Resectability versus Operability in Early-Stage Non-Small Cell Lung Cancer.

PURPOSE OF REVIEW: With increased detection of early-stage non-small cell lung cancer (NSCLC) owing to screening, determining optimal management increasingly hinges on assessing resectability and operability. Resectability refers to the feasibility of achieving microscopically negative margins based on tumour size, location and degree of local invasion and achieving an anatomical lobar resection. Operability reflects the patient's tolerance for resection based on comorbidities, cardiopulmonary reserve and frailty. Standardized criteria help guide these assessments, but application variability contributes to practice inconsistencies. This review synthesizes a strategic approach to evaluating resectability and operability in contemporary practice. Standardization promises reduced care variability and optimized patient selection to maximize curative outcomes in this new era of early detection. RECENT FINDINGS: Recent pivotal trials demonstrate equivalency of sublobar resection to lobectomy for small, peripheral, node-negative NSCLC, expanding options for parenchymal preservation in borderline surgical candidates. Furthermore, recent phase 3 trials have highlighted the benefit of chemoimmunotherapy as a neoadjuvant treatment with an excellent pathological response and a down staging of the tumour, improving the resectability of the early-stage NSCLC. A good assessment of the operability and resectability is paramount in order to offer the best course of treatment for our patients. European and American societies have issued recommendations to help clinicians assess the cardiopulmonary function and predict the extension of pulmonary resection that could afford the patient. This operability assessment is closely linked with the evaluated tumour resectability which will determine the extension of pulmonary resection that is needed for the patient in order to achieve a good oncological outcome. Some major progresses have been done recently to improve the operability and resectability of patients. For instance, prehabilitation program allows better postoperative morbidity. Some studies have shown a potential good oncological outcome with sublobar resection expending access to surgery for patient with reduced lung function. Some others have identified the neoadjuvant immunochemotherapy as a potential solution for downstaging tumours. Work-up of early-stage NSCLC is a key moment and has to be done thoroughly and in full knowledge of the recent findings in order to propose the most appropriate treatment for the patient.

Endoscopic pyloromyotomy in minimally invasive esophagectomy: a novel approach.

BACKGROUND: Pyloric drainage procedures, namely pyloromyotomy or pyloroplasty, have long been considered an integral aspect of esophagectomy. However, the requirement of pyloric drainage in the era of minimally invasive esophagectomy (MIE) has been brought into question. This is in part because of the technical challenges of performing the pyloric drainage laparoscopically, leading many surgical teams to explore other options or to abandon this procedure entirely. We have developed a novel, technically facile, endoscopic approach to pyloromyotomy, and sought to assess the efficacy of this new approach compared to the standard surgical pyloromyotomy. METHODS: Patients who underwent MIE for cancer from 01/2010 to 12/2019 were identified from a prospectively maintained institutional database and were divided into two groups according to the pyloric drainage procedure: endoscopic or surgical pyloric drainage. 30-day outcomes (complications, length of stay, readmissions) and pyloric drainage-related outcomes [conduit distension/width, nasogastric tube (NGT) duration and re-insertion, gastric stasis] were compared between groups. RESULTS: 94 patients were identified of these 52 patients underwent endoscopic PM and 42 patients underwent surgical PM. The groups were similar with respect to age, gender and comorbidities. There were more Ivor-Lewis esophagectomies in the endoscopic PM group than the surgical PM group [45 (86%), 15 (36%) p < 0.001]. There was no significant difference in the rate of complications and readmissions. Gastric stasis requiring NGT re-insertion was rare in the endoscopic PM group and did not differ significantly from the surgical PM group (1.9-4.7% p = 0.58). CONCLUSIONS: Endoscopic pyloromyotomy using a novel approach is a safe, quick and reproducible technique with comparable results to a surgical PM in the setting of MIE.

Feasibility analysis for the development of a video-assisted thoracoscopic (VATS) lobectomy 23-hour recovery pathway.

