Video-assisted thoracoscopic lobectomy after neoadjuvant chemotherapy for non-small cell lung cancer: a multicenter propensity-matched study.

BACKGROUND: The role of video-assisted thoracoscopic surgery for the treatment of non-small-cell lung cancer after neoadjuvant chemotherapy remains controversial. The aim of this study is to demonstrate the reliability of video-assisted lobectomy compared to the open approach by evaluating perioperative and long-term outcomes. METHODS: In this retrospective, multicentric study from January 2010 to December 2018, we included all patients with non-small-cell lung cancer who underwent lobectomy through the video-assisted or open approach after neoadjuvant chemotherapy. The perioperative outcomes, including data concerning the feasibility of the surgical procedure, the occurrence of any medical and surgical complications and long-term oncological evidence, were collected and compared between the two groups. To minimize selection bias, propensity score matching was performed. RESULTS: A total of 286 patients were enrolled: 193 underwent thoracotomy lobectomy, and 93 underwent VATS lobectomy. The statistical analysis showed that surgical time (P < 0.001), drainage time (P < 0.001), days of hospitalization (P < 0.001) and VAS at discharge (P = 0.042) were lower in the VATS group. The overall survival and disease-free survival were equivalent for the two techniques on long-term follow-up. CONCLUSIONS: VATS lobectomy represents a valid therapeutic option in patients affected by non-small-cell lung cancer after neoadjuvant chemotherapy. The VATS approach in our experience seems to be superior in terms of the perioperative outcomes, while maintaining oncological efficacy.

VATS-US1: Thoracoscopic ultrasonography for the identification of nodules during lung metastasectomy.

Open thoracotomy during pulmonary metastasectomy allows lung palpation and may discover unexpected further nodules. We assess the validity of intraoperative lung ultrasonography via thoracoscopy in identifying lung nodules. A first surgeon will perform an ultrasonographic investigation on the deflated lung by thoracoscopy. A second surgeon will then perform a manual exploration of the organ by thoracotomy. Data on number and localization of nodules will be matched and compared with final histology report. Sensitivity and specificity will be assessed. Concordance will be assessed with Cohen K test. Calculated sample size is 89 patients. This study might have an important role in shifting the surgical practice towards a less invasive approach, with consequent benefits for the patient. Protocol is registered on clinicaltrials.gov. Protocol registration number: NCT03864874.

Lymphadenectomy during pulmonary metastasectomy: Impact on survival and recurrence.

BACKGROUND AND OBJECTIVES: Lymphadenectomy during pulmonary metastasectomy (PM) is widely carried out. We assessed the potential benefit on patient survival and tumor recurrence of this practice. METHODS: One hundred eighty-one patients undergoing a first PM were studied. Eighty-six patients (47.5%) underwent lymphadenectomy (L+ group) whereas 95 (52.5%) did not undergo nodal harvesting (L-group). Main outcomes were overall survival (OS) and disease-free survival (DFS). Median follow-up was 25 months (interquartile range [IQR], 13-49). RESULTS: At follow-up 84 patients (46.4%) died, whereas 97 (53.6%) were still alive with recurrence in 78 patients (43%). There was no difference in 5-year survival (L+ 30.0% vs L- 43.2%; P = .87) or in the 5-year cumulative incidence of recurrence (L + 63.2% vs L-80%; P = .07) between the two groups. Multivariable analysis indicated that disease-free interval (DFI) less than 29 months (P < .001) and lung comorbidities (P = .003) were significant predictors of death. Metastases from non-small-cell lung cancer increased the risk of lung comorbidities by a factor of 19.8, whereas the risk of DFI less than 29 months was increased nearly 11-fold. Competing risk regression identified multiple metastases (P = .004), head/neck primary tumor (P = .009), and age less than 67 years (P = .024) as independent risk factors for recurrence. CONCLUSION: Associated lymphadenectomy showed not to give any additional advantage in terms of survival and recurrence after PM.

Hybrid minimally invasive treatment of intralobar pulmonary sequestration: a single-centre experience.

