Comparing the Efficacy of Video-Assisted Thoracoscopic Surgery and Open Thoracotomy in Sleeve Lobectomy for the Treatment of Central-Type Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Objective: Central-type Non-small Cell Lung Cancer (NSCLC) treatment involves different surgical techniques, including Video-Assisted Thoracoscopic Surgery (VATS) and Open Thoracotomy Sleeve Lobectomy. However, there remains a lack of consensus on the most effective treatment modality. Methods: This study strictly adhered to PRISMA guidelines. Four electronic databases were searched without time or language limitation, and studies comparing VATS and Open Thoracotomy in patients with central-type NSCLC undergoing sleeve lobectomy were included. Primary outcomes were perioperative outcomes (blood loss, operation time, intraoperative lymph node dissection count, postoperative hospital stay, and complication rates), 3-year Progression-Free Survival (PFS) rate, and Overall Survival (OS) rate. Results: The meta-analysis included six studies with 569 patients. VATS was associated with longer operation time [SMD = 0.75, 95% CI (0.29, 1.21)], less intraoperative blood loss [SMD = -0.23; 95% CI (-0.44, -0.01)], and shorter hospital stay [SMD = -0.53; 95% CI (-0.73, -0.34)]. There were no significant differences in the number of lymph nodes dissected, postoperative complications, and 3-year PFS and OS rates between the two groups. Conclusions: VATS sleeve lobectomy for central-type NSCLC results in less surgical trauma and quicker postoperative recovery without adversely impacting tumor prognosis compared to open thoracotomy sleeve lobectomy. Despite a longer operation time, VATS could be considered an alternative to open thoracotomy sleeve lobectomy. VATS sleeve lobectomy is a safe and effective alternative to open thoracotomy in treating central-type NSCLC, as it results in less surgical trauma and quicker postoperative recovery without impacting tumor prognosis negatively. More well-designed randomized controlled trials are required to verify these findings.

Disparities and Underutilization of Surgery for Early Stage Small Cell Lung Cancer.

BACKGROUND: The National Comprehensive Cancer Network recommends surgical resection for stage I small cell lung cancer (SCLC). Despite these recommendations and the curative potential of such surgery, many continue to underutilize surgery. Our aim is to investigate factors that contribute to underutilization of surgery for stage I SCLC. METHODS: The National Cancer Database was queried to identify patients with SCLC stage I-IV from 2004 to 2018. Staging was defined by the American Joint Committee on Cancer guidelines. Cochran-Armitage analysis was performed to analyze trends in surgical treatment for patients diagnosed with stage I SCLC. Multivariable logistic regression assessed relationships between patient factors and surgical treatment. RESULTS: A total of 296,583 patients were diagnosed with SCLC. Of the stage I patients (n = 13,003), only 29.4.% (n = 3823) underwent surgery. Trend analysis demonstrated increased frequency of surgical treatment for stage I SCLC over years 2004 to 2017, from 14.9% to 39.6% (P < .0001). Factors that were associated with underutilization of surgery for stage I SCLC include African American race, lower median income, nonprivate insurance or Medicare, community facility, and geographic regions other than the Northeast. CONCLUSIONS: Surgical treatment for stage I SCLC remains underutilized and our study identifies notable associated factors. The recognition of these factors may help patients overcome barriers to receiving recommended treatments, improve guideline adherence, and overall quality of care for stage I SCLC patients.

Lung volume reduction for emphysema using one-way endobronchial valves: An Australian cohort.

Emphysema can be associated with gas trapping and hyperinflation, which negatively impacts on quality of life, life expectancy, and functional capacity. Lung volume reduction (LVR) surgery can reduce gas trapping and improve mortality in select patients but carries a high risk of major complications. Bronchoscopic techniques for LVR using one-way endobronchial valves (EBV) have become an established efficacious alternative to surgery. A bi-center retrospective cohort study was conducted on patients with severe emphysema who underwent endoscopic lung volume reduction (ELVR) using Pulmonx Zephyr EBVs. Symptomatic patients with gas-trapping and hyperinflation on lung function testing were selected. Target-lobe selection was based on quantitative imaging analysis and ventilation-perfusion scintigraphy. Successful procedures were determined from clinical review, imaging and follow-up testing. Thirty-nine patients underwent ELVR. Mean pre-procedure forced expiratory volume in 1 second (FEV1) was 0.75 L, residual volume (RV) was 225% predicted and total lung capacity was 129% predicted. Most common treated-lobe was left upper lobe. Post-procedure pneumothorax occurred in 36.5% of patients with 73% requiring intercostal catheter insertion for drainage. Mean FEV1 improvement was +140 mL and 57% of patients achieved minimal clinical important difference FEV1 increase of ≥12%. Maximal mean RV change was -1010 mL with 69% of patients achieving minimal clinical important difference RV decrease of ≥350 mL. Clinician-determined success of ELVR was 78%. Procedure-related mortality was absent. LVR using EBVs is safe and can lead to significant improvements in lung function, particularly reduction of gas trapping and hyperinflation. Occurrence of pneumothorax post-procedure is a complication that must be monitored for and managed appropriately.

