Safety and Feasibility of Thoracic Malignancy Surgery During the COVID-19 Pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has decreased surgical activity, particularly in the field of oncology, because of the suspicion of a higher risk of COVID-19-related severe events. This study aimed to investigate the feasibility and safety of thoracic cancer surgery in the most severely affected European and Canadian regions during the COVID-19 pandemic. METHODS: The study investigators prospectively collected data on surgical procedures for malignant thoracic diseases from January 1 to April 30, 2020. The study included patients from 6 high-volume thoracic surgery departments: Nancy and Strasbourg (France), Freiburg (Germany), Milan and Turin (Italy), and Montreal (Canada). The centers involved in this research are all located in the most severely affected regions of those countries. An assessment of COVID-19-related symptoms, polymerase chain reaction (PCR)-confirmed COVID-19 infection, rates of hospital and intensive care unit admissions, and death was performed for each patient. Every deceased patient was tested for COVID-19 by PCR. RESULTS: In the study period, 731 patients who underwent 734 surgical procedures were included. In the whole cohort, 9 cases (1.2%) of COVID-19 were confirmed by PCR, including 5 in-hospital contaminants. Four patients (0.5%) needed readmission for oxygen requirements. In this subgroup, 2 patients (0.3%) needed intensive care unit and mechanical ventilatory support. The total number of deaths in the whole cohort was 22 (3%). A single death was related to COVID-19 (0.14%). CONCLUSIONS: Maintaining surgical oncologic activity in the era of the COVID-19 pandemic seems safe and feasible, with very low postoperative morbidity or mortality. To continue to offer the best care to patients who do not have COVID-19, reports on other diseases are urgently needed.

Bilateral Lobar Transplants Using One Donor for Two Small-Sized Recipients.

Cadaveric lobar lung transplantation is an alternative for patients whose chest cavities have small dimensions. We present here a case where 1 donor was used for bilateral lobar transplantations in 2 high-risk patients. Coordination between the graft preparation at the back table and the 2 concomitant lung transplant teams was necessary to minimize the ischemic injury of the grafts and to plan for adequate vascular and bronchial cuffs for both implantations.

Organized Management of Diabetes Mellitus in Lung Transplantation: Study of Glycemic Control and Patient Survival in a Single Center.

OBJECTIVE: To study patient survival and glycemic control before and after lung transplantation (LTx) according to the diabetes status in patients submitted to an organized management of diabetes mellitus (DM) at the Strasbourg University Hospital, France. MATERIAL AND METHODS: Two hundred and sixty-seven LTx recipients were included retrospectively and analyzed according to diabetes status: pretransplant diabetes, new-onset diabetes mellitus after transplant (NODAT) or no diabetes. Organized DM management was coordinated by a diabetologist trained in DM management before and after transplantation and included pretransplant screening, a close monitoring of glycemia after transplant and optimized treatment before and after LTx. RESULTS: DM was well-controlled after transplantation: mean glycosylated hemoglobin and fasting blood glucose levels after LTx were 5.8 ± 0.2% and 5.4 ± 0.1 mmol/L respectively, in pretransplant DM patients and 5.7 ± 0.1% and 5.6 ± 0.2 mmol/L respectively, in NODAT patients. The overall median survival time was 8.3 ± 1.9 years. Pretransplant DM increased the risk of mortality (1.82-fold increase; 95% confidence interval, 1.08-3.06; P = .02) in LTx recipients. CONCLUSIONS: Organized management of diabetes achieved very satisfactory glycemic control in both pretransplant DM and NODAT patients. However, no specific protocols have been created for managing DM following LTx. As DM continues to become an increasing comorbidity in LTx, there exist a significant need of studies in this area.

KRAS-specific Amino Acid Substitutions are Associated With Different Responses to Chemotherapy in Advanced Non-small-cell Lung Cancer.

