Surgical Correction of Nasal Obstruction and Its Effect on Eustachian Tube Dysfunction Symptoms.

OBJECTIVES: To investigate how eustachian tube dysfunction symptoms change following surgical treatment of nonsinusitis-related nasal obstruction. STUDY DESIGN: Retrospective chart review. SETTING: Single academic center. METHODS: We assessed patients who underwent septoplasty, turbinate reduction, or both for nasal obstruction. Chronic sinusitis patients were excluded. Eustachian tube dysfunction (ETD) symptoms were studied using the Eustachian Tube Dysfunction Questionnaire (ETDQ-7), collected preoperatively and postoperatively (1 week, 1 month, 3 months, 6 months postop). Patients with preoperative ETDQ-7 > 14.5 were considered to have clinically significant symptoms. Sinonasal outcomes test scores were also assessed. Pre- and postoperative ETDQ-7 scores were compared using t test. Multivariate linear regression analysis identified factors associated with ETDQ-7 change. RESULTS: We analyzed 259 patients. Preoperatively, 37.5% of patients with nasal obstruction had clinically significant ETD symptoms. These patients exhibited significant improvement in ETDQ-7 at all postoperative timepoints from 23.3 ± 7.6 at baseline to 19.1 ± 9.1 at 1 week, 16.5 ± 8.0 at 1 month, 16.2 ± 7.8 at 3 months, and 16.7 ± 10.4 at 6 months (all P < .01). In patients without baseline ETD symptoms, (baseline ETDQ-7: 9.1 ± 2.3) ETDQ-7 scores did not change significantly at postoperative timepoints, except for an acute worsening at 1 week postoperatively (10.7 ± 5.1, P < .001). Regression analysis showed that higher preoperative ETDQ-7 score (ß = -0.84, 95% confidence interval [CI]: -1.10 to -0.59) and postoperative antihistamine spray usage (ß = -8.70, 95% CI: -14.20 to -3.20) were associated with ETDQ-7 improvement, while comorbid GERD (ß = 7.50, 95% CI: 3.42-11.58) and asthma (ß = 5.62, 95% CI: 0.80-10.45) were negatively associated with improvement. CONCLUSION: Surgical correction of nasal obstruction may improve ETD symptoms.

Social determinants of health Z-codes and postoperative outcomes after colorectal surgery: A national population-based study.

BACKGROUND: We sought to evaluate the impact of social determinants of health (SDOH) on postoperative outcomes following colorectal surgery. METHODS: This retrospective cohort study used PearlDiver-Mariner, an all-payer insurance claims database. Patients who underwent colectomy or proctectomy between 2010 and 2020 were included. SDOH were identified using International Classification of Diseases diagnosis codes. Outcomes were compared using multivariable regression models. RESULTS: The 30-day postoperative complication rate among 333,387 patients (mean age, 59 years; 58% female) was 27%. Approximately 5% of patients reported at least one SDOH at baseline. SDOH were not associated with length of stay but were associated with higher odds of 30-day postoperative complications (OR:1.16, 95% CI:1.12-1.20), including urinary tract infection (OR:1.27, 95% CI:1.20-1.35) anastomotic leak (OR:1.22, 95% CI:1.16-1.28), pneumonia (OR:1.19, 95% CI:1.11-1.27), deep vein thrombosis (OR:1.13, 95% CI:1.02-1.23), sepsis (OR:1.12, 95% CI:1.07-1.18), disruption of wound (OR:1.12, 95% CI:1.03-1.21), and acute kidney injury (OR:1.04, 95% CI:0.99-1.10). CONCLUSIONS: SDOH Z-codes were associated with worse postoperative complications following colorectal surgery and may help target high-risk patients.

Flexible Bronchoscopy Simulation as a Tool to Improve Surgical Skills in Otolaryngology Residency.

