Study protocol for Near-infrared molecular imaging for lung cancer detection and treatment during mini-invasive surgery (phase II Trial) - (the RECOGNISE study).

INTRODUCTION: To date, radical surgery remains the best curative option in patients with early-stage lung cancer. In patients with small lung lesions, video-assisted thoracic surgery (VATS) should be increasingly chosen as a fundamental alternative to thoracotomy as it is associated with less postoperative pain and better quality of life. This scenario necessarily increases the need for thoracic surgeons to implement new localization techniques. The conventional near-infrared (NIR) indocyanine green (ICG) method demonstrated a significant limitation in deep cancer recognition, principally due to its intrinsic low-depth tissue penetration. Similarly, the lymph-node sentinel approach conducted by the ICG method was demonstrated to be inefficient, mainly due to the non-specificity of the tracker and the irregular pathway of pulmonary lymph node drainage. Our study aims to evaluate the effectiveness of Cetuximab- IRDye800CW in marking lung nodules and mediastinal lymph nodes. METHODS AND ANALYSIS: This study is defined as an open-label, single-arm, single-stage phase II trial evaluating the effectiveness of Cetuximab-IRDye800CW in detecting tumors and lymph-node metastases in patients with lung cancer who are undergoing video-assisted thoracic surgery (VATS). Cetuximab is a monoclonal antibody that binds, inhibits, and degrade the EGFR. The IRDye® 800CW, an indocyanine-type NIR fluorophore, demonstrated enhanced tissue penetration compared to other NIR dyes. The combination with the clinical approved monoclonal antibody anti-epidermal growth factor EGFR Cetuximab (Cetuximab-IRDye800) has shown promising results as a specific tracker in different cancer types (i.e., brain, pancreas, head, and neck). The study's primary outcome is focused on the proportion of patients with lung nodules detected during surgery using an NIR camera. The secondary outcomes include a broad spectrum of items, including the proportion of patients with detection of unexpected cancer localization during surgery by NIR camera and the proportion of patients with negative surgical margins, the evaluation of the time spawns between the insertion of the NIR camera and the visualization of the nodule and the possible morbidity of the drug assessed during and after the drug infusion. ETHICS AND DISSEMINATION: This trial has been approved by the Ethical Committee of Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino (Torino, Italy) and by the Italian Medicines Agency (AIFA). Findings will be written as methodology papers for conference presentations and published in peer-reviewed journals. The Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, the University of Torino, and the AIRC Public Engagement Divisions will help identify how best to publicize the findings.Trial registration EudraCT 202,100,645,430. CLINICALTRIALS: gov NCT06101394 (October 23, 2023).

A Practical Guide for Using the EZ-Blocker Endobronchial Blocker: Tips and Tricks After 10 Years of Experience.

The EZ-Blocker (EZB) is a "Y-shaped," semirigid endobronchial blocker used for lung isolation and one-lung ventilation during thoracic surgery. Like many medical tools, initial efforts to use this endobronchial blocker may prove challenging for the uninitiated. However, some tips and tricks can be applied fairly rapidly to aid the clinician in properly placing the device, and, furthermore, may help the clinician get the most out of this innovative device. This article focuses on some of the technical aspects of its placement that the authors have developed over time. Additionally, other facets and potential pitfalls are discussed that relate to intraprocedural issues that may sometimes arise when using this device. The following aspects of the EZB as a lung-isolation device are discussed: standard positioning techniques, alternative positioning techniques, use in pediatric patients, approaches to achieving exceptional lung isolation, advanced uses, and limitations and potential issues. Although some information was taken from the authors' rather extensive experience with using this endobronchial blocker, some of the relevant literature are also reviewed, with the goal of being to improve the reader's knowledge of the device and improve the likelihood of its successful placement. The underlying design of the EZB remains unique among commercially available bronchial blockers in improving positional stability. The Y-shaped conformation, however, can lead to challenges when positioning the device in some patients. Therefore, some very practical tips and tricks are provided to assist the clinician in correctly positioning the device and other hints to improve the quality of lung isolation and surgical conditions.

