The rarity of thymic epithelial tumors and absence of targetable alterations present significant challenges for identifying improved systemic therapies. Recent advances in single-cell sequencing have enhanced our understanding of normal thymus development and the factors underlying malignant transformation. During medullary epithelial differentiation in adulthood, anti-apoptotic factors are expressed, potentially increasing resistance to cell death and thus facilitating tumorigenic processes. We hypothesized that this resistance to apoptotic cell death might be a hallmark of thymic epithelial tumorigenesis and could generate therapeutic vulnerabilities. To investigate this possibility, we measured apoptotic priming and dependencies on anti-apoptotic proteins in metastatic, surgically-resected thymic epithelial tumors. We utilize dynamic BH3 profiling, a functional assay that detects induction of apoptosis in response to titrated doses of pro-apoptotic signals in viable cancer cells freshly isolated from resection specimens. Our interim results show that advanced, WHO B-subtype thymomas are highly primed for apoptotic cell death, even in chemotherapy-resistant tumors, supporting the notion that thymomas may be more radiosensitive than chemosensitive. Furthermore, we find that thymomas consistently exhibit dependence on anti-apoptotic proteins, which may be targeted by recently-developed BH3 mimetics that inhibit these proteins. Apoptotic priming and dependencies are further enhanced by co-treated with clinically-relevant, targeted anti-cancer agents. To understand the basis for these findings, we evaluate the role of apoptotic priming during normal thymic epithelial development to determine how apoptotic resistance aligns with other molecular features of medullary epithelial biology, including the transcription of non-thymic tissue antigens and DNA damage response. These findings have significant therapeutic implications for further clinical investigation and deepen the foundational knowledge of molecular factors contributing to tumorigenesis, revealing new opportunities for preclinical modeling. Citation Format: Christopher Nabel, Yin P. Hung, Brian Do, Xingping Qin, Cameron Fraser, Yolonda Colson, Michael Lanuti, Uma Sachdeva, Cameron Wright, Kris Sarosiek. Assessment of apoptotic priming in thymic epithelial tumors to define hallmarks of pathogenesis and novel therapeutic strategies [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr B015.

Objective Few studies have evaluated postoperative recovery of patients after thoracic surgery using patient-reported outcome measures. This multi-institutional study analyzed postoperative pain and opioid use among patients undergoing thoracic surgery based on patient-reported outcome measures data collected through an electronic symptom management system. Methods The electronic symptom management system is a multi-symptom questionnaire based on a Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events that is integrated into the electronic health record and administered via the patient portal. Patients undergoing lung resections were invited to complete electronic symptom surveys within the electronic symptom management system during their 90-day postoperative period. Baseline patient demographics, surgical data, and postoperative opioid data were gathered from the electronic health record. Multivariable hierarchical regression was used to evaluate predictors of postoperative pain and opioid prescriptions. Results Of 680 patients who met the inclusion criteria, 258 (37.9%) reported at least 1 severe pain score. Patients reporting severe pain were more likely to have undergone open surgery, to receive at least 1 postoperative opioid prescription, and to become persistent opioid users compared with patients reporting no severe pain. In multivariable logistic regression analysis, the only factor associated with a severe pain score was female sex (odds ratio, 1.67, 95% CI, 1.17-2.39; P = .005). Conclusions This multicenter study used patient-reported outcome measures to evaluate predictors of postoperative pain and opioid prescriptions in patients undergoing thoracic surgery. Further investigation into the administration of patient-reported outcome measures is needed to assess their ability to impact postsurgical care and postoperative outcomes.

