Background Preclinical studies require models that recapitulate the cellular diversity of human tumors and provide insight into the drug sensitivities of specific cellular populations. The ideal platform would enable rapid screening of cell type-specific drug sensitivities directly in patient tumor tissue and reveal strategies to overcome intratumoral heterogeneity. Methods We combine multiplexed drug perturbation in acute slice culture from freshly resected tumors with single-cell RNA sequencing (scRNA-seq) to profile transcriptome-wide drug responses in individual patients. We applied this approach to drug perturbations on slices derived from six glioblastoma (GBM) resections to identify conserved drug responses and to one additional GBM resection to identify patient-specific responses. Results We used scRNA-seq to demonstrate that acute slice cultures recapitulate the cellular and molecular features of the originating tumor tissue and the feasibility of drug screening from an individual tumor. Detailed investigation of etoposide, a topoisomerase poison, and the histone deacetylase (HDAC) inhibitor panobinostat in acute slice cultures revealed cell type-specific responses across multiple patients. Etoposide has a conserved impact on proliferating tumor cells, while panobinostat treatment affects both tumor and non-tumor populations, including unexpected effects on the immune microenvironment. Conclusions Acute slice cultures recapitulate the major cellular and molecular features of GBM at the single-cell level. In combination with scRNA-seq, this approach enables cell type-specific analysis of sensitivity to multiple drugs in individual tumors. We anticipate that this approach will facilitate pre-clinical studies that identify effective therapies for solid tumors.

Objective Laryngeal verrucous carcinoma (LVC) is a rare, locally invasive neoplasm comprising 1% to 3.4% of laryngeal carcinomas. Management strategies are a topic of ongoing conversation, and no definitive treatment protocol based on T stage and presentation exists. This review examines characteristics, treatment modalities, and patient outcomes of LVC. Data Sources PubMed, MEDLINE, EMBASE, and Web of Science. Methods Databases were searched through October 29, 2015, for literature detailing individual patient cases of LVC. Variables analyzed included patient demographics, tumor characteristics, tumor size, treatment, and outcomes. Results Thirty-seven articles with 369 cases were included. LVC was found more commonly in males (13.8:1), at an average age of 58.7 years, and located in the glottis (74.0%). Most patients had local disease at presentation (94.9%). The most common presenting symptom was hoarseness (92.3%). The most common primary treatment was surgery alone (72.3%), with local excision as the most common technique (56.8%). In patients with data available on both surgical modality and T stage, most patients who presented as T1 and were managed surgically underwent local excision (79.2%). Surgical treatment alone led to high rates of disease-free survival at follow-up (86.8%). A large number of patients presenting with T1 disease were disease free at follow-up (88.6%). Overall survival was 80.3%. Conclusion LVC is most often managed surgically. The extent of surgical resection may be guided by T stage, with smaller tumors resected via local excision and larger tumors via partial or total laryngectomy. Regardless of T stage or therapy, LVC has a good posttreatment prognosis.

DM is associated with greater length of stay and hospital charges among HNCA patients. DM patients have significantly greater rates of postoperative complications, including postoperative infections, cardiac events, and acute renal failure.

Objectives/Hypothesis Inflammatory pseudotumor is a benign idiopathic inflammatory process often misdiagnosed as an infection or neoplasm. This review analyzes all reported cases of sinonasal and ventral skull base inflammatory pseudotumor to date, and provides a framework for evaluation and management of this uncommon condition. Data Sources MEDLINE/PubMed database. Review Methods A search for articles related to sinonasal and ventral skull base inflammatory pseudotumor, along with bibliographies of those articles, was performed. Demographics, presentation, radiographic findings, treatment, follow‐up, and outcome were analyzed. Results Thirty‐three articles were reviewed, including a total of 87 patients. The most common presenting symptom was vision change (58.6%). Sinonasal and ventral skull base inflammatory pseudotumor was found in the cavernous sinus in 46.0% of cases. The lesion appeared isointense (66.7% of cases) and homogeneously enhancing on T1‐weighted magnetic resonance imaging (MRI), whereas it appeared hypointense on T2‐weighted MRI in 90.7% of cases. Inflammatory pseudotumor appeared hyperdense on computed tomography in 78.9% of cases. Histopathological analysis of biopsied specimens revealed presence of inflammatory cells (94.4%) and fibrosis (80.3%). Corticosteroids alone were the most common treatment modality (55.2%), resulting in disease‐free patients in 22.9% of cases over a median follow‐up period of 17.6 months. Surgical management alone was uncommon (8.0%), but showed high success rate (57.1%). Conclusion This review is the most comprehensive analysis of sinonasal and ventral skull base inflammatory pseudotumor to date. Radiologic findings and histopathological analysis are essential for diagnosis. Corticosteroids are the most common treatment modality. Surgery, although uncommon, appears to be an efficacious treatment modality. Level of Evidence N/A Laryngoscope, 125:813–821, 2015