A Study on the Efficacy of Three-Dimensional CT Bronchial Angiography in Thoracoscopic Precision Resection of Lung Segments.

Objective: This study aimed to evaluate the effectiveness of three-dimensional CT bronchial angiography (3D-CTBA) in facilitating precise lung segmental resection. Methods: A total of 80 patients with peripheral lung nodules undergoing anatomical lung segmentectomy were randomly divided into two groups: a control group (n = 40) and a study group (n = 40). The control group received surgical treatment based on chest CT prompts and traditional lung segmentation, while the study group's chest CT imaging data were reconstructed into 3D images before surgery, followed by lung segmentectomy. Surgical parameters and complication rates were compared between the two groups. Results: The study group exhibited significantly shorter operation time, drainage time, and hospitalization time, as well as reduced intraoperative bleeding, lung tissue resection size, and drainage volume, compared to the control group (P < .05). Hospitalization costs did not differ significantly between the two groups (P > .05). The incidence of lung infection, pulmonary atelectasis, and arrhythmia showed no significant difference between the groups (P > .05). However, the study group demonstrated significantly lower rates of hemoptysis and lung leakage compared to the control group (P < .05). There was no significant difference in the composition of postoperative pathological staging between the two groups (χ2 = 0.721, P > .05). Conclusions: The application of 3D-CTBA technology provides clear visualization of the lung's anatomical structure and contributes to enhanced safety and effectiveness in thoracoscopic lung segmental precision resection.

Association between imaging surveillance frequency and outcomes following surgical treatment of early-stage lung cancer.

BACKGROUND: Recent studies have suggested that more frequent postoperative surveillance imaging via computed tomography following lung cancer resection may not improve outcomes. We sought to validate these findings using a uniquely compiled dataset from the Veterans Health Administration, the largest integrated health-care system in the United States. METHODS: We performed a retrospective cohort study of veterans with pathologic stage I non-small cell lung cancer receiving surgery (2006-2016). We assessed the relationship between surveillance frequency (chest computed tomography scans within 2 years after surgery) and recurrence-free survival and overall survival. RESULTS: Among 6171 patients, 3047 (49.4%) and 3124 (50.6%) underwent low-frequency (<2 scans per year; every 6-12 months) and high-frequency (≥2 scans per year; every 3-6 months) surveillance, respectively. Factors associated with high-frequency surveillance included being a former smoker (vs current; adjusted odds ratio [aOR] = 1.18, 95% confidence interval [CI] = 1.05 to 1.33), receiving a wedge resection (vs lobectomy; aOR = 1.21, 95% CI = 1.05 to 1.39), and having follow-up with an oncologist (aOR = 1.58, 95% CI = 1.42 to 1.77), whereas African American race was associated with low-frequency surveillance (vs White race; aOR = 0.64, 95% CI = 0.54 to 0.75). With a median (interquartile range) follow-up of 7.3 (3.4-12.5) years, recurrence was detected in 1360 (22.0%) patients. High-frequency surveillance was not associated with longer recurrence-free survival (adjusted hazard ratio = 0.93, 95% CI = 0.83 to 1.04, P = .22) or overall survival (adjusted hazard ratio = 1.04, 95% CI = 0.96 to 1.12, P = .35). CONCLUSIONS: We found that high-frequency surveillance does not improve outcomes in surgically treated stage I non-small cell lung cancer. Future lung cancer treatment guidelines should consider less frequent surveillance imaging in patients with stage I disease.

Preoperative percutaneous needle indigo carmine and lipiodol mixture marking in lung segmentectomy.

