A Comprehensive Study of Reactive Oxygen Species Explicit Dosimetry for Pleural Photodynamic Therapy.

Photodynamic therapy (PDT) relies on the interactions between light, photosensitizers, and tissue oxygen to produce cytotoxic reactive oxygen species (ROS), primarily singlet oxygen (O) through Type II photochemical reactions, along with superoxide anion radicals (O), hydrogen peroxide (HO), and hydroxyl radicals (OH) through Type I mechanisms. Accurate dosimetry, accounting for all three components, is crucial for predicting and optimizing PDT outcomes. Conventional dosimetry tracks only light fluence rate and photosensitizer concentration, neglecting the role of tissue oxygenation.

Intraoperative Molecular Imaging With Pafolacianine: Histologic Characteristics of Identified Nodules.

Background: With increased early detection efforts, surgery for early-stage lung cancer is expected to rise. Pafolacianine is the first FDA approved targeted optical imaging agent indicated as an adjunct for intraoperative identification of malignant and nonmalignant pulmonary lesions in adult patients with known or suspected cancer in the lung.

Methods: This is a retrospective review of the malignant and nonmalignant lesions identified by pafolacianine with intraoperative molecular imaging (IMI) in the multi-center Phase 2 and Phase 3 ELUCIDATE clinical trials.

Intraoperative Molecular Imaging With Pafolacianine in Resection of Occult Pulmonary Malignancy in the ELUCIDATE Trial.

Background: Clinical studies have demonstrated that intraoperative molecular imaging (IMI) with pafolacianine identifies occult pulmonary lesions that are not identified by preoperative computed tomography or by intraoperative inspection techniques in ∼20% of patients. This study describes occult lesion clinical data and evaluates characteristics so that surgeons can better incorporate this emerging technology into clinical decision making.

Methods: Participants (n = 100) enrolled in a phase 3 trial of IMI with pafolacianine during pulmonary resection (Enabling Lung Cancer Identification Using Folate Receptor Targeting [ELUCIDATE]; NCT04241315) were identified.

Resident Self-Efficacy in Grantsmanship Lags Behind Key Funding Deadlines.

Purpose: Extramural funding is critical to career success and advancement in academic surgery, and surgical residents can apply for both societal and federal funding. Many federal funding mechanisms require proposals to be submitted before residents' formal research years.

Methods: To better understand the resident experience with grantsmanship, we distributed a validated grantsmanship self-efficacy assessment inventory for voluntary completion at our academic general surgery training program with 2 years of dedicated research.

Antisense targeting of FOXP3+ Tregs to boost anti-tumor immunity.

Our goal is to improve the outcomes of cancer immunotherapy by targeting FOXP3+ T-regulatory (Treg) cells with a next generation of antisense oligonucleotides (ASO), termed FOXP3 AUMsilence ASO. We performed experiments with human healthy donor PBMC and clinical samples from patients with lung cancer, mesothelioma and melanoma, and tested our approach using ASO FOXP3 in syngeneic murine cancer models and in humanized mice. ASO FOXP3 had no effects on cell viability or cell division, did not affect expression of other FOXP members, but decreased expression of FOXP3 mRNA in PBMC by 54.

Non-Small Cell Lung Cancer Imaging Using a Phospholipase A2 Activatable Fluorophore.

Lung cancer, the most common cause of cancer-related death in the United States, requires advanced intraoperative detection methods to improve evaluation of surgical margins. In this study we employed DDAO-arachidonate (DDAO-A), a phospholipase A2 (PLA2) activatable fluorophore, designed for the specific optical identification of lung cancers in real-time during surgery. The fluorescence activation of DDAO-A by porcine sPLA2 was tested in various liposomal formulations, with 100 nm extruded EggPC showing the best overall characteristics.

Convolutional neural network advances in demosaicing for fluorescent cancer imaging with color-near-infrared sensors.

