Comparative effectiveness of perioperative physical activity in older adults with lung cancer and their family caregivers: design of a multicenter pragmatic randomized trial.

BACKGROUND: With a median age at diagnosis of 70, lung cancer remains a significant public health challenge for older Americans. Surgery is a key component in treating most patients with non-metastatic lung cancer. These patients experience postoperative pain, fatigue, loss of respiratory capacity, and decreased physical function. Data on quality of life (QOL) in older adults undergoing lung cancer surgery is limited, and few interventions are designed to target the needs of older adults and their family caregivers (FCGs). The primary aim of this comparative effectiveness trial is to determine whether telephone-based physical activity coaching before and after surgery will be more beneficial than physical activity self-monitoring alone for older adults and their FCGs. METHODS: In this multicenter comparative effectiveness trial, 382 older adults (≥ 65 years) with lung cancer and their FCGs will be recruited before surgery and randomized to either telephone-based physical activity coaching or physical activity self-monitoring alone. Participants allocated to the telephone-based coaching comparator will receive five telephone sessions with coaches (1 pre and 4 post surgery), an intervention resource manual, and a wristband pedometer. Participants in the self-monitoring only arm will receive American Society of Clinical Oncology (ASCO) physical activity information and wristband pedometers. All participants will be assessed at before surgery (baseline), at discharge, and at days 30, 60, and 180 post-discharge. The primary endpoint is the 6-minute walk test (6MWT) at 30 days post-discharge. Geriatric assessment, lower extremity function, self-reported physical function, self-efficacy, and QOL will also be assessed. DISCUSSION: The trial will determine whether this telephone-based physical activity coaching approach can enhance postoperative functional capacity and QOL outcomes for older adults with lung cancer and their FCGs. Trial results will provide critical findings to inform models of postoperative care for older adults with cancer and their FCGs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06196008.

Cutdown is Associated with Higher 30-day Unplanned Readmissions and Wound Complications than Percutaneous Access for EVAR.

BACKGROUND: A 2023 Cochrane review showed no difference in bleeding/wound infection complications, short-term mortality and aneurysm exclusion between the percutaneous and cut-down approach for femoral access in endovascular aortic aneurysm repair (EVAR). In contrast, single-center studies have shown bilateral cutdown resulting in higher readmission rates due to higher rates of groin wound infections. Whether 30-day readmission rates vary by type of access during EVAR procedures is unknown. The goal of this study was to ascertain which femoral access approach for EVAR is associated with the lowest risk of 30-day readmission. METHODS: The Targeted Vascular Module from the American College of Surgeons National Surgical Quality Improvement Program was queried to identify patients undergoing EVAR for aortic disease from 2012-2021. All ruptures and other emergency cases were excluded. Cohorts were divided into bilateral cutdown, unilateral cutdown, failed percutaneous attempt converted to open and successful percutaneous access. The primary 30-day outcomes were unplanned readmission and wound complications. Univariate analyses were performed using the Fisher's exact test, Chi-Square test and the Student's t-test. Multivariable analysis was performed using logistic regression. RESULTS: From 2012 to 2021, 14,002 patients met study criteria. Most (7,395 [53%]) underwent completely percutaneous access, 5,616 (40%) underwent bilateral cutdown, 849 (6%) underwent unilateral cutdown, and 146 (1%) had a failed percutaneous access which was converted to open. Unplanned readmissions by access strategy included 7.6% for bilateral cutdown, 7.3% for unilateral cutdown, 7.8% for attempted percutaneous converted to cutdown, and 5.7% for completely percutaneous access (P < 0.001, Figure 1). After multivariable analysis, unplanned readmissions compared to percutaneous access yielded: percutaneous converted to cutdown adjusted odds ratio (AOR): 1.38, 95% CI [0.76-2.53], P = 0.29; unilateral cutdown AOR: 1.18, 95% CI [0.92-1.51], P = 0.20; bilateral cutdown AOR: 1.26, 95% CI [1.09-1.43], P = 0.001. Bilateral cutdown was also associated with higher wound complications compared to percutaneous access (AOR: 4.41, CI [2.86-6.79], P < 0.001), as was unilateral cutdown (AOR: 3.04, CI [1.46-6.32], P = 0.003). CONCLUSIONS: Patients undergoing cutdown for EVAR are at higher risk for 30-day readmission compared to completely percutaneous access. If patient anatomy allows for percutaneous EVAR, this access option should be prioritized.

A machine learning approach to high-risk cardiac surgery risk scoring.