BACKGROUND: Emerging data highlight different clinical behaviors according to KRAS amino acid substitutions (AASs) in patients with non-small-cell lung cancer (NSCLC). We aimed to evaluate whether different KRAS AASs were associated with different responses to chemotherapy. PATIENTS AND METHODS: We retrospectively reviewed data from 1190 patients with KRAS mutations who underwent first-line platinum-based chemotherapy for stage IV NSCLC. The response to different chemotherapy regimens was evaluated using the Response Evaluation Criteria In Solid Tumors criteria (v 1.1). Overall survival and time to progression (TTP) were secondary endpoints. RESULTS: Taxane was associated with the best response in the entire cohort (odds ratio, 2.52; 95% confidence interval [CI], 1.82-3.48; P < .001), especially in G12V patients (odds ratio, 2.15; 95% CI, 1.05-4.41; P = .036). Taxane was associated with improved TTP in the entire cohort (hazard ratio [HR], 0.31; 95% CI, 0.26-0.38; P < .001), especially in G13D patients (HR, 0.47; 95% CI, 0.22-1.01; P = .054). Pemetrexed was associated with the worst TTP in the entire cohort, particularly in G12V patients, who had the worst response rates (HR, 0.55; 95% CI, 0.30-0.99; P = .049). No impact on overall survival was observed according to different chemotherapy regimens and AASs. CONCLUSION: KRAS-specific AAS appears to induce different responses to chemotherapy regimens after first-line platinum-based chemotherapy in advanced NSCLC.

Prognostic Value of Exon 19 Versus 21 EGFR Mutations Varies According to Disease Stage in Surgically Resected Non-small Cell Lung Cancer Adenocarcinoma.

BACKGROUND: The prognostic value of exon 19 and 21 EGFR mutations in stage IV non-small cell lung cancer (NSCLC) is well established. OBJECTIVE: We aimed to evaluate the prognostic value of the mutations in surgically resected NSCLC. METHODS: We retrospectively reviewed data from 1798 surgically resected NSCLC adenocarcinomas between 2007 and 2017 in three departments of thoracic surgery (Nancy/Strasbourg, France, and Torino, Italy) for whom mutational status was known. Overall survival (OS) was evaluated using log-rank and Cox proportional hazard models. RESULTS: EGFR exon 19 deletion was observed in 108 patients (55.1%) and exon 21 L858R mutations were observed in 88 patients (44.9%). In stage I, the median OS was not significantly different between exons 19 and 21 (p = 0.54), while, in stage II, the median OS reached 65 months [95% confidence interval (CI) 41.67-88.33] for exon 19 mutations and decreased to 48 months for exon 21 mutations (95% CI 44.21-51.79; p = 0.027). In multivariate analysis, exon 19 deletion remained a favorable prognostic factor [hazard ratio (HR) 0.314, 95% CI 0.098-0.997; p = 0.05]. In stage III, the median OS reached 66 months (95% CI 44.67-87.32) for exon 19 mutations and decreased to 32 months for exon 21 mutations (95% CI 29.86-34.14; p = 0.03). In multivariate analysis, exon 19 deletion remained a significantly favorable prognostic factor (HR 0.165, 95% CI 0.027-0.999; p = 0.05). CONCLUSION: The prognostic value of EGFR exon 19 and 21 mutations appears to be different according to disease stage in surgically resected NSCLC.

Clamshell Closure With Absorbable Sternal Pins in Lung Transplant Recipients.

Clamshell (bilateral anterolateral thoracotomy combined to transverse sternotomy) is an invasive surgical approach that is helpful in particular situations, especially bilateral lung transplantation. The closure technique remains challenging because clamshell incision can end with override, separation, or sternal pseudarthrosis complications. We describe the use of new absorbable sternal pins to stabilize the sternal closure and to help avoid additional sternal complications.

Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome After Pneumonectomy.