Significance: Single-chip imaging devices featuring vertically stacked photodiodes and pixelated spectral filters are advancing multi-dye imaging methods for cancer surgeries, though this innovation comes with a compromise in spatial resolution. To mitigate this drawback, we developed a deep convolutional neural network (CNN) aimed at demosaicing the color and near-infrared (NIR) channels, with its performance validated on both pre-clinical and clinical datasets.

Aim: We introduce an optimized deep CNN designed for demosaicing both color and NIR images obtained using a hexachromatic imaging sensor.

A Phase 2 Multicenter Clinical Trial of Intraoperative Molecular Imaging of Lung Cancer with a pH-Activatable Nanoprobe.

Purpose: Intraoperative molecular imaging (IMI) uses tumor-targeted optical contrast agents to improve identification and clearance of cancer. Recently, a probe has been developed that only fluoresces when activated in an acidic pH, which is common to many malignancies. We report the first multicenter Phase 2 trial of a pH-activatable nanoprobe (pegsitacianine, ONM-100) for IMI of lung cancer.

Trends and Disparities in the Utilization of Thymectomy for Myasthenia Gravis in the United States.

Background And Objectives: In 2016, a randomized controlled trial demonstrated the clinical efficacy of trans-sternal thymectomy for patients with non-thymomatous myasthenia gravis (MG). Whether large-scale changes occurred in clinical practice after this trial is unknown.

Methods: We performed a retrospective longitudinal cross-sectional analysis using National Inpatient Sample (NIS) data from 2012 to 2019.

Phase 2 Clinical Trial of VGT-309 for Intraoperative Molecular Imaging During Pulmonary Resection.

Background: Advances in intraoperative molecular imaging (IMI) may improve surgical outcomes when resecting tumors in the lung. A single-center trial was conducted using VGT-309, a cathepsin-targeted near-infrared imaging agent that causes lung nodules to fluoresce during surgical resection. The end point of this phase 2 study was to evaluate the frequency that IMI with VGT-309 resulted in a clinically significant event (CSE): localization of pulmonary nodules, discovery of unsuspected additional cancers, or identification of positive margins.

Transcriptomic analysis-guided assessment of precision-cut tumor slices (PCTS) as an ex-vivo tool in cancer research.

With cancer immunotherapy and precision medicine dynamically evolving, there is greater need for pre-clinical models that can better replicate the intact tumor and its complex tumor microenvironment (TME). Precision-cut tumor slices (PCTS) have recently emerged as an ex vivo human tumor model, offering the opportunity to study individual patient responses to targeted therapies, including immunotherapies. However, little is known about the physiologic status of PCTS and how culture conditions alter gene expression.

Red blood cells function as reservoirs of tumor DNA.

Novel screening techniques for early detection of lung cancer are urgently needed. Profiling circulating tumor cell-free DNA (ctDNA) has emerged as a promising tool for biopsy-free tumor genotyping. However, both the scarcity and short half-life of ctDNA substantially limit the sensitivity and clinical utility of ctDNA detection methodologies.

Precision Oncology in Lung Cancer Surgery.

Precision in lung cancer surgery is our ability to use the most cutting edge and up to date information to provide personalized and targeted surgical care to our patients. It aims to tailor patient care to patient and tumor characteristics and susceptibilities as well as to optimize the ways treatments are administered. This may include specific perioperative medical treatment, changing operative techniques to more minimally invasive ones if the situation permits, performing sub-anatomical surgeries when possible, and using innovative tumor visualization methods to enhance detection of previously occult disease to ultimately decrease the extent of the planned resection.

Clinical PDT dose dosimetry for pleural Photofrin-mediated photodynamic therapy.

Significance: Photodynamic therapy (PDT) is an established cancer treatment utilizing light-activated photosensitizers (PS). Effective treatment hinges on the PDT dose-dependent on PS concentration and light fluence-delivered over time. We introduce an innovative eight-channel PDT dose dosimetry system capable of concurrently measuring light fluence and PS concentration during treatment.

