The Liquid Biopsy Consortium: Challenges and opportunities for early cancer detection and monitoring.

The emerging field of liquid biopsy stands at the forefront of novel diagnostic strategies for cancer and other diseases. Liquid biopsy allows minimally invasive molecular characterization of cancers for diagnosis, patient stratification to therapy, and longitudinal monitoring. Liquid biopsy strategies include detection and monitoring of circulating tumor cells, cell-free DNA, and extracellular vesicles. In this review, we address the current understanding and the role of existing liquid-biopsy-based modalities in cancer diagnostics and monitoring. We specifically focus on the technical and clinical challenges associated with liquid biopsy and biomarker development being addressed by the Liquid Biopsy Consortium, established through the National Cancer Institute. The Liquid Biopsy Consortium has developed new methods/assays and validated existing methods/technologies to capture and characterize tumor-derived circulating cargo, as well as addressed existing challenges and provided recommendations for advancing biomarker assays.

Bronchoscopy-guided removal of intrabronchial coil migration after coil embolization of pulmonary arteriovenous malformation.

Pulmonary arteriovenous malformations develop in approximately 50% of hereditary hemorrhagic telangiectasia patients. Pulmonary arteriovenous malformations are often treated with coil embolization therapy. We report a case of a 45-year-old female with multiple pulmonary arteriovenous malformations due to underlying hereditary hemorrhagic telangiectasia who had undergone 14 coil embolization procedures over 16 years. She presented with sudden onset severe, unremitting, nonproductive cough from a foreign body sensation in the airway. Computed tomography of the chest demonstrated a metallic foreign body extending from the left lower lobe of the lung into the left mainstem bronchus and trachea. Bronchoscopy-guided removal of the foreign body revealed an intact embolization coil placed 8 years prior to presentation had partially migrated through the vessel and airway walls into the airway lumen, extending from the left lower lobe bronchus to the left mainstem bronchus. Coil migration is a rare, but potentially dangerous, complication of coil embolization therapy.

Lung ultrasound is non-inferior to bronchoscopy for confirmation of double-lumen endotracheal tube positioning: a randomized controlled noninferiority study.

BACKGROUND: Appropriate placement of left-sided double-lumen endotracheal tubes (LDLTs) is paramount for optimal visualization of the operative field during thoracic surgeries that require single lung ventilation. Appropriate placement of LDLTs is therefore confirmed with fiberoptic bronchoscopy (FOB) rather than clinical assessment alone. Recent studies have demonstrated lung ultrasound (US) is superior to clinical assessment alone for confirming placement of LDLT, but no large trials have compared US to the gold standard of FOB. This noninferiority trial was devised to compare lung US with FOB for LDLT positioning and achievement of lung collapse for operative exposure. METHODS: This randomized, controlled, double-blind, noninferiority trial was conducted at the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand from October 2017 to July 2019. The study enrolled 200 ASA classification 1-3 patients that were scheduled for elective thoracic surgery requiring placement of LDLT. Study patients were randomized into either the FOB group or the lung US group after initial blind placement of LDLT. Five patients were excluded due to protocol deviation. In the FOB group (n = 98), fiberoptic bronchoscopy was used to confirm lung collapse due to proper positioning of the LDLT, and to adjust the tube if necessary. In the US group (n = 97), lung ultrasonography of four pre-specified zones (upper and lower posterior and mid-axillary) was used to assess lung collapse and guide adjustment of the tube if necessary. The primary outcome was presence of adequate lung collapse as determined by visual grading by the attending surgeon on scale from 1 to 4. Secondary outcomes included the time needed to adjust and confirm lung collapse, the time from finishing LDLT positioning to the grading of lung collapse, and intraoperative parameters such has hypotension or hypertension, hypoxia, and hypercarbia. The patient, attending anesthesiologist, and attending thoracic surgeon were all blinded to the intervention arm. RESULTS: The primary outcome of lung collapse by visual grading was similar between the intervention and the control groups, with 89 patients (91.8%) in the US group compared to 83 patients (84.1%) in the FOB group (p = 0.18) experiencing adequate collapse. This met criteria for noninferiority per protocol analysis. The median time needed to confirm and adjust LDLT position in the US group was 3 min (IQR 2-5), which was significantly shorter than the median time needed to perform the task in the FOB group (6 min, IQR 4-10) (p = 0.002). CONCLUSIONS: In selected patients undergoing thoracic surgery requiring LDLT, lung ultrasonography was noninferior to fiberoptic bronchoscopy in achieving adequate lung collapse and reaches the desired outcome in less time. TRIAL REGISTRATION: This study was registered at clinicaltrials.gov, NCT03314519 , Principal investigator: Kasana Raksamani, Date of registration: 19/10/2017.