Italian survey on non-intubated thoracic surgery: results from INFINITY group.

BACKGROUND: Non-Intubated Thoracic Surgery (NITS) is becoming increasingly adopted all over the world. Although it is mainly used for pleural operations,, non-intubated parenchymal lung surgery has been less frequently reported. Recently, NITS utilization seems to be increased also in Italy, albeit there are no multi-center studies confirming this finding. The objective of this survey is to assess quantitatively and qualitatively the performance of NITS in Italy. METHODS: In 2018 a web-based national survey on Non-Intubated management including both thoracic surgeons and anesthesiologists was carried out. Reference centers have been asked to answer 32 questions. Replies were collected from June 26 to November 31, 2019. RESULTS: We raised feedbacks from 95% (55/58) of Italian centers. Seventy-eight percent of the respondents perform NITS but only 38% of them used this strategy for parenchymal surgery. These procedures are more frequently carried out in patients with severe comorbidities and/or with poor lung function. Several issues as obesity, previous non-invasive ventilation and/or oxygen therapy are considered contraindications to NITS. The regional anesthesia technique most used to provide intra- and postoperative analgesia was the paravertebral block (37%). Conversion to general anesthesia is not anecdotal (31% of answerers). More than half of the centers believed that NITS may reduce postoperative intensive care unit admissions. Approximately a quarter of the centers are conducting trials on NITS and, three quarters of the respondent suppose that the number of these procedures will increase in the future. CONCLUSIONS: There is a growing interest in Italy for NITS and this survey provides a clear view of the national management framework of these procedures.

Video-assisted thoracic surgery or thoracotomy for lung cancer surgery in obese patients? An analysis of the European Society of Thoracic Surgeons database.

OBJECTIVES: There is a lack of evidence on whether perioperative outcomes differ in obese patients after video-assisted thoracic surgery (VATS) or open lobectomy. We queried the European Society of Thoracic Surgeons database to assess morbidity and postoperative length of hospital stay in obese patients submitted to VATS and open pulmonary lobectomy for non-small-cell lung cancer. METHODS: We collected all consecutive patients from 2007 to 2021 submitted to lobectomy through VATS or thoracotomy with a body mass index greater than or equal to 30. An intention-to-treat analysis was carried out. Primary outcomes were morbidity rate, mortality and postoperative length of stay (LOS). Differences in outcomes were assessed through univariable, multivariable-adjusted and propensity score-matched analysis. RESULTS: Out of a total of 78 018 patients submitted to lung lobectomy, 13 999 cases (17.9%) were considered in the analysis, including 5562 VATS lobectomies and 8437 thoracotomy lobectomies. The VATS group showed a lower complication rate (23.2% vs 30.2%, P < 0.001), mortality (0.8% vs 1.5%, P < 0.001) and postoperative LOS (median 5 vs 7 days, P < 0.001). After propensity score matching, the VATS approach confirmed a lower complication rate (24.7% vs 29.7%, P = 0.002) and postoperative LOS (median 5 vs 7 days, P < 0.001). Moreover, these results were consistently observed when analyzing the severe obese subgroup (body mass index 35-39.9) and morbid obese subgroup (body mass index ≥40). CONCLUSIONS: In obese patients with non-small cell lung cancer, VATS lobectomy was found to be associated with improved postoperative outcomes than open lobectomy. Consequently, it should be considered the approach of choice for the Obese population.

The effect of peripheral regional analgesia in thoracic surgery: a systematic review and a meta-analysis of randomized-controlled trials.