Background: Video-assisted thoracoscopic (VATS) lobectomy has been demonstrated to offer several benefits over open surgery. The purpose of this study was to assess the feasibility and safety of an ultra-fast-track 23-hour recovery pathway for VATS lobectomy. Methods: A prospectively maintained institutional database was queried for patients who underwent VATS lobectomy from 2006 to 2016 at the McGill University Health Centre in Montreal, Quebec, and data were supplemented with focused chart review. Patients discharged with a length of stay (LOS) of 23 hours or less were compared with those with an LOS of 2 days or more. Logistic regression was performed to identify predictors of LOS of 23 hours or less. Results: Two hundred and five patients were included in the study. Perioperative 30-day mortality for our cohort was 0% and the major complication rate was 8.3%. The median LOS was 3 days (interquartile range [IQR] 2-4 d). Thirty-four patients were discharged within 23 hours and none of them required readmission; 171 patients were discharged on postoperative day 2 or later and 9 of them (5.3%) required readmission (p = 0.36). The proportion of patients discharged within 23 hours increased in 2016 compared with previous years (25.8% v. 12.0%, p = 0.05). Patients discharged within 23 hours had shorter chest tube duration (odds ratio [OR] 0.20, 95% confidence interval [CI] 0.09-0.46, p < 0.001), lower clinical stage disease (stages II-III v. stage I OR 0.07, 95% CI 0.01-0.52, p = 0.011), lower pathologic stage lesions (stages II-III v. stage I OR 0.26, 95% CI 0.07-0.91, p = 0.035), fewer surgical complications (OR 0.04, 95% CI 0.01-0.30, p = 0.002) and shorter operative time (surgery duration > 120 min OR 0.42, 95% CI 0.18-0.95, p = 0.04). Our exploratory prediction modelling showed that chest tube duration, clinical stage and surgeon were the most influential predictors of discharge within 23 hours. Conclusion: The only preoperative factors that predicted shorter LOS in our cohort were clinical stage and surgeon. A significant proportion of patients can be discharged safely by adopting a VATS lobectomy 23-hour enhanced recovery pathway.

Contexte: Il a été démontré que la lobectomie par chirurgie thoracique vidéoassistée (CTVA) offre plusieurs avantages comparativement à la chirurgie ouverte. La présente étude avait pour but d'évaluer la faisabilité et la sûreté d'un protocole de récupération ultrarapide en 23 heures pour la lobectomie par CTVA. Méthodes: Nous avons extrait d'une base de données d'établissement maintenue de manière prospective des données sur les patients ayant subi une lobectomie par CTVA entre 2006 et 2016 au Centre universitaire de santé McGill à Montréal (Québec), complétées par un examen ciblé des dossiers. Les patients ayant reçu leur congé après une hospitalisation de 23 heures ou moins ont été comparés à ceux dont l'hospitalisation avait duré 2 jours ou plus. Nous avons ensuite mis en évidence les facteurs prédictifs d'une hospitalisation de 23 heures ou moins par une analyse de régression logistique. Résultats: Deux cent cinq patients ont été inclus dans l'étude. La mortalité périopératoire dans les 30 jours suivant l'intervention était de 0 % dans notre cohorte, et le taux de complications majeures était de 8,3 %. La durée d'hospitalisation médiane était de 3 jours (écart interquartile [EI] 2 à 4 jours). Trente-quatre patients ont reçu leur congé dans les 23 heures suivant l'intervention, et aucun n'a dû être réhospitalisé; comparativement, 171 patients ont reçu leur congé au deuxième jour ou après, et 9 d'entre eux (5,3 %) ont dû être réhospitalisés (p = 0,36). Le pourcentage de patients ayant reçu leur congé dans les 23 heures a augmenté en 2016 par rapport aux années précédentes (25,8 % c. 12,0 %, p = 0,05). Les patients au congé dans les 23 heures conservaient leur drain thoracique moins longtemps (rapport de cotes [RC] 0,20, intervalle de confiance [IC] de 95 % 0,09 à 0,46, p < 0,001); leur stade clinique était moins élevé (stades II à III c. stade I ­ RC 0,07, IC de 95 % 0,01 à 0,52, p = 0,011); le stade pathologique de leurs lésions était plus faible (stades II à III c. stade I ­ RC 0,26, IC de 95 % 0,07 à 0,91, p = 0,035); ils avaient moins de complications chirurgicales (RC 0,04, IC de 95 % 0,01 à 0,30, p = 0,002); et la durée de leur intervention était plus courte (durée de la chirurgie > 120 minutes ­ RC 0,42, IC de 95 % 0,18 à 0,95, p = 0,04). Notre modèle prédictif exploratoire a montré que le délai avant le retrait du drain thoracique, le stade clinique et le chirurgien était les facteurs prédictifs les plus importants du congé dans les 23 heures. Conclusion: Les seuls facteurs préopératoires permettant de prédire une hospitalisation plus courte dans notre cohorte étaient le stade clinique et le chirurgien. Un pourcentage important des patients peuvent recevoir leur congé sans danger si on suit un protocole de récupération optimisée en 23 heures après une lobectomie par CTVA.