OBJECTIVES: For successful nodule localization and appropriate surgical margin distances in pulmonary segmentectomy for patients with lung malignancies, the effectiveness and feasibility of preoperative marking using an indigo carmine and lipiodol mixture remain unclear. METHODS: Patients who underwent thoracoscopic pulmonary segmentectomy with (marking group, n = 69) and without (non-marking group, n = 265) preoperative marking at our institution from January 2013 to March 2020 were retrospectively reviewed and compared in terms of surgical outcomes. All markings were performed using a fine needle to percutaneously inject an indigo carmine and lipiodol mixture under the guidance of computed tomography fluoroscopy. RESULTS: Successful localization was achieved in 66 (96%) patients, of whom 62 (94%) underwent dye pigmentation and 4 (6%) underwent intraoperative fluoroscopy. On images, the marking group showed a significantly longer distance between the lung surface and tumour [mm, 9 (1-17) vs 0 (0-10); P < 0.01] and smaller maximum tumour size [mm, 16 (11-21) vs 17 (13-23); P = 0.03] and consolidation tumour ratio [0.4 (0.3-1) vs 0.8 (0.4-1); P < 0.01] than the non-marking group. Both groups had comparable operative outcomes, perioperative complications, pulmonary function changes and surgical margin distances [mm, 20 (15-21) vs 20 (15-20); P = 0.96] without any local recurrence on the surgical margin. Propensity score-matching analysis also showed similar findings for both groups. CONCLUSIONS: Thoracoscopic pulmonary segmentectomy with preoperative marking using an indigo carmine and lipiodol mixture may be an acceptable therapeutic option for small malignancies located in deep lung parenchyma.

Cost-Effectiveness Analysis of Robotic-assisted Lobectomy for Non-Small Cell Lung Cancer.

BACKGROUND: Robot-assisted thoracic surgery has emerged as an alternative to video-assisted thoracic surgery (VATS) for treating patients with resectable non-small cell lung cancer. The objective of this study was to evaluate the cost effectiveness of robotic-assisted lobectomy (RAL) compared with VATS and open lobectomy for adults with NSCLC. METHODS: A decision analysis model was employed to compare the cost effectiveness of RAL, VATS, and open lobectomy with 1-year time horizon from both health care and societal perspectives. Health care costs (2020$) and quality-adjusted life-years were compared between the approaches. The incremental cost-effectiveness ratio was calculated in terms of cost per quality-adjusted life-years gained. Sensitivity analyses were performed to identify variables driving cost effectiveness across several willingness-to-pay thresholds. RESULTS: Open thoracotomy was not cost effective compared with both RAL and VATS lobectomy. From the health care sector perspective, RAL was $394.97 more expensive per case than VATS resulting in an incremental cost-effectiveness ratio of $180 755.10 per quality-adjusted life-year. From the societal perspective, RAL was $247.77 more expensive per case than VATS, resulting in an incremental cost-effectiveness ratio of $113 388.80 per quality-adjusted life-years. Robotic-assisted lobectomy becomes cost effective with marginally lower robotic instrument costs, shorter operating room times, lower conversion rates, shorter lengths of stay, higher hospital volumes, and improved quality of life. Robotic-assisted lobectomy is also cost effective if surgeons can increase the proportion of minimally invasive lobectomies using robotic technology. CONCLUSIONS: Compared with VATS, RAL is not cost effective for lung cancer lobectomy at lower willingness-to-pay thresholds. However, several factors may drive RAL to emerge as the more cost-effective approach for minimally invasive lung cancer resection.

[Comparison of Short-term Results of Preoperative Planning Combined with 
Fluorescence Video-assisted Thoracoscopic Precision Segmentectomy and Traditional Thoracoscopic Segmentectomy in the Treatment of Early Lung Adenocarcinoma].

BACKGROUND: The mortality of lung cancer ranks first among all malignant tumors, but there are few studies on the effect of different segmentectomy on lung function in patients with early lung adenocarcinoma. The purpose of this study was to evaluate the degree of lung function preservation and short-term results of preoperative planning combined with fluorescence thoracoscopic precision segmentectomy and traditional segmentectomy in patients with early lung adenocarcinoma. METHODS: From January 1, 2020 to October 31, 2020, 60 patients underwent thoracoscopic segmentectomy in the Department of Thoracic Surgery of the First Affiliated Hospital of University of Science and Technology of China: 30 patients in precision segmentectomy group and 30 patients in traditional segmentectomy group. The clinicopathological features, perioperative data and postoperative pulmonary function of the two groups were compared. RESULTS: The operation time of the precision group was shorter than that of the traditional group, and the difference was statistically significant (P<0.05). The preoperative pulmonary function accuracy group and the traditional group in forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and carbon monoxide diffusing capacity (DLCO) were (3.65±0.63) L vs (3.54±0.64) L, (2.72±0.50) L vs (2.54±0.48) L and (20.36±3.02) mL/mmHg/min vs (19.16±3.18) mL/mmHg/min, respectively. One month after operation, the FVC, FEV1 and DLCO of pulmonary function accuracy group and traditional group were (3.35±0.63) L vs (2.89±0.57) L, (2.39±0.54) L vs (2.09±0.48) L and (17.43±3.10) mL/mmHg/min vs (15.78±2.865) mL/mmHg/min, respectively. Three months after operation, the FVC and DLCO of pulmonary function accuracy group and traditional group were (3.47±0.63) L vs (3.20±0.56) L and (19.38±3.02) mL/mmHg/min vs (17.79±3.21) mL/mmHg/min, respectively. CONCLUSIONS: Preoperative planning combined with fluorescence thoracoscopic precise segmentectomy provides advantages in intersegmental plane recognition, vascular anatomy and postoperative recovery, which significantly shortens the operation time and makes the treatment more accurate.

