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Papers by Robert Cameron

The Annals of Thoracic Surgery, 2004

Background. Malignant pleural mesothelioma (MPM) is an uncommon but highly fatal neoplasm for whi... more Background. Malignant pleural mesothelioma (MPM) is an uncommon but highly fatal neoplasm for which only limited treatment is available. Methods. Immunohistochemical analysis was used to determine the expression of interleukin-4 receptors (IL-4R) on mesothelioma cell lines and resected mesothelioma tumors. Radioreceptor binding assays were used to show that these IL-4R were high-affinity receptors. Previously, we had shown that a chimeric protein composed of a circularly permuted IL-4 molecule fused to a truncated form of Pseudomonas exotoxin A, IL-4(38-37)-PE38KDEL, could be used to kill IL-4R-bearing tumor cells in vitro. The toxicity of this molecule to mesothelioma cell lines was tested using a protein synthesis inhibition assay. A human mesothelioma xenograft model was then developed to assess the efficacy of this molecule in vivo. Results. All MPM cell lines tested were found to express high-affinity cell-surface IL-4R. Immunohistochemical analysis of resected mesothelioma tumor specimens from 13 patients revealed that all tumors expressed moderate-to-high levels of IL-4R. Coculture of malignant mesothelioma cell lines with IL-4(38-37)-PE38KDEL resulted in a dose-dependent inhibition of tumor cell protein synthesis through an interaction with cell-surface IL-4R. In a nude mouse xenograft model of human MPM, intratumoral administration of IL-4(38-37)-PE38KDEL mediated a dose-dependent decrease in tumor volume and a dose-dependent increase in survival. Conclusions. The chimeric protein, IL-4(38-37)-PE38KDEL, has potent antitumor effects against MPM both in vitro and in vivo.

JTCVS Techniques, 2021

Although organ transplantation has been successful for a variety of organs, the trachea is not on... more Although organ transplantation has been successful for a variety of organs, the trachea is not one of them. Furthermore, biologic and tissue-engineered tracheal replacements have suffered from a pandemic of overly simplistic concepts regarding the use of tissue scaffolds and stem cells as well as patently fraudulent claims of success. 1,2 The main challenges for tracheal transplants/replacements stem from the trachea's lack of an anastomosable blood supply and simultaneously its exposure to the outside contaminated world. Clearly, more work is required before thoracic surgeons routinely are able to replace large segments of airway; however, resection of more limited segments and reconstruction of portions of the airways currently are and remain viable options. In this issue of JTCVS Techniques, Huang and colleagues 3 describe a novel method of reconstructing limited tracheobronchial airway defects. Four cases illustrate the use of toenail grafts in the reconstruction of the anterolateral airway. Three patients had tracheostomy-site issues (stenosis, malacia, and nonhealing) whereas the fourth had a focal right lateral tracheal wall defect from resection of a lymph node with metastatic lung cancer. All were repaired successfully with toenail grafts. An instructional video, which accompanies the paper, demonstrates this rather novel approach, and toenail harvesting, something likely foreign FIGURE 1. Human feet showing relative toenail sizes (CB 3762 Studio; licensed from Shutterstock.com).

Journal of Thoracic Disease, 2019

According to the Diagnostic and Statistical Manual of Mental Disease (DSM-5), delirium is an acut... more According to the Diagnostic and Statistical Manual of Mental Disease (DSM-5), delirium is an acute fluctuating disturbance in attention and awareness. Due to physiologic perturbations, delirium results in cerebral dysfunction and cognitive impairment (1). Among hospitalized patients delirium is associated with increased morbidity, length of stay (LOS), costs and mortality (2). Moreover, there is evidence that patients who develop delirium experience an accelerated degree of long-term cognitive decline compared to those that do not experience delirium while hospitalized (3). In their paper, "Preoperative STOP-BANG Scores and Postoperative Delirium and Coma in Thoracic Surgery Patients," Wang and colleagues sought to assess the relationships between obstructive sleep apnea (OSA), delirium and postoperative outcomes among thoracic surgery intensive care unit (ICU) patients. Upwards of 20% of hospitalized patients suffer from delirium and is some series that number is as high as 50% among the surgical population (4). Gross and colleagues documented that patients with delirium maintained a more rapid pace of cognitive deterioration throughout a 5-year period following hospitalization (3). Further, patients who developed delirium had a 62% increased risk of mortality compared to patients without delirium (5). Associated with the loss of life, delirium also significantly effects on the cost of healthcare. Patients over 65 years old who developed

Ear, Nose & Throat Journal, 2006

We report an unusual case in which a patient presented with a large posterior mediastinal goiter ... more We report an unusual case in which a patient presented with a large posterior mediastinal goiter that extended to the level of the aorta. The goiter was resected through a standard Kocher neck incision with mediastinoscopic assistance. The large goiter was completely excised without the need for a sternotomy.