BACKGROUND: Postpneumonectomy acute respiratory distress syndrome (ppARDS) is a life-threatening condition with a disastrous prognosis. This study assessed the efficacy of venovenous extracorporeal membrane oxygenation (VV-ECMO) in adult patients with unresponsive severe ppARDS. METHODS: We retrospectively reviewed data of all patients treated with VV-ECMO for ppARDS from January 2009 to December 2015. We calculated the Sequential Organ Failure Assessment score before ECMO insertion and monitored the subsequent mechanical ventilation settings. The primary end point was hospital survival. The secondary end point was the ability to achieve a protective ventilatory strategy allowing lung recovery on ECMO. RESULTS: VV-ECMO was indicated in 8 ppARDS patients for refractory hypoxemia (median partial pressure of arterial oxygen/fraction of inspired oxygen: 68 [range, 60 to 75] mm Hg). Median Sequential Organ Failure Assessment before ECMO was 15 (range, 12 to 17), predicting a mortality rate greater than 80%. Median duration of ECMO was 9.5 (range, 5 to 16) days. Tidal volumes and plateau pressures both decreased on ECMO (pre-ECMO tidal volume: 412 [range, 250 to 450 mL] vs ECMO tidal volume: 277 [range, 105 to 367 mL], p = 0.0156; pre-ECMO plateau pressure: 34 [range, 32 to 40] cm H2O vs ECMO plateau pressure: 24.5 [range, 23.3 to 27.3] cm H2O, p = 0.0195). ECMO could be weaned in 7 patients (87.5%). Hospital survival was 50%. CONCLUSIONS: Hospital survival was better than predicted before ECMO insertion. In severe and refractory ppARDS, VV-ECMO allows lung recovery and therefore increased survival.

Perioperative bevacizumab improves survival following lung metastasectomy for colorectal cancer in patients harbouring v-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue exon 2 codon 12 mutations†.

OBJECTIVES: The role of perioperative chemotherapy (POC) and targeted therapies in lung metastasectomy for colorectal cancer (CRC) is still subject to debate. We aimed to evaluate whether POC and targeted therapies were associated with different outcomes according to the mutational status. METHODS: We reviewed data from 223 patients who underwent pulmonary metastasectomy for CRC from 1998 to 2015 and for whom the V-Ki-ras2 Kirsten sarcoma viral oncogene homologue (KRAS) and V-raf Murine sarcoma viral oncogene homologue B1 (BRAF) mutational statuses were known. RESULTS: A total of 167 patients (74%) underwent POC: 62 (37%) received neoadjuvant therapy, 59 (35%) were in the adjuvant setting and 46 (28%) were in both the neoadjuvant and adjuvant settings. POC did not significantly influence either the loco-regional recurrence free survival (LRRFS) (P = 0.21) or the overall survival (OS) (P = 0.29). Furthermore, in cases of adjuvant chemotherapy, outcomes were not significantly different in cases of neoadjuvant chemotherapy or both neoadjuvant and adjuvant treatment (P = 0.26 for OS, P = 0.14 for LRRFS). For patients with KRAS mutation, perioperative bevacizumab was associated with a significant improvement in both LRRFS [70 months (41.58­98.42) vs 24 months (1.15­46.86), P = 0.001] and OS [101 vs 55 months (49.77­60.23), P = 0.004]. However, this benefit was only significant in cases of KRAS exon 2 codon 12 mutations [median OS: 101 months (83.97­118.02) vs 60 months (53­66.99), P < 0.001; median LRRFS: 76 months (64.62­87.38) vs 44 months (35.27­52.73), P < 0.001]. CONCLUSION: Perioperative bevacizumab appears to be beneficial in patients with exon 2 codon 12 KRAS mutations who have undergone lung metastasectomy for CRC.

Video-assisted thoracoscopic surgery is a safe option for benign lung diseases requiring lobectomy.