OBJECTIVE:To evaluate differences in patient-reported quality of life after lobectomy versus sublobar resection. METHODS:This was a retrospective analysis of patients enrolled in a prospective trial evaluating recovery after thoracic surgery using wearable devices and patient-reported outcome measures. Patients who underwent elective lobectomy or sublobar resection were included. Patients wore a wearable device preoperatively to postoperative day 90 and completed the 36-Item Short Form Survey (SF-36) preoperatively and on postoperative days 30 and 90. SF-36 total, Physical Component Summary (PCS), and Mental Component Summary (MCS) scores at each timepoint were compared between patients who underwent lobectomy and those who underwent sublobar resection in both the overall cohort and a propensity score-matched cohort. Changes in SF-36 scores from baseline to postoperative day 30 and day 90 were compared in the lobectomy and sublobar resection groups using multivariable-adjusted linear regression models. RESULTS:A total of 30 patients undergoing lobectomy and 55 undergoing sublobar resection were included. In both groups, overall quality of life was significantly lower at 30 days postoperatively compared to preoperatively but recovered to baseline levels by 90 days postoperatively. There were no significant differences in quality-of-life scores preoperatively and at 30 days and 90 days postoperatively between the 2 groups in unadjusted analysis or propensity score-matched analysis. There were also no statistically significant differences in changes in the SF-36, PCS, or MCS scores from baseline to postoperative day 30 and 90 between the 2 groups. CONCLUSIONS:In this retrospective analysis, patients undergoing lobectomy and those undergoing sublobar resection reported similar changes in quality of life after surgery.

Objective The makeup of the thoracic surgical workforce can influence policy, training, and certification, but it is not well defined. Using data from the American Board of Thoracic Surgery, this study explored practice-based demographics concerning geography, gender, age, subspecialty, and university affiliation. Methods American Board of Thoracic Surgery Diplomates taking the 10-year Maintenance of Certification examination opted for the cardiac, general thoracic, cardiothoracic, or congenital modular exam. Using module selection as a surrogate for the examinee's predominant clinical practice, we explored the relationship regarding type of practice, geography (metropolitan vs other), gender, age, and university affiliation. Results A total of 2273 American Board of Thoracic Surgery Diplomates took the Maintenance of Certification exam from 2018 to 2024. Adult cardiac surgery was the predominant subspecialty (46%), followed by cardiothoracic (24%), general thoracic (22%), and congenital surgery (8%). Significant gender disparity persisted, with women constituting 7% of certified Diplomates and 5% of adult cardiac surgeons. Mean ages ranged from 58.0 years (general thoracic) to 63.3 years (cardiothoracic), with younger surgeons trending toward specialized practices (cardiac P = .01, congenital P = .04). Most surgeons practiced in metropolitan areas (80%), particularly congenital surgeons (96%). Surgeons practicing in university (47%) and nonuniversity settings (53%) were nearly evenly distributed. Conclusions Thoracic surgery is increasingly subspecializing, with younger surgeons choosing cardiac, general thoracic, or congenital surgery modular Maintenance of Certification exams. The percentage of female Diplomates remains low. Maintenance of Certification exam-eligible diplomates constitute a predominantly older workforce with noticeable urbanization. Understanding our workforce provides important insight for American Board of Thoracic Surgery certification, the development of training paradigms, and anticipating workforce needs.

OBJECTIVE:To evaluate whether a machine-learning algorithm (ie, the "NightSignal" algorithm) can be used for the detection of postoperative complications before symptom onset after cardiothoracic surgery. BACKGROUND:Methods that enable the early detection of postoperative complications after cardiothoracic surgery are needed. METHODS:This was a prospective observational cohort study conducted from July 2021 to February 2023 at a single academic tertiary care hospital. Patients aged 18 years or older scheduled to undergo cardiothoracic surgery were recruited. Study participants wore a Fitbit watch continuously for at least 1 week preoperatively and up to 90 days postoperatively. The ability of the NightSignal algorithm-which was previously developed for the early detection of Covid-19-to detect postoperative complications was evaluated. The primary outcomes were algorithm sensitivity and specificity for postoperative event detection. RESULTS:A total of 56 patients undergoing cardiothoracic surgery met the inclusion criteria, of which 24 (42.9%) underwent thoracic operations and 32 (57.1%) underwent cardiac operations. The median age was 62 (Interquartile range: 51-68) years and 30 (53.6%) patients were female. The NightSignal algorithm detected 17 of the 21 postoperative events at a median of 2 (Interquartile range: 1-3) days before symptom onset, representing a sensitivity of 81%. The specificity, negative predictive value, and positive predictive value of the algorithm for the detection of postoperative events were 75%, 97%, and 28%, respectively. CONCLUSIONS:Machine-learning analysis of biometric data collected from wearable devices has the potential to detect postoperative complications-before symptom onset-after cardiothoracic surgery.