Pulmonary sequestrations are rare congenital malformations. They are often located in the lower lobes, and they are supplied by an aberrant systemic vessel arising from the thoracic aorta or abdominal arteries. These pulmonary malformations are divided into intra- and extralobar sequestrations, depending on the respective lack or presence of an independent pleural covering. Pulmonary sequestration can be asymptomatic or lead to recurrent pulmonary infections. The goal of this study was to analyse the feasibility and safety of a hybrid sequential approach. We report a small series of intralobar pulmonary sequestrations, from November 2017 to December 2018, successfully treated with a hybrid minimally invasive approach consisting of endovascular embolization of the aberrant arterial branch followed by video-assisted thoracoscopic lobectomy the day after. Thoracic pain following endovascular embolization was noted in all cases. Patients were discharged early in the absence of major postoperative complications. Prolonged air leak was observed in only 1 case. Despite the presence of sequestration-related pulmonary inflammation, in our experience, hybrid treatment for intralobar pulmonary sequestration is a safe and reproducible approach in terms of postoperative complications and hospital stay.

Fluorescence-Guided Identification of the Thoracic Duct by VATS for Treatment of Postoperative Chylothorax: A Short Case Series.

Background: Chylothorax is a relatively rare complication after surgery of the mediastinum. The occurrence and the results of surgical treatment of this condition are difficult to foresee due to the wide heterogeneity in thoracic duct anatomy. Case summary: We report two cases of postoperative chylothorax treated with ligation by video-assisted thoracoscopic surgery (VATS). The first patient developed a massive left chylothorax shortly after discharge, following radical excision of a seminoma-involved left para-aortic lymphadenopathy. The second patient developed a high-output right chylothorax following VATS upper bilobectomy. In both cases, a surgical revision by VATS was performed. Inguinal injection of indocyanine green allowed an easy visualization of the lymphatic leakage point. In both cases, oral feeding was rapidly restarted after surgery. No recurrence of chylothorax was observed. Conclusion: The use of indocyanine green may greatly improve the identification of the thoracic duct during surgical ligation by VATS, with a favorable impact on the postoperative course and overall admission costs.

Work in progress report of a multicentre retrospective observational study to evaluate the association between the airflows and the intrapleural pressures digitally recorded after video-assisted lobectomy.

OBJECTIVES: Digital chest drainage systems allow real-time and continuous monitoring and recording of air leak flow rate and intrapleural pressure (IPP) from the immediate postoperative period to the chest drainage removal. A multicentre retrospective observational analysis of consecutive patients undergoing pulmonary lobectomy for lung cancer was performed to evaluate the association between the airflow and IPP digitally recorded during the immediate postoperative period after video-assisted thoracic surgery (VATS) lobectomy for lung cancer. Here, we present a work in progress report. METHODS: All patients treated with VATS lobectomies for lung cancer were included. Multiple airflow measurements and minimum and maximum IPP through the chest tubes were digitally monitored and recorded using microelectronic mechanical sensor technology. The PALs were defined as an air leak lasting >5 days from the conclusion of the surgical procedure. The cessation of air leaks was defined as an airflow <10 ml/min during 6 consecutive hours. RESULTS: This analysis comprised 76 patients who underwent VATS lobectomy for lung cancer. Nineteen patients (25%) showed prolonged air leaks (PAL) (≥5 days). The operative time was higher in the PAL group (mean difference = 44 min) without a statistically significant difference. Before the 7th postoperative hours, there were no statistically significant differences in IPPs. CONCLUSIONS: Patients with PAL showed less negative IPP in the first 24 postoperative hours. Therefore, the 7th-24th postoperative hours were critical in PAL prediction since the mechanism for PAL seems to develop after the 7th postoperative hour.

A risk stratification scheme for synchronous oligometastatic non-small cell lung cancer developed by a multicentre analysis.

