Accepted Manuscript Can We Make Pneumonectomy Great Again? Kenneth A. Kesler, MD PII: S0022-5223(18)31793-8 DOI: 10.1016/j.jtcvs.2018.06.048 Reference: YMTC 13173 To appear in: The Journal of Thoracic and Cardiovascular Surgery Received Date: 15 June 2018 Revised Date: 15 June 2018 Accepted Date: 18 June 2018 Please cite this article as: Kesler KA, Can We Make Pneumonectomy Great Again?, The Journal of Thoracic and Cardiovascular Surgery (2018), doi: 10.1016/j.jtcvs.2018.06.048. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Can We Make Pneumonectomy Great Again? Kenneth A. Kesler MD 1 Indiana University Melvin and Bren Simon Cancer Center, Department of Surgery, Division of Thoracic Surgery (1) The author declares no conflict of interest. There was no external funding source. Corresponding author: Kenneth A. Kesler MD Indiana University Department of Surgery Thoracic Surgery Division Barnhill Drive EM #212 Indianapolis, Indiana 46202 kkesler@iupui.edu
Can We Make Pneumonectomy Great Again? Kenneth A. Kesler MD 1 Indiana University Melvin and Bren Simon Cancer Center, Department of Surgery, Division of Thoracic Surgery (1) The author declares no conflict of interest. There was no external funding source. Corresponding author: Kenneth A. Kesler MD Indiana University Department of Surgery Thoracic Surgery Division Barnhill Drive EM #212 Indianapolis, Indiana 46202 kkesler@iupui.edu
Central Message: Risk factors for postpneumonectomy ARDS and the high ARDS associated mortality have been identified in a large series performed at a center of excellence. Further study is needed to prevent or establish successful treatment strategies for postpneumonectomy ARDS. Central Picture (Kenneth A. Kesler MD)
Since the first pneumonectomy performed by Evarts Graham in 1933, surgeons have for the most part very successfully accomplished pneumonectomy in the treatment of lung neoplasms. And pneumonectomy is a very straightforward technical procedure involving division and closure of just four structures, one main artery and bronchus, and two veins. Data from the National Cancer Database however demonstrate a significant decline in the use of pneumonectomy over the past two decades for locally advanced non-small cell lung cancer (NSCLC), which is a main indication. (1) Although parenchymal sparing bronchoplastic/arterioplastic techniques and CT screening efforts to identify earlier stage disease may play a role in this decline, a reported pneumonectomy mortality of 26% after induction chemoradiation in a prospective multicenter randomized trial has undoubtedly influenced a reluctance to incorporate pneumonectomy into a multimodality treatment strategy for NSCLC. (2) While a recent query of the STS database found the 30-day mortality of pneumonectomies following induction therapy performed by dedicated thoracic surgeons to be at a more acceptable rate of 5.6%, the perception of high mortality remains. (3) Add to this perception, the potential for long-term morbidity, and encouraging improvements in non-surgical therapy for locally advanced NSCLC. (4) Postpneumonectomy pulmonary edema (ARDS) and bronchopleural fistula (BPF) are both dreaded complications following pneumonectomy, which account for the majority of morbidity and mortality. (5,6) Our thoracic surgery community is unfortunately well aware of the potential for precipitous failure of the remaining lung due to a combination of less pulmonary reserve, entirety of cardiac output through one lung, higher pulmonary artery resistance/right heart pressures. Ditto to the awareness of BPF consequences. While risk factors for postpneumonectomy BPF have been extensively studied, similar studies to identify risk factors and outcomes for postpneumonectomy ARDS have been lacking. Bland and coworkers have retrospectively reviewed a remarkable 543 patients undergoing pneumonectomy at their institution over a 10-year interval with a specific focus on patients who developed postoperative ARDS. (7) Their finding of 60 (11%) patients in this series developing postoperative ARDS, which was associated with an overall 56.7% risk of death, is sobering. Equally sobering is the 17.6% long-term survival in ARDS patients. While their findings of right pneumonectomy and