men (55%); median age was 65 years. Dysphagia (87%) and regurgitation (71%) were the most common symptoms. Three patients (10%) presented acutely: 2 with ruptured diverticula and 1 with hematemesis. All patients underwent an open transthoracic approach. Diverticulectomy was performed in 28 patients (90%), myotomy in 28 (90%), and a concomitant antireflux procedure in 6 (19%). A total of 22 patients (71%) underwent diverticulectomy and myotomy, 4 (13%) underwent diverticulectomy with myotomy and antireflux procedure, 2 (6%) had myotomy and antireflux, 2 had diverticulectomy alone, and 1 patient had imbrication of the diverticulum after myotomy. Overall, morbidity occurred in 11 patients (35.5%), with major morbidity in 6 (19.4%). There was one postoperative esophageal leak (3%). Ninety-day mortality was zero. Mean follow-up was 30 ± 43 months in 28 patients. Additional procedures (ie, reoperation, balloon dilation) were needed in 7 patients (25%). An excellent outcome (ie, absence of symptoms) was accomplished in 21 patients (75%). Acute presentation was associated with need for further procedures (p = 0.011) and symptoms at follow-up (p = 0.011). CONCLUSIONS: A tailored transthoracic approach to the surgical management of epiphrenic diverticula can provide excellent results. The need for a concomitant antireflux procedure remains controversial and may not be routinely necessary. Acute presentation is associated with poor functional outcome.

Optimization of a Collagen-Targeted PET Probe for Molecular Imaging of Pulmonary Fibrosis.

There is a large unmet need for a simple, accurate, noninvasive, quantitative, and high-resolution imaging modality to detect lung fibrosis at early stage and to monitor disease progression. Overexpression of collagen is a hallmark of organ fibrosis. Here, we describe the optimization of a collagen-targeted PET probe for staging pulmonary fibrosis. Methods: Six peptides were synthesized, conjugated to a copper chelator, and radiolabeled with 64Cu. The collagen affinity of each probe was measured in a plate-based assay. The pharmacokinetics and metabolic stability of the probes were studied in healthy rats. The capacity of these probes to detect and stage pulmonary fibrosis in vivo was assessed in a mouse model of bleomycin-induced fibrosis using PET imaging. Results: All probes exhibited affinities in the low micromolar range (1.6 µM < Kd < 14.6 µM) and had rapid blood clearance. The probes showed 2- to 8-fold-greater uptake in the lungs of bleomycin-treated mice than sham-treated mice, whereas the distribution in other organs was similar between bleomycin-treated and sham mice. The probe 64Cu-CBP7 showed the highest uptake in fibrotic lungs and the highest target-to-background ratios. The superiority of 64Cu-CBP7 was traced to a much higher metabolic stability compared with the other probes. The specificity of 64Cu-CBP7 for collagen was confirmed by comparison with a nonbinding isomer. Conclusion:64Cu-CBP7 is a promising candidate for in vivo imaging of pulmonary fibrosis.

Type I collagen-targeted PET probe for pulmonary fibrosis detection and staging in preclinical models.

Pulmonary fibrosis is scarring of the lungs that can arise from radiation injury, drug toxicity, environmental or genetic causes, and for unknown reasons [idiopathic pulmonary fibrosis (IPF)]. Overexpression of collagen is a hallmark of organ fibrosis. We describe a peptide-based positron emission tomography (PET) probe (68Ga-CBP8) that targets collagen type I. We evaluated 68Ga-CBP8 in vivo in the bleomycin-induced mouse model of pulmonary fibrosis. 68Ga-CBP8 showed high specificity for pulmonary fibrosis and high target/background ratios in diseased animals. The lung PET signal and lung 68Ga-CBP8 uptake (quantified ex vivo) correlated linearly (r2 = 0.80) with the amount of lung collagen in mice with fibrosis. We further demonstrated that the 68Ga-CBP8 probe could be used to monitor response to treatment in a second mouse model of pulmonary fibrosis associated with vascular leak. Ex vivo analysis of lung tissue from patients with IPF supported the animal findings. These studies indicate that 68Ga-CBP8 is a promising candidate for noninvasive imaging of human pulmonary fibrosis.

Regenerative potential of human airway stem cells in lung epithelial engineering.

Bio-engineered organs for transplantation may ultimately provide a personalized solution for end-stage organ failure, without the risk of rejection. Building upon the process of whole organ perfusion decellularization, we aimed to develop novel, translational methods for the recellularization and regeneration of transplantable lung constructs. We first isolated a proliferative KRT5(+)TP63(+) basal epithelial stem cell population from human lung tissue and demonstrated expansion capacity in conventional 2D culture. We then repopulated acellular rat scaffolds in ex vivo whole organ culture and observed continued cell proliferation, in combination with primary pulmonary endothelial cells. To show clinical scalability, and to test the regenerative capacity of the basal cell population in a human context, we then recellularized and cultured isolated human lung scaffolds under biomimetic conditions. Analysis of the regenerated tissue constructs confirmed cell viability and sustained metabolic activity over 7 days of culture. Tissue analysis revealed extensive recellularization with organized tissue architecture and morphology, and preserved basal epithelial cell phenotype. The recellularized lung constructs displayed dynamic compliance and rudimentary gas exchange capacity. Our results underline the regenerative potential of patient-derived human airway stem cells in lung tissue engineering. We anticipate these advances to have clinically relevant implications for whole lung bioengineering and ex vivo organ repair.