Clinical Activity of Nivolumab for Human Papilloma Virus-Related Juvenile-Onset Recurrent Respiratory Papillomatosis.

BACKGROUND: Juvenile-onset recurrent respiratory papillomatosis (JO-RRP) is a human papilloma virus-mediated progressive benign neoplasm that affects children and young adults. Primary management consists of regular surgical debulking to maintain airway patency and vocal function. Like condyloma acuminata, JO-RRP is associated with immune dysregulation, and T cells isolated from papillomas express an anergic phenotype. Therefore, we hypothesized that programmed death protein 1 axis inhibition could stabilize tumor growth. MATERIALS AND METHODS: We treated two patients with refractory JO-RRP using nivolumab, with the primary objective of assessing clinical activity. We explored baseline papilloma features using immunohistochemistry and comprehensive genomic profiling. RESULTS: Both patients experienced symptomatic improvement, and interval laryngoscopies revealed a reduction in papillomatosis burden. One patient has not required subsequent surgical debridement for almost 2 years. On pathologic examination of pretreatment papillomas from both cases, infiltrating T cells were evident in the papilloma stroma, and papilloma programmed death ligand 1 expression was absent. Papilloma mutational load ranged between three and six mutations per megabase for each case. From on-treatment biopsy tissue, a higher amount of intraepithelial T cells and programmed death ligand 1 expression were detected in the papilloma. CONCLUSION: Nivolumab appears to have promising activity in JO-RRP, and further clinical investigation with more patients in clinical trials is warranted. IMPLICATIONS FOR PRACTICE: To the authors' knowledge, this article is the first report describing clinical activity with a programed cell death-1 (PD-1) inhibitor to treat a rare but detrimental type of respiratory tract epithelial neoplasm that afflicts young adults. Two patients were treated, and tumor features, such as mutational load, were examined with the intent to stimulate future hypotheses for translational research. The safety and activity of PD-1 inhibitors in this population still need to be corroborated in clinical trials and should not yet be adopted into clinical practice.

Extensive plastic bronchitis: etiology of a rare condition.

We present the case of a 55-year-old man who developed extensive occlusive bronchial casts after trachea-esophageal (TE) fistula repair. The bronchial casts were treated by bronchoscopic extraction, high dose steroids, antibiotics, and antifungals. Despite this multi-modality treatment, the rapid formation of these occlusive bronchial casts was very aggressive and could not be controlled even with a series of five rigid bronchoscopic extractions within a 48-hour period. The patient quickly deteriorated and succumbed to the inflammatory state. The multiple factors that might have led to the patient's bronchial cast formation are discussed.

Minimally invasive mediastinal staging of non-small-cell lung cancer: emphasis on ultrasonography-guided fine-needle aspiration.

BACKGROUND: Mediastinal staging in patients with non-small-cell lung cancer (NSCLC) is crucial in dictating surgical vs nonsurgical treatment. Cervical mediastinoscopy is the "gold standard" in mediastinal staging but is invasive and limited in assessing the posterior subcarinal, lower mediastinal, and hilar lymph nodes. Less invasive approaches to NSCLC staging have become more widely available. METHODS: This article reviews several of these techniques, including noninvasive mediastinal staging of NSCLC, endobronchial ultrasound (EBUS) and fine-needle aspiration (FNA), endoscopic ultrasound (EUS) and FNA, and the combination of EBUS/EUS. RESULTS: Noninvasive mediastinal staging with computed tomography and positron-emission tomography scans has significant false-negative and false-positive rates and requires lymph node tissue confirmation. FNA techniques, with guidance by EBUS and EUS, have become more widely available. The combination of EBUS-FNA and EUS-FNA of mediastinal lymph nodes can be a viable alternative to surgical mediastinal staging. Current barriers to the dissemination of these techniques include initial cost of equipment, lack of access to rapid on-site cytology, and the time required to obtain sufficient skills to duplicate published results. CONCLUSIONS: Within the last decade, these approaches to NSCLC staging have become more widely available. Continued study into these noninvasive techniques is warranted.