BACKGROUND: Lobectomy for benign lung disease is renowned to be technically complex and to be subjected to an increased complication rate. The objective of this study was to evaluate whether the results obtained with video-assisted surgery (VATS) in benign disease are comparable to those obtained in oncologic surgery, where VATS has been validated. METHODS: We have reviewed the files of 246 consecutive patients who underwent VATS lobectomy from January 2012 to August 2015. The cohort was divided into two groups according to pathology (benign or malignant). Outcome parameters on scrutiny were demographics, pathology, duration of air leak, drainage and hospital stay, conversion, and perioperative complication rate. Comparisons were made with the χ 2 test and Student's t test; any p value ≤0.05 was considered as significant. RESULTS: Group 1 (36 patients) included patients who underwent lobectomy for benign disease and group 2 (210 patients) patients affected by lung cancer or pulmonary metastases. The two groups differed with reference to age (p < 0.001), history of cancer (p < 0.001), history of stroke (p = 0.05), and the presence of pleural adhesions (p = 0.03). There was no difference for duration of air leaks, chest tube drainage and hospital stay, conversion rate, and perioperative complication rate. CONCLUSIONS: We conclude that pathology did not impact on outcomes after VATS lobectomy. This study suggests that VATS is as a safe option in selected patients with benign disease requiring lobectomy, despite a more complex technical context.

Bronchial complications after lung transplantation are associated with primary lung graft dysfunction and surgical technique.

BACKGROUND: After lung transplantation, bronchial complications are one of the major concerns for surgeons and physicians. In the era of evolving immunosuppressive regimens and surgical approaches, we have reassessed risk factors for bronchial complications after lung transplantation. METHODS: We undertook a retrospective study of all consecutive lung transplantations performed at a single center from 2004 to 2014. We monitored the incidence of symptomatic bronchial complications. Demographic data of donors and recipients were also studied. Our objective was to evaluate the impact of 3 subsequent immunosuppressive regimens (including the use of induction therapy), and of a technical modification of bronchial anastomosis on the incidence of airway complications. RESULTS: We performed 270 consecutive lung transplantations during the study period. On multivariate analysis, bronchial complications were not directly associated with the different immunosuppressive regimens. In subgroup analysis, when comparing different immunosuppressive regimens, primary graft dysfunction within 72 hours (odds ratio [OR] = 2.55; p = 0.08), lung infection within the first month (OR = 2.96; p = 0.039), diabetes before transplantation (OR = 2.66; p = 0.11) and chronic obstructive pulmonary disease (OR = 2.20; p = 0.04) appeared as major risk factors (c-index = 0.77 on multivariate analysis). The use of a modified bronchial suture technique was associated with fewer bronchial complications (OR = 0.47; p = 0.059) (c-index = 0.71 on multivariate analysis). CONCLUSIONS: The mode of immunosuppression had no influence on airway complications. We were able to reproduce the beneficial effect of a modified suture technique.

N2-IIIA non-small cell lung cancer: a plea for surgery!

Management of stage IIIA-N2 non-small cell lung cancer is still matter of ongoing controversy. The debate is flawed by the heterogeneity of this group of patients, lack of strong evidence from controlled trials, diverging treatment strategies, and hesitating estimation of prognosis. Surgery is credited a survival advantage in a trimodality setting. For many teams, N2 is by principle managed with induction chemotherapy, followed by surgery if the patient is down-staged. However, surgery remains a suitable option even in case of persistent N2. On the other hand, outcomes are comparable, regardless whether chemotherapy has been given as induction or adjuvant treatment. Hence, upfront surgery without invasive staging, followed by adjuvant therapies, appears reasonable in resectable single station N2 disease, simplifying patient care and reducing cost. We expect that molecular biomarkers will improve estimation of prognosis and patient selection in the future.

Epidermal growth factor receptor and v-Ki-ras2 Kirsten rat sarcoma viral oncogen homologue-specific amino acid substitutions are associated with different histopathological prognostic factors in resected non-small-cell lung cancer.