INTRODUCTION: In patients undergoing high-risk cardiac surgery, the uncertainty of outcome may complicate the decision process to intervene. To augment decision-making, a machine learning approach was used to determine weighted personalized factors contributing to mortality. METHODS: American College of Surgeons National Surgical Quality Improvement Program was queried for cardiac surgery patients with predicted mortality ≥10% between 2012 and 2019. Multiple machine learning models were investigated, with significant predictors ultimately used in gradient boosting machine (GBM) modeling. GBM-trained data were then used for local interpretable model-agnostic explanations (LIME) modeling to provide individual patient-specific mortality prediction. RESULTS: A total of 194 patient deaths among 1291 high-risk cardiac surgeries were included. GBM performance was superior to other model approaches. The top five factors contributing to mortality in LIME modeling were preoperative dialysis, emergent cases, Hispanic ethnicity, steroid use, and ventilator dependence. LIME results individualized patient factors with model probability and explanation of fit. CONCLUSIONS: The application of machine learning techniques provides individualized predicted mortality and identifies contributing factors in high-risk cardiac surgery. Employment of this modeling to the Society of Thoracic Surgeons database may provide individualized risk factors contributing to mortality.

Electromagnetic navigation bronchoscopy to access lung lesions in 1,000 subjects: first results of the prospective, multicenter NAVIGATE study.

BACKGROUND: Electromagnetic navigation bronchoscopy (ENB) is an image-guided, minimally invasive approach that uses a flexible catheter to access pulmonary lesions. METHODS: NAVIGATE is a prospective, multicenter study of the superDimension™ navigation system. A prespecified 1-month interim analysis of the first 1,000 primary cohort subjects enrolled at 29 sites in the United States and Europe is described. Enrollment and 24-month follow-up are ongoing. RESULTS: ENB index procedures were conducted for lung lesion biopsy (n = 964), fiducial marker placement (n = 210), pleural dye marking (n = 17), and/or lymph node biopsy (n = 334; primarily endobronchial ultrasound-guided). Lesions were in the peripheral/middle lung thirds in 92.7%, 49.7% were <20 mm, and 48.4% had a bronchus sign. Radial EBUS was used in 54.3% (543/1,000 subjects) and general anesthesia in 79.7% (797/1,000). Among the 964 subjects (1,129 lesions) undergoing lung lesion biopsy, navigation was completed and tissue was obtained in 94.4% (910/964). Based on final pathology results, ENB-aided samples were read as malignant in 417/910 (45.8%) subjects and non-malignant in 372/910 (40.9%) subjects. An additional 121/910 (13.3%) were read as inconclusive. One-month follow-up in this interim analysis is not sufficient to calculate the true negative rate or diagnostic yield. Tissue adequacy for genetic testing was 80.0% (56 of 70 lesions sent for testing). The ENB-related pneumothorax rate was 4.9% (49/1,000) overall and 3.2% (32/1,000) CTCAE Grade ≥2 (primary endpoint). The ENB-related Grade ≥2 bronchopulmonary hemorrhage and Grade ≥4 respiratory failure rates were 1.0 and 0.6%, respectively. CONCLUSIONS: One-month results of the first 1,000 subjects enrolled demonstrate low adverse event rates in a generalizable population across diverse practice settings. Continued enrollment and follow-up are required to calculate the true negative rate and delineate the patient, lesion, and procedural factors contributing to diagnostic yield. TRIAL REGISTRATION: ClinicalTrials.gov NCT02410837 . Registered 31 March 2015.

Effect of Obesity on Perioperative Outcomes After Robotic-Assisted Pulmonary Lobectomy.

OBJECTIVE: We investigated whether higher body mass index (BMI) affects perioperative and postoperative outcomes after robotic-assisted video-thoracoscopic pulmonary lobectomy. METHODS: We retrospectively studied all patients who underwent robotic-assisted pulmonary lobectomy by one surgeon between September 2010 and January 2015. Patients were grouped according to the World Health Organization's definition of obesity, with "obese" being defined as BMI >30.0 kg/m2. Perioperative outcomes, including intraoperative estimated blood loss (EBL) and postoperative complication rates, were compared. RESULTS: Over 53 months, 287 patients underwent robotic-assisted pulmonary lobectomy, with 7 patients categorized as "underweight," 94 patients categorized as "normal weight," 106 patients categorized as "overweight," and 80 patients categorized as "obese." Because of the relatively low sample size, "underweight" patients were excluded from this study, leaving a total cohort of 280 patients. There was no significant difference in intraoperative complication rates, conversion rates, perioperative outcomes, or postoperative complication rates among the 3 groups, except for lower risk of prolonged air leaks ≥7 days and higher risk of pneumonia in patients with obesity. CONCLUSIONS: Patients with obesity do not have increased risk of intraoperative or postoperative complications, except for pneumonia, compared with "normal weight" and "overweight" patients. Robotic-assisted pulmonary lobectomy is safe and effective for patients with high BMI.