The role of immunosenescence, particularly the natural process of thymic involution during aging, is increasingly acknowledged as a factor contributing to the development of autoimmune diseases and cancer. Recently, a concern has been raised about deleterious consequences of the surgical removal of thymic tissue, including for patients who undergo thymectomy for myasthenia gravis (MG) or resection of a thymoma. This review adopts a multidisciplinary approach to scrutinize the evidence concerning the long-term risks of cancer and autoimmunity postthymectomy. We conclude that for patients with acetylcholine receptor antibody-positive MG and those diagnosed with thymoma, the removal of the thymus offers prominent benefits that well outweigh the potential risks. However, incidental removal of thymic tissue during other thoracic surgeries should be minimized whenever feasible.

Background The role of tyrosine kinase inhibitors (TKIs) in early-stage and metastatic oncogene-driven non-small cell lung cancer (NSCLC) is established, but it remains unknown how best to integrate TKIs with concurrent chemoradiotherapy (cCRT) in locally advanced disease. The phase 2 ASCENT trial assessed the efficacy and safety of afatinib and cCRT with or without surgery in locally advanced epidermal growth factor receptor (EGFR)-mutant NSCLC.Patients and Methods Adults >= 18 years with histologically confirmed stage III (AJCC 7th edition) NSCLC with activating EGFR mutations were enrolled at Mass General and Dana-Farber/Brigham Cancer Centers, Boston, Massachusetts. Patients received induction afatinib 40 mg daily for 2 months, then cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 IV every 3 weeks during RT (definitive or neoadjuvant dosing). Patients with resectable disease underwent surgery. All patients were offered consolidation afatinib for 2 years. The primary endpoint was the objective response rate (ORR) to induction TKI. Secondary endpoints were safety, conversion to operability, progression-free survival (PFS), and overall survival (OS). Analyses were performed on the intention-to-treat population.Results Nineteen patients (median age 56 years; 74% female) were enrolled. ORR to induction afatinib was 63%. Seventeen patients received cCRT; 2/9 previously unresectable became resectable. Ten underwent surgery; 6 had a major or complete pathological response. Thirteen received consolidation afatinib. With a median follow-up of 5.0 years, median PFS and OS were 2.6 (95% CI, 1.4-3.1) and 5.8 years (2.9-NR), respectively. Sixteen recurred or died; 6 recurrences were isolated to CNS. The median time to progression after stopping consolidation TKI was 2.9 months (95% CI, 1.1-7.2). Four developed grade 2 pneumonitis. There were no treatment-related deaths.Conclusion We explored the efficacy of combining TKI with cCRT in oncogene-driven NSCLC. Induction TKI did not compromise subsequent receipt of multimodality therapy. PFS was promising, but the prevalence of CNS-only recurrences and rapid progression after TKI discontinuation speak to unmet needs in measuring and eradicating micrometastatic disease. The phase 2 ASCENT trial assessed the efficacy and safety of afatinib and concurrent chemoradiotherapy with or without surgery in locally advanced epidermal growth factor receptor-mutant non-small cell lung cancer.

Rationale: Idiopathic pulmonary fibrosis (IPF) affects the subpleural lung but is considered to spare small airways. Micro-computed tomography (micro-CT) studies demonstrated small airway reduction in end-stage IPF explanted lungs, raising questions about small airway involvement in early-stage disease. Endobronchial optical coherence tomography (EB-OCT) is a volumetric imaging modality that detects microscopic features from subpleural to proximal airways. Objectives: In this study, EB-OCT was used to evaluate small airways in early IPF and control subjects in vivo. Methods: EB-OCT was performed in 12 subjects with IPF and 5 control subjects (matched by age, sex, smoking history, height, and body mass index). Subjects with IPF had early disease with mild restriction (FVC: 83.5% predicted), which was diagnosed per current guidelines and confirmed by surgical biopsy. EB-OCT volumetric imaging was acquired bronchoscopically in multiple, distinct, bilateral lung locations (total: 97 sites). IPF imaging sites were classified by severity into affected (all criteria for usual interstitial pneumonia present) and less affected (some but not all criteria for usual interstitial pneumonia present). Bronchiole count and small airway stereology metrics were measured for each EB-OCT imaging site. Measurements and Main Results: Compared with the number of bronchioles in control subjects (mean = 11.2/cm3; SD = 6.2), there was significant bronchiole reduction in subjects with IPF (42% loss; mean = 6.5/cm3; SD = 3.4; P = 0.0039), including in IPF affected (48% loss; mean: 5.8/cm3; SD: 2.8; P < 0.00001) and IPF less affected (33% loss; mean: 7.5/cm3; SD: 4.1; P = 0.024) sites. Stereology metrics showed that IPF-affected small airways were significantly larger, more distorted, and more irregular than in IPF-less affected sites and control subjects. IPF less affected and control airways were statistically indistinguishable for all stereology parameters (P = 0.36-1.0). Conclusions: EB-OCT demonstrated marked bronchiolar loss in early IPF (between 30% and 50%), even in areas minimally affected by disease, compared with matched control subjects. These findings support small airway disease as a feature of early IPF, providing novel insight into pathogenesis and potential therapeutic targets.

