Establishment of a diverse head and neck squamous cancer cell bank using conditional reprogramming culture methods.

Most laboratory models of head and neck squamous cell cancer (HNSCC) rely on established immortalized cell lines, which carry inherent bias due to selection and clonality. We established a robust panel of HNSCC tumor cultures using a "conditional reprogramming" (CR) method, which utilizes a rho kinase inhibitor (Y-27632) and co-culture with irradiated fibroblast (J2 strain) feeder cells to support indefinite tumor cell survival. Sixteen CR cultures were successfully generated from 19 consecutively enrolled ethnically and racially diverse patients with HNSCC at a tertiary care center in the Bronx, NY. Of the 16 CR cultures, 9/16 were derived from the oral cavity, 4/16 were derived from the oropharynx, and 3/16 were from laryngeal carcinomas. Short tandem repeat (STR) profiling was used to validate culture against patient tumor tissue DNA. All CR cultures expressed ΔNp63 and cytokeratin 5/6, which are markers of squamous identity. Human papillomavirus (HPV) testing was assessed utilizing clinical p16 staining on primary tumors, reverse transcription polymerase chain reaction (RT-PCR) of HPV16/18-specific viral oncogenes E6 and E7 in RNA extracted from tumor samples, and HPV DNA sequencing. Three of four oropharyngeal tumors were p16 and HPV-positive and maintained HPV in culture. CR cultures were able to establish three-dimensional spheroid and murine flank and orthotopic tongue models. CR methods can be readily applied to all HNSCC tumors regardless of patient characteristics, disease site, and molecular background, providing a translational research model that properly includes patient and tumor diversity.

COVID-19 and the resurgence of telehealth in otolaryngology.

The objective of this review is to examine the impact of the ongoing Coronavirus disease 2019 (COVID-19) pandemic on the use of telehealth in Otolaryngology. The use of telemedicine rose dramatically during the pandemic to meet the need for continued patient care while allowing for physical separation of providers and patients. Telemedicine has been used to evaluate patients with a variety of pathologies including dysphonia, vertigo, and anosmia. Innovative use of at-home exams, such as video-otoscopy has aided providers in overcoming challenges associated with a highly specialized physical exam. The use of telemedicine in Otolaryngology will likely remain essential in the post-pandemic era and has promising results for improving clinical efficiency.

Impact of Nonadherence to NCCN Adjuvant Radiotherapy Initiation Guidelines in Head and Neck Squamous Cell Carcinoma in an Underserved Urban Population.

BACKGROUND: Nonadherence to NCCN Guidelines during time from surgery to postoperative radiotherapy (S-PORT) can alter survival outcomes in head and neck squamous cell carcinomna (HNSCC). There is a need to validate this impact in an underserved urban population and to understand risk factors and reasons for delay. We sought to investigate the impact of delayed PORT with outcomes of overall survival (OS) in HNSCC, to analyze predictive factors of delayed PORT, and to identify reasons for delay. METHODS: We conducted a retrospective cohort study in an urban, community-based academic center. A total of 184 patients with primary HNSCC were identified through the Montefiore Medical Center cancer registry who had been treated between March 1, 2005, and March 8, 2017, and met the inclusion and exclusion criteria. The primary exposure was S-PORT. OS, recurrence, and risk factors and reasons for treatment delay were the main outcomes and measures. RESULTS: Among 184 patients with HNSCC treated with PORT, the median S-PORT was 48.5 days (interquartile range, 41-67 days). The S-PORT threshold that optimally differentiated worse OS outcomes was >50 days (46.7% of our cohort; n=86). Independent of other relevant factors, patients with HNSCC and S-PORT >50 days had worse OS (hazard ratio, 2.30; 95% CI, 1.34-3.95) and greater recurrence (odds ratio, 3.51; 95% CI, 1.31-9.39). Predictors of delayed S-PORT included being underweight or obese, prolonged postoperative length of stay, and age >70 years. The most frequent reasons for PORT delay were complications related to surgery (22.09%), unrelated medical comorbidities (18.60%), and nonadherence/missed appointments (6.98%). CONCLUSIONS: Delayed PORT beyond 50 days after surgery was associated with decreased OS and greater recurrence. Identification of predictive factors and reasons for treatment delay helps to target at-risk patients and facilitates interventions in underserved populations.

HIV Modifies the Effect of Tobacco Smoking on Oral Human Papillomavirus Infection.