Anatomical Resections Improve Survival Following Lung Metastasectomy of Colorectal Cancer Harboring KRAS Mutations.

OBJECTIVE: The aim of this study was to evaluate the benefit of anatomical resection (AR) in lung metastasectomy (LM) of colorectal cancer (CRC) harboring KRAS mutations SUMMARY BACKGROUND DATA:: KRAS mutations are related to high aggressiveness in the lung metastasis of CRC. It is unknown whether AR can lead to better outcomes than can non-AR (NAR) in KRAS patients. METHODS: We retrospectively reviewed the data from 574 consecutive patients who underwent a LM for CRC. We focused on patients exhibiting 1 lung metastasis who underwent an AR (segmentectomy) or an NAR (wedge) and for whom the KRAS mutational status was known. Overall survival (OS) and time to pulmonary recurrence (TTPR) were analyzed. RESULTS: We included 168 patients, of whom 95 (56.5%) harbored KRAS mutations. An AR was performed in 74 patients (44%). The type of resection did not impact the median OS in wild-type (WT) patients (P = 0.67) but was significantly better following AR in KRAS patients (101 vs 45 months, P = 0.02) according to the multivariate analysis [hazard ratio (HR): 6.524; 95% confidence interval (CI), 2.312-18.405; P < 0.0001). TTPR was not affected by the type of resection in WT patients (P = 0.32) but was significantly better for AR in KRAS patients (50 vs 15 months, P = 0.01) in the multivariate analysis (HR: 5.273; 95% CI, 1.731-16.064; P = 0.003). The resection-margin recurrence rate was significantly higher for NAR in KRAS patients (4.8% vs 54.2%, P = 0.001) but not in WT patients (P = 0.97). CONCLUSION: AR seems to improve both the OS and TTPR in LM of CRC harboring KRAS mutations.

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

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

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

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

Specific KRAS amino acid substitutions and EGFR mutations predict site-specific recurrence and metastasis following non-small-cell lung cancer surgery.

BACKGROUND: We aimed to evaluate whether EGFR mutations (mEGFR) and KRAS amino acid substitutions can predict first site of recurrence or metastasis after non-small-cell lung cancer (NSCLC) surgery. METHODS: Data were reviewed from 481 patients who underwent thoracic surgery for NSCLC between 2007 and 2012. RESULTS: Patients with KRAS G12C developed significantly more bone metastases compared with the remainder of the cohort (59% vs 16%, P<0.0001). This was confirmed in multivariate analysis (MA) (odds ratio (OR): 0.113 (95% confidence interval (CI): 0.055-0.231), P<0.0001). Significantly, more patients with mEGFR developed liver and brain metastases compared with the remainder of the cohort (30% vs 10%, P=0.006; 59% vs 1%, P<0.0001, respectively). These were confirmed in MA (OR: 0.333 (95% CI: 0.095-0.998), P=0.05; OR: 0.032 (95% CI: 0.008-0.135), P<0.0001, respectively). Patients with KRAS G12V developed significantly more pleuro-pericardial metastases compared with the remainder of the cohort (94% vs 12%, P<0.0001). This was confirmed in MA (OR: 0.007 (95% CI: 0.001-0.031), P<0.0001). Wild-type patients developed significantly more lung metastases (35% vs 10%, P<0.0001). This was confirmed in MA (OR: 0.383 (95% CI: 0.193-0.762), P=0.006). CONCLUSION: Epidermal growth factor receptor mutation and KRAS amino acid substitutions seem to predict site-specific recurrence and metastasis after NSCLC surgery.

