Transitioning to Neoadjuvant Therapy for Resectable Non-Small Cell Lung Cancer: Trends and Surgical Outcomes in a Regionalized Pulmonary Oncology Network.

BACKGROUND: Several regulatory agencies have approved the use of the neoadjuvant chemo-immunotherapy for resectable stage II and III of non-small cell lung cancer (NSCLC) and numerous trials investigating novel agents are underway. However, significant concerns exist around the feasibility and safety of offering curative surgery to patients treated within such pathways. The goal in this study was to evaluate the impact of a transition towards a large-scale neoadjuvant therapy program for NSCLC. METHODS: Medical charts of patients with clinical stage II and III NSCLC who underwent resection from January 2015 to December 2020 were reviewed. The primary outcome was perioperative complication rate between neoadjuvant-treated versus upfront surgery patients. Multivariable logistic regression estimated occurrence of postoperative complications and overall survival was assessed as an exploratory secondary outcome by Kaplan-Meier and Cox-regression analyses. RESULTS: Of the 428 patients included, 106 (24.8%) received neoadjuvant therapy and 322 (75.2%) upfront surgery. Frequency of minor and major postoperative complications was similar between groups (P = .22). Occurrence in postoperative complication was similar in both cohort (aOR = 1.31, 95% CI 0.73-2.34). Neoadjuvant therapy administration increased from 10% to 45% with a rise in targeted and immuno-therapies over time, accompanied by a reduced rate of preoperative radiation therapy use. 1-, 2-, and 5-year overall survival was higher in neoadjuvant therapy compared to upfront surgery patients (Log-Rank P = .017). CONCLUSIONS: No significant differences in perioperative outcomes and survival were observed in resectable NSCLC patients treated by neoadjuvant therapy versus upfront surgery. Transition to neoadjuvant therapy among resectable NSCLC patients is safe and feasible from a surgical perspective.

Teaching Chest Tube Insertion by Blended Learning: A Multi-Dimensional Analysis.

BACKGROUND: Emerging technologies are being incorporated in surgical education. The use of such technology should be supported by evidence that the technology neither distracts nor overloads the learner and is easy to use. To teach chest tube insertion, we developed an e-learning module, as part of a blended learning program delivered prior to in-person hands-on simulation. This pilot study was aimed to assess learning effectiveness of this blended learning, and cognitive load and the usability of e-learning. METHODS: The interactive e-learning module with multimedia content was created following learning design principles. In advance of the standard simulation, 13 first-year surgical residents were randomized into two groups: 7 received the e-learning module and online reading materials (e-learning group); 6 received only the online reading materials (controls). Knowledge was evaluated by pre-and post-tests; technical performance was assessed using a Global Rating Scale by blinded assessors. Cognitive load and usability were evaluated using rating scales. RESULTS: The e-learning group showed significant improvement from baseline in knowledge (P = .047), while controls did not (P = .500). For technical skill, 100% of residents in the e-learning group reached a predetermined proficiency level vs 60% of controls (P = .06). The addition of e-learning was associated with lower extrinsic and greater germane cognitive load (P = .04, .03, respectively). Usability was evaluated highly by all participants in e-learning group. CONCLUSION: Interactive e-learning added to hands-on simulation led to improved learning and desired cognitive load and usability. This approach should be evaluated in teaching of other procedural skills.

The 8th Edition TNM Stage Reclassification of T4 Non-Small Cell Lung Cancer: A Granular Examination of Short and Long-Term Outcomes.

INTRODUCTION: Whilst the American Joint Committee on Cancer 7th edition (AJCC7) classified pT4 non-small-cell lung cancers (NSCLC) as those with extra-pulmonary invasion, the revised 8th edition (AJCC8) included tumors > 7cm regardless of extra-pleural spread. We examined perioperative and long-term outcomes of classical T4 definitions with patients whose tumors were greater than 7cm without extra-pulmonary invasion. MATERIALS AND METHODS: A retrospective single center cohort study was performed. All consecutive patients with pT4 lesions between 2011 and 2018 were identified based on either the AJCC7 or AJCC8 classification. Clinicopathological variables were extracted and compared in a univariate manner. A multivariate Cox regression analysis was performed to assess factors associated with overall survival. RESULTS: Forty patients were allocated to AJCC7 and 118 to AJCC8. Patients in the former were more likely to have positive lymph nodes, synchronous metastasis, multifocal disease and lymphovascular invasion. AJCC7 patients were more likely to undergo pneumonectomy despite significantly more being treated with neoadjuvant therapy. Ninety-day mortality was higher in the AJCC7 group. There was no difference in long-term overall survival. On multivariate analysis male gender, squamous cell histology and increasing tumor size were associated with an increased risk of death. CONCLUSION: Although long-term outcomes were similar, the heterogenicity within the AJCC8 classification emphasizes the need to contextualize the perioperative outcomes for patients with pT4 NSCLC. These data are important for future iterations of the TNM classification in view of emerging neoadjuvant options for patients with cT4 operable NSCLC.