higher Charlson Comorbidity Index as independent risk factors for ARDS and additionally that severe ARDS was predictive of mortality does not particularly surprise us, this study represents a solid contribution to our fundamental understanding none-the-less. Besides large patient numbers operated in a thoracic surgery center of excellence, this study has other strengths including maintaining a modern standard of intraoperative and postoperative care including judicious fluid administration and avoidance of high airway pressures. There are however some unanswered questions raised by this report. BPF was identified in 25% of ARDS patients. Perhaps an early BPF resulted in internal aspiration and was actually responsible for the ARDS in some cases rather than a
sequella? At the very least, their data confirms prolonged mechanical ventilation remains a significant risk factor for BPF. The incidence of atrial tackyarrhythmias, which are commonly observed after pneumonectomy, is not provided. There seems to be at least potential for these arrhythmias to be a confounding if not a frankly contributing factor in the development of ARDS. After a rapid decline in survival following surgery in ARDS patients, long-term survival curves comparing non-ards and ARDS patients seem to mirror one another. Without stage specific etiologies of late deaths being provided, it appears plausible that survivors of postpneumonectomy ARDS may actually have long-term survival not too dissimilar to non-ards patients. Finally, this study does not seem to provide significant insight into strategies, which might prove successful for this life threatening complication. For example, both inhaled nitrous oxide and extracorporeal membrane oxygenation were more frequently applied in non-survivors of ARDS as compared to survivors. Were these interventions utilized too late in the course of ARDS as a last ditch effort and therefore doomed to failure, somehow used in the wrong patient subsets, or simply not effective? This may be worthy of further investigation along with other types of pulmonary vasodilator/inotropic therapy. The ever-evolving technology of extracorporeal oxygenation might also hold promise. More simple measures potentially deserving of consideration include temporary tracheostomy tube placement at the time of surgery for higher risk patients to lessen the work of breathing, facilitate secretion removal, and allow as needed intermittent positive pressure support without sedation and reintubation. Unless durable alternative treatments can be established, to date, surgery remains the mainstay of successful therapy for NSCLC. The relatively high morbidity and mortality of entire lung removal and encouraging outcomes of non-surgical therapy have however, lead to a trend where pneumonectomy is avoided. Development of surgical techniques to minimize the risk of BPF would seem worthy of study. Improving outcomes following pneumonectomy to reduce the incidence or successfully manage postoperative ARDS might be a daunting task. Who knows. Regardless, this is probably worth the effort.
References 1. Hancock J, Rosen J, Moreno A, et al. Management of Clinical Stage IIIA Primary Lung Cancers in the National Cancer Database. Ann Thorac Surg 2014;98:424-32. 2. Albain KS, Swann RS, Rusch VW, et al. Radiotherapy Plus Chemotherapy With or Without Surgical Resection for Stage III Non-Small-Cell Lung Cancer: A Phase III Randomized Controlled Trial. Lancet 2009;374:379-86. 3. Boffa D, Fernandez FG, Kim S, et al. Surgically Managed Clinical Stage IIIA- Clinical N2 Lung Cancer in the Society of Thoracic Surgeons Database. Ann Thorac Surg 2017;104:395-403. 4. Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after Chemotherapy in Stage III Non-Small-Cell Lung Cancer. N Eng J Med 2017;377:1919-29 5. Darling GE, Abdurahman A, Yi QL, et al. Risk of right pneumonectomy: role of bronchopleural fistula. Ann Thorac Surg 2005;79:433-7. 6. Alvarez JM, Ranjit PK, Newman MA, et al. Postpneumonectomy Pulmonary Edema. J Cardiothorac and Vasc Anesthesia 2003;17:388-95. 7. Bland K, Zaimi R, Dechartres A, et al. Early ARDS After Pneumonectomy: Presentation, Management, and Short and Long-Term Outcomes. J Thorac and Cardiovasc Surg 2018;XXX:XXX-XXX.