BACKGROUND: Several peripheral regional anaesthesia (RA) techniques are commonly used in thoracic surgery even in the absence of precise indications regarding their effectiveness on postoperative pain management. OBJECTIVE: This systematic review and meta-analysis aims to describe and evaluate the relative effectiveness of different peripheral regional blocks and systemic analgesia in the context of video-assisted thoracoscopic surgery (VATS) or thoracotomy. DESIGN: Systematic review of randomized controlled clinical trials (RCTs) with meta-analyses. DATA SOURCES: We searched PubMed and Embase for all RCTs comparing the 24 hour morphine equivalents (MMEs) consumption following peripheral regional blocks and systemic analgesia (SA). ELIGIBILITY CRITERIA: We selected only RCTs including adult participants undergoing thoracic surgery, including esophagectomy and reporting on postoperative pain outcomes including 24 hour MMEs consumption. RESULTS: Among the 28 randomized studies including adult participants undergoing thoracic surgery and reporting on 24 hour opioid consumption, 11 reporting a comparison of individual blocks with systemic analgesia were meta-analyzed. RA was effective for almost all peripheral blocks. Regarding intercostal block, its antalgic effect was not well evaluated SMD -1.57 (CI -3.88, 0.73). RA in VATS was more effective in reducing MMEs than thoracotomy SMD -1.10 (CI -1.78, -0.41). CONCLUSIONS: RA is a useful choice in thoracic surgery. However, it is still not possible to determine the most appropriate block in the individual surgical settings to be performed due to RCTs paucity.

Impact of intubated vs. non-intubated anesthesia on postoperative diaphragmatic function: Results from a prospective observational study.

Background: An altered diaphragmatic function was associated with the development of postoperative pulmonary complications following thoracic surgery. Methods: To evaluate the impact of different anesthetic techniques on postoperative diaphragmatic dysfunction, patients undergoing video-assisted thoracoscopic surgery (VATS) lung biopsy for interstitial lung disease were enrolled in a monocentric observational prospective study. Patients received intubated or non-intubated anesthesia according to risk assessment and preferences following multidisciplinary discussion. Ultrasound measured diaphragmatic excursion (DIA) and Thickening Fraction (TF) were recorded together with arterial blood gases and pulmonary function tests (PFT) immediately before and 12 h after surgery. Pain control and postoperative nausea and vomiting (PONV) were also evaluated. Results: From February 2019 to September 2020, 41 consecutive patients were enrolled. Five were lost due to difficulties in collecting postoperative data. Of the remaining 36 patients, 25 underwent surgery with a non-intubated anesthesia approach whereas 11 underwent intubated general anesthesia. The two groups had similar baseline characteristics. On the operated side, DIA and TF showed a lower residual postoperative function in the intubated group compared to the non-intubated group (54 vs. 82% of DIA and 36 vs. 97% of TF; p = 0.001 for both). The same was observed on the non-operated side (58 vs. 82% and 62 vs. 94%; p = 0.005 and p = 0.045, respectively, for DIA and TF). No differences were observed between groups in terms of pain control, PONV, gas exchange and PFT. Conclusion: This study suggests that maintenance of spontaneous breathing during VATS lung biopsy is associated with better diaphragmatic residual function after surgery.

The Anesthesiologist's Perspective Regarding Non-intubated Thoracic Surgery: A Scoping Review.

Non-intubated thoracic surgery (NITS) is a growing practice, alongside minimally invasive thoracic surgery. To date, only a consensus of experts provided opinions on NITS leaving a number of questions unresolved. We then conducted a scoping review to clarify the state of the art regarding NITS. The systematic review of all randomized and non-randomized clinical trials dealing with NITS, based on Pubmed, EMBASE, and Scopus, retrieved 665 articles. After the exclusion of ineligible studies, 53 were assessed examining: study type, Country of origin, surgical procedure, age, body mass index, American Society of Anesthesiologist's physical status, airway management device, conversion to orotracheal intubation and pulmonary complications rates and length of hospital stay. It emerged that NITS is a procedure performed predominantly in Asia, and certain European Countries. In China, NITS is more frequently performed for parenchymal resection surgery, whereas in Europe, it is mainly employed for pleural pathologies. The most commonly used device for airway management is the laryngeal mask. The conversion rate to orotracheal intubation is a~3%. The results of the scoping review seem to suggest that NITS procedures are becoming increasingly popular, but its role needs to be better defined. Further randomized clinical trials are needed to better define the role of the clinical variables possibly impacting on the technique effectiveness. Systematic Review Registration: https://osf.io/mfvp3/, identifier: 10.17605/OSF.IO/MFVP3.

Impact of analgesia on cancer recurrence and mortality within 5 years after stage I non-small cell lung cancer resection.