Cathepsin detection to identify malignant cells during robotic pulmonary resection.

Background: Intraoperative molecular imaging (IMI) uses a fluorescent probe to identify occult cancers. VGT-309 is a quenched activity-based probe that is activated in the presence of cathepsins, enzymes overexpressed in cancer cells, and detected by near-infrared (NIR) light. This study aims to evaluate the sensitivity and the positive predictive value (PPV) of robotic-assisted thoracic surgery (RATS) with intraoperative molecular imaging (RIMI) using VGT-309 to localize tumors using NIR light to detect areas with increased cathepsin activity.

Preoperative predictors of successful tumour localization by intraoperative molecular imaging with pafolacianine in lung cancer to create predictive nomogram.

Objectives: Intraoperative molecular imaging (IMI) uses cancer-targeted fluorescent probe to locate nodules. Pafolacianine is a Food and Drug Administration-approved fluorescent probe for lung cancer. However, it has a 8-12% false negative rate for localization.

Fluorescence-guided surgery with indocyanine green to identify an idiopathic chyle leak-case report.

Background: Chylothorax is the leakage of chyle into the pleural space and is associated with up to 50% morbidity. Although, the identification of traumatic chylothoraces is well described, non-traumatic chylothoraxes, mostly idiopathic, present therapeutic challenges as they are difficult to localize. We describe an attempt at localizing and treating an idiopathic chylothorax refractory to conservative and minimally invasive techniques.

A pH-Activatable Nanoprobe Labels Diverse Histologic Subtypes of Human Lung Cancer During Resection.

Background: Intraoperative molecular imaging (IMI) uses tumor-targeted optical contrast agents to improve identification and clearance of cancer during surgery. Recently, pH-activatable contrast agents have been developed but none has been tested in lung cancer. Here, we report the successful clinical translation of pegsitacianine (ONM-100), a pH-activatable nanoprobe, for fluorescence-guided lung cancer resection.

Strategies to reduce morbidity following pleurectomy and decortication for malignant pleural mesothelioma.

Background: Pleurectomy and decortication (PD) in malignant pleural mesothelioma has a high morbidity mostly associated with aspiration pneumonia (PNA), deep vein thrombosis (DVT), and foreign catheter sepsis. We instituted four strategies to reduce these complications and report our experience.

Methods: This was a retrospective review of patients who underwent PD at the University of Pennsylvania between 2015 and 2022.

Preclinical Lymph Node Model for Intraoperative Molecular Imaging of Cancer.

Purpose: Lymph node(LN) dissection is part of most oncologic resections. Intraoperatively identifying a positive LN(+ LN), that harbors malignant cells, can be challenging. We hypothesized that intraoperative molecular imaging(IMI) using a cancer-targeted fluorescent prober can identify + LNs.

Bioinspired color-near infrared endoscopic imaging system for molecular guided cancer surgery.

Significance: Fluorescently guided minimally invasive surgery is improving patient outcomes and disease-free survival, but biomarker variability hinders complete tumor resection with single molecular probes. To overcome this, we developed a bioinspired endoscopic system that images multiple tumor-targeted probes, quantifies volumetric ratios in cancer models, and detects tumors in samples.

Aim: We present a new rigid endoscopic imaging system (EIS) that can capture color images while simultaneously resolving two near-infrared (NIR) probes.

Intraoperative molecular imaging: 3rd biennial clinical trials update.

Significance: This third biennial intraoperative molecular imaging (IMI) conference shows how optical contrast agents have been applied to develop clinically significant endpoints that improve precision cancer surgery.

Aim: National and international experts on IMI presented ongoing clinical trials in cancer surgery and preclinical work. Previously known dyes (with broader applications), new dyes, novel nonfluorescence-based imaging techniques, pediatric dyes, and normal tissue dyes were discussed.