OBJECTIVE: To evaluate the benefits of simulation to teach flexible bronchoscopy. STUDY DESIGN: A prospective cohort study to assess the bronchoscopic skills of residents in an otolaryngology training program using a commercially available bronchoscopy simulator. SETTING: Tertiary care otolaryngology residency program. METHODS: Thirty-two otolaryngology residents and 4 expert faculty across 2 academic institutions were assessed on 3 flexible bronchoscopy tasks: diagnostic bronchoscopy, foreign body removal, and tracheal lesion biopsy. Performance was evaluated with a modified version of the validated Bronchoscopy Skills and Tasks Assessment Tool. At 1 of the 2 academic institutions, an additional tool was implemented to evaluate the simulator. RESULTS: There was a correlation between postgraduate training year and time taken to complete tasks, including bronchoscopy, foreign body extraction, and passing through the glottis (P < .001, P = .04, and P < .01, respectively). There was a significant difference between residents and faculty laryngologists for a range of skills and tasks, including percentage of time in middle lumen, contact with bronchial walls, inadvertent esophagus entry, and biopsy of healthy tissue (P < .001, P = .003, P < .001, and P < .001). Additionally, increasing postgraduate level was correlated with a higher percentage of time in the center of the lumen and reduced time to task completion (P = .05 and P < .001). Of 32 residents, 20 evaluated the simulator on its realism, with an average score of 4.1 of 5. CONCLUSION: The commercially available flexible bronchoscopy simulator provides a valid assessment of bronchoscopic skill and is a useful tool for practicing bronchoscopy in a safe, controlled environment. LEVEL OF EVIDENCE: Individual cohort study.

Nephrobiliary fistula resulting from a gunshot wound in a young healthy male: A case report.

Biliary fistulas are most commonly caused by cholelithiasis. Other causes include malignancies and peptic ulcer disease. A biliary fistula caused by a penetrating trauma is a rare entity, and a post-traumatic biliary fistula to the renal collecting system is extremely uncommon. We present an extremely rare case of a post-traumatic nephrobiliary fistula incurred after penetrating trauma that was successfully treated with endoscopic retrograde cholangiopancreatography (ERCP), biliary stents, and percutaneous drainage.

Primary small cell carcinoma of the adrenal gland: Case presentation of a rare extrapulmonary small cell carcinoma.

Small cell carcinoma (SCC) is an aggressive histologic subtype of neuroendocrine tumor and is most commonly of bronchogenic origin. However, it can present in an extrapulmonary fashion. Primary extrapulmonary small cell carcinoma (EPSCC) is a rare disease entity, especially within the genitourinary system and furthermore of the adrenal gland. There are scarce case reports that describe management of primary adrenal SCC. We present a case of localized primary adrenal SCC diagnosed on adrenal mass biopsy and successfully treated via neoadjuvant chemotherapy and extirpative surgery.

Should a Drain Be Routinely Required After Transperitoneal Robotic Partial Nephrectomy?

Introduction: Closed drains have traditionally been placed after partial nephrectomy because of risks of bleeding and urine leak. We sought to study the safety of a nonroutine drain (NRD) approach after transperitoneal robotic partial nephrectomy (RPN). Patients and Methods: From a multi-institutional database, we have analyzed the data of 904 patients who underwent RPN. Five hundred forty-six (60.40%) patients underwent RPN by a surgeon who routinely placed drains. Three hundred fifty-eight (39.60%) patients underwent RPN by a surgeon who did not routinely placed drains. Perioperative outcomes, length of stay (LOS), and readmission rates were compared between the two groups. Baseline characteristics, perioperative, and postoperative outcomes were compared using Mann-Whitney U test, chi-square test, and Fisher's exact test. Results: Patients in the NRD group were more likely to have higher body mass index (30.10 kg/m2vs 28.07 kg/m2; P < 0.001), higher tumor size (3.0 cm vs 2.5 cm; P = 0.001), and higher renal score (8 vs 7; P < 0.001). Rate of transfusion (0.00% NRD vs 0.56% RD; P = 0.157) and overall complication (7.33% NRD vs 7.82% RD; P = 0.782) were comparable. Median hospital stay is 1 day for both groups. Readmission rate was also similar (0.55% NRD vs 1.40% RD; P = 0.279). In a multivariable analysis, NRD approach was associated with shorter length of hospital stay (incidence rate ratio [IRR] - 0.72, P < 0.001). Conclusion: An NRD approach for RPN yielded a decreased LOS and similar perioperative outcomes. Placement of surgical drains should be based on individual circumstances, and not required on a routine basis.