A patient with ALK-positive lung adenocarcinoma who survived alectinib-refractory postoperative recurrence for 4 years by switching to ceritinib.

Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangements are found in ~ 5% of patients with non-small cell lung cancer (NSCLC). Several tyrosine kinase inhibitors (TKIs) have been developed for treatment of so-called ALK-positive NSCLC. In cases of tumor progression during treatment with second-generation ALK-TKIs, such as alectinib, brigatinib, or ceritinib, National Comprehensive Cancer Network guidelines propose a switch to lorlatinib, a third-generation ALK-TKI, or to cytotoxic chemotherapy. However, they do not mention switching to other second-generation ALK-TKIs. Here, we present a rare case of a 53-year-old Japanese woman, who had never smoked, with ALK-positive lung adenocarcinoma who survived alectinib-resistant postoperative recurrence for 4 years by switching to ceritinib. She underwent curative resection for lung adenocarcinoma, but the cancer recurred at the bronchial stump and mediastinal lymph nodes. After platinum-doublet chemotherapy, the patient still had a single growing liver metastasis, but the tumor was found to harbor EML4-ALK rearrangement. Therefore, the patient started to take ALK-TKIs. Alectinib was the second ALK-TKI used to treat this patient. Alectinib shrank the liver metastasis, which was surgically resected. The tumor relapsed again during continued treatment with alectinib, which was switched to ceritinib. Ceritinib was effective for the relapsed tumor and treatment continued well for 4 years. This case report suggests that, in case of tumor progression during treatment with a second-generation ALK-TKI, switching to another second-generation ALK-TKI may be one of the treatment options. Further analyses are warranted to find robust markers to determine which ALK-TKI is best for each patient.

Effects of Preoperative Breathing Exercise on Postoperative Outcomes for Patients With Lung Cancer Undergoing Curative Intent Lung Resection: A Meta-analysis.

OBJECTIVE: To determine the benefits of preoperative breathing exercises on hospital length of stay (LOS), pneumonia, postoperative pulmonary complications (PPC), 6-minute walk distance (6MWD), forced expiratory volume in 1 second (FEV1), and health-related quality of life (HRQOL) in patients undergoing surgical lung cancer resection. DATA SOURCES: PubMed, EMBASE, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials were comprehensively searched from inception to March 2021. STUDY SELECTION: Only studies including preoperative inspiratory muscle training (IMT) and/or breathing exercises compared with a nontraining control group were included. The meta-analysis was done using Cochrane software for multiple variables including LOS, pneumonia, PPC, 6MWD, FEV1, mortality, and HRQOL. DATA EXTRACTION: Two authors extracted the data of the selected studies. The primary outcomes were LOS and PPC. DATA SYNTHESIS: A total of 10 studies were included in this meta-analysis, 8 of which had both IMT and aerobic exercise. Pooled data for patients who performed preoperative breathing exercises, compared with controls, demonstrated a decrease in LOS with a pooled mean difference of -3.44 days (95% confidence interval [CI], -4.14 to -2.75; P<.01). Subgroup analysis also demonstrated that LOS was further reduced when breathing exercises were combined with aerobic exercise (χ2, 4.85; P=.03). Preoperative breathing exercises reduce pneumonia and PPCs with an odds ratio of 0.37 (95% CI, 0.18-0.75; P<.01) and 0.37 (95% CI, 0.21-0.65; P<.01), respectively. An increase in 6MWD of 20.2 meters was noted in those performing breathing exercises (95% CI, 9.12-31.21; P<.01). No significant differences were noted in FEV1, mortality, or HRQOL. CONCLUSIONS: Preoperative breathing exercises reduced LOS, PPC, and pneumonia and potentially improved 6MWD in patients undergoing surgical lung cancer resection. Breathing exercises in combination with aerobic exercise yielded greater reductions in LOS. Randomized controlled trials are needed to test the feasibility of introducing a preoperative breathing exercise program in this patient population.

Excellent Prognosis of Patients With Invasive Lung Adenocarcinomas During Surgery Misdiagnosed as Atypical Adenomatous Hyperplasia, Adenocarcinoma In Situ, or Minimally Invasive Adenocarcinoma by Frozen Section.