Impact of EGFR mutations and KRAS amino acid substitution on the response to radiotherapy for brain metastasis of non-small-cell lung cancer.

BACKGROUND: Our study aimed to evaluate response rate (RR) to brain metastasis radiotherapy (RT), depending on the genomic status of non-small-cell lung cancer. MATERIAL & METHODS: We retrospectively reviewed 1971 non-small-cell lung cancer files of patients with EGFR and KRAS testing and focused on 157 patients who had undergone RT for brain metastasis. RESULTS: A total of 16 patients (10.2%) harbored EGFR mutations (mEGFR) and 45 patients (28.7%) KRAS (mKRAS). In univariate analysis, RR was significantly higher for mEGFR compared with wild-type EGFR/KRAS (odds ratio [OR]: 4.96; p = 0.05) or mKRAS (OR: 1.81; p = 0.03). In multivariate analysis, KRAS G12V or G12C status was associated with both poor RR (OR: 0.1; p < 0.0001) and overall survival (OR: 3.41; p < 0.0001). CONCLUSION: mEGFR are associated with higher RR to brain RT than wild-type EGFR/RAS or mKRAS.

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

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

Clinicopathological factors associated with sentinel lymph node detection in non-small-cell lung cancer.

BACKGROUND: Mapping of the pulmonary lymphatic system by near-infrared (NIR) fluorescence imaging might not always identify the first lymph node relay. The aim of this study was to determine the clinicopathologic factors allowing the identification of sentinel lymph nodes (SLNs) by NIR fluorescence imaging in thoracic surgery for non-small-cell lung cancer (NSCLC). METHODS: We conducted a retrospective review of 92 patients treated for suspected or confirmed cN0 lung cancer with curative intent who underwent an intraoperative injection of indocyanine green (ICG) either by direct peritumoral injection or by endobronchial injection using electromagnetic navigational bronchoscopy (ENB). After exclusion of patients for technical failure, benign disease and metastasis, we analyzed the clinicopathologic findings of 65 patients treated for localized-stage NSCLC, comparing the group with identification of SLNs (SLN-positive group) with the group without identification of SLNs (SLN-negative group). RESULTS: Forty-eight patients (73.8%) were SLN-positive. Patients with SLN positivity were more frequently female (50%) than the SLN-negative patients were (11.8%) (p = 0.006). The mean value of diffusing capacity for carbon monoxide (DLCO) was lower among the patients in the SLN-negative group (64.7% ± 16.7%) than the SLN-positive group (77.6% ± 17.2%, p < 0.01). The ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FCV) was higher in the SLN-positive group (69.0% vs. 60.8%, p = 0.02). Patients who were SLN-negative were characterized by a severe degree of emphysema (p = 0.003). There was no significant difference in pathologic characteristics. On univariate analyses, age, female sex, DLCO, FEV1/FVC, degree of emphysema, and tumor size were significantly associated with SLN detection. On multivariate analysis, DLCO > 75% (HR = 4.92, 95% CI: 1.27-24.7; p = 0.03) and female sex (HR = 5.55, 95% CI: 1.25-39.33; p = 0.04) were independently associated with SLN detection. CONCLUSIONS: At a time of resurgence in the use of the sentinel lymph node mapping technique in the field of thoracic surgery, this study enabled us to identify, using multivariate analysis, two predictive factors for success: DLCO > 75% and female sex. Larger datasets are needed to confirm our results.

Impact of surgical approach on 90-day mortality after lung resection for nonsmall cell lung cancer in high-risk operable patients.