The Effect of Endoscopic Sinus Surgery on Eustachian Tube Dysfunction Symptoms.

OBJECTIVE: We assessed how eustachian tube dysfunction (ETD) changed with endoscopic sinus surgery (ESS) and identified factors associated with improvement. STUDY DESIGN: Retrospective chart review. SETTING: Academic center. SUBJECTS AND METHODS: Patients undergoing ESS for chronic rhinosinusitis with and without nasal polyposis (CRSwNP, CRSsNP) or recurrent acute rhinosinusitis (RARS) completed the Eustachian Tube Dysfunction Questionnaire 7 (ETDQ-7) preoperatively and postoperatively at 2 weeks, 6 weeks, 3 months, and 6 months. Included in analyses were demographics, comorbidities, Sinonasal Outcome Test 22 (SNOT-22), radiographic score, endoscopy score, procedure, and medication use. Regression analysis identified factors associated with improvement, defined as ΔETDQ-7 >3.5. RESULTS: In total, 302 patients were studied. ETD prevalence was 68% in CRSsNP, 48% in CRSwNP, and 88% in RARS. Patients with ETD had a mean baseline ETDQ-7 of 25.8 ± 8.0 and improved postoperatively at 2 weeks (19.9 ± 8.1, P < .001), 6 weeks (17.8 ± 9.3, P < .001), 3 months (16.8 ± 8.5, P < .001), and 6 months (16.4 ± 7.9, P < .001). At 6 months, ETD improved in 89% of patients with CRSsNP, 68% with CRSwNP, and 78% with RARS. On multivariate analysis, ETD improvement was associated with higher preoperative ETDQ-7 score (adjusted odds ratio [aOR], 1.12; 95% confidence interval [CI], 1.04-1.22; P = .030), higher preoperative SNOT-22 score (aOR, 1.02; 95% CI, 1.02-1.08; P = .001), higher preoperative SNOT-22 ear subscore (aOR, 1.27; 95% CI, 1.02-1.65; P = .034), posterior ethmoidectomy (aOR, 1.59; 95% CI, 1.22-4.92; P = .025), and postoperative corticosteroid spray use (aOR, 1.57; 95% CI, 1.17-1.66; P = .008). CONCLUSION: ETD symptoms often improve following ESS. Factors associated with improvement include higher preoperative disease burden, posterior ethmoidectomy, and postoperative corticosteroid spray. LEVEL OF EVIDENCE: 4.

Novel HDAC11 inhibitors suppress lung adenocarcinoma stem cell self-renewal and overcome drug resistance by suppressing Sox2.

Non-small cell lung cancer (NSCLC) is known to have poor patient outcomes due to development of resistance to chemotherapy agents and the EGFR inhibitors, which results in recurrence of highly aggressive lung tumors. Even with recent success in immunotherapy using the checkpoint inhibitors, additional investigations are essential to identify novel therapeutic strategies for efficacious treatment for NSCLC. Our finding that high levels of histone deacetylase 11 (HDAC11) in human lung tumor tissues correlate with poor patient outcome and that depletion or inhibition of HDAC11 not only significantly reduces self-renewal of cancer stem cells (CSCs) from NSCLC but also decreases Sox2 expression that is essential for maintenance of CSCs, indicates that HDAC11 is a potential target to combat NSCLC. We find that HDAC11 suppresses Sox2 expression through the mediation of Gli1, the Hedgehog pathway transcription factor. In addition, we have used highly selective HDAC11 inhibitors that not only target stemness and adherence independent growth of lung cancer cells but these inhibitors could also efficiently ablate the growth of drug-insensitive stem-like cells as well as therapy resistant lung cancer cells. These inhibitors were found to be efficacious even in presence of cancer associated fibroblasts which have been shown to contribute in therapy resistance. Our study presents a novel role of HDAC11 in lung adenocarcinoma progression and the potential use of highly selective inhibitors of HDAC11 in combating lung cancers.