BACKGROUND: Our previous study revealed that intraoperative frozen section (FS) analysis could differentiate invasive lung adenocarcinoma (LUAD) accurately from preinvasive lesions. However, few articles have analyzed the clinical impact of FS errors such as underestimation of invasive adenocarcinomas (IACs), and whether complementary therapy is needed remains controversial. RESEARCH QUESTION: What is the prognosis of patients undergoing limited resection for invasive LUAD misdiagnosed as atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), or minimally invasive adenocarcinoma (MIA) by intraoperative FS analysis? STUDY DESIGN AND METHODS: From 2012 through 2018, data on 3031 patients undergoing sublobar resection of AAH, AIS, or MIA diagnosed by FS analysis were collected. The concordance rate between FS analysis and final pathologic results was evaluated. To assess the clinical significance of a discrepancy between FS and final pathologic results, patients with final pathologic results of IAC were identified for prognostic evaluation. RESULTS: When AAH, AIS, and MIA were classified together as a group, the overall concordance rate between FS and final pathologic results was 93.7%, and 192 patients (6.3%) received an upgraded diagnosis from the final pathologic results. Misdiagnosed IACs consisted of 94 patients (48.9%) with lepidic-predominant adenocarcinoma, 77 patients (40.1%) with acinar predominant adenocarcinoma, 19 patients (9.9%) with papillary predominant adenocarcinoma, one patient with solid predominant adenocarcinoma, and one patient with invasive mucinous adenocarcinoma. Among these patients, no positive N1 or N2 lymph node findings were observed. Moreover, the 5-year recurrence-free survival was still 100%, although the final pathologic results turned out to be IAC. INTERPRETATION: Patients undergoing limited resection of invasive LUAD misdiagnosed as AAH, AIS, or MIA by FS analysis showed excellent prognoses. Sublobar resection guided by FS diagnosis would be adequate for these underestimated cases of invasive LUAD.

Transcutaneous Stimulation of Auricular Branch of the Vagus Nerve Attenuates the Acute Inflammatory Response After Lung Lobectomy.

OBJECTIVES: Systemic inflammation is a potentially debilitating complication of thoracic surgeries with significant physical and economic morbidity. There is compelling evidence for the role of the central nervous system in regulating inflammatory processes through humoral mechanisms. Activation of the afferent vagus nerve by cytokines triggers anti-inflammatory responses. Peripheral electrical stimulation of the vagus nerve in vivo during lethal endotoxemia in rats inhibited tumor necrosis factor synthesis and prevented shock development. However, the vagal regulatory role of systemic inflammation after lung lobectomy is unknown. METHODS: One hundred patients who underwent lobectomy via thoracotomy were recruited and equally randomized to treated group or controls. Intermittent stimulation of the auricular branch of vagus nerve in the triangular fossa was applied in the treated group using neurostimulator V (Ducest®, Germany), starting 24 h preoperatively and continued till the 4th postoperative day (POD). Inflammatory interleukins (IL) were analyzed using ELISA preoperatively, on the 1st and 4th POD. RESULTS: On the 1st POD, patients who underwent neurostimulation had reduced serum concentrations of CRP (p = 0.01), IL6 (p = 0.02) but elevated IL10 (p = 0.03) versus controls. On the 4th POD, serum concentrations of CRP, IL6 and IL10 were similar in both groups. Moreover, the treated group was associated with lower incidence of pneumonia (p = 0.04) and shorter hospitalization time (p = 0.04) versus controls. CONCLUSIONS: Modulations in the brain stem caused by noninvasive transcutaneous stimulation of the vagus nerve after lung lobectomy attenuate the acute postsurgical inflammatory response by the regulation of IL6 and IL10, resulting in  reduced incidence of postoperative pneumonia and short hospitalization time. CLINICAL TRIAL REGISTRY NUMBER: NCT03204968.

Use of 3-D navigation to target the site of autologous blood installation for lung volume reduction in bullous emphysema.

Bronchoscopic lung volume reduction (BLVR) using intrabullous autologous blood instillation has been reported in single cases where other techniques are not possible. We present the use of three-dimensional navigation to instill autologous blood into emphysematous bullae for BLVR. A 62-year-old man presented with increasing dyspnea, due to emphysema with a conglomerate of giant bullae with two particularly large bullae. Surgical treatment was refused, so bronchoscopic autologous blood instillation into the bronchial segment leading to the large bullae was attempted, but was unsuccessful; blood failed to penetrate into the bullous cavity. Dyspnea worsened over the following year. We therefore performed another bronchoscopy and punctured a large bulla with a needle and created a tunnel from the central airways. Puncture position and direction were determined using a prototype of an electromagnetic navigation system. Under fluoroscopic guidance, a catheter was placed via the tunnel into the bulla and blood was instilled. This resulted in an almost complete shrinkage of the bullae, reduction of residual volume, and marked improvement in dyspnea within 4 months. To our knowledge, this is the first reported case of successful BLVR by navigated bronchoscopy with transbronchial puncture, dilatation, and autologous blood instillation into a giant bulla.