BACKGROUND: People living with HIV (PLWH) are more likely to smoke and harbor oral human papillomavirus (HPV) infections, putting them at higher risk for head and neck cancer. We investigated effects of HIV and smoking on oral HPV risk. METHODS: Consecutive PLWH (n = 169) and at-risk HIV-negative individuals (n = 126) were recruited from 2 US health centers. Smoking history was collected using questionnaires. Participants provided oral rinse samples for HPV genotyping. We used multivariable logistic regression models with interaction terms for HIV to test for smoking effect on oral HPV. RESULTS: PLWH were more likely to harbor oral HPV than HIV-negative individuals, including α (39% vs 28%), ß (73% vs 63%), and γ-types (33% vs 20%). HIV infection positively modified the association between smoking and high-risk oral HPV: odds ratios for smoking 3.46 (95% confidence interval [CI], 1.01-11.94) and 1.59 (95% CI, .32-8.73) among PLWH and HIV-negative individuals, respectively, and relative excess risk due to interaction (RERI) 3.34 (95% CI, -1.51 to 8.18). RERI for HPV 16 was 1.79 (95% CI, -2.57 to 6.16) and 2.78 for ß1-HPV (95% CI, -.08 to 5.65). CONCLUSION: Results show tobacco smoking as a risk factor for oral HPV among PLWH.

Oral Human Papillomavirus Infection and Oral Lesions in HIV-Positive and HIV-Negative Dental Patients.

We evaluated the risk factors associated with oral human papillomavirus (HPV) infection and oral lesions in 161 human immunodeficiency virus (HIV)-positive patients and 128 HIV-negative patients presenting for oral examination at 2 urban healthcare centers. Patients were interviewed on risk factors and provided oral-rinse samples for HPV DNA typing by polymerase chain reaction. Statistical associations were assessed by logistic regression. Oral HPV was prevalent in 32% and 16% of HIV-positive patients and HIV-negative patients, respectively, including high-risk HPV type 16 (8% and 2%, respectively; P = .049) and uncommon HPV types 32/42 (6% and 5%, respectively; P = .715). Among HIV-negative patients, significant risk factors for oral HPV included multiple sex partners (≥21 vs ≤5; odds ratio [OR], 9.1; 95% confidence interval [CI], 1.7-49.3), heavy tobacco smoking (>20 pack-years vs none; OR, 9.2; 95% CI, 1.4-59.4), and marijuana use (OR, 4.0; 95% CI, 1.3-12.4). Among HIV-positive patients, lower CD4(+) T-cell count only was associated with oral HPV detection (≤200 vs ≥500 cells/mm(3); OR, 4.5; 95% CI, 1.3-15.5). Detection of high-risk HPV was also associated with concurrent detection of potentially cancerous oral lesions among HIV-negative patients but not among HIV-positive patients. The observed risk factor associations with oral HPV in HIV-negative patients are consistent with sexual transmission and local immunity, whereas in HIV-positive patients, oral HPV detection is strongly associated with low CD4(+) T-cell counts.

Transoral resection of stylopharyngeus calcification: a unique manifestation of a stylohyoid complex syndrome.

BACKGROUND: Eagle syndrome is often considered in the work-up of odynophagia and neck pain. Classically, this is manifested by ossification or calcification of the stylohyoid ligament or styloid process. There are no reported cases of stylopharyngeal calcification leading to these symptoms. CASE: We describe a patient with a suspected submucosal pharyngeal foreign body who was found to have a calcified stylopharyngeus muscle and tendon during surgery. The patient experienced full resolution of symptoms after transoral robotic resection. This diagnosis was initially missed because the radiology was inconsistent with Eagle syndrome. CONCLUSION: This is the first report of isolated stylopharyngeal calcification, and this unique manifestation of a stylohyoid complex syndrome should be considered in patients with symptoms of Eagle syndrome without styloid elongation.

Reconstruction of the pediatric midface following oncologic resection.

BACKGROUND: Sarcoma is the most common midface malignancy in children. While first-line treatment in adults is resection, the challenges associated with resection and reconstruction of these tumors in children often lead to radiation therapy as primary treatment. This report highlights the feasibility and efficacy of midface reconstruction in the pediatric population after resection. In most cases, the same principles utilized in reconstructing midface defects in adults hold for the pediatric population. PATIENTS AND METHODS: From 2008 to 2013 seven pediatric patients underwent resection and reconstruction for maxillary sarcomas. These patients ranged in age from 18 months to 20 years. Five patients were reconstructed with six microvascular free flaps. Two patients received pedicled flaps. Follow-up ranged from 15 months to 4.5 years. Reconstructive, oncological, and functional outcomes were analyzed. RESULTS: Seven patients underwent eight reconstructions for sarcomas of the maxilla. Flaps utilized included vertical rectus abdominis, anterolateral thigh, fibula, and temporoparietal fascia. One flap was complicated by venous thrombosis but was successfully salvaged after thrombectomy and revision using vein graft. One patient developed recurrence after initial flap placement and required salvage resection and a second free flap. Six patients were judged to have good facial symmetry and tolerated a regular oral diet with normal or near-normal dental occlusion. CONCLUSIONS: Standard primary therapy for sarcomas of the maxilla in the pediatric population consists of nonsurgical management. However, a radiation-first approach is associated with significant morbidity and makes surgical salvage more difficult. Based on our experience, microsurgical reconstruction of the pediatric midface is safe and effective, and should be considered a first-line treatment option for midface sarcomas in children. In general, there is no significant area of departure between the principles that govern midface reconstruction in adults and children.