Neoadjuvant Prehabilitation Therapy for Locally Advanced Non-Small-Cell Lung Cancer: Optimizing Outcomes Throughout the Trajectory of Care.

BACKGROUND: Prehabilitation is well established for improving outcomes in cancer surgery. Combining prehabilitation with neoadjuvant treatments may provide an opportunity to rapidly initiate cancer-directed therapy while improving functional status in preparation for local consolidation. In this proof-of-concept study, we analyzed non-small-cell lung cancer patients who underwent simultaneous prehabilitation and neoadjuvant therapy. PATIENTS AND METHODS: We retrospectively analyzed all patients who underwent neoadjuvant treatment for non-small-cell lung cancer followed by curative intent surgery between 2015 and 2021. Patients who were screened for the prehabilitation program were identified. The screening included assessment of physical performance, nutritional status, and signs of anxiety and depression. RESULTS: We identified a total of 141 patients who underwent neoadjuvant therapy. Twenty patients were screened to undergo a prehabilitation program. Four patients did not complete the exercise program (1 surgical intervention too soon, 1 drop-out after the first session, and 2 patients were deemed fit without intervention). The postoperative median length of stay was 2 days (range 1-18). Patients improved their 6-minute-walk test despite undergoing neoadjuvant treatment by a mean of 33 meters (± 50, P = .1). Self-reported functional status (DASI) showed significant improvement by a mean of 10 points (± 11, P = .03), and HADS-anxiety-score was significantly reduced after the prehabilitation program by a mean of 1.5 points (± 1, P = .005). CONCLUSION: Neoadjuvant prehabilitation therapy is feasible and associated with encouraging results. The performance of all measures remains a logistic challenge. With multimodal strategies for lung cancer treatment becoming key to optimal outcomes, neoadjuvant prehabilitation therapy is a concept worthy of prospective multi-center evaluation.

Factors predicting recurrence in thymic epithelial neoplasms.

OBJECTIVES: Thymic epithelial neoplasms (TENs) represent a heterogeneous group of rare thoracic malignancies. We analysed the clinicopathological features, survival outcomes, risk factors, and patterns of recurrence in patients undergoing resection. METHODS: Records were reviewed for adult patients with TEN who underwent resection from 2006 to 2019. Survival rates were assessed using the Kaplan-Meier method. Univariable and multivariable analyses were performed using the log-rank test and Cox proportional hazards model. RESULTS: A total of 100 patients were analysed (51 females, median age 58 years). Thymoma was the most common histology (n = 92), followed by thymic carcinoma (n = 5) and thymic neuroendocrine tumour (n = 3). Stage II (Masaoka) tumours were most common (n = 51), followed by stage I (n = 27). World Health Organization B2/B3 was the most prominent histological subtype (n = 34). Complete resection (R0) was achieved in 91 patients: 86/92 thymoma, 4/5 thymic carcinoma and 1/3 neuroendocrine tumour. The most common treatment modality was surgery alone in 72 patients, followed by surgery and radiation therapy in 24, and adjuvant chemoradiotherapy in 3 patients. Only one patient with thymic carcinoma received neoadjuvant chemotherapy. The 10-year overall and disease-free survival rates were 86.6% and 83.9%, respectively. Recurrence was most common in neuroendocrine tumours (3/3). Risk factors for recurrence identified on multivariable analyses were: R1/2 resection (hazard ratio 9.30; 95% confidence interval 1.82-36.1), TEN subtype (hazard ratio 8.08; 95% confidence interval 1.24-34.6), and presence of lymphovascular invasion (hazard ratio 9.56; 95% confidence interval 2.56-25.8). CONCLUSIONS: Complete resection remains critical in patients with TEN. Incomplete resection, high-risk histology, and lymphovascular invasion highlight the need for effective adjuvant modalities. Given the rarity of these diseases, emphasis must be placed on collaborative research conducted on TEN.