Introduction: Non-small cell lung cancer (NSCLC) is often associated with compromised lung function. Real-world data on the impact of surgical approach in NSCLC patients with compromised lung function are still lacking. The objective of this study is to assess the potential impact of minimally invasive surgery (MIS) on 90-day post-operative mortality after anatomic lung resection in high-risk operable NSCLC patients. Methods: We conducted a retrospective multicentre study including all patients who underwent anatomic lung resection between January 2010 and October 2021 and registered in the Epithor database. High-risk patients were defined as those with a forced expiratory volume in 1 s (FEV1) or diffusing capacity of the lung for carbon monoxide (DLCO) value below 50%. Co-primary end-points were the impact of risk status on 90-day mortality and the impact of MIS on 90-day mortality in high-risk patients. Results: Of the 46 909 patients who met the inclusion criteria, 42 214 patients (90%) with both preoperative FEV1 and DLCO above 50% were included in the low-risk group, and 4695 patients (10%) with preoperative FEV1 and/or preoperative DLCO below 50% were included in the high-risk group. The 90-day mortality rate was significantly higher in the high-risk group compared to the low-risk group (280 (5.96%) versus 1301 (3.18%); p<0.0001). In high-risk patients, MIS was associated with lower 90-day mortality compared to open surgery in univariate analysis (OR=0.04 (0.02-0.05), p<0.001) and in multivariable analysis after propensity score matching (OR=0.46 (0.30-0.69), p<0.001). High-risk patients operated through MIS had a similar 90-day mortality rate compared to low-risk patients in general (3.10% versus 3.18% respectively). Conclusion: By examining the impact of surgical approaches on 90-day mortality using a nationwide database, we found that either preoperative FEV1 or DLCO below 50% is associated with higher 90-day mortality, which can be reduced by using minimally invasive surgical approaches. High-risk patients operated through MIS have a similar 90-day mortality rate as low-risk patients.

Place of robotic surgery in completion lobectomy after anatomical segmentectomy.

OBJECTIVES: Although segmentectomy is steadily increasing in early-stage non-small-cell lung cancer, recurrence in the ipsilateral lobe is also increasing. Completion lobectomy (CL) is a challenging procedure that has already been described in a few studies using video-assisted thoracic surgery or thoracotomy. In this study, we aimed to show the feasibility and safety of robot-assisted thoracic surgery in cases of CL. METHODS: Among 2073 major resections performed between January 2018 and september 2022 in the Department of Thoracic Surgery at Nancy University Regional Hospital, we retrospectively included patients who underwent CL by robot-assisted thoracic surgery after previous segmentectomy for non-small-cell lung cancer. Data and perioperative results were described and analysed. RESULTS: Seventeen patients underwent CL with a median recurrence time after previous segmentectomy of 18 months [interquartile range (IQR): 12]. Four patients (23.5%) had a pulmonary artery injury that was controlled, and no conversion to open thoracotomy was needed. The operative time was 150 min (IQR: 20), and blood loss was 300 ml (IQR: 150). The median postoperative chest tube duration was 2 days (IQR: 1), and the length of hospital stay was 3 days (IQR: 3), with no postoperative deaths. CONCLUSIONS: Completion lobectomy is a challenging procedure due to severe adhesions surrounding vessels, which potentially could cause higher rate of PA bleeding than conventional surgeries. With experienced team and surgeons, CL with robotic surgery may be reported as a safe and feasible procedure.

Triggering Receptors Expressed on Myeloid Cells 1 : Our New Partner in Human Oncology?

Inflammation is recognized as one of the hallmarks of cancer. Indeed, strong evidence indicates that chronic inflammation plays a major role in oncogenesis, promoting genome instability, epigenetic alterations, proliferation and dissemination of cancer cells. Mononuclear phagocytes (MPs) have been identified as key contributors of the inflammatory infiltrate in several solid human neoplasia, promoting angiogenesis and cancer progression. One of the most described amplifiers of MPs pro-inflammatory innate immune response is the triggering receptors expressed on myeloid cells 1 (TREM-1). Growing evidence suggests TREM-1 involvement in oncogenesis through cancer related inflammation and the surrounding tumor microenvironment. In human oncology, high levels of TREM-1 and/or its soluble form have been associated with poorer survival data in several solid malignancies, especially in hepatocellular carcinoma and lung cancer. TREM-1 should be considered as a potential biomarker in human oncology and could be used as a new therapeutic target of interest in human oncology (TREM-1 inhibitors, TREM-1 agonists). More clinical studies are urgently needed to confirm TREM-1 (and TREM family) roles in the prognosis and the treatment of human solid cancers.