Endobronchial and surgical treatment of pulmonary carcinoid tumors: A systematic literature review.

The treatment of pulmonary carcinoid has changed over the last decades. Although surgical resection is still the gold standard, minimally invasive endobronchial procedures have emerged as a parenchyma sparing alternative for tumors located in the central airways. This review was performed to identify the optimal treatment strategy for pulmonary carcinoid, with a particular focus on the feasibility and outcome of parenchyma sparing techniques versus surgical resection. A systematic review of the literature was carried out using MEDLINE, Embase and the Cochrane databases, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. Two separate searches of publications in endobronchial and surgical treatment in patients with pulmonary carcinoid, were performed. Outcomes were overall survival, disease free survival, recurrence rate, complications, quality of life, and healthcare costs. Combining the two main searches for endobronchial therapy and surgical therapy yielded 3111 records. Finally, 43 studies concerning surgical treatment and 9 studies related to endobronchial treatment for pulmonary carcinoid were included. Assessment of included studies showed that lymph node involvement, histological grade, tumor location and tumor diameter were identified as poor prognostic factors and seem to be important for patients with pulmonary carcinoid. For patients with a more favorable prognosis, tumor location and tumor diameter are important factors that can help decide on the optimal treatment strategy. Centrally located small intraluminal pulmonary carcinoids, without signs of metastasis can be treated with minimally invasive alternatives such as endobronchial treatment or parenchyma sparing surgical resection. Patients with parenchyma sparing resections should be followed with long term follow up to exclude recurrence of disease. In a multidisciplinary setting, it should be determined whether individual patients are eligible for parenchyma sparing procedures or anatomical resection. Overall evidence is of low quality and future studies should focus on prospective trials in the treatment of pulmonary carcinoid.

Adjuvant Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (TKIs) in Resected Non-Small Cell Lung Cancer (NSCLC): A Systematic Review and Meta-analysis.

The role of adjuvant tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) is not well defined. Recent randomized controlled trials showed a disease-free survival (DFS) benefit in patients harboring an epidermal growth factor receptor (EGFR) mutation. Yet, older trials on patients with any EGFR status did not demonstrate the same benefit. We aimed to assess the efficacy and safety of adjuvant TKIs in NSCLC patients. The electronic databases Medline (PubMed) and EMBASE were searched for relevant randomized controlled trials. Random effect models were used. The primary outcome was DFS measured as hazard ratio (HR). The secondary outcomes were overall survival (OS) measured as HR, 2-year DFS and toxicity expressed as risk ratio and odds ratio (OR), respectively. Subgroup analyses assessed DFS by trial design. Six trials incorporating 1860 patients were included. In patients harboring an EGFR mutation, adjuvant TKIs decreased the risk of disease recurrence by 48% (HR: 0.52, 95% confidence interval [CI]: 0.35-0.78), improved 2-year DFS (HR: 0.53, 95% CI: 0.43-0.66) but did not improve OS (HR: 0.64, 95% CI: 0.22-1.89). The risk of developing ≥grade 3 skin toxicity (OR: 6.07, 95% CI: 4.34-8.51) and diarrhea (OR: 4.05; 95% CI: 2.44-6.74) was increased. In subgroup analyses, the DFS benefit was more pronounced in trials using TKIs over chemotherapy compared with trials using TKIs postchemotherapy. In conclusion, adjuvant TKIs decrease the risk of recurrence in NSCLC patients harboring an EGFR mutation but do not improve OS. Longer follow-up is needed for a definitive assessment of OS and to define the role of adjuvant TKI for NSCLC in the clinical practice.

The Bronchus First and Vessels Simultaneously Stapled Technique: A Safe and Simple Method for Video-Assisted Right Upper Lobe Lobectomy.