Combined Percutaneous Tracheostomy and Endoscopic Gastrostomy Tubes in COVID-19: A Prospective Series of Patient Outcomes.

Background: A significant number of patients with severe respiratory failure related to COVID-19 require prolonged mechanical ventilation. Minimal data exists regarding the timing, safety, and efficacy of combined bedside percutaneous tracheostomy and endoscopy gastrostomy tube placement in these patients. The safety for healthcare providers is also in question. This study's objective was to evaluate the effectiveness and safety of combined bedside tracheostomy and gastrostomy tube placement in COVID-19 patients. Design and Methods: This is a single arm, prospective cohort study in patients with COVID-19 and acute respiratory failure requiring prolonged mechanical ventilation who underwent bedside tracheostomy and percutaneous endoscopic gastrostomy placement. Detailed clinical and procedural data were collected. Descriptive statistics were employed and time to event curves were estimated and plotted using the Kaplan Meier method for clinically relevant prespecified endpoints. Results: Among 58 patients, the median total intensive care unit (ICU) length of stay was 29 days (24.7-33.3) with a median of 10 days (6.3-13.7) postprocedure. Nearly 88% of patients were weaned from mechanical ventilation postprocedure at a median of 9 days (6-12); 94% of these were decannulated. Sixty-day mortality was 10.3%. Almost 90% of patients were discharged alive from the hospital. All procedures were done at bedside with no patient transfer required out of the ICU. A median of 3.0 healthcare personnel total were present in the room per procedure. Conclusion: This study shows that survival of critically ill COVID-19 patients after tracheostomy and gastrostomy was nearly 90%. The time-to-event curves are encouraging regarding time to weaning, downsizing, decannulation, and discharge. A combined procedure minimizes the risk of virus transmission to healthcare providers in addition to decreasing the number of anesthetic episodes, transfusions, and transfers patients must undergo. This approach should be considered in critically ill COVID-19 patients requiring prolonged mechanical ventilation.

Pre-Procedural COVID-19 Nasopharyngeal Swab Has Good Concordance with Bronchoalveolar Lavage in Patients at Low Risk for Viral Infection.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has drastically affected hospital and operating room (OR) workflow around the world as well as trainee education. Many institutions have instituted mandatory preoperative SARS-CoV-2 PCR nasopharyngeal swab (NS) testing in patients who are low risk for COVID-19 prior to elective cases. This method, however, is challenging as the sensitivity, specificity, and overall reliability of testing remains unclear. OBJECTIVES: The objective of this study was to assess the concordance of a negative NS in low risk preoperative patients with lower airway bronchoalveolar lavage (BAL) specimens obtained from the same patients. METHODS: We prospectively sent intraoperative lower airway BAL samples collected within 48 h of a negative mandatory preoperative NS for SARS-CoV-2 PCR testing. All adult patients undergoing a scheduled bronchoscopic procedure for any reason were enrolled, including elective and nonelective cases. RESULTS: One-hundred eighty-nine patients were included. All BAL specimens were negative for SARS-CoV-2 indicative of 100% concordance between testing modalities. CONCLUSIONS: These results are promising and suggest that preoperative nasopharyngeal SARS-CoV-2 testing provides adequate screening to rule out active COVID-19 infection prior to OR cases in a population characterized as low risk by negative symptom screening. This information can be used for both pre-procedural screening and when reintroducing trainees into the workforce.