Sentinel Lymph Node in Non-Small Cell Lung Cancer: Assessment of Feasibility and Safety by Near-Infrared Fluorescence Imaging and Clinical Consequences.

Occult micrometastases can be missed by routine pathological analysis. Mapping of the pulmonary lymphatic system by near-infrared (NIR) fluorescence imaging can identify the first lymph node relay. This sentinel lymph node (SLN) can be analyzed by immunohistochemistry (IHC), which may increase micrometastasis detection and improve staging. This study analyzed the feasibility and safety of identifying SLNs in thoracic surgery by NIR fluorescence imaging in non-small cell lung cancer (NSCLC). This was a prospective, observational, single-center study. Eighty adult patients with suspected localized stage NSCLC (IA1 to IIA) were included between December 2020 and May 2022. All patients received an intraoperative injection of indocyanine green (ICG) directly in the peri tumoural area or by electromagnetic navigational bronchoscopy (ENB). The SLN was then assessed using an infrared fluorescence camera. SLN was identified in 60 patients (75%). Among them, 36 SLNs associated with a primary lung tumor were analyzed by IHC. Four of them were invaded by micrometastases (11.1%). In the case of pN0 SLN, the rest of the lymphadenectomy was cancer free. The identification of SLNs in thoracic surgery by NIR fluorescence imaging seems to be a feasible technique for improving pathological staging.

Neutrophil-to-lymphocyte ratio is correlated to driver gene mutations in surgically-resected non-small cell lung cancer and its post-operative evolution impacts outcomes.

BACKGROUND: We sought to evaluate prognostic value of neutrophil-to-lymphocyte ratio (NLR) in surgically resected non-small cell lung cancer (NSCLC) and its correlation to oncogenic drivers. We retrospectively reviewed data of patients who underwent anatomic lung resection for NSCLC and whose mutational status was known, from 4 department of thoracic surgery, over the period 2008 to 2019. Primary endpoints were overall survival (OS) and time to recurrence (TTR). Clinical and molecular factors were investigated in the univariate and multivariate analysis for their association with the primary endpoints. RESULTS: 2027 patients were included in the analysis. Correlations between NLR and OS (R2=0.21), NLR and TTR (R2=0.085) were significant (P<0.0001), with corresponding Pearson R of -0.46 (P<0.0001) and -0.292 (P<0.001), respectively. ROC curve analysis defined NLR cut-off value at 4.07. In the univariable analysis, the median OS was 66 months (95% CI: 62.94 - 69.06) in case of pre-operative NLR ≤ 4.07 and 38 months (95% CI: 36.73 - 39.27) in case of pre-operative NLR > 4.07 (P<0.0001), with corresponding 5-y OS of 72% and 29% respectively. Median TTR was associated with pre-operative NLR. Median TTR was 25 months (95% CI: 21.52 - 28.48) in case of pre-operative NLR ≤ 4.07 and 17 months (95% CI: 16.04 - 17.96) in case of pre-operative NLR > 4.07 (P<0.0001), with corresponding 5-years TTR of 18% and 9% respectively. Significant correlations between NLR >4.07 and KRAS (Cramer's V = 0.082, P < 0.0001) and EGFR mutations (Cramer's V = 0.064, P = 0.004) were observed. CONCLUSIONS: Low pre-operative NLR is associated with longer OS in patients with resected NSCLC. Low pre-operative NLR is not associated with longer TTR in multivariate analysis. Correlation between the high NLR and KRAS/EGFR mutations were observed.

What is the appropriate "first lymph node" in the era of segmentectomy for non-small cell lung cancer?

