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.

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

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

C3a elicits unique migratory responses in immature low-density neutrophils.

Neutrophils represent the immune system's first line of defense and are rapidly recruited into inflamed tissue. In cancer associated inflammation, phenotypic heterogeneity has been ascribed to this cell type, whereby neutrophils can manifest anti- or pro-metastatic functions depending on the cellular/micro-environmental context. Here, we demonstrate that pro-metastatic immature low-density neutrophils (iLDNs) more efficiently accumulate in the livers of mice bearing metastatic lesions compared with anti-metastatic mature high-density neutrophils (HDNs). Transcriptomic analyses reveal enrichment of a migration signature in iLDNs relative to HDNs. We find that conditioned media derived from liver-metastatic breast cancer cells, but not lung-metastatic variants, specifically induces chemotaxis of iLDNs and not HDNs. Chemotactic responses are due to increased surface expression of C3aR in iLDNs relative to HDNs. In addition, we detect elevated secretion of cancer-cell derived C3a from liver-metastatic versus lung-metastatic breast cancer cells. Perturbation of C3a/C3aR signaling axis with either a small molecule inhibitor, SB290157, or reducing the levels of secreted C3a from liver-metastatic breast cancer cells by short hairpin RNAs, can abrogate the chemotactic response of iLDNs both in vitro and in vivo, respectively. Together, these data reveal novel mechanisms through which iLDNs prefentially accumulate in liver tissue harboring metastases in response to tumor-derived C3a secreted from the liver-aggressive 4T1 breast cancer cells.

Primary tumors induce neutrophil extracellular traps with targetable metastasis promoting effects.

Targeting the dynamic tumor immune microenvironment (TIME) can provide effective therapeutic strategies for cancer. Neutrophils are the predominant leukocyte population in mice and humans, and mounting evidence implicates these cells during tumor growth and metastasis. Neutrophil extracellular traps (NETs) are networks of extracellular neutrophil DNA fibers that are capable of binding tumor cells to support metastatic progression. Here we demonstrate for the first time that circulating NET levels are elevated in advanced esophageal, gastric and lung cancer patients compared to healthy controls. Using pre-clinical murine models of lung and colon cancer in combination with intravital video microscopy, we show that NETs functionally regulate disease progression and that blocking NETosis through multiple strategies significantly inhibits spontaneous metastasis to the lung and liver. Further, we visualize how inhibiting tumor-induced NETs decreases cancer cell adhesion to liver sinusoids following intrasplenic injection - a mechanism previously thought to be driven primarily by exogenous stimuli. Thus, in addition to neutrophil abundance, the functional contribution of NETosis within the TIME has critical translational relevance and represents a promising target to impede metastatic dissemination.

Neural network and logistic regression diagnostic prediction models for giant cell arteritis: development and validation.

PURPOSE: To develop and validate neural network (NN) vs logistic regression (LR) diagnostic prediction models in patients with suspected giant cell arteritis (GCA). Design: Multicenter retrospective chart review. METHODS: An audit of consecutive patients undergoing temporal artery biopsy (TABx) for suspected GCA was conducted at 14 international medical centers. The outcome variable was biopsy-proven GCA. The predictor variables were age, gender, headache, clinical temporal artery abnormality, jaw claudication, vision loss, diplopia, erythrocyte sedimentation rate, C-reactive protein, and platelet level. The data were divided into three groups to train, validate, and test the models. The NN model with the lowest false-negative rate was chosen. Internal and external validations were performed. RESULTS: Of 1,833 patients who underwent TABx, there was complete information on 1,201 patients, 300 (25%) of whom had a positive TABx. On multivariable LR age, platelets, jaw claudication, vision loss, log C-reactive protein, log erythrocyte sedimentation rate, headache, and clinical temporal artery abnormality were statistically significant predictors of a positive TABx (P≤0.05). The area under the receiver operating characteristic curve/Hosmer-Lemeshow P for LR was 0.867 (95% CI, 0.794, 0.917)/0.119 vs NN 0.860 (95% CI, 0.786, 0.911)/0.805, with no statistically significant difference of the area under the curves (P=0.316). The misclassification rate/false-negative rate of LR was 20.6%/47.5% vs 18.1%/30.5% for NN. Missing data analysis did not change the results. CONCLUSION: Statistical models can aid in the triage of patients with suspected GCA. Misclassification remains a concern, but cutoff values for 95% and 99% sensitivities are provided (https://goo.gl/THCnuU).

Application of an individualized operative strategy for wedge resection of gastric gastrointestinal stromal tumors: Effectiveness for tumors in difficult locations.

BACKGROUND: There is some concern that wedge resection of gastric gastrointestinal stromal tumors is not feasible in certain anatomic locations, such as the cardia or antrum. We sought to review our experience with treatment of gastric gastrointestinal stromal tumors with a particular focus on nonanatomic wedge resections in these challenging locations. METHODS: Patients undergoing resection of gastrointestinal stromal tumors from 2000-2014 at the Montreal General Hospital were identified from a prospectively collected database, and outcomes were tabulated. An individualized operative strategy was used to guide resection based on tumor location, size, and characteristics. Disease-free survival and overall survival analyzed using the Kaplan-Meier method. Data are presented as median (range). RESULTS: We identified 59 patients who underwent operative resection for gastric gastrointestinal stromal tumors. Tumor location was fundus/body/greater curvature in 35 (59%) patients, lesser curvature in 8 (14%) patients, antrum in 8 (14%) patients, and cardia in 8 (14%) patients. Median tumor size was 4.5 cm (1.4-25 cm). The majority of cardia and antral lesions were removed with wedge resections (14/16, 87%). For cardial and antral tumors, on-table gastroscopy was used to guide the operative approach and prevent narrowing of the Gastroesophageal junction or pylorus in all patients undergoing wedge resection. Negative pathologic margins were achieved in all patients. The 5-year disease-free survival was 91% and 5-year overall survival was 95%. CONCLUSION: When selected appropriately, and under the guidance of on-table gastroscopy, laparoscopic nonanatomic wedge resection can be performed successfully in the majority of cases, even for gastrointestinal stromal tumors near the GEJ or pylorus, with excellent oncologic outcomes.