BACKGROUNDS: Oligometastatic Non-Small Cell Lung Cancer (NSCLC) patients represent a category without a standard therapeutic approach. However, in selected oligometastatic NSCLC, radical surgery seems to offer a good prognosis. This retrospective study aimed to analyse the long-term outcomes of synchronous oligometastatic patients treated with curative intent and identify the factors associated with better results and the proposal of a risk stratification system for classifying the synchronous oligometastatic NSCLC. METHODS: The medical records of patients from 18 centres with pathologically diagnosed synchronous oligometastatic NSCLC were retrospectively reviewed. The inclusion criteria were synchronous oligometastatic NSCLC, radical surgical treatment of the primary tumour with or without neoadjuvant/adjuvant therapy and radical treatment of all metastatic sites. The Kaplan - Meier method estimated survivals. A stratified backward stepwise Cox regression model was assessed for multivariable survival analyses. RESULTS: 281 patients were included. The most common site of metastasis was the brain, in 50.89 % patients. Median overall survival was 40 months (95 % CI: 29-53). Age ≤65 years (HR = 1.02, 95 % CI: 1.00-1.05; p = 0.019), single metastasis (HR = 0.71, 95 % CI: 0.45-1.13; p = 0.15) and presence of contralateral lung metastases (HR = 0.30, 95 % CI: 0.15 - 0.62; p = 0.001) were associated with a good prognosis. The presence of pathological N2 metastases negatively affected survival (HR = 2.00, 95 % CI: 1.21-3.32; p = 0.0065). These prognostic factors were used to build a simple risk classification scheme. CONCLUSIONS: Treatment of selected synchronous oligometastatic NSCLC with curative purpose could be conducted safely and at acceptable 5-year survival levels, especially in younger patients with pN0 disease.

The Role of Obesity in Early and Long-Term Outcomes after Surgical Excision of Lung Oligometastases from Colorectal Cancer.

Obesity correlates with better outcomes in many neoplastic conditions. The aim of this study was to assess its role in the prognosis and morbidity of patients submitted to resection of lung oligometastases from colorectal cancer. Seventy-six patients undergoing a first pulmonary metastasectomy were retrospectively included in the study. Seventeen (22.3%) were obese (body mass index (BMI) >30 kg/m2). Assessed outcomes were overall survival, time to recurrence, and incidence of post-operative complications. Median follow-up was 33 months (IQR 16-53). At follow-up, 37 patients (48.6%) died, whereas 39 (51.4%) were alive. A significant difference was found in the 3-year overall survival (obese 80% vs. non-obese 56.8%, p = 0.035). Competing risk analysis shows that the cumulative incidence of recurrence was not different between the two groups. Multivariate analysis reveals that the number of metastases (p = 0.028), post-operative pneumonia (p = 0.042), and DFS (p = 0.007) were significant predictors of death. Competing risk regression shows that no independent risk factor for recurrence has been identified. The complication rate was not different between the two groups (17.6% vs. 13.6%, p = 0.70). Obesity is a positive prognostic factor for survival after pulmonary metastasectomy for colorectal cancer. Overweight patients do not experience more post-operative complications. Our results need to be confirmed by large multicenter studies.

Surgery versus stereotactic radiotherapy for treatment of pulmonary metastases. A systematic review of literature.

It is not clear as to which is the best treatment among surgery and stereotactic radiotherapy (SBRT) for lung oligometastases. A systematic review of literature with a priori selection criteria was conducted on articles on the treatment of pulmonary metastases with surgery or SBRT. Only original articles with a population of patients of more than 50 were selected. After final selection, 61 articles on surgical treatment and 18 on SBRT were included. No difference was encountered in short-term survival between pulmonary metastasectomy and SBRT. In the long-term surgery seems to guarantee better survival rates. Mortality and morbidity after treatment are 0-4.7% and 0-23% for surgery, and 0-2% and 4-31% for SBRT. Surgical metastasectomy remains the treatment of choice for pulmonary oligometastases.

The Impact of Preoperative Inflammatory Markers on the Prognosis of Patients Undergoing Surgical Resection of Pulmonary Oligometastases.