OBJECTIVES: Epidermal growth factor receptor (mEGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogen homologue (mKRAS) mutations are the two main oncogenic drivers in resected non-small-cell lung cancer (NSCLC). We aimed to evaluate the correlation between histopathological prognostic factors and these mutations in resected NSCLC. METHODS: We retrospectively reviewed data from 841 patients who underwent a surgical resection with a curative intent for NSCLC between 2007 and 2012. RESULTS: KRAS mutations were observed in 255 patients (32%) and mEGFR in 103 patients (12%). A correlation was observed between mKRAS patients and lymph node involvement [Cramer's V: 0.451, P < 0.001, OR: 7.5 (95% CI: 5.3-10.7), P < 0.001]. Otherwise, a correlation was observed between mKRAS and the risk of harbouring 2 N2 stations [Cramer's V: 0.235, P = 0.02, OR: 3.04 (95% CI: 1.5-6.3), P = 0.004]. High lymph node ratio and angioinvasion were also significantly more frequent in mKRAS [Cramer's V: 0.373, P < 0.001, OR: 6.37 (95% CI: 3.9-10.5), P < 0.001; and Cramer's V: 0.269, P < 0.001, OR: 3.25 (95% CI: 2.4-4.4), P < 0.001, respectively]. Skip N2 and microscopic N2 were significantly more frequent in mEGFR [Cramer's V: 0.459, P < 0.001, OR: 18 (95% CI: 5.6-57.8), P < 0.001; and (Cramer's V: 0.45, P < 0.001 OR: 21.14 (95% CI: 9.2-48.3), P < 0.001, respectively]. CONCLUSIONS: We observed a correlation between mKRAS and negative histopathological prognostic factors and between mEGFR and positive prognostic factors. One can wonder whether histopathological prognostic factors are only clinical reflections of molecular alterations.

Microparticles: A new insight into lung primary graft dysfunction?

Lung transplantation is the only life-saving treatment for end stage respiratory disease. The immediate outcome is still hampered by primary graft dysfunction. The latter is a form of acute lung injury occurring within the 30min following the unclamping of the pulmonary artery that prompts ischemia reperfusion injury. Severe forms may need prolonged mechanical ventilation and extra-corporeal membrane oxygenation. Overall, primary graft dysfunction accounts for at least one third of the deaths during the first post-operative month. Despite increasing experience and knowledge on the underlying cellular events, there is still a lack of an early marker of ischemia reperfusion graft injuries. Microparticles are plasma membrane vesicles that are released from damaged or stressed cells in biological fluids and remodeling tissues, among which the lung parenchyma during acute or chronic injury. We recently evidenced alveolar microparticles as surrogate markers of strong ischemia injury in ex-vivo reperfusion experimental models. We propose herein new insights on how microparticles may be helpful to evaluate the extent of lung ischemia reperfusion injuries and predict the occurrence of primary graft dysfunction.

Vascular access for extracorporeal life support: tips and tricks.

In thoracic surgery, extracorporeal life support (ECLS) techniques are performed to (I) provide a short to mid term extracorporeal mechanical support; (II) realize the gas exchanges; and (III)-depending the configuration of the circuit-substitute the failed heart function. The objective of this review is to describe the rational of the different ECLS techniques used in thoracic surgery and lung transplantation (LTx) with a specific attention to the vascular access. Venovenous extracorporeal membrane oxygenation (VV ECMO) is the most common ECLS technique used in thoracic surgery and represents the best strategy to support the lung function. VV ECMO needs peripheral vascular access. The selection between his double-site or single-site configuration should be decided according the level of O2 requirements, the nosological context, and the interest to perform an ECLS ambulatory strategy. Venoarterial (VA) ECMO uses peripheral and/or central cannulation sites. Central VA ECMO is mainly used in LTx instead a conventional cardiopulmonary bypass (CPB) to decrease the risk of hemorrhagic issues and the rate of primary graft dysfunction (PGD). Peripheral VA ECMO is traditionally realized in a femoro-femoral configuration. Femoro-femoral VA ECMO allows a cardiocirculatory support but does not provide an appropriate oxygenation of the brain and the heart. The isolated hypercapnic failure is currently supported by extracorporeal CO2 removal (ECCO2R) devices inserted in jugular or subclavian veins. The interest of the Novalung (Novalung GmbH, Hechingen, Germany) persists due to his central configuration indicated to bridge to LTx patients suffering from pulmonary hypertension. The increasing panel of ECLS technologies available in thoracic surgery is the results of a century of clinical practices, engineering progress, and improvements of physiological knowledges. The selection of the ECLS technique-and therefore the vascular access to implant the device-for a given nosological context trends to be defined according an evidence-based medicine.