HDAC11 deficiency disrupts oncogene-induced hematopoiesis in myeloproliferative neoplasms.

Protein acetylation is an important contributor to cancer initiation. Histone deacetylase 6 (HDAC6) controls JAK2 translation and protein stability and has been implicated in JAK2-driven diseases best exemplified by myeloproliferative neoplasms (MPNs). By using novel classes of highly selective HDAC inhibitors and genetically deficient mouse models, we discovered that HDAC11 rather than HDAC6 is necessary for the proliferation and survival of oncogenic JAK2-driven MPN cells and patient samples. Notably, HDAC11 is variably expressed in primitive stem cells and is expressed largely upon lineage commitment. Although Hdac11is dispensable for normal homeostatic hematopoietic stem and progenitor cell differentiation based on chimeric bone marrow reconstitution, Hdac11 deficiency significantly reduced the abnormal megakaryocyte population, improved splenic architecture, reduced fibrosis, and increased survival in the MPLW515L-MPN mouse model during primary and secondary transplantation. Therefore, inhibitors of HDAC11 are an attractive therapy for treating patients with MPN. Although JAK2 inhibitor therapy provides substantial clinical benefit in MPN patients, the identification of alternative therapeutic targets is needed to reverse MPN pathogenesis and control malignant hematopoiesis. This study establishes HDAC11 as a unique type of target molecule that has therapeutic potential in MPN.

Patient preferences regarding the communication of biopsy results in the general otolaryngology clinic.

OBJECTIVES: To determine the preferred methods of communicating biopsy results for patients in our comprehensive otolaryngology clinic, and to examine factors associated with preferring remote vs. in-person communication of results. STUDY DESIGN: Cross-sectional study. SETTING: Academic comprehensive otolaryngology clinic. SUBJECTS AND METHODS: A survey instrument was administered to 107 consecutive adult otolaryngology patients undergoing head and neck fine needle aspiration biopsy from March 1, 2017 to April 30, 2018 assessing their health literacy using the Brief Health Literacy Score and their preferred method of notification of biopsy results (in-person vs. remote). RESULTS: 69% of patients preferred remote notification of their biopsy results (either by telephone or via an online portal). 54% of patients prioritized clear explanation of the results as the most important factor when communicating a malignant result. Adequate health literacy was associated with lower odds of preferring in-person notification (adjusted odds ratio 0.11, 95% CI 0.03 to 0.39). Patients who prioritized clear explanation of the results were more likely to prefer in-person notification (adjusted OR 4.13, 95% CI 1.31 to 14.88). CONCLUSIONS: A significant proportion of patients in our comprehensive otolaryngology clinic undergoing fine needle aspiration biopsy preferred remote communication of their biopsy results. Patients most valued clear explanations from the provider and prompt receipt of the result when communicating malignant results. This highlights the need for individualized results communication plans, for patients undergoing biopsy.

Discovery of novel N-hydroxy-2-arylisoindoline-4-carboxamides as potent and selective inhibitors of HDAC11.

N-Hydroxy-2-arylisoindoline-4-carboxamides are potent and selective inhibitors of HDAC11. The discovery, synthesis, and structure activity relationships of this novel series of inhibitors are reported. An advanced analog (FT895) displays promising cellular activity and pharmacokinetic properties that make it a useful tool to study the biology of HDAC11 and its potential use as a therapeutic target for oncology and inflammation indications.

Evaluation of an abbreviated screening MRI protocol for patients at risk for hepatocellular carcinoma.