OBJECTIVE: Video-assisted thoracic surgery lobectomy is a minimally invasive procedure for major pulmonary resection. The purpose of this study was to present a novel approach with a thoracoscope in the right upper lobe and to compare different lobectomy methods at our institution. METHODS: We reviewed the medical records of patients who underwent a thoracoscopic right upper lobectomy for lung cancer between September 2015 and September 2016. We performed 128 thoracoscopic right upper lobectomies: group A (n = 50) was treated with the bronchus-first and vessels simultaneously stapled method and group B (n = 78) was treated with the conventional isolation-ligation method. Preoperative mediastinal staging and lymphadenectomy followed the National Comprehensive Cancer Network guidelines. The intra- and postoperative outcomes were recorded and statistically compared. RESULTS: All patients underwent successful thoracoscopic right upper lobectomies. No significant differences in mean intraoperative blood loss, massive hemorrhage (>500 mL), and postoperative complications were observed between the two groups (p < 0.05). The mean operative time of group A was less than that of group B (110.80 ± 34.74 versus 167.01 ± 48.38 minutes, p = 0.000). The mean duration of chest drainage in group A was 4.34 ± 2.06 days, which was shorter than that of group B (5.85 ± 3.13 days, p = 0.017). No significant differences were observed in the local recurrence and distant recurrence between the two groups during the postoperative follow-up. CONCLUSIONS: Thoracoscopic right upper lobectomy with the lobectomy bronchus-first and vessels simultaneously stapled method is a safe and efficient procedure that leads to better recovery.

Early Versus Late Paravertebral Block for Analgesia in Video-Assisted Thoracoscopic Lung Resection. A Double-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVES: Paravertebral local analgesia is effective in providing pain relief after video assisted thoracoscopic surgery. This randomized, double-blind pilot clinical trial investigated the effect of early perioperative delivery of paravertebral local analgesia to reduce postoperative pain after video assisted thoracoscopic lung resection and the feasibility of a larger trial. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: University hospital, single institution. PARTICIPANTS: Patients over 18 years of age having video assisted lung resection surgery. INTERVENTIONS: 90 patients undergoing video assisted lung resection were randomized to receive bupivacaine via paravertebral catheter either before lung resection (early; n = 47) or at the end of the operation (late; n = 43). The primary outcome measure was pain on coughing during the first 24 postoperative hours. The 95% confidence interval for a median difference was calculated using the Hodges-Lehman median difference method. MEASUREMENTS AND MAIN RESULTS: There was no difference in pain scores between groups over the first 24 postoperative hours. The median (range) morphine equivalent consumption after 24 hours was 34 (7.3-105) mg with early paravertebral bupivacaine and 40.7 (3-91) mg after late paravertebral bupivacaine. The prevalence of chronic pain at 12 months postoperatively was 8.7% with early paravertebral bupivacaine and 25.8% with late paravertebral bupivacaine; the difference was not statistically significant. CONCLUSIONS: The authors found no difference in acute postoperative pain, but the decrease in morphine consumption and prevalence of chronic pain with early paravertebral bupivacaine, although not statistically significant, may warrant further investigation with a larger trial.

A bicenter study on adjuvant surgery following treatment with tyrosine kinase inhibitors in patients with advanced lung adenocarcinoma.

OBJECTIVES: A small number of patients with advanced pulmonary adenocarcinomas treated with tyrosine kinase inhibitors (TKIs) was subsequently considered eligible for surgery. Our goal was to report the clinical characteristics, pathological features and prognosis of these patients with the aim of exploring the feasibility of this strategy of care. METHODS: We retrospectively reviewed the medical files of 19 patients in whom systemic treatment, including TKIs, resulted in a possible stabilization of the disease such that they were considered eligible for surgery (adjuvant surgery). RESULTS: Lobectomy, pneumonectomy or segmentectomy was performed in 68.4%, 26.3% and 5.3% of cases, respectively. Limited fibrotic tissues were detected intraoperatively in 8 patients who received TKIs as the sole systemic treatment. The postoperative course in the hospital was uneventful in 13 (68.4%) cases; 3 (15.8%) patients suffered major complications. The post-pneumonectomy early morbidity rate was 60%. A pathological analysis of the tumours showed that the median rate of fibrosis was 32.5% (0-100); of viable neoplastic tissue, 25.0% (0-90); and of necrosis, 12.5% (0-80%). Four tumours (21.1%) exhibited no viable tumour cells. The fibrosis ratio was higher in patients older than 60 years (P = 0.01) and in those treated with erlotinib (P = 0.03). The 3- and 5-year overall survival and disease-free survival rates were 79.5%/39.8% and 44.4%/29.6%, respectively. Pneumonectomy and <50% fibrosis or >30% viable tumour cells in the pathological specimens were factors significantly associated with lower disease-free survival. CONCLUSIONS: In a subset of highly selected patients, adjuvant lung surgery following treatment with TKI showed a large spectrum of histological changes in the pathological specimens and encouraging preliminary survival results. Pending further research, it may prove a relatively reliable and safe therapeutic choice, except when an extensive resection like a pneumonectomy is planned.

Effectiveness of Implemented Interventions on Pathologic Nodal Staging of Non-Small Cell Lung Cancer.