Bilateral Cardiac Sympathectomy and Extrapericardial Coil Implantation for the Management of Electrical Storm.

We present a novel multidisciplinary approach for the treatment of electrical storm combining bilateral cardiac sympathectomy, extrapericardial coil insertion, and implantable cardioverter defibrillator upgrade in a patient with nonischemic cardiomyopathy and ventricular arrhythmias refractory to conventional therapies. (Level of Difficulty: Advanced.).

Systemic sarcoidosis mimicking metastatic renal cell carcinoma with subsequent cardiac involvement.

There exists a well-established association between sarcoidosis and many solid and hematologic malignancies however it is a less frequently described phenomenon in patients with renal cell carcinoma. Moreover the majority of described cases presented with local sarcoid-like reactions in close proximity to the tumor with comparatively few reports of more distant disease. Given the relatively low number of cases there remains a great deal of uncertainty surrounding the clinical behaviour of sarcoidosis in the setting of renal cell carcinoma. We report the case of a patient with surgically resected renal cell carcinoma who, several years later, developed bilateral pulmonary nodules, intra-thoracic lymphadenopathy as well as splenic, hepatic and osseous lesions. After extensive investigation, culminating in video-assisted thoracoscopic surgical resection, he was found to have sarcoidosis. He remained asymptomatic for many years before being diagnosed with cardiac sarcoidosis, which was found to be inactive and did not require any treatment. Both his sarcoidosis and underlying renal cell carcinoma have remained in remission to date. This case highlights the variable behaviour of sarcoidosis in these patients and underscores the importance of obtaining an accurate tissue diagnosis in the setting of suspected metastatic disease. Additionally, it underscores the importance of close monitoring and long-term follow up as these patients may develop significant organ involvement, even many years after diagnosis. Interestingly the patient's renal cell carcinoma remained in remission, raising questions about whether the development of sarcoidosis portends a better prognosis in patients with an underlying solid malignancy.

Multimodal Prehabilitation for Lung Cancer Surgery: A Randomized Controlled Trial.

BACKGROUND: The study was conducted to determine whether a multimodal prehabilitation program enhances postoperative functional recovery compared with multimodal rehabilitation. METHODS: Patients scheduled for non-small cell lung cancer resection were randomized to 2 groups receiving home-based moderate-intensity exercise, nutritional counseling with whey protein supplementation, and anxiety-reducing strategies for 4 weeks before the operation (PREHAB, n = 52) or 8 weeks after (REHAB, n = 43). Functional capacity (FC) was measured by the 6-minute walk test (6MWT) at baseline, immediately before the operation, and 4 and 8 weeks after operation. All patients were treated according to enhanced recovery pathway guidelines. RESULTS: There was no difference in FC at any point during the perioperative period between the 2 multimodal programs. By 8 weeks after operation, both groups returned to baseline FC, and a similar proportion of patients (>75%) in both groups had recovered to their baseline. CONCLUSIONS: In patients undergoing surgical resection for lung cancer within the context of an enhanced recovery pathway, multimodal prehabilitation initiated 4 weeks before operation is as effective in recovering FC as multimodal rehabilitation.

Implication of a novel postoperative recovery protocol to increase day 1 discharge rate after anatomic lung resection.