PURPOSE: In this study, we compare an abbreviated screening MRI protocol (aMRI), utilizing only dynamic contrast-enhanced images, to a conventional liver MRI (cMRI) for the characterization of observations in at-risk patients. MATERIALS AND METHODS: 164 consecutive HCC screening MRIs were retrospectively analyzed. Two sets of de-identified image sets were created: one with all acquired sequences including T2- and diffusion-weighted sequences (cMRI), and one with only T1-weighted precontrast and dynamic post-contrast images utilizing an extracellular gadolinium contrast agent (aMRI). Three readers assigned a LI-RADS score based on the lesion with the highest LI-RADS category using the aMRI and cMRI datasets during separate reads. RESULTS: There was no change between the aMRI and cMRI LI-RADS categorization in 93%, 96%, and 96% of cases for readers 1, 2, and 3, respectively. In the majority of the discrepant cases, the score increased from LI-RADS 3 to LI-RADS 4 due to the presence of ancillary features on T2 and DWI. Kappa values for interobserver variability demonstrated fair-to-moderate LI-RADS agreement among the 3 readers. CONCLUSION: There was strong agreement between the abbreviated T1-only MRI protocol and a full liver MRI, with only 5% of cases changing LI-RADS categorization due to the inclusion of T2 and DWI. The estimated time to run this abbreviated MRI is approximately 7-10 min, possibly allowing for a more cost-effective screening MRI than our cMRIs.

Health Literacy Assessment in an Otolaryngology Clinic Population.

OBJECTIVE: To assess health literacy in an adult tertiary care otolaryngology clinic population and to explore potential determinants of inadequate health literacy. STUDY DESIGN: Cross-sectional study. SETTING: Tertiary care otolaryngology clinic. SUBJECTS AND METHODS: The study population included all adult patients treated at 3 of Stanford University's adult otolaryngology clinic sites between March 1 and 11, 2016. Data were collected via an anonymous questionnaire. Health literacy was assessed with the Brief Health Literacy Screen. RESULTS: Ten percent of patients had inadequate health literacy. White race (odds ratio [OR], 0.23) and having English as the primary language (OR, 0.12) were associated with adequate health literacy, while high school or lower level of education (OR, 3.2) was associated with inadequate health literacy. Age, sex, and Hispanic ethnicity were not associated with health literacy. CONCLUSION: Our study highlights the need for health literacy screening in the otolaryngology clinic setting and identifies sociodemographic risk factors for inadequate health literacy. Further studies are needed to assess the impact of health literacy on patient outcomes and to test specific interventions to address health literacy and health outcomes.

BRD7, a tumor suppressor, interacts with p85α and regulates PI3K activity.

Phosphoinositide 3-kinase (PI3K) activity is important for regulating cell growth, survival, and motility. We report here the identification of bromodomain-containing protein 7 (BRD7) as a p85α-interacting protein that negatively regulates PI3K signaling. BRD7 binds to the inter-SH2 (iSH2) domain of p85 through an evolutionarily conserved region located at the C terminus of BRD7. Via this interaction, BRD7 facilitates nuclear translocation of p85α. The BRD7-dependent depletion of p85 from the cytosol impairs formation of p85/p110 complexes in the cytosol, leading to a decrease in p110 proteins and in PI3K pathway signaling. In contrast, silencing of endogenous BRD7 expression by RNAi increases the steady-state level of p110 proteins and enhances Akt phosphorylation after stimulation. These data suggest that BRD7 and p110 compete for the interaction to p85. The unbound p110 protein is unstable, leading to the attenuation of PI3K activity, which suggests how BRD7 could function as a tumor suppressor.

Inflammatory protein expression in human subglottic stenosis tissue mirrors that in a murine model.