The Journal of thoracic and cardiovascular surgery, 2018

Patients undergoing esophagectomy remain one of the most difficult patient groups in thoracic sur... more Patients undergoing esophagectomy remain one of the most difficult patient groups in thoracic surgery to manage successfully, both perioperatively and postoperatively. Numerous factors influence both morbidity and mortality, including age; sex; preexisting comorbidities, such as pulmonary disease, cardiovascular disease, renal failure, and diabetes; and American Society of Anesthesiologists score. One of the most vexing postoperative problems in this patient group is delirium. Risk factors for postoperative delirium, as pointed out by Jung and colleagues 1 in their article in this issue of the Journal, include many of the factors listed as well as others, such as intensive care and opioid medication use. 2 Postoperative delirium and its treatment, which often includes medications with sedative properties, further increase the risk of other postoperative complications, particularly pulmonary problems. Although preventive measures, such as avoidance of opioid and psychotropic medications, promotion of nocturnal sleep, and minimizing intensive care stays, may diminish the incidence and severity of postoperative delirium, the use of specific fluids, such as hydroxyethyl starch (HES), for perioperative resuscitation has not to date been associated with either increased or decreased postoperative delirium. Jung and colleagues, 1 in their retrospective review of factors associated with postoperative delirium in 980 patients undergoing esophagectomy between April 2010 and February 2015, surprisingly implicate the use of HES for perioperative resuscitation in 509 patients as an important factor. This unexpected finding is potentially important, but it also must be interpreted in the context of the study as well as other available information. First, although Jung and colleagues' report 1 includes relatively current data, from within the past 7 years, and is propensity matched, it is still retrospective. Furthermore, the choice of resuscitation fluid was far from random, with the determination made by the attending anesthesiologist on

The Journal of thoracic and cardiovascular surgery, Jan 14, 2015

See related article on pages 514-20.

Current Treatment Options in Oncology, 2008

Tumors of the thymus are an uncommon entity, constituting 30% and 15% of anterior mediastinal mas... more Tumors of the thymus are an uncommon entity, constituting 30% and 15% of anterior mediastinal masses in adults and children, respectively. The majority of these tumors are thymomas, with thymic carcinomas less common, and thymic carcinoids exceedingly rare. Recognition of the distinct clinicopathologic behavior of various thymic neoplasms is crucial to providing optimal treatment. Evidence guiding the treatment of early stage thymic tumors is limited secondary to the low incidence and resulting lack of randomized data. Proper management requires a careful analysis of the available literature with particular attention paid to limitations of the existing studies. This article provides a discussion of the presentation, evaluation, diagnosis, surgical techniques, and treatment outcomes relevant to early stage thymomas, thymic carcinomas, and thymic carcinoid tumors. The role of radiation therapy in the management of early stage thymic tumors remains controversial and is discussed in detail. Thymic neoplasms Although lymphomas, carcinoid tumors, and germcell tumors all may arise within the thymus, only thymomas, thymic carcinomas, and thymolipomas arise from true thymic elements. Thymic neoplasms constitute 30% and 15% of anterior mediastinal masses in adults and children, respectively, with thymomas being the most common [1, 2]. Ninety percent of thymomas occur in the anterior mediastinum, and the remainder arise in the neck or other areas of the mediastinum including, rarely, the heart [3]. Thymomas grossly are lobulated, firm, tan-pink to gray tumors that may contain cystic spaces, calcification, or hemorrhage. They may be encapsulated, adherent to surrounding structures, or frankly invasive. To unify the pathology of thymic neoplasms, the World Health Organization (WHO) adopted a new classification system for thymic neoplasms (Table 1)

Mathematics and Engineering Techniques in Medicine and Biological Scienes, 2005

One of the most significant factors influencing the practice of medicine is the tremendous increa... more One of the most significant factors influencing the practice of medicine is the tremendous increase in personal mobility and the upcoming deployment of a wide array of non-invasive microsensors to monitor a person's condition, along with advances in medical imaging devices. Wireless communications, the Internet, and low-cost air travel has now created a new class of patients, the "mobile sick," and likewise the "mobile physician." This has created the need for mobile monitoring of patients as well as for mobile physician access to medical information, leading to recently developed lightweight , easy-to-wear, and affordable vests. In parallel, smaller medical imaging devices and soon capsule size video cameras for body ducts are producing increasingly large and detailed amounts of imaging data, from which to identify conditions of interest such as malignant tumors. We present the necessary requirements that current medical information technology infrastructure needs to meet to enable monitoring of mobile patients by mobile physicians, in addition to a timeline user-interface to access patient information anywhere and anytime.