Delta-Opioid Receptor (δOR) Targeted Near-Infrared Fluorescent Agent for Imaging of Lung Cancer: Synthesis and Evaluation In Vitro and In Vivo.

In the United States, lung cancer is the leading cause of cancer death and ranks second in the number of new cases annually among all types of cancers. Better methods or tools for diagnosing and treating this disease are needed to improve patient outcomes. The delta-opioid receptor (δOR) is reported to be overexpressed in lung cancers and not expressed in normal lung. Thus, we decided to develop a lung cancer-specific imaging agent targeting this receptor. We have previously developed a δOR-targeted fluorescent imaging agent based on a synthetic peptide antagonist (Dmt-Tic) conjugated to a Cy5 fluorescent dye. In this work, we describe the synthesis of Dmt-Tic conjugated to a longer wavelength near-infrared fluorescent (NIRF) dye, Li-cor IR800CW. Binding affinity of Dmt-Tic-IR800 for the δOR was studied using lanthanide time-resolved fluorescence (LTRF) competitive binding assays in cells engineered to overexpress the δOR. In addition, we identified lung cancer cell lines with high and low endogenous expression of the δOR. We confirmed protein expression in these cell lines using confocal fluorescence microscopy imaging and used this technique to estimate the cell-surface receptor number in the endogenously expressing lung cancer cell lines. The selectivity of Dmt-Tic-IR800 for imaging of the δOR in vivo was shown using both engineered cell lines and endogenously expressing lung cancer cells in subcutaneous xenograft models in mice. In conclusion, the δOR-specific fluorescent probe developed in this study displays excellent potential for imaging of lung cancer.

Design of a prospective, multicenter, global, cohort study of electromagnetic navigation bronchoscopy.

BACKGROUND: Electromagnetic navigation bronchoscopy (ENB) procedures allow physicians to access peripheral lung lesions beyond the reach of conventional bronchoscopy. However, published research is primarily limited to small, single-center studies using previous-generation ENB software. The impact of user experience, patient factors, and lesion/procedural characteristics remains largely unexplored in a large, multicenter study. METHODS/DESIGN: NAVIGATE (Clinical Evaluation of superDimension™ Navigation System for Electromagnetic Navigation Bronchoscopy) is a prospective, multicenter, global, cohort study. The study aims to enroll up to 2,500 consecutive subjects presenting for evaluation of lung lesions utilizing the ENB procedure at up to 75 clinical sites in the United States, Europe, and Asia. Subjects will be assessed at baseline, at the time of procedure, and at 1, 12, and 24 months post-procedure. The pre-test probability of malignancy will be determined for peripheral lung nodules. Endpoints include procedure-related adverse events, including pneumothorax, bronchopulmonary hemorrhage, and respiratory failure, as well as quality of life, and subject satisfaction. Diagnostic yield and accuracy, repeat biopsy rate, tissue adequacy for genetic testing, and stage at diagnosis will be reported for biopsy procedures. Complementary technologies, such as fluoroscopy and endobronchial ultrasound, will be explored. Success rates of fiducial marker placement, dye marking, and lymph node biopsies will be captured when applicable. Subgroup analyses based on geography, demographics, investigator experience, and lesion and procedure characteristics are planned. DISCUSSION: Study enrollment began in April 2015. As of February 19, 2016, 500 subjects had been enrolled at 23 clinical sites with enrollment ongoing. NAVIGATE will be the largest prospective, multicenter clinical study on ENB procedures to date and will provide real-world experience data on the utility of the ENB procedure in a broad range of clinical scenarios. TRIAL REGISTRATION: ClinicalTrials.gov NCT02410837 . Registered 31 March 2015.

Robotic-Assisted Videothoracoscopic Mediastinal Surgery.

