Transoral Robotic Surgery (TORS) Versus Non-TORS Tongue Resection for Obstructive Sleep Apnea.

OBJECTIVE: To compare transoral robotic surgery (TORS) versus non-TORS tongue resection procedures performed for obstructive sleep apnea from January 2010 to September 2015 using a national database, focusing on patient characteristics, performance of concurrent procedures, operative time, length of hospital stay, and postoperative complications. METHODS: A cohort of adults undergoing TORS and non-TORS tongue resection procedures was identified in the Nationwide Inpatient Sample, a publicly-available national administrative database incorporating a stratified sample of hospital discharge records. Outcomes were annual case volumes, prolonged (≥3 days) hospital stay, and complications. Statistical analyses examined potential associations between TORS and prolonged hospital stay and complications. RESULTS: From 2010 to 2015, 5709 hospital discharges included tongue resection surgery to treat obstructive sleep apnea. There was a gradual decline and stabilization in overall volumes, with the proportion of TORS use showing an initial increase, followed by a decrease and rebound increase. TORS patients were less likely to undergo concurrent nasal surgery (15% vs. 44%, P < .01), but there was no association between the use of TORS and concurrent palatal surgery. TORS use was not associated with concurrent hypopharyngeal surgery overall, but it was associated with specific types of hypopharyngeal surgery. TORS use was associated with patient age, payor, and certain hospital characteristics. TORS use was associated with an increased risk of prolonged hospital stay (33% vs. 25%, P = .045) but was not associated with complications. CONCLUSION: This study provides insight into TORS use in tongue resection surgery for obstructive sleep apnea during this period of early TORS adoption. LEVEL OF EVIDENCE: Level 3 (cohort study). Laryngoscope, 131:E1735-E1740, 2021.

Malignancy rates after surgical excision of discordant breast biopsies.

BACKGROUND: Vacuum-assisted core-needle biopsy (VAB) is increasingly used to perform breast biopsies instead of automated-gun core-needle biopsy (CNB). The significance of discordance between radiologic and pathologic findings has not been well established in the era of VAB predominance. This retrospective study was conducted to determine the rate of malignancy after surgical excisional biopsy (EXB) of these lesions at our two institutions. MATERIALS AND METHODS: We reviewed medical records from January 2008-June 2013 to identify female patients who underwent EXB for a Breast Imaging-Reporting and Data System (BI-RADS) 4 or 5 lesions found to be benign and discordant on CNB. Clinicopathologic data were gathered, and analysis was performed using descriptive statistics. RESULTS: A total of 8081 core biopsies were performed in the study timeframe. Six of 81 (7.4%) patients who had an EXB for a benign discordant breast lesion were found to have malignant pathology (two invasive, four in situ). Four of 63 (6.3%) lesions originally biopsied by VAB were upgraded, compared with 2 of 17 (11.8%) originally biopsied by CNB. There were no statistically significant differences in the rates of upgrade to malignancy when data were stratified by BI-RADS score or method of biopsy. CONCLUSIONS: The overall rate of malignancy after EXB of benign discordant lesions was 7.4%. Despite the widespread adoption of VAB, EXB is still warranted for clarification of discordant radiologic-pathologic findings.

Transformation of the fallopian tube secretory epithelium leads to high-grade serous ovarian cancer in Brca;Tp53;Pten models.

High-grade serous ovarian carcinoma presents significant clinical and therapeutic challenges. Although the traditional model of carcinogenesis has focused on the ovary as a tumor initiation site, recent studies suggest that there may be additional sites of origin outside the ovary, namely the secretory cells of the fallopian tube. Our study demonstrates that high-grade serous tumors can originate in fallopian tubal secretory epithelial cells and also establishes serous tubal intraepithelial carcinoma as the precursor lesion to high-grade serous ovarian and peritoneal carcinomas in animal models targeting the Brca, Tp53, and Pten genes. These findings offer an avenue to address clinically important questions that are critical for cancer prevention and early detection in women carrying BRCA1 and BRCA2 mutations.

Targeting Notch, a key pathway for ovarian cancer stem cells, sensitizes tumors to platinum therapy.

Chemoresistance to platinum therapy is a major obstacle that needs to be overcome in the treatment of ovarian cancer patients. The high rates and patterns of therapeutic failure seen in patients are consistent with a steady accumulation of drug-resistant cancer stem cells (CSCs). This study demonstrates that the Notch signaling pathway and Notch3 in particular are critical for the regulation of CSCs and tumor resistance to platinum. We show that Notch3 overexpression in tumor cells results in expansion of CSCs and increased platinum chemoresistance. In contrast, γ-secretase inhibitor (GSI), a Notch pathway inhibitor, depletes CSCs and increases tumor sensitivity to platinum. Similarly, a Notch3 siRNA knockdown increases the response to platinum therapy, further demonstrating that modulation of tumor chemosensitivity by GSI is Notch specific. Most importantly, the cisplatin/GSI combination is the only treatment that effectively eliminates both CSCs and the bulk of tumor cells, indicating that a dual combination targeting both populations is needed for tumor eradication. In addition, we found that the cisplatin/GSI combination therapy has a synergistic cytotoxic effect in Notch-dependent tumor cells by enhancing the DNA-damage response, G(2)/M cell-cycle arrest, and apoptosis. Based on these results, we conclude that targeting the Notch pathway could significantly increase tumor sensitivity to platinum therapy. Our study suggests important clinical applications for targeting Notch as part of novel treatment strategies upon diagnosis of ovarian cancer and at recurrence. Both platinum-resistant and platinum-sensitive relapses may benefit from such an approach as clinical data suggest that all relapses after platinum therapy are increasingly platinum resistant.

The song must go on: resilience of the songbird vocal motor pathway.

Stereotyped sequences of neural activity underlie learned vocal behavior in songbirds; principle neurons in the cortical motor nucleus HVC fire in stereotyped sequences with millisecond precision across multiple renditions of a song. The geometry of neural connections underlying these sequences is not known in detail though feed-forward chains are commonly assumed in theoretical models of sequential neural activity. In songbirds, a well-defined cortical-thalamic motor circuit exists but little is known the fine-grain structure of connections within each song nucleus. To examine whether the structure of song is critically dependent on long-range connections within HVC, we bilaterally transected the nucleus along the anterior-posterior axis in normal-hearing and deafened birds. The disruption leads to a slowing of song as well as an increase in acoustic variability. These effects are reversed on a time-scale of days even in deafened birds or in birds that are prevented from singing post-transection. The stereotyped song of zebra finches includes acoustic details that span from milliseconds to seconds--one of the most precise learned behaviors in the animal kingdom. This detailed motor pattern is resilient to disruption of connections at the cortical level, and the details of song variability and duration are maintained by offline homeostasis of the song circuit.