Proceedings …, 2003

Data retrieved from body sensors such as ECG machines and new-generation multi-sensor systems suc... more Data retrieved from body sensors such as ECG machines and new-generation multi-sensor systems such as respiratory monitors are varied and abundant. Managing and integrating this streaming data with existing types of medical information such as patient records, laboratory results, procedures, medical documents, and medical images in a logical and intuitive way is a challenge. Not only is the management of such data difficult but so is the visualization and presentation of the data to physicians, specialists, and patients. Using a new generation of lifeshirts embedded with real time monitors for respiratory and heart functions as a testbed, we propose and have initiated development of a data management system for dealing with such streaming body sensor data, under the framework of an extensible architecture that will support easy visualization of such data.

CHEST Journal, 2012

Epithelial-myoepithelial carcinomas are rare tumors that primarily originate in the salivary glan... more Epithelial-myoepithelial carcinomas are rare tumors that primarily originate in the salivary glands but have also been found in the tracheobronchial tree. We report the first case of epithelial-myoepithelial carcinoma associated with sarcoidosis. A 61 year old Hispanic man presented with altered mental status and hypercalcemia. Imaging revealed diffuse intra-thoracic and intra-abdominal lymphadenopathy. A diagnostic bronchoscopy was performed where an incidental tracheal nodule was discovered and biopsied. Pathology was consistent with epithelial-myoepithelial carcinoma. Lymph node biopsy demonstrated non-caseating granulomas consistent with sarcoidosis. Patient underwent tracheal resection of the primary tumor with primary tracheal reconstruction. Hypercalcemia subsequently normalized with clinical improvement. Repeat CT imaging demonstrated complete resolution of lymphadenopathy. Our findings are suggestive of a possible paraneoplastic sarcoid-like reaction to the epithelial-myoepithelial carcinoma with associated lymphadenopathy and symptomatic hypercalcemia.

Annals of Surgical Oncology, 2006

Journal of thoracic disease, 2018

The Journal of Thoracic and Cardiovascular Surgery, 2014

Background: To date, reported surgical morbidity and mortality for pleurectomy/decortication and ... more Background: To date, reported surgical morbidity and mortality for pleurectomy/decortication and extrapleural pneumonectomy performed for malignant pleural mesothelioma primarily represent the experience of a few specialized centers. For comparison, we examined early outcomes of pleurectomy/decortication and extrapleural pneumonectomy from a broader group of centers/surgeons participating in the Society of Thoracic Surgeons-General Thoracic Database. Methods: All patients in the Society of Thoracic Surgeons-General Thoracic Database (version 2.081, representing 2009-2011) who underwent pleurectomy/decortication or extrapleural pneumonectomy for malignant pleural mesothelioma were identified. Patient characteristics, morbidity, mortality, center volume, and procedure were examined using univariable and multivariable analyses.

Cancers, 2021

Immune checkpoint blockade (ICB) with checkpoint inhibitors has led to significant and durable re... more Immune checkpoint blockade (ICB) with checkpoint inhibitors has led to significant and durable response in a subset of patients with advanced stage EGFR and ALK wild-type non-small cell lung cancer (NSCLC). This has been consistently shown to be correlated with the unique characteristics of each patient’s tumor immune micro-environment (TIME), including the composition and distribution of the tumor immune cell infiltrate; the expression of various checkpoints by tumor and immune cells, such as PD-L1; and the presence of various cytokines and chemokines. In this review, the classification of various types of TIME that are present in NSCLC and their correlation with response to ICB in NSCLC are discussed. This is conducted with a focus on the characteristics and identifiable biomarkers of different TIME subtypes that may also be used to predict NSCLC’s clinical response to ICB. Finally, treatment strategies to augment response to ICB in NSCLC with unresponsive types of TIME are explored.

Journal of Clinical Oncology, 2005

Background: Normal metabolism generates several volatile organic compounds (VOCs) that are excret... more Background: Normal metabolism generates several volatile organic compounds (VOCs) that are excreted in the breath (e.g. alkanes). In patients with lung cancer, induction of high-risk cytochrome p450 genotypes may accelerate catabolism of these VOCs, so that their altered abundance in breath may provide biomarkers of lung cancer. Methods: VOCs in 1.0 L alveolar breath were analyzed in 193 subjects with primary lung cancer and 211 controls with a negative chest CT. Subjects were randomly assigned to a training set or to a prediction set in a 2:1 split. A fuzzy logic model of breath biomarkers of lung cancer was constructed in the training set and then tested in subjects in the prediction set by generating their typicality scores for lung cancer. Results: Mean typicality scores employing a 16 VOC model were significantly higher in lung cancer patients than in the control group (p < 0.0001 in all TNM stages). The model predicted primary lung cancer with 84.6% sensitivity, 80.0% specificity, and 0.88 area under curve (AUC) of the receiver operating characteristic (ROC) curve. Predictive accuracy was similar in TNM stages 1 through 4, and was not affected by current or former tobacco smoking. The predictive model achieved near-maximal performance with six breath VOCs, and was progressively degraded by random classifiers. Predictions with fuzzy logic were consistently superior to multilinear analysis. If applied to a population with 2% prevalence of lung cancer, a screening breath test would have a negative predictive value of 0.985 and a positive predictive value of 0.163 (true positive rate = 0.277, false positive rate = 0.029).