e20624 Background: The rarity of thymic epithelial tumors has limited mechanistic understanding of tumor biology and the rational identification of potential therapeutic targets for patients with advanced disease. While the Cancer Genome Atlas Project enabled multi-omic profiling of thymic epithelial tumors, the majority of samples were early-stage and chemotherapy-naïve. Furthermore, next generation sequencing for patients with advanced disease often provides only a limited breadth of genome coverage. The genetic changes in thymic epithelial tumors that evolve through disease progression and treatment represent a current knowledge gap and opportunity for reassessment of new therapeutic targets. Methods: To address these points, we conducted whole exome and bulk RNA transcriptome sequencing for serially-collected FFPE archival tumor samples from a patient with Stage IVA, WHO B2/B3 thymoma using the BostonGene Tumor Portrait Test version 1.3. Samples analyzed include the initial primary tumor resected without induction treatment; two subsequent, metachronous pleural recurrences resected without any induction treatment; and a third pleural metastasis resected following two cycles of induction chemotherapy with Cisplatin/Adriamycin/Cyclophosphamide without interval radiographic evidence of treatment response. Results: Tumor characteristics were largely consistent with prior molecular studies, and without significant evidence of major clonal evolutionary changes based on single nucleotide polymorphisms, insertions/deletions or copy number alterations. Tumor mutational burden was recurrently low (< 1 mutation per megabase) with stable microsatellite status. EGFR copy number gain was observed (+1 copy) across recurrent pleural resection specimens. While the degree of copy number gain did not change with disease progression, increasing EGFR transcript counts were observed and evaluated by IHC. Other notable therapeutic biomarkers included absent TGFB1 and present VEGFA expression. Collective RNA-based gene expression changes were compared with the Thymic TCGA cohort for reference. Conclusions: Our analysis illustrates the narrow clonal evolution of a thymic epithelial tumor through treatment—both with and without the selective pressures of induction chemotherapy. This suggests that the genomic features of advanced thymoma may reflect the treatment-naïve state as described in the TCGA, one marked by a low mutational burden but with recurrent copy number alterations in select genes. Complementary transcriptome sequencing identified EGFR expression as a promising therapeutic target for further study. Taken together, these findings illustrate the hypothesis-generating potential for deep molecular analysis with whole exome and transcriptome sequencing to improve the understanding of rare tumors.

Background:The propensity of thymic cysts to mimic solid thymic epithelial tumors (TETs) on computed tomography (CT), on account of attenuation values greater than water and thickened or calcified walls, can lead to non-therapeutic thymectomy. These lesions can fluctuate in volume, CT attenuation, and magnetic resonance imaging (MRI) signal over time. We hypothesized that spontaneous hemorrhage and resorption may contribute to their variable appearance over time.Methods:Completely excised thymic cysts were identified retrospectively over a 20-year period by their pathologic diagnosis. Cysts were excluded if they did not have available presurgical imaging, were not prevascular, were located within or contained an enhancing mass by imaging, or were of non-thymic origin upon microscopic review. Histopathological analysis of all available resected thymic cyst material and radiologic analysis of the cysts on pre-operative imaging were performed.Results:Upon application of exclusion criteria, we identified 18 thymic cysts from the initial 85 mediastinal cystic specimens. Most cysts were unilocular (11/15, 73%), showed turbid-to-semisolid, hemorrhagic fluid (10/12, 83%) and showed histopathological findings suggestive of intralesional microbleeding (14/18, 78%), remodeling (8/18, 44%), pathological wound healing/scarring of the capsule (16/18, 89%), and fat necrosis in the surrounding thymic tissue (12/18, 67%). On CT, 6/17 (35%) cysts demonstrated wall calcification. Sixty-five percent (11/17) had attenuation values ≥20 Hounsfield units (HU). Two of the 4 cysts imaged by MRI were T1-isointense, one was mixed hyper- and isointense, and one T1-hypointense to muscle, with iso- and hyperintensity indicating hemorrhagic or proteinaceous content. Twenty-five percent (1/4) of cyst walls imaged by MRI were T1/T2-hypointense, indicating presence of calcification, hemosiderin, and/or fibrosis.Conclusions:Resected thymic cysts in this cohort often showed features suggestive of intralesional microbleeding, inflammation, and fibrosis, which may explain their appearance and behavior over time on CT and MRI.