Superficial temporal artery and vein as recipient vessels for scalp and facial reconstruction: radiographic support for underused vessels.

BACKGROUND: The choice of the recipient vessels for microsurgical reconstruction is based on proximity to the defect, vessel caliber, anatomic reliability, and ease of dissection. Traditionally in head and neck reconstruction, the superficial temporal artery and vein (STA/V) have been reserved as secondary recipient vessels. Others, including the facial artery (FA) and vein have been the preferred choice for facial reconstruction. METHODS: A retrospective analysis of all consecutive head and neck reconstructions using the STA/V by the senior author (E.S.G.) over a 5-year period was performed. Perioperative data were reviewed for all the patients. In a subset of patients, radiographic analysis was used to delineate STA and FA anatomy including vessel diameter and distances to standard anatomic landmarks. RESULTS: A total of 31 patients had 32 microsurgical reconstructions using the STA/V as recipient vessels. Radiographic analysis revealed no significant difference between the STA and FA diameters. The distances from the STA to the upper and middle face were significantly shorter relative to the FA, 64 versus 102 mm (p < 0.0001) and 72 versus 80 mm (p < 0.04), respectively. The distances from the lower face to the STA and FA were 56 and 30 mm, respectively (p < 0.0001). CONCLUSIONS: The STA/V can be used as first choice recipient vessels in head and neck reconstruction. Key features of these vessels include proximity to defect, acceptable caliber, predictable anatomic location, and relative ease of dissection. We recommend that the STA/V be considered recipient vessels of choice for reconstruction of defects of the face and scalp.

Combined P16 and human papillomavirus testing predicts head and neck cancer survival.

While its prognostic significance remains unclear, p16(INK4a) protein expression is increasingly being used as a surrogate marker for oncogenic human papillomavirus (HPV) infection in head and neck squamous cell carcinomas (HNSCC). To evaluate the prognostic utility of p16 expression in HNSCC, we prospectively collected 163 primary tumor specimens from histologically confirmed HNSCC patients who were followed for up to 9.4 years. Formalin fixed tumor specimens were tested for p16 protein expression by immunohistochemistry (IHC). HPV type-16 DNA and RNA was detected by MY09/11-PCR and E6/E7 RT-PCR on matched frozen tissue, respectively. P16 protein expression was detected more often in oropharyngeal tumors (53%) as compared with laryngeal (24%), hypopharyngeal (8%) or oral cavity tumors (4%; p<0.0001). With respect to prognosis, p16-positive oropharyngeal tumors exhibited significantly better overall survival than p16-negative tumors (log-rank test p=0.04), whereas no survival benefit was observed for nonoropharyngeal tumors. However, when both p16 and HPV DNA test results were considered, concordantly positive nonoropharyngeal tumors had significantly better disease-specific survival than concordantly negative nonoropharyngeal tumors after controlling for sex, nodal stage, tumor size, tumor subsite, primary tumor site number, smoking and drinking [adjusted hazard ratio (HR)=0.04, 0.01-0.54]. Compared with concordantly negative nonoropharyngeal HNSCC, p16(+)/HPV16(-) nonoropharyngeal HNSCC (n=13, 7%) demonstrated no significant improvement in disease-specific survival when HPV16 was detected by RNA (adjusted HR=0.83, 0.22-3.17). Our findings show that p16 IHC alone has potential as a prognostic test for oropharyngeal cancer survival, but combined p16/HPV testing is necessary to identify HPV-associated nonoropharyngeal HNSCC with better prognosis.

Risk factors for perioperative airway difficulty and evaluation of intubation approaches among patients with benign goiter.