The aim of this study was to assess the prognostic value of preoperative neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) levels in patients undergoing resection of pulmonary oligometastases. A retrospective analysis on 141 patients undergoing a first pulmonary metastasectomy in a single center was carried out. Two distinct analysis were performed subdividing patients according to their NLR ratio and CRP level. The main outcomes were survival and time to recurrence. At completion of follow-up 74 patients were still alive (52.5%). Subdividing patients according to their NLR yielded a significant difference in five-year progression-free survival (PFS, NLR < 4:32% vs. NLR ≥ 4:18%, p = 0.01). When subdivided by their CRP levels, patients with preoperative CRP < 5 mg/L demonstrated higher values of five-year overall survival (OS, 57% vs. 34%, p = 0.006) and five-year PFS (35% vs. 22%, p = 0.04). At multivariate analysis, level of neutrophils (p = 0.009) and lung comorbidities (p = 0.021) were independent predictors of death, whereas preoperative CRP (p = 0.002), multiple metastases (p = 0.003) and presence of lung comorbidities (p = 0.001) were independent predictors of recurrence. NLR and CRP are important predictors of prognostic outcome in patients undergoing pulmonary metastasectomy.

Chest wall reconstruction using a new titanium mesh: a multicenters experience.

BACKGROUND: Many new surgical techniques and materials have been introduced in the last decade for chest wall reconstruction or stabilization with the purpose of improving the incorporation, maintaining chest wall stability with reduction of infections. However, none of them are yet considered a gold standard procedure. The aim of this work is to evaluate the initial experience using a new titanium mesh for chest wall reconstruction in four Italian Thoracic Surgery Departments. METHODS: A review was performed of all patients undergoing chest wall reconstruction using a new titanium mesh between January 2014 and September 2018. Surgical indications, the location and size of the chest wall defect, intraoperative variables and postoperative complications were analyzed. RESULTS: A total of 26 consecutive patients were included. The most common indications for surgery were primary or secondary chest wall tumors (38%) followed by lung cancer invading chest wall (31%). The most common localization of chest wall defect was anterolateral (46%). Sternal reconstruction was required in 3 patients (12%). The average size of the defect was 9.3×7.8 cm. The median number of resected ribs was 3.6. No perioperative deaths occurred. Mean hospital stay was 11.9 days. Overall morbidity was 19%. One failure of reconstruction (4%) was reported during follow up. CONCLUSIONS: In our early clinical experience chest wall reconstruction using titanium mesh can be performed as a safe and effective surgical procedure. This mesh has excellent biomechanical characteristics between rigid and malleable materials, it's easy to trim and fix for optimal adaptation without necessity of dedicated instruments. The early and mid-term results are satisfactory with low incidence of complications related to the titanium mesh implant.

Small incisions, major complications: video-assisted thoracoscopic surgery management of intraoperative complications.

The object of our study is to show the causes leading to conversion, in order to observe the responsible variables and analyses if conversion influences the patient's outcome. Between January 2013 and December 2016, Udine Thoracic Department performed 180 video-assisted thoracoscopic surgery (VATS) lobectomies, and 24 cases were converted to thoracotomy due to an intra-operative complication such as arterial or venous bleeding, airway and other injuries. The VATS lobectomies' number increased over the three years: from 27 in 2013 to 55 in 2015 and 48 in 2016. While conversion's rate decreased from 33% in 2013 to 5.5% in 2015 and 10% in 2016. We performed a univariate and a multivariate analysis looking for the variables affecting the conversion rate. This was significantly related to intraoperative bleeding and airway injuries (P<0,001). Seventy-year older patients were not associated to a higher conversion rate, instead they showed an increased risk of post-operative complications (P<0,018, RR =1.8). We have focused our attention on all the variables leading to conversion and conditioning the patient's outcome in terms of post-operative complications and length of stay. The best strategy to face VATS complication is to prevent them. Young surgeons at the beginning of their learning curve should perform VATS lobectomies under close supervision of a skilled VATS surgeon. Moreover, conversion to open thoracotomy should be not considered a failure of VATS, but rather a procedure for patient's safety.

Tumor measurements on computed tomographic images of non-small cell lung cancer were similar among cancer professionals from different specialties.