In this issue of The Annals of Thoracic Surgery, Zhao and colleagues 1 Zhao Z.R. Lin Z.C. Shen J.F. Xie Z.H. Jiang L. Neoadjuvant immunotherapy in oncogene-positive non–small cell lung cancer: a multicenter study. Ann Thorac Surg. 2023; 116: 703-711 Abstract Full Text Full Text PDF Google Scholar report a retrospective series of locally advanced lung cancers treated with neoadjuvant immunotherapy and investigate the role of positive oncogenes on major pathologic response. The patient population is unusual for the United States, in that 67% of the patients had squamous histology. There were 137 patients, and most (83%) were at stage IIIA/B. Approximately one-half of patients had invasive mediastinal staging. Most patients received combination immunotherapy and chemotherapy, although the regimens were not standardized. Many patients had only 1 or 2 cycles of neoadjuvant therapy. Almost all patients had a complete resection, after which there were no unusual surgical complications, and the perioperative surgical outcomes were excellent. Neoadjuvant Immunotherapy in Oncogene-Positive Non-Small Cell Lung Cancer: A Multicenter StudyThe Annals of Thoracic SurgeryVol. 116Issue 4PreviewPreoperative immunotherapy has shed light on the management of resectable non-small cell lung cancer (NSCLC). However, whether neoadjuvant immunotherapy benefits patients with oncogene-positive NSCLC remains unknown. Full-Text PDF

Lung cancer is the leading cause of cancer-related deaths worldwide. Surgery and chemoradiation are the standard of care in early stages of non-small cell lung cancer (NSCLC), while immunotherapy is the standard of care in late-stage NSCLC. The immune composition of the tumor microenvironment (TME) is recognized as an indicator for responsiveness to immunotherapy, although much remains unknown about its role in responsiveness to surgery or chemoradiation. In this pilot study, we characterized the NSCLC TME using mass cytometry (CyTOF) and bulk RNA sequencing (RNA-Seq) with deconvolution of RNA-Seq being performed by Kassandra, a recently published deconvolution tool. Stratification of patients based on the intratumoral abundance of B cells identified that the B-cell rich patient group had increased expression of CXCL13 and greater abundance of PD1(+) CD8 T cells. The presence of B cells and PD1(+) CD8 T cells correlated positively with the presence of intratumoral tertiary lymphoid structures (TLS). We then assessed the predictive and prognostic utility of these cell types and TLS within publicly available stage 3 and 4 lung adenocarcinoma (LUAD) RNA-Seq datasets. As previously described by others, pre-treatment expression of intratumoral 12-chemokine TLS gene signature is associated with progression free survival (PFS) in patients who receive treatment with immune checkpoint inhibitors (ICI). Notably and unexpectedly pre-treatment percentages of intratumoral B cells are associated with PFS in patients who receive surgery, chemotherapy, or radiation. Further studies to confirm these findings would allow for more effective patient selection for both ICI and non-ICI treatments.