BACKGROUND: Tumors of the mediastinum as well as normal thymus glands in patients with myasthenia gravis have traditionally been resected using large and morbid incisions. However, robotic-assisted mediastinal resections are gaining popularity because of the many advantages that the robot provides. However, few comprehensive reviews of the literature on robotic-assisted mediastinal resections exist. METHODS: A systemic review of the current medical literature was performed, excluding cases related to esophageal pathology. These studies were evaluated and their findings are reported in this comprehensive review. Approximately 48 papers met the inclusion criteria for review. RESULTS: Robotic-assisted surgical systems are increasingly being used in mediastinal resections. Based on the available literature, robotic-assisted thoracoscopic surgery in the mediastinum is feasible and safe. Robotic-assisted mediastinal surgery appears to be superior to open approaches of the mediastinum and is comparable with videothoracoscopic surgery when patient outcomes are considered. CONCLUSIONS: Increased robotic experience and more studies, including randomized controlled trials, are needed to validate the findings of the current literature.

Robotic-Assisted Videothoracoscopic Surgery of the Lung.

BACKGROUND: Despite initial concerns about the general safety of videothoracoscopic surgery, minimally invasive videothoracoscopic surgical procedures have advantages over traditional open thoracic surgery via thoracotomy. Robotic-assisted minimally invasive surgery has expanded to almost every surgical specialty, including thoracic surgery. Adding a robotic-assisted surgical system to a videothoracoscopic surgical procedure corrects several shortcomings of videothoracoscopic surgical cameras and instruments. METHODS: We performed a literature search on robotic-assisted pulmonary resections and compared the published robotic series data with our experience at the H. Lee Moffitt Cancer Center & Research Institute. All perioperative outcomes, such as intraoperative data, postoperative complications, chest tube duration, hospital length of stay (LOS), and in-hospital mortality rates were noted. RESULTS: Our literature search found 23 series from multiple surgical centers. We divided the literature into 2 groups based on the year published (2005-2010 and 2011-2014). Operative times from earlier studies ranged from 150 to 240 minutes compared with 90 to 242 minutes for later studies. Conversion rates (to open lung resection) from the earlier studies ranged from 0% to 19% compared with 0% to 11% in the later studies. Mortality rates for the earlier studies ranged from 0% to 5% compared with 0% to 2% for the later studies. Since 2010, our group has performed more than 600 robotic-assisted thoracic surgical procedures, including more than 200 robotic-assisted pulmonary lobectomies, which we also divided into 2 groups. Our median skin-to-skin operative time improved from 179 minutes for our early group (n = 104) to 172 minutes for our later group (n = 104). The overall conversion rate was 9.6% and the emergent conversion rate (for bleeding) was 5% for our robotic-assisted lobectomies. The most common postoperative complications in our cohort were prolonged air leak (> 7 days; 16.8%) and atrial fibrillation (12%). Hospital LOS for the early series ranged from 3 to 11 days compared with 2 to 6 days for the later series. Median hospital LOS decreased from 6 to 4 days. Our mortality rate was 1.4%; 3 in-hospital deaths occurred in the early 40 cases. Mediastinal lymph node (LN) dissection and detection of occult mediastinal LN metastases were improved during robotic-assisted lobectomy for non-small-cell lung cancer, as demonstrated by an overall 30% upstaging rate, including a 19% nodal upstaging rate, in our cohort. CONCLUSIONS: Robotic-assisted videothoracoscopic pulmonary lobectomy appears to be as safe as conventional videothoracoscopic surgical lobectomy, which has decreased perioperative complications and a shorter hospital LOS than open lobectomy. Both mediastinal LN dissection and the early detection of occult mediastinal LN metastatic disease were improved by robotic-assisted videothoracoscopic surgical compared with conventional videothoracoscopic surgical or open thoracotomy.

Robotic-Assisted Esophageal Surgery.

BACKGROUND: The adoption of minimally invasive approaches to the management of esophageal disease has been slow, except for the laparoscopic management of gastroesophageal reflux disease. However, the advent of new surgical technologies - in particular, robotic-assisted surgical systems - has revolutionized esophageal surgery. METHODS: The literature was systematically reviewed using the keywords "robotic," "esophageal surgery," "esophagectomy," "fundoplication," and "esophageal myotomy." The reference lists from these articles were then also analyzed. RESULTS: Forty-nine studies were included in our comprehensive review of robotic-assisted esophageal surgery, and they consisted of literature reviews, case reports, retrospective and prospective case series, and randomized controlled trials. CONCLUSIONS: Robotic-assisted esophageal surgery is a safe and effective way of treating esophageal disorders, including gastroesophageal reflux disease, achalasia, leiomyomas, and cancer. The use of robotic surgical systems has many benefits for managing disorders of the esophagus, but more studies, including randomized controlled trials, are necessary.