OBJECTIVE: In this study, we addressed the influence of the observer's background and experience on the accuracy of imaging-based tumor measurements. The consistency of measures with Response Evaluation Criteria in Solid Tumors (RECIST) vs. WHO criteria is also reported. STUDY DESIGN AND SETTING: Twenty-five observers (five radiologists, five thoracic surgeons, five radiotherapists, five pulmonologists, and five medical oncologists) were asked to measure three lesions on selected serial chest computed tomographic images from three non-small cell lung cancer patients treated with chemotherapy. The observers were asked to measure the longest diameter (RECIST), along with its perpendicular diameter (WHO criteria). Measurements by radiologists were used as reference values. RESULTS: There was no significant difference in the accuracy of measurements among the different groups. The highest intraobserver consistency was achieved by radiologists. Neither familiarity with measuring tumor lesions nor years since the MD degree correlated with measurement accuracy. A comparison of RECIST and WHO criteria showed consistent response ratings (kappa=.74, CI 95%=.57-.91). CONCLUSION: Measurements of selected lesions were consistent among specialists, suggesting that assessment of tumor response is reliable even when it is not done by radiologists.

Sequential chemotherapy with paclitaxel plus cisplatin, followed by vinorelbine, followed by gemcitabine in advanced non-small cell lung cancer: an Alpe-Adria Thoracic Oncology Multidisciplinary group study (ATOM 001).

Aim of this study was to determine the activity and toxicity of a sequential chemotherapy regimen in advanced non-small cell lung cancer (NSCLC). Fifty-one previously untreated stage IIIB/IV NSCLC patients were enrolled to receive two cycles of cisplatin plus paclitaxel (80/175 mg/m(2) every 21 days), followed by two cycles of vinorelbine (30 mg/m(2) on days 1 and 8 every 21 days), followed by two cycles of gemcitabine (1000 mg/m(2) on days 1, 8, and 15 every 28 days). Forty-one patients (82%) completed the planned six cycles. Grade 3-4 neutropenia was the major toxicity (41% of patients) and it was mainly associated with vinorelbine administration. Response rate after cisplatin plus paclitaxel was 18%; this percentage increased to 41% after vinorelbine, and it reached 43% upon completion of the entire six cycle treatment program. Median survival time was 14.4 months, 1-year survival rate was 53%, and 2-year survival rate was 18%. Median time to disease progression was 6.8 months. This sequential chemotherapy regimen is feasible and active in patients with advanced NSCLC. This pilot experience provides the basis for an ongoing randomized phase III trial comparing our sequential regimen versus cisplatin plus gemcitabine.

Video-assisted thoracoscopic surgery for primary chylopericardium after orthotopic heart transplantation.

Chylopericardium is a rare complication of cardiac surgical procedures. We describe a 41-year-old woman who underwent orthotopic heart transplantation and developed chylopericardium early in the post-operative period. Because of unsuccessful conservative treatment (pericardiocentesis, pericardial drainage, low-fat diet with medium-chain triglycerides, and total parenteral nutrition), surgical intervention was indicated and the patient successfully underwent right-sided thoracoscopic duct ligation and partial pericardiectomy (pericardial window).

The dos and do knots of central venous catheterization.

Central venous catheterization plays an important role in patients with end-stage renal disease undergoing hemodialysis. Placement of a right subclavian hemodialysis catheter was complicated by looping and entrapment of the guidewire. Computed tomographic and three-dimensional scans were essential in locating and determining that the guidewire was outside the vessel.

Adopting integrated care pathways in non-small-cell lung cancer: from theory to practice.

INTRODUCTION: Integrated care pathways (ICPs) have been proposed as effective strategies for quality improvement. To date, limited data are available that detail the methodology to design an optimal care pathway for patients with non-small-cell lung cancer (NSCLC). The main aim of this study was to assess the quality of health care delivered to lung cancer patients referred to a hub university hospital. METHODS: All professionals involved with the management of NSCLC patients, in cooperation with health care researchers, identified 11 quality indicators and associated benchmarks. These were used to estimate the quality and efficiency of health care delivered to a cohort of 175 NSCLC patients. RESULTS: The gap between "desired" and "actual" performance has been measured by benchmarking current practice against key quality indicators. Diagnostic workup, multidisciplinary team care and medical treatment of advanced disease have emerged as areas of good performance. Conversely, the management of early-stage disease offers room for improvement, in terms of both accuracy of nodal staging and surgical timeliness. CONCLUSIONS: Analyzing the process of caring for NSCLC patients is feasible and offers room for improvement. Acquired knowledge may be shared with hospital administrators, guide the revision of ICPs, and enable the delivery of consistent, high-quality clinical standards.