Journal of Vascular and Interventional Radiology, 2015

Purpose: To determine safety and early-term efficacy of CT-guided cryoablation for treatment of r... more Purpose: To determine safety and early-term efficacy of CT-guided cryoablation for treatment of recurrent mesothelioma and assess risk factors for local recurrence. Materials and Methods: During the period 2008-2012, 24 patients underwent 110 cryoablations for recurrent mesothelioma tumors in 89 sessions. Median patient age was 69 years (range, 48-82 y). Median tumor size was 30 mm (range, 9-113 mm). Complications were graded using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). Recurrence was diagnosed on CT or positron emission tomography/CT by increasing size, nodular enhancement, or hypermetabolic activity and analyzed using the Kaplan-Meier method. Cox proportional hazards model was used to determine covariates associated with local tumor recurrence. Results: Median duration of follow-up was 14.5 months. Complications occurred in 8 of 110 cryoablations (7.3%). All but 1 complication were graded CTCAE v4.0 1 or 2. No procedure-related deaths occurred. Freedom from local recurrence was observed in 100% of cases at 30 days, 92.5% at 6 months, 90.8% at 1 year, 87.3% at 2 years, and 73.7% at 3 years. Tumor recurrence was diagnosed 4.5-24.5 months after cryoablation (mean 5.7 months). Risk of tumor recurrence was associated with a smaller ablative margin from the edge of tumor to iceball ablation margin (multivariate hazard ratio 0.68, CI 0.48-0.95, P ¼ .024). Conclusions: CT-guided cryoablation is safe for local control of recurrent mesothelioma, with a low rate of complications and promising early-term efficacy. A smaller ablative margin may predispose to tumor recurrence. ABBREVIATIONS CI = confidence interval, CTCAE v4.0 = Common Terminology Criteria for Adverse Events version 4, PET = positron emission tomography

American journal of respiratory cell and molecular biology, 2014

Malignant pleural mesothelioma (MPM) is a rare malignancy of the pleura that is frequently resist... more Malignant pleural mesothelioma (MPM) is a rare malignancy of the pleura that is frequently resistant to conventional therapies. Immunotherapy is a promising investigational approach for MPM that has shown some evidence of clinical benefit in select patients. However, tumor-induced immunosuppression is likely a major impediment to achieving optimal clinical responses to immunotherapeutic intervention. MPM contains a variable degree of infiltrating T-regulatory cells and M2 macrophages, which are believed to facilitate tumor evasion from the host immune system. Additional immunosuppressive factors identified in other human tumor types, such as tumor-associated programmed death ligand-1 expression, may be relevant for investigation in MPM. Conventional cytoreductive therapies, such as radiation, chemotherapy, and surgery, may play a critical role in successful immunotherapeutic strategies by ablating intratumoral and/or systemic immunosuppressive factors, thus creating a host environme...

The Journal of thoracic and cardiovascular surgery, 2015

See related article on pages 369-75. FIGURE 1. Demonstration of differential gene expressions in ... more See related article on pages 369-75. FIGURE 1. Demonstration of differential gene expressions in simultaneous 2-dimensional (2D) adherent and 3-dimensional (3D) spheroid tumor cultures.

Cancer Management and Research, 2015

Malignant pleural mesothelioma (MPM) is a rare tumor that is challenging to control. Despite some... more Malignant pleural mesothelioma (MPM) is a rare tumor that is challenging to control. Despite some benefit from using the multimodality-approach (surgery, combination chemotherapy and radiation), survival remains poor. However, current research produced a list of potential therapies. Here, we summarize significant new preclinical and early clinical developments in treatment of MPM, which include mesothelin specific antibody and toxin therapies, interleukin-4 (IL-4) receptor toxins, dendritic cell vaccines, immune checkpoint inhibitors, and gene-based therapies. In addition, several local modalities such as photodynamic therapy, postoperative lavage using betadine, and cryotherapy for local recurrence, have also shown to be effective for local control of disease.