OBJECTIVE: The objective was to determine patient and gland characteristics associated with difficult intubation in patients undergoing thyroidectomy for goiter and to assess different methods of intubation in these patients. METHODS: This study was an IRB-approved, retrospective chart review of 112 consecutive patients undergoing hemithyroidectomy or total thyroidectomy for thyroid goiter from 2009-2012 at an academic tertiary care facility in Bronx, New York. Patient demographics, thyroid gland characteristics (gland weight and nodule size), presence of preoperative symptoms (dyspnea, dysphagia, and hoarseness), and radiographical findings (tracheal compression, tracheal deviation, and substernal extension of the thyroid gland) were recorded. Anesthesia records were reviewed for method of intubation, as well as success or failure of intubation attempts. RESULTS: Nineteen patients (17.0%) were men and 93 (83.0%) were women. The age of the patients included in the study ranged from 14 to 86 years with a mean ± SD age of 53.5 ± 14.7 years. Difficult intubation was noted with 13 (11.6%) patients. Only patient age was significantly associated with difficult intubation. The mean age of patients with airway difficulty was 60.7 ± 3.7 years compared to 52.1 ± 1.5 years in those who did not experience airway difficulty (P = .04). No other reviewed risk factors were found to be significantly associated with difficult intubation. Fiberoptic intubation (FOI) was used in 38 patients and difficult intubation occurred in 18.4% (7/38). Direct laryngoscopy with transoral intubation (LTOI) was used in 58 patients, in whom 3.4% (2/58) experienced a difficult intubation. FOI was aborted 6 times and LTOI was subsequently successful in each of these cases. CONCLUSIONS: Our results suggest that benign nodular goiter disease does not pose significant challenges to intubation in our patient cohort. The technique of intubation deviated from the initial plan several times in the FOI group, whereas LTOI was ultimately successful in every case. Our data suggest that the role of fiberoptic intubation for patients with large goiters should be further refined.

Value of Adherence to Posttreatment Follow-Up Guidelines for Head and Neck Squamous Cell Carcinoma.

OBJECTIVES: The utility of intensive posttreatment surveillance of head and neck squamous cell carcinoma (HNSCC) has been debated. The objective is to investigate adherence to the National Comprehensive Cancer Network (NCCN) posttreatment follow-up guidelines and assess the association with recurrence and survival. METHODS: A total of 452 patients diagnosed with HNSCC at an academic medical center in a socioeconomically disadvantaged, urban setting were categorized by adherence to NCCN follow-up guidelines. Survival analyses were conducted to study the association between adherence and the 5-year overall survival and disease-specific survival in the entire cohort and subset of patients with documented recurrence. RESULTS: We found that 23.5% of patients were adherent to NCCN follow-up guidelines in the first year after treatment, and 15.9% were adherent over 5 years. Adherence in the first year was significantly associated with 5-year overall survival (HR 0.634; 95% CI 0.443-0.906; p = 0.0124) and disease-specific survival (HR 0.556; 95% CI 0.312-0.992; p = 0.0470), but consistent adherence over 5 years did not show a significant association. Among the 21.7% of the cohort with recurrence, adherence was not associated with early-stage recurrence (AJCC stage I/II). In this subset, first year adherence was associated with improved disease-specific but not overall survival, and adherence over 5 years was not associated with survival. CONCLUSION: Adherence to NCCN follow-up guidelines in the first year after treatment was associated with a better chance of 5-year overall and disease-specific survival, but this significant association was not observed among those who demonstrated consistent adherence over 5 years. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:708-716, 2024.

Association of tumor growth rate with overall survival and recurrence among patients with laryngeal squamous cell carcinoma.

BACKGROUND: Delay in time to treatment initiation (TTI) is associated with worsened survival outcomes in laryngeal squamous cell carcinoma (LSCC). It is unclear whether this is due to tumor growth or an increased risk of metastatic disease. METHODS: This retrospective cohort study at one academic center included patients with LSCC who underwent radiotherapy/chemoradiotherapy between 2005 and 2017. We examined the association between tumor growth rate (TGR) and survival outcomes. RESULTS: Among 105 patients (mean age, 63.8 ± 11.1 years; 72% male), the threshold between "slow-growing" and "fast-growing" tumors was >0.036 mL/day (survival) and >0.082 mL/day (recurrence). Faster growth was associated with worse overall survival (OS) (hazard ratio, 1.97; 95% confidence interval [CI], 0.94-4.13) and increased recurrence (odds ratio, 9.10; 95% CI, 2.40-34.4). CONCLUSIONS: TGR >0.036 mL/day during TTI was associated with decreased OS, and >0.082 mL/day was associated with increased recurrence. Tumor measurement in patients experiencing delay may identify those who could benefit from escalated therapy.