Supplementary Figure 1-5, Supplementary Tables 1-3

2017;5:691–706. 8. Cantero C, Adler D, Pasquina P, Uldry C, Egger B, Prella M, et al. Longterm noninvasive ventilation in the Geneva Lake area: indications, prevalence, and modalities. Chest 2020;158:279–291. 9. Garner DJ, Berlowitz DJ, Douglas J, Harkness N, Howard M, McArdle N, et al. Home mechanical ventilation in Australia and New Zealand. Eur Respir J 2013;41:39–45. 10. Borel J-C, Guerber F, Jullian-Desayes I, Joyeux-Faure M, Arnol N, Taleux N, et al. Prevalence of obesity hypoventilation syndrome in ambulatory obese patients attending pathology laboratories. Respirology 2017;22:1190–1198.

Central MessageThe early results of PEA in segmental CTEPH are essentially equivalent to more proximal disease, but at 10 years many segmental patients require medical therapy for residual pulmonary hypertension.See Article page 696. The early results of PEA in segmental CTEPH are essentially equivalent to more proximal disease, but at 10 years many segmental patients require medical therapy for residual pulmonary hypertension. See Article page 696. De Perrot and colleagues1de Perrot M. Donahoe L. McRae K. Thenganatt J. Moric J. Chan J. et al.Outcome after pulmonary endarterectomy for segmental chronic thromboembolic pulmonary hypertension.J Thorac Cardiovasc Surg. 2022; 164: 696-707.e4Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar report a large series of pulmonary endarterectomies (PEAs), emphasizing the excellent results that were achieved in patients with segmental disease (2.8% operative mortality). Patients with segmental disease are technically more challenging (note the longer circulatory arrest times, intensive care unit stay, and hospital stay), but despite the surgical challenge the results were essentially the same as those with more proximal disease. The reason why segmental disease rose from 7% to 41% in their last cohort is not discussed, but I postulate that this was due to an increased surgical confidence in tackling more difficult patients. Their center is a high-volume center of excellence with a nationwide referral pattern that represents the ideal paradigm to treat this complex disease. That preoperative medical therapy is a risk factor for a worse result in segmental disease is intriguing and has important clinical implications. I agree with their recommendation that prompt referral to an experienced chronic thromboembolic pulmonary hypertension (CTEPH) center once the diagnosis is suspected or confirmed before initiation of medical therapy is prudent. An early decision favoring an operative approach may obviate the development of distal vasculopathy and the need for later medical therapy. This concept is opposite that of the current balloon pulmonary angioplasty (BPA) paradigm where many now favor medical therapy to reduce pulmonary artery pressure in patients with high pulmonary artery pressure to reduce procedure-related complications. Of particular importance in this study is the long-term follow-up facilitated by the close collaboration with referring physicians. It is challenging to obtain long-term clinical follow-up in CTEPH patients because they typically are referred from distant centers and communication is lost. The 79% 10-year overall survival is impressive, and the need for medical therapy at 10 years in the segmental patients of 38% is new, important information and clearly defines these patients requiring close observation. There remain many unresolved issues regarding the evaluation of CTEPH, and the decision regarding the optimal therapy, including imaging (the Toronto group now relies on the computed tomography pulmonary angiogram and not the pulmonary angiogram), the assessment of distal vasculopathy (currently approximated by a PAP out of proportion to the imaging), and the role of BPA versus PEA in segmental disease. The somewhat artificial delineation of CTEPH disease found at PEA into 4 subtypes, with distal disease divided into 3 and 4 is perhaps too complicated and does not mirror the intraoperative findings in my opinion. Main pulmonary artery disease is rare and lobar disease is relatively common and both are easy to diagnose on imaging. Distal disease is almost always a continuum and telling precisely where it starts, and especially where it stops is difficult and can be different in each segmental vessel. Interpreting imaging studies is also more challenging in distal patients. What is clear is that patients with segmental disease require more surgical expertise, but can greatly benefit from PEA. Outcome after pulmonary endarterectomy for segmental chronic thromboembolic pulmonary hypertensionThe Journal of Thoracic and Cardiovascular SurgeryVol. 164Issue 3PreviewDetermine the long-term outcome and need for additional therapy after pulmonary endarterectomy (PEA) for segmental chronic thromboembolic pulmonary hypertension. Full-Text PDF

1. Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, et al.; American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society. Diagnosis of idiopathic pulmonary fibrosis: an official ATS/ERS/JRS/ ALAT clinical practice guideline. Am J Respir Crit Care Med 2018;198: e44–e68. 2. Ravaglia C, Bonifazi M, Wells AU, Tomassetti S, Gurioli C, Piciucchi S, et al. Safety and diagnostic yield of transbronchial lung cryobiopsy in diffuse parenchymal lung diseases: a comparative study versus video-assisted thoracoscopic lung biopsy and a systematic review of the literature. Respiration 2016;91:215–227. 3. Nandy S, Raphaely RA, Muniappan A, Shih A, Roop BW, Sharma A, et al. Diagnostic accuracy of endobronchial optical coherence tomography for the microscopic diagnosis of usual interstitial pneumonia. Am J Respir Crit Care Med 2021;204:1164–1179. 4. Wijmans L, de Bruin D, Jonkers R, Roelofs J, van den Berk I, Bonta P, et al. Visualizing the alveolar compartment in ILD patients by optical coherence tomography [abstract]. Eur Respir J 2017;50:OA1467. 5. Vaselli M, Wijsman PC, Willemse J, Goorsenberg AWM, Feroldi F, d’Hooghe JNS, et al. Polarization sensitive optical coherence tomography for bronchoscopic airway smooth muscle detection in bronchial thermoplasty-treated patients with asthma. Chest 2021;160:432–435. 6. Vaselli M, Mooij-Kalverda KA, Bonta P, De Boer J, Annema J. In vivo PS-OCT to detect fibrotic lung disease [abstract]. Eur Respir J 2021;58:OA234.

The growing stature of minimally invasive approaches to esophageal diseases does not diminish the importance of the equivalent open approaches. This chapter describes common open operations performed to excise Zenker diverticulum, to manage complex gastroesophageal reflux disease, and to resect esophageal and proximal gastric tumors. For each of these open procedures, the preoperative evaluation, operative planning, steps of the operative techniques, postoperative care, complications, and outcome evaluation are described. Over two dozen figures show many of the operative steps for a cricopharyngeal myotomy and excision of Zenker diverticulum, a transthoracic hiatal hernia repair, a transhiatal esophagectomy, Ivor-Lewis esophagectomy, and a left thoracoabdominal esophagogastrectomy. This review contains 27 figures, 21 tables, 14 references Keywords: Zenker diverticulum, esophageal cancer, gastroesophageal reflux disease, gastric tumor, cricopharyngeal myotomy, transthoracic hiatal hernia repair, transhiatal esophagectomy, Ivor-Lewis esophagectomy, left thoracoabdominal esophagogastrectomy

BACKGROUND:Esophageal perforation is a morbid condition and remains a therapeutic challenge. We report the outcomes of a large institutional experience with esophageal perforation and identify risk factors for morbidity and mortality.METHODS:A retrospective analysis was conducted on 142 patients who presented with a thoracic or gastroesophageal junction esophageal perforation from 1995 to 2020. Baseline characteristics, operative or interventional strategies, and outcomes were analyzed by etiology of the perforation and management approach. Multivariable cox and logistic regression models were constructed to identify predictors of mortality and morbidity.RESULTS:Overall, 109 (77%) patients underwent operative intervention, including 80 primary reinforced repairs and 21 esophagectomies and 33 (23%) underwent esophageal stenting. Stenting was more common in iatrogenic (27%) and malignant (64%) perforations. Patients who presented with a postemetic or iatrogenic perforation had similar 90-day mortality (16% and 16%) and composite morbidity (51% and 45%), whereas patients who presented with a malignant perforation had a 45% 90-day mortality and 45% composite morbidity. Risk factors for mortality included age >65 years (hazard ratio [HR] 1.89 [1.02-3.26], P = 0.044) and a malignant perforation (HR 4.80 [1.31-17.48], P = 0.017). Risk factors for composite morbidity included pleural contamination (odds ratio [OR] 2.06 [1.39-4.43], P = 0.046) and sepsis (OR 3.26 [1.44-7.36], P = 0.005). Of the 33 patients who underwent stent placement, 67% were successfully managed with stenting alone and 30% required stent repositioning.CONCLUSIONS:Risk factors for morbidity and mortality after esophageal perforation include advanced age, pleural contamination, septic physiology, and malignant perforation. Primary reinforced repair remains a reasonable strategy for patients with an esophageal perforation from a benign etiology.