BACKGROUND: Accurate pathologic nodal staging improves early stage non-small cell lung cancer survival. In an ongoing implementation study, we measured the impact of a surgical lymph node specimen collection kit and a more thorough pathologic gross dissection method on attainment of guideline-recommended pathologic nodal staging quality. METHODS: We prospectively collected data on curative intent non-small cell lung cancer resections from 2009 to 2016 from 11 hospitals in four contiguous Dartmouth Hospital referral regions. We categorized patients into four groups based on exposure to the two interventions in our staggered implementation study design. We used χ2 tests to examine the differences in demographic and disease characteristics and surgical quality criteria across implementation groups. RESULTS: Of 2,469 patients, 1,615 (65%) received neither intervention; 167 (7%) received only the pathology intervention; 264 (11%) received only the surgery intervention; and 423 (17%) had both. Rates of nonexamination of lymph nodes reduced sequentially in the order of no intervention, novel dissection, kit, and combined interventions, including nonexamination of any lymph nodes and hilar/intrapulmonary and mediastinal nodes (p < 0.001 for all comparisons). The rates of attainment of National Comprehensive Cancer Network, Commission on Cancer, American Joint Committee on Cancer, and American College of Surgeons Oncology Group guidelines increased significantly in the same sequential order (p < 0.001 for all comparisons). CONCLUSIONS: The combined effect of two interventions to improve pathologic lymph node examination has a greater effect on attainment of a range of surgical quality criteria than either intervention alone.

Radical multimodality therapy for malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma is an almost always fatal tumour, for which palliative platinum-based chemotherapy is currently the standard treatment. Multimodal therapeutic strategies incorporating surgery, radiation therapy or photodynamic therapy and chemotherapy have been recommended for selected patients but there is no consensus about their effectiveness. OBJECTIVES: To assess the benefits and harms of radical multimodal treatment options (including radical surgery ± radical radiotherapy ± photodynamic therapy ± systemic therapy) compared to each other or to palliative treatments, for people with malignant pleural mesothelioma. SEARCH METHODS: We reviewed data from the Cochrane Lung Cancer group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase. We also checked reference lists of primary original studies, review articles and relevant conference proceedings manually for further related articles up to 21 March 2017. SELECTION CRITERIA: We included parallel-group randomised controlled trials of multimodal therapy for people with malignant pleural mesothelioma (stages I, II or III) that measured at least one of the following endpoints: overall survival, health-related health-related quality of life, adverse events or progression-free survival. We considered studies regardless of language or publication status. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted relevant information on participant characteristics, interventions, study outcomes, and data on the outcomes for this review, as well as information on the design and methodology of the studies. Two review authors assessed the risk of bias in the included trials using pre-defined 'Risk of bias' domains. We assessed the methodological quality using GRADE. MAIN RESULTS: We conducted this review in accordance with the published Cochrane protocol. Two randomised clinical trials with 104 participants fulfilled our inclusion criteria. Both trials were at high risk of bias (for outcomes other than overall survival), and we rated the evidence as moderate quality for overall survival and low quality for all other outcomes. One trial compared combined extrapleural pneumonectomy (EPP) plus neoadjuvant platinum-based chemotherapy plus postoperative high-dose hemithoracic radiotherapy with combined EPP plus platinum-based chemotherapy. The other trial compared EPP plus postoperative hemithoracic radiotherapy with standard (non-radical) therapy alone following platinum-based chemotherapy (patients in the standard therapy arm received continued oncological management according to local policy, which could include further chemotherapy or palliative radiotherapy).For the first trial, median overall survival calculated from registration was 20.8 months (95% confidence interval (CI) 14.4 to 27.8) in the no-radiotherapy group and 19.3 months (95% CI 11.5 to 21.8) in the radiotherapy group. For the second trial, median overall survival was 14.4 months (95% CI 5.3 to 18.7) for patients allocated to EPP and 19.5 months (95% CI 13.4 to time not yet reached) for patients randomised to standard non-radical therapy. In the second trial, 12 serious adverse events were reported during the study period: ten in the EPP group and two in the non-radical therapy group. Overall health-related quality of life scores were not different between the two arms in either study. We could not perform a meta-analysis of the two included trials due to clinical heterogeneity. We also identified three ongoing trials evaluating the topic of our review. AUTHORS' CONCLUSIONS: The overall strength of the evidence gathered in this review is low and there is a lack of available evidence to support the use of radical multimodality therapy in routine clinical practice (particularly as one trial suggests greater harm). Given the added cost of multimodality treatment and the possible increase in risk of adverse effects, the lack of evidence of their effectiveness probably means that these interventions should currently be limited to clinical trials alone.