Ex vivo lung perfusion.

Lung transplantation is an established life-saving therapy for patients with end-stage lung disease. Unfortunately, greater success in lung transplantation is hindered by a shortage of lung donors and the relatively poor early-, mid-, and long-term outcomes associated with severe primary graft dysfunction. Ex vivo lung perfusion has emerged as a modern preservation technique that allows for a more accurate lung assessment and improvement in lung quality. This review outlines the: (i) rationale behind the method; (ii) techniques and protocols; (iii) Toronto ex vivo lung perfusion method; (iv) devices available; and (v) clinical experience worldwide. We also highlight the potential of ex vivo lung perfusion in leading a new era of lung preservation.

Prognostic value of the KRAS G12V mutation in 841 surgically resected Caucasian lung adenocarcinoma cases.

BACKGROUND: Identifying patients who will experience lung cancer recurrence after surgery remains a challenge. We aimed to evaluate whether mutant forms of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (mEGFR and mKRAS) are useful biomarkers in resected non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed data from 841 patients who underwent surgery and molecular testing for NSCLC between 2007 and 2012. RESULTS: mEGFR was observed in 103 patients (12.2%), and mKRAS in 265 (31.5%). The median overall survival (OS) and time to recurrence (TTR) were significantly lower for mKRAS (OS: 43 months; TTR: 19 months) compared with mEGFR (OS: 67 months; TTR: 24 months) and wild-type patients (OS: 55 months; disease-free survival (DFS): 24 months). Patients with KRAS G12V exhibited worse OS and TTR compared with the entire cohort (OS: KRAS G12V: 26 months vs COHORT: 60 months; DFS: KRAS G12V: 15 months vs COHORT: 24 months). These results were confirmed using multivariate analyses (non-G12V status, hazard ratio (HR): 0.43 (confidence interval: 0.28-0.65), P<0.0001 for OS; HR: 0.67 (0.48-0.92), P=0.01 for TTR). Risk of recurrence was significantly lower for non-KRAS G12V (HR: 0.01, (0.001-0.08), P<0.0001). CONCLUSIONS: mKRAS and mEGFR may predict survival and recurrence in early stages of NSCLC. Patients with KRAS G12V exhibited worse OS and higher recurrence incidences.

Expanding the lung donor pool: advancements and emerging pathways.

PURPOSE OF REVIEW: The number of patients listed for lung transplantation largely exceeds the number of available transplantable organs because of a shortage of organ donors and a low utilization rate of lungs from those donors who are available. In recent years, novel strategies have been developed to increase the donor lung pool: improved donor management, the use of lungs from donations after cardiac death (DCD), the use of lobar lung living-donors (LLLD) and the use of ex-vivo lung perfusion (EVLP) to assess and repair injured donor lungs. RECENT FINDINGS: An adapted donor management strategy could expand the donor pool up to 20%. DCD lung transplant is an increasing part of the donor pool expansion. Outcomes after controlled DCD seem to be similar to donation after brain death. LLLD transplantation has excellent results for small and critically ill patients. EVLP treatment allows for a significant increase in the rate of suitable lungs and represents an optimal platform for lung reconditioning and specific lung therapies. SUMMARY: A significant increase in the number of available lungs for transplantation is expected in the future because of the wider use of lungs from controlled or uncontrolled DCD and LLLD lungs, and with organ-specific EVLP treatment strategies.

Anomalous Pulmonary Venous Return of the Left Upper Lobe in a Donor Lung.

We report a case of partial anomalous pulmonary venous return from the left upper lobe in a donor lung discovered during lung transplantation. The upper lobe vein could be implanted successfully into the donor atrial cuff to restore physiologic venous drainage. The abnormality was retrospectively identified on the donor's chest computed tomographic scan. Cardiac magnetic resonance imaging performed in the recipient 6 months after transplantation demonstrated patent left pulmonary venous drainage. This is the third reported case of partial anomalous pulmonary venous return in a donor lung, but the first description of direct ex vivo suture into the donor cuff.