Introduction: The place of segmentectomy in the management of lung cancer is shifting following the inspiring results of the Japanese JCOG0802 trial. I n this study, authors suggested that performing segmentectomy would require in an optimal way an intraoperative confirmation of pN0 tumor with a frozen section. Our objective was to determine whether the proposed technique, i.e. adjacent lymph node analysis, is consistent with the results of our study on sentinel lymph node (SLN) detection using fluorescence. Methods: This is a retrospective, observational, single center study. Eighty-one patients with suspected localized stage NSCLC (IA to IIA) were included between December 2020 and March 2022. All patients received an intra-operative injection of indocyanine green (ICG) directly in the peritumoral area or by electromagnetic navigational bronchoscopy (ENB). The SLN was then assessed by using an infrared fluorescence camera. Results: In our cohort, SLN was identified in 60/81 patients (74.1%). In 15/60 patients with identified SLN (25%), NIR-guided SLN was concordant with the suggestions of JCOG0802 study. A retrospective SLN pathological analysis was performed in 43 patients/60 cases with identified SLN (71.2%), including 37 cases of malignant disease. Occult micro-metastases were found in 4 patients out of 37 SLN analyzed, leading to a 10.8% upstaging with NIR-guided SLN analysis. Dicussion: At the time of segmentectomies, ICG technique allowed the identification of the SLN in a high percent of cases and in some areas usually out of the recommended stations for lymph node dissection.

Pulmonary metastasectomy in renal cell carcinoma: a mainstay of multidisciplinary treatment.

Renal cell carcinoma (RCC) remains a public health issue and seems to be increasing. A significant proportion of RCC patients will develop pulmonary metastasis at some point in their evolution. In this review, we aimed to update the surgical management of pulmonary metastases as well as systemic therapy, including targeted therapies, according to recent data in the literature. We retrospectively reviewed studies evaluating the benefit of pulmonary metastasectomy in RCC patients and evaluating the place of different chemotherapies, targeted therapies and immunotherapies through November 1, 2019. Several retrospective studies have shown the benefit of pulmonary metastasectomy in metastatic RCC (mRCC), most in a situation with only pulmonary metastases. According to the prognostic criteria of the IMDC risk model, the patient is classified into a prognostic group to identify the best systemic treatment. With the development of targeted therapies, the modalities are multiple and may involve tyrosine kinase inhibitors/checkpoint inhibitors and soon vaccine therapy or CAR-T cells. At the local level, in patients who cannot benefit from surgery, stereotactic radiotherapy or radiofrequency has a place to be considered. Although there is a lack of a randomized study, pulmonary metastasectomy appears to be feasible and effective. The place and modalities of systemic therapies in the era of targeted therapies remain to be more clearly defined.

Let-7b-3p inhibits tumor growth and metastasis by targeting the BRF2-mediated MAPK/ERK pathway in human lung adenocarcinoma.

BACKGROUND: Lung cancer is a malignant tumor with the highest morbidity and mortality rates worldwide, of which lung adenocarcinoma (LUAD) is the most common subtype. Overall, current treatments of LUAD are not satisfactory; therefore, novel targets need to be explored. Let-7b-3p is an important member of the let-7 family of microRNAs (miRNAs), and has not been studied separately in LUAD. This study aimed to investigate the role and molecular mechanism of let-7b-3p in LUAD. METHODS: Herein, let-7b-3p expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH) assays. MTT, colony formation assay, flow cytometry analysis, wound-healing, Transwell and in vivo experiments were conducted to assess let-7b-3p's function in LUAD. The downstream target TFIIB-related factor 2 (BRF2) was predicted using bioinformatics analyses and confirmed by dual-luciferase reporter assay and rescue experiments. Additionally, BRF2 was found to affect the MAPK/ERK pathway through transcriptome sequencing analysis and western blot (WB) assay. RESULTS: Let-7b-3p is downregulated in LUAD cells and tissue samples and low let-7b-3p expression is correlated with a poor prognosis in LUAD patients. Let-7b-3p suppresses the proliferation and metastasis of LUAD cells both in vivo and in vitro by directly targeting the BRF2-mediated MAPK/ERK pathway. CONCLUSIONS: Let-7b-3p inhibits the development of LUAD and is an ideal novel therapeutic target for the treatment of LUAD.

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

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