BACKGROUND: Chest-tube drainage and prolonged air leak after anatomic lung resection (ALR) continue to drive admission days for most programs employing minimal access techniques. The aim of the study was to evaluate the impact of a novel postoperative recovery protocol with revised chest tube management strategies to target discharge on post-operative day 1 (POD1) after ALR. METHODS: This is a pilot study investigating a novel enhanced recovery protocol which either allowed chest tube removal on POD1 or ambulatory management with indwelling chest tube using a portable closed drainage system. We included all patients undergoing video-assisted thoracoscopic surgery (VATS)-ALR; exclusion criteria were open surgery, non-anatomic or extended resections. RESULTS: A total of 139 patients were included in the study [N=29 portable drainage (PD), N=110 standard pathway (SP)]. POD1 discharge rate was 72% in PD vs. 15% in SP cohort (P<0.001). Median length of stay (LOS) was 1 day [interquartile range (IQR), 1-2 days] in PD cohort, while it was 3 days (IQR, 2-5 days) in SP cohort (P<0.001). There were no significant differences in length of indwelling chest-tube, rate of discharge with chest-tube, post-operative complications, or readmissions. On multivariate analysis, PD pathway as well as short surgical time were significant predictors of discharge on POD1. CONCLUSIONS: Our results indicate that POD1 discharge rates of 72% after VATS-ALR can be safely achieved by a well-developed perioperative care pathway and simple chest tube drainage interventions. Based on these findings we are currently drafting a follow-up study to investigate the possibility of performing ALRs as day surgery.

Relationship between Catamenial Pneumothorax or Non-catamenial Pneumothorax and Endometriosis.

STUDY OBJECTIVE: To evaluate the clinical characteristics of women presenting with catamenial pneumothorax and compare them with those with noncatamenial pneumothorax. DESIGN: A case-control study (Canadian Task Force II-2). SETTING: A multicenter study. PATIENTS: Forty-two women with pneumothorax: 21 women had catamenial pneumothorax (study group), and 21 were age-matched women with noncatamenial pneumothorax (control group). INTERVENTIONS: All patients underwent video-assisted thoracoscopy and pleural biopsy. We also evaluated the presence and stage of pelvic endometriosis in 16 women with catamenial pneumothorax who had undergone laparoscopic surgery. MEASUREMENTS AND MAIN RESULTS: The number of known episodes of catamenial pneumothorax before treatment was between 2 and 8 episodes. Symptoms were mainly chest pain and shortness of breath; 1 patient had hemoptysis. The prevalence of right-sided pneumothorax was 95.2% in the study group and 57.1% in the control group (p = .004). Besides 2 cases with complete collapse of the right lung, most of the cases in the study group had apical pneumothorax. Pelvic endometriosis was found in 15 of 16 women (93.7%), mainly stage 3 or 4, and thoracic endometriosis in 12 of 20 women (60%). None of the patients in the control group had thoracic endometriosis. CONCLUSION: Thoracic endometriosis is found in over half of women with catamenial pneumothorax but absent in those with noncatamenial pneumothorax. Right apical pneumothorax is predominant in women with catamenial pneumothorax. Endometriosis plays an important role in the mechanism of catamenial pneumothorax.

Intraoperative Pneumothorax Presenting as Abdominal Distention.

A 74-year-old man with a history of lung cancer presented for right upper lobectomy. After induction of anesthesia, it was noted that the abdomen became progressively more distended. Soon afterward, there was a significant decrease in tidal volume. Ultrasonography of the lung showed no sign of pneumothorax at the anterior second intercostal space. However, the roentgenograms showed a massive right-sided pneumothorax and extensive pneumoperitoneum. Both the pneumothorax and the pneumoperitoneum were decompressed in the operating room, and the elective lobectomy proceeded as previously planned. The patient was extubated at the end of the operation, and there were no sequelae postoperatively.

An enhanced recovery pathway reduces duration of stay and complications after open pulmonary lobectomy.

BACKGROUND: Few studies have investigated the effectiveness of enhanced recovery pathways (ERP) for lung resection. This study estimates the impact of an ERP for lobectomy on duration of stay, complications, and readmissions. METHODS: Patients undergoing open lobectomy were identified from an OR database between 2011 and 2013. Beginning September 2012, all patients were managed according to a 4-day multidisciplinary ERP with written daily patient education treatment plans, multimodal analgesia, early diet, structured mobilization and standardized drain management. Pre-pathway (PRE) and post-pathway (POST) patients were compared in terms of duration of stay, complications, and readmissions. RESULTS: We identified 234 patients (PRE, 127; POST, 107). Groups were similar with respect to age, gender, American Society of Anesthesiologists score, and baseline pulmonary function. Compared with the PRE group, the POST group had decreased duration of stay (median, 6 [interquartile range (IQR), 5-7] vs 7 [6-10] days; P < .05), total complications (40 [37%] vs 64 [50%]; P < .05), urinary tract infections (3 [3%] vs 15 [12%]; P < .05), and chest tube duration (median, 4 [IQR, 3-6] vs 5 [4-7] days; P < .05), with no difference in readmissions (7 [7%] vs 6 [5%]; P < .05) or chest tube reinsertion (4 [4%] vs 6 [5%]; P < .05). Decreased duration of stay was driven by patients without complications (median, 5 [IQR, 4-6] vs 6 [5-7] days; P < .05). CONCLUSION: Implementation of a multimodal ERP for lobectomy was associated with decreased duration of stay and complications with no difference in readmissions.