Partitioning of bronchopulmonary carcinoids in two different prognostic categories by ki-67 score.

INTRODUCTION: Histological distinction between typical and atypical bronchopulmonary carcinoids is based on mitotic activity and necrosis. Regardless of these two parameters, outcome after surgery is often unpredictable. In this study the prognostic value of different clinico-pathological factors was retrospectively analyzed in a large series of patients with bronchopulmonary carcinoid. MATERIALS AND METHODS: The long-term post-surgical outcome of 106 radically treated patients affected by bronchopulmonary carcinoid from two Italian centers was correlated with tumor characteristics assessed by combining conventional histology with a panel of immunohistochemical markers of neuroendocrine differentiation (chromogranin-A, NSE) and proliferation activity (Ki-67 score). RESULTS: Carcinoids were assessed as typical (TC = 75; 70.8%) and atypical (AC = 31; 29.2%). Mean follow-up was 8.3 years (range: 0-20; median: 8.0). All cases expressed neuroendocrine markers. At univariate analysis, tumor recurrence [14/75 TC (18.7%), 15/31 AC (48.4%)] correlated with carcinoid histotype (P = 0.003), tumor size (P = 0.012), mitotic index (P = 0.044), Ki-67 score (P < 0.0001), and synchronous node metastasis (P = 0.037). Of these, Cox multivariate analysis confirmed only Ki-67 score as independent predictor of disease recurrence (P = 0.009). The best cut-off for Ki-67 score (calculated by ROC curves) discriminating recurrent vs non-recurrent disease was 4% (sensitivity 79.3%; specificity 83.8%; area under the curve 0.85). By stratifying patients according to this cut-off, a significantly different disease-free survival was found (log-rank test P < 0.0001). CONCLUSION: Ki-67 score accurately separates bronchopulmonary carcinoids in two well-distinct histo-prognostic categories. Ki-67 score predicts the patients outcome better than mitotic count, histotype, and tumor stage and it is therefore helpful in establishing the appropriate follow-up.

Prognostic stratification of stage IIIA pN2 non-small cell lung cancer by hierarchical clustering analysis of tissue microarray immunostaining data: an Alpe Adria Thoracic Oncology Multidisciplinary Group study (ATOM 014).

INTRODUCTION: Stage IIIA non-small cell lung cancer (NSCLC) with ipsilateral mediastinal lymph node metastases (N2) is a heterogeneous disease with differing prognoses. In this study, we retrospectively investigated the prognostic value of the expression of 10 molecular markers in 87 patients with stage IIIA pN2 NSCLC treated with radical surgery. METHODS: Primary tumor tissue microarrays (TMAs) were constructed and sections used for immunohistochemical analysis of epidermal growth factor receptor, ErbB-2, c-kit, cyclooxygenase-2, survivin, bcl-2, cyclin D1, cyclin B1, metalloproteinase (MMP)-2, and MMP-9. Univariate and multivariate analyses and unsupervised hierarchical clustering analysis of clinical pathologic and immunostaining data were performed. RESULTS: Bcl-2 (p < 0.0001) and cyclin D1 (p = 0.015) were more highly expressed in squamous cell carcinoma (SCC), whereas MMP-2 (p = 0.009), MMP-9 (p = 0.005), and survivin (p = 0.032) had increased expression in other histologic subtypes. In univariate analysis, SCC histology and cyclin D1 expressions were favorable prognostic factors (p = 0.015 and p < 0.0001, respectively); by contrast, MMP-9 expression was associated with worse prognosis (p = 0.042). In multivariate analysis, cyclin D1 was the only positive prognostic factor (p < 0.0001). Unsupervised hierarchical clustering analysis of TMA immunostaining data identified five distinct clusters. They formed two subsets of patients with better (clusters 1 and 2) and worse (clusters 3, 4, and 5) prognoses, and median survival of 51 and 10 months, respectively (p < 0.0001). The better prognosis subset mainly comprised patients with SCC (80%). CONCLUSIONS: Hierarchical clustering of TMA immunostaining data using a limited set of markers identifies patients with stage IIIA pN2 NSCLC at high risk of recurrence, who may benefit from more aggressive treatment.