OBJECTIVE: The choice of analgesia after cancer surgery may play a role in the onset of cancer recurrence. Particularly opioids seem to promote cancer cell proliferation and migration. Based on this consideration, we assessed the impact of perioperative analgesia choice on cancer recurrence after curative surgery for stage I non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed the records of all patients undergoing lung resection for stage I NSCLC between January 2005 and December 2012. Patients received analgesia either by peridural (PERI group) or intravenous analgesia with opioids (EV group). Follow-up was concluded in August 2019. Five-year cumulative incidence of recurrence and overall survival were evaluated and adjusted using a propensity score matching method. RESULTS: A total of 382 patients were evaluated, 312 belonging to the PERI group (81.7%) and 70 to the EV group (18.3%). There was no statistically significant difference between the two groups in 5-year cumulative incidence of recurrence (p = 0.679) or overall survival rates (p = 0.767). These results were confirmed after adjustment for propensity score matching for cumulative incidence of recurrence (p = 0.925) or overall survival (p = 0.663). CONCLUSIONS: We found no evidence suggesting an association between perioperative analgesia choice and recurrence-free survival or overall survival in patients undergoing surgical resection of stage I NSCLC.

Lung Biopsy With a Non-intubated VATS Approach in an Obese Population: Indications and Results.

Background: According to the international guidelines, patients affected by interstitial lung disease with unusual clinical presentation and radiological findings that are not classic for usual interstitial pneumonia end up meeting criteria for surgical lung biopsy, preferably performed with video-assisted thoracic surgery. The growing appeal of non-intubated thoracic surgery has shown the benefits in several different procedures, but the strict selection criteria of candidates are often considered a limitation to this approach. Although several authors define obesity as a contraindication for non-intubated thoracoscopic surgery, the assessment of obesity as a dominant risk factor represents a topic of debate when minor tubeless procedures such as lung biopsy are considered. Our study aims to investigate the impact of obesity on morbidity and mortality in non-intubated lung biopsy patients with interstitial lung disease, analyzing the efficacy and safeness of this procedure. Materials and Methods: The study group of 40 obese patients consecutively collected from 202 patients who underwent non-intubated lung biopsy was compared with overweight and normal-weight patients, according to their body mass index. Post-operative complications were identified as the primary endpoint. The other outcomes explored were the early 30-day mortality rate and intraoperative complications, length of surgery, post-operative hospitalization, patient's pain feedback, and diagnostic yield. Results: The overall median age of the patients was 67.4 years (60, 73.5). No 30-day mortality or significant differences in terms of post-operative complications (P = 0.93) were noted between the groups. The length of the surgery was moderately longer in the group of obese patients (P = 0.02). The post-operative pain rating scale was comparable among the three groups (P = 0.45), as well as the post-operative length of stay (P = 0.96). The diagnosis was achieved in 99% of patients without significant difference between groups (P = 0.38). Conclusion: Our analysis showed the safety and efficacy of surgical lung biopsy with a non-intubated approach in patients affected by lung interstitiopathy. In the context of perioperative risk stratification, obesity would not seem to affect the morbidity compared to normal-weight and overweight patients undergoing this kind of diagnostic surgical procedure.

Continuous erector spinae plane block for postoperative analgesia in robotic lung lobectomy: a case report.

BACKGROUND: Erector spinae plane block (ESPB) has been described as an effective regional anesthesia technique in thoracic parenchymal surgery. Evidence highlighting the use of this technique continuously via perifascial catheter is lacking. CASE PRESENTATION: In this case report, we present the case of a patient scheduled for robotic-assisted thoracic surgery for a pulmonary neoformation in the lower right lobe. We decided to manage this patient with a multimodal approach in order to have an opioid-sparing effect. This is the first reported case of continuous ESPB in robot-assisted thoracic surgery. CONCLUSIONS: Anesthesiologists should consider this method in surgery that is slower than conventional surgery, such as robot-assisted, and less invasive than thoracotomy, which does not warrant the use of neuroaxial or paravertebral techniques that increase the risk of iatrogenic complications.