Validity of the EuroQol-5 dimensions as a measure of recovery after pulmonary resection.

BACKGROUND: Surgical innovations advocated to improve patient recovery are often costly. Economic evaluation requires preference-based measures that reflect the construct of patient recovery. We investigated the responsiveness and construct validity of the EuroQol-5 dimensions (EQ-5D) as a measure of postoperative recovery after planned pulmonary resection for suspected malignant tumors. METHODS: Patients undergoing pulmonary resection completed the EQ-5D questionnaire and visual analog scales (VAS) for pain and fatigue at baseline (preoperatively) and at 1 and 3 mo postoperatively. Responsiveness and construct validity (discriminant and convergent) were investigated by testing a priori hypotheses. RESULTS: Fifty-five patients were analyzed (45% male, 62 ± 12 y, 29% video-assisted). There was no significant difference between median EQ-5D scores obtained at baseline (0.83 [interquartile range {IQR 0.80-1}]) compared to scores at 1 mo (0.83 [0.80-1], P = 0.86) and 3 mo after surgery (1 [0.83-1]; P = 0.09). At 1 mo after surgery, EQ-5D scores were significantly lower in patients undergoing thoracotomy versus video-assisted surgery (0.82 [IQR 0.77-0.89] versus 1 [0.83-1], P = 0.003), but there were no significant differences between patients ≥ 70-y old versus younger (0.95 [IQR 0.82-1] versus 0.83 [0.77-1], P = 0.09) or between patients with versus without complications (0.82 [IQR 0.79-0.95] versus 0.83 [0.80-1], P = 0.10). There was a low but significant correlation between EQ-5D and VAS scores of pain and fatigue (Rho -0.30 to -0.47, P ≤ 0.01). CONCLUSIONS: Despite evidence of convergent validity, the EQ-5D was not sensitive to the hypothesized trajectory of postoperative recovery and showed limited discriminant validity. This study suggests that the EQ-5D may not be appropriate to value recovery after lung resection.

Reconstruction after major chest wall resection: can rigid fixation be avoided?

BACKGROUND: Rigid fixation is advocated as the best method to achieve good respiratory outcomes after chest wall resection at the expense of a high complication rate. The following study aims to examine the role of myocutaneous pedicled flaps, with or without soft prosthesis, in the reconstruction of small and large chest wall defects. METHODS: All patients who underwent resection of chest wall tumors between 2003-2010 were identified from a prospectively entered database. Operative and postoperative outcomes were documented. Patients were stratified into 2 separate groups based on the size of the residual chest wall defect; the Small Defect (SD) group (<60 cm(2)) and the Large Defect (LD) group (>60 cm(2)). RESULTS: Thirty-seven patients were identified over a 7-year period: 9 in the SD group and 28 in the LD group. Primary sarcoma was the most common indication for resection (57%). The mean size of the chest wall defect was 50.8 cm(2) in the SD group and 149.4 cm(2) in the LD group (P = .001). All patients underwent reconstruction with autologous tissue, nonrigid prosthesis, or a combination of the two. Prosthesis was used in 11% of patients in the SD group and 61% of patients in the LD group (P = .018). The rate of immediate postoperative extubation was 100% in the SD group and 89% in the LD group (P = .42). The rate of postoperative pneumonia was 7% in the LD group vs 0% in the SD group. The rate of surgical site infection was 7% in the LD group and 0% in the SD group. A subgroup analysis of the LD group demonstrated no statistical differences in any of the measured outcomes between patients in whom mesh prosthesis was used and patients in whom a myocutaneous flap alone was used. However, there was a clinical suggestion of prolonged ventilation in the subgroup where mesh was not used and of higher infection rates in the subgroup where mesh was used. CONCLUSION: Small chest wall defects can be reconstructed with pedicled myocutaneous flaps alone without compromising respiratory outcomes. In carefully selected patients with moderate size defects larger than 60 cm(2), reconstruction with pedicled myocutaneous flap alone offers similar postoperative outcomes as reconstruction with nonrigid prosthesis, at the expense of a possible need for a short period of mechanical ventilation.