Accuracy of a Robotic Endoscopic System in Cadaver Models with Simulated Tumor Targets: ACCESS Study.

BACKGROUND: Bronchoscopy for the diagnosis of peripheral pulmonary lesions continues to present clinical challenges, despite increasing experience using newer guided techniques. Robotic bronchoscopic platforms have been developed to potentially improve diagnostic yields. Previous studies in cadaver models have demonstrated increased reach into the lung periphery using robotic systems compared to similarly sized conventional bronchoscopes, although the clinical impact of additional reach is unclear. OBJECTIVES: This study was performed to evaluate the performance of a robotic bronchoscopic system's ability to reach and access artificial tumor targets simulating peripheral nodules in human cadaveric lungs. METHODS: Artificial tumor targets sized 10-30 mm in axial diameter were implanted into 8 human cadavers. CT scans were performed prior to procedures and all cadavers were intubated and mechanically ventilated. Electromagnetic navigation, radial probe endobronchial ultrasound, and fluoroscopy were used for all procedures. Robotic-assisted bronchoscopy was performed on each cadaver by an individual bronchoscopist to localize and biopsy peripheral lesions. RESULTS: Sixty-seven nodules were evaluated in 8 cadavers. The mean nodule size was 20.4 mm. The overall diagnostic yield was 65/67 (97%) and there was no statistical difference in diagnostic yield for lesions <20 mm compared with lesions measuring 21-30 mm, the presence of a concentric or eccentric radial ultrasound image, or relative distance from the pleura. CONCLUSIONS: The robotic bronchoscopic system was successful at biopsying 97% of peripheral pulmonary lesions 10-30 mm in size in human cadavers. These findings support further exploration of this technology in prospective clinical trials in live human subjects.

Transbronchial Cryobiopsies.

Transbronchial lung cryobiopsy (TBLCB) is a relatively new and promising technique for the acquisition of larger amounts of higher quality lung tissue for the diagnosis of lung diseases. There is a growing body of literature describing a diagnostic yield comparable to surgical lung biopsy with a favorable safety profile. Due to its advantages TBLCB has garnered significant interest with more institutions beginning to adopt this technique. However, several questions remain including its role in the diagnostic algorithm, indications, and technique. Herein we provide a review of the available literature describing diagnostic yield, complications, and differing techniques as well as a perspective from pathology.

Resolution of a Mobile Right Atrial Thrombus Complicating Acute Pulmonary Embolism With Low-Dose Tissue Plasminogen Activator in a Patient With Recent Craniotomy.

Right heart thrombus in transit (RHTT) is a rare, severe form of venous thromboembolism that carries a high mortality rate. The optimal treatment for RHTT has not been well established. Thrombolysis is a therapeutic modality for RHTT but carries the risk of bleeding complications including intracranial hemorrhage. Low-dose thrombolysis has been shown to be effective in treating submassive pulmonary emboli without an increased risk in bleeding complications, but it has not been studied in patients with RHTT. Here, we discuss the case of a 74-year-old male with lung cancer and recent craniotomy with metastasectomy 30 days prior to admission presenting with RHTT and bilateral pulmonary emboli (PE). He was treated successfully with low-dose thrombolysis, despite his relative contraindication to thrombolytics. To our knowledge, this is the first reported case of low-dose alteplase (tissue plasminogen activator [tPA]) used to treat an in-transit PE in the setting of recent craniotomy with metastasectomy.

Tracheal epithelial-myoepithelial carcinoma associated with sarcoid-like reaction: A case report.

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.

Management of autism in the adult intensive care unit.

Autism comprises a growing segment of the population and can be a management challenge in the intensive care unit (ICU). We present the case of a 22-year-old male with severe autism and intellectual disorder who developed respiratory failure and required a prolonged ICU course. This patient exhibited severe distress, aggression, and self-injurious behavior. Management challenges included sedation, weaning from sedation, and liberation from mechanical ventilation. Success was achieved with a multispecialty team and by tailoring the environment and interactions to the patient's known preferences. The use of dexmedetomidine to wean high-dose benzodiazepines and opiates also permitted successful liberation from mechanical ventilation.