OBJECTIVES: We undertook to describe the genetic and protein composition of subglottic stenosis (SGS) by measuring an array of protein expression and messenger RNA levels within human SGS tissue. We also sought to compare this human array to cytokine expression from a murine model of SGS in order to confirm the effective translational nature of our animal model. METHODS: Human granulation tissue from 10 patients with early symptomatic SGS was compared to control bronchus. The expression levels of 24 different cytokines were measured by a Luminex protein assay and real-time polymerase chain reaction. RESULTS: The protein expression in human SGS mirrors that seen in murine SGS. Transforming growth factor ß1, interleukin 1ß, and matrix metalloproteinase 9 were markedly elevated in both human and mouse SGS tissues. The protein array showed a statistically significant elevation in the proinflammatory cytokines tumor necrosis factor α, interleukin 1, granulocyte macrophage colony-stimulating factor, and interferon γ. CONCLUSIONS: This is the first study, to our knowledge, to measure an array of protein expression within human SGS tissue. The expression profile suggests that symptomatic tracheal granulation tissue is mostly within the early inflammatory phase of wound healing and has only begun fibrotic and angiogenic remodeling. This study validates our murine model of SGS, and also helps to define the exact pathways of tissue injury, in the hope of leading to new treatments for this difficult condition.

18-FDG-PET in the initial staging of sinonasal malignancy.

OBJECTIVES/HYPOTHESIS: The utility of fluorine-18 fluorodeoxyglucose-positron emission tomography (PET) has been gradually defined for most head and neck cancers, However, its utility in the initial diagnosis of sinonasal malignancy has not been extensively studied. The aim of this study was to determine if PET scanning accurately diagnoses and stages malignant sinonasal lesions and if maximum standard uptake value (SUV max) correlates with clinically advanced disease. STUDY DESIGN: Retrospective chart review. METHODS: There were 51 patients with sinonasal malignancy who underwent diagnostic whole body PET or PET-computed tomography scans that were analyzed for patient and disease characteristics, SUV max, and staging. RESULTS: Of the 51 patients, 48 scans were positive at the primary site, with a sensitivity of 94%. Four patients were found to have intensely avid uptake, in which the numerical SUV max was not documented, and three patients did not have any uptake in the region of their tumor. Mean SUV max at the primary site was 16.1 (range, 3.1-59). Metastasis was detected in 31% (16/51) of the patients. There was a potential positive correlation between SUV max at the primary site and detection of metastasis on univariate analysis (r = 0.19, P = .09), but on multivariate analysis, SUV max was not found to correlate with T staging or metastasis. CONCLUSIONS: For diagnosis of sinonasal malignancy, PET scans have a high sensitivity, although false negatives occurred in 6% of cases. PET scanning detected metastasis in 31% of patients, but SUV max did not function as a marker for clinically advanced disease. The role of diagnostic PET for sinonasal malignancy is currently limited to cases with a high suspicion of metastatic disease.

Sphenoid sinus anatomy and suprasellar extension of pituitary tumors.

OBJECT: As tumors enlarge, they generally grow along paths of least resistance. For pituitary macroadenomas, extrasellar extension into the suprasellar region, cavernous sinus, or sphenoid sinus may occur. The sphenoid sinus is known to have a variable anatomical configuration, and the authors hypothesize that certain anatomical factors may resist tumor expansion into the sphenoid sinus, thereby directing tumor growth into the suprasellar space. In this paper the authors' goal was to determine if sphenoid anatomy influences pituitary tumor growth. METHODS: The authors conducted a retrospective analysis of 106 consecutive surgical cases of pituitary macroadenoma. Patient demographics, suprasellar extension, sellar width, and features of the sphenoid intersinus septum were recorded on radiographic review. The chi-square test, t-test, logistic regression, and classification and regression tree analysis were used for statistical analysis. RESULTS: Of the 106 patients included in the study, 71 (67%) demonstrated suprasellar extension of their tumor. Patients with suprasellar tumor extension had significantly greater intersinus septum width (width > 1.27 mm: OR = 14.32; p = 0.0012) and were significantly older (age > 54 yrs: OR = 3.33; p = 0.0176). They also tended to be male and to have two or more sphenoid partitions (OR = 6.58; p = 0.0306). While patients with suprasellar extension tended to be more likely to have a midline partition and a larger sellar width than their counterparts, these differences did not reach statistical significance. CONCLUSIONS: Certain aspects of the sphenoid sinus anatomy may function to resist pituitary tumor growth into the sphenoid sinus. Progressive enlargement of pituitary macroadenomas may extend in a suprasellar direction, in part, as a consequence of the sphenoid sinus anatomy.