Estimating the risk of prolonged air leak after pulmonary resection using a simple scoring system.

BACKGROUND: The high rate of prolonged air leak (PAL) after pulmonary resection has prompted interest in surgical adjuncts designed to prevent this complication. However, these adjuncts are costly and might not be beneficial if used routinely. Identification of patients at highest risk might allow for more effective use of these adjuncts. Therefore, we sought to develop a simple scoring system to predict PAL. STUDY DESIGN: A derivation set of 580 patients was identified from a prospectively entered database of consecutive pulmonary resections at a single institution from 2002 to 2007. Patient and operative characteristics were compared using Student's t-test and chi-square tests. Significant variables on univariate analysis were entered into a stepwise logistic regression to establish a simple predictive model to estimate the risk of PAL. This scoring system was then validated in a consecutive set of 381 patients operated at the same institution from 2007 to 2009. RESULTS: The rate of PAL was 14% in the derivation set and 18% in the validation set. Poor pulmonary function (forced expiratory volume in 1 second and carbon monoxide diffusing capacity, percent predicted) and pleural adhesions were significantly associated with PAL in the derivation set. A weighted scoring system was devised using pleural adhesions (+2 points), forced expiratory volume in 1 second (+1 per 10% below 100%), and carbon monoxide diffusing capacity (+1 per 20% below 100%). Total number of points estimated the probability of PAL. Hosmer-Lemeshow goodness-of-fit test confirmed validity (p > 0.2) of this scoring system in the validation set. CONCLUSIONS: We have devised and validated a simple scoring system to predict the probability of PAL after pulmonary resection.

Impact of FDG-PET/CT on radiotherapy volume delineation in non-small-cell lung cancer and correlation of imaging stage with pathologic findings.

PURPOSE: Fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomography (CT) is more accurate than CT in determining the extent of non-small-cell lung cancer. We performed a study to evaluate the impact of FDG-PET/CT on the radiotherapy volume delineation compared with CT without using any mathematical algorithm and to correlate the findings with the pathologic examination findings. METHODS AND MATERIALS: A total of 32 patients with proven non-small-cell lung cancer, pathologic specimens from the mediastinum and lung primary, and pretreatment chest CT and FDG-PET/CT scans were studied. For each patient, two data sets of theoretical gross tumor volumes were contoured. One set was determined using the chest CT only, and the second, done separately, was based on the co-registered FDG-PET/CT data. The disease stage of each patient was determined using the TNM staging system for three data sets: the CT scan only, FDG-PET/CT scan, and pathologic findings. RESULTS: Pathologic examination altered the CT-determined stage in 22 (69%) of 32 patients and the PET-determined stage in 16 (50%) of 32 patients. The most significant alterations were related to the N stage. PET altered the TNM stage in 15 (44%) of 32 patients compared with CT alone, but only 7 of these 15 alterations were confirmed by the pathologic findings. With respect to contouring the tumor volume for radiotherapy, PET altered the contour in 18 (56%) of 32 cases compared with CT alone. CONCLUSION: The contour of the tumor volume of non-small-cell lung cancer patients with co-registered FDG-PET/CT resulted in >50% alterations compared with CT targeting, findings similar to those of other publications. However, the significance of this change is unknown. Furthermore, pathologic examination showed that PET is not always accurate and histologic examination should be obtained to confirm the findings of PET whenever possible.

Late presentation of retained intracardiac ice pick with papillary muscle injury.

An unusual case of a penetrating intracardiac injury is described in a 16-year-old boy who presented with a retained 14-cm segment of an ice pick that went unnoticed by the patient for 4 days. The ice pick had lacerated the anterior papillary muscle of the left ventricle causing avulsion of its tip and prolapse of the anterior leaflet of the mitral valve resulting in severe mitral regurgitation. The urgency for surgical correction of the traumatic mitral valve injury at the time of extraction of the intracardiac foreign body through a single-stage approach versus a two-stage approach is discussed.