Complications related to thyroidectomy among patients with hyperthyroidism: Exploring the potential for ambulatory surgery.

BACKGROUND: Total thyroidectomy for hyperthyroidism is typically followed by overnight admission to monitor for complications including thyrotoxicosis. Outpatient thyroid surgery is increasingly common, but its safety in patients with hyperthyroidism has not been well studied. METHODS: This retrospective study reviewed 183 patients with hyperthyroidism who underwent total thyroidectomy from 2015 to 2022 at one urban, academic center. The main outcomes were rates of thyroid storm, surgical complications, and 30-day ED visits and readmissions. RESULTS: Among 183 patients with hyperthyroidism (mean age, 45 ± 14.5 years; 82.5% female), there were no cases of thyroid storm and complications included recurrent laryngeal nerve (RLN) palsy (7.0%), symptomatic hypocalcemia (4.4%), and hematoma (1.6%). ED visits were present in 1.1% and no patients were readmitted. CONCLUSION: Total thyroidectomy was not associated with thyroid storm and <6% of patients required inpatient management. Ambulatory total thyroidectomy for hyperthyroidism warrants further consideration through identification of predictive factors for postoperative complications.

Characterization of a Diverse Set of Conditionally Reprogrammed Head and Neck Cancer Cell Cultures.

OBJECTIVE: To establish and characterize a diverse library of head and neck squamous cell cancer (HNSCC) cultures using conditional reprogramming (CR). METHODS: Patients enrolled on an IRB-approved protocol to generate tumor cell cultures using CR methods. Tumor and blood samples were collected and clinical information was recorded. Successful CR cultures were validated against banked reference tumors with short tandem repeat genotyping. Cell morphology was archived with photodocumentation. Clinical and demographic factors were evaluated for associations with successful establishment of CR culture. Human papilloma virus (HPV) genotyping, clonogenic survival, MTT assays, spheroid growth, and whole exome sequencing were carried out in selected cultures. RESULTS: Forty four patients were enrolled, with 31 (70%) successful CR cultures, 32% derived from patients who identified as Black and 61% as Hispanic. All major head and neck disease sites were represented, including 15 (48%) oral cavity and 8 (26%) p16-positive oropharynx cancers. Hispanic ethnicity and first primary tumors (vs. second primary or recurrent tumors) were significantly associated with successful CR culture. HPV expression was conserved in CR cultures, including CR-024, which carried a novel HPV-69 serotype. CR cultures were used to test cisplatin responses using MTT assays. Previous work has also demonstrated these models can be used to assess response to radiation and can be engrafted in mouse models. Whole exome sequencing demonstrated that CR cultures preserved tumor mutation burden and driver mutations. CONCLUSION: CR culture is highly successful in propagating HNSCC cells. This study included a high proportion of patients from underrepresented minority groups. LEVEL OF EVIDENCE: Not Applicable Laryngoscope, 134:2748-2756, 2024.

Comprehensive functional evaluation of head and neck squamous cell carcinoma with BH3-profiling demonstrates apoptotic competency and therapeutic efficacy of BH3-mimetics.

Evasion of apoptosis promotes tumor survival and contributes to resistance to cancer therapeutics in head and neck squamous cell carcinoma (HNSCC). Our recent work has demonstrated that HNSCC's highly express pro-survival anti-apoptotic proteins Bcl-xL and Mcl-1. Nevertheless, the mechanism of HNSCC to evade apoptosis is still not well understood. We used BH3 profiling, a functional assay which measures mitochondrial depolarization in response to the introduction of BH3 peptides, to evaluate apoptosis competency and dependency upon BCL-2 family anti-apoptotic proteins in a panel of immortalized and patient-derived HNSCC lines. We assessed response to BH3 mimetics including ABT-263 (navitoclax), an inhibitor of Bcl-2/Bcl-xL/Bcl-w, and S63845, an inhibitor of Mcl-1, both as single agents and in combination. We demonstrate that apoptosis signaling appears to be intact in the majority of HNSCC cells, and they are co-dependent upon Bcl-xL and Mcl-1 for survival. We found the combination to be highly synergistic in 2D culture and in 3D organoid models of HHNSCC. Given our findings that co-dependency on Bcl-xL and Mcl-1 is common, and co-inhibition of these molecules is synergistic for growth suppression in HNSCC cells, these results elucidate the therapeutic potential of BCL-xL and MCL-1 inhibition in HNSCC.

Development and Interrater Agreement of a Novel Classification System Combining Medical and Surgical Adverse Event Reporting.

Importance: Categorization systems for adverse events are not standardized across care settings and specialties and do not always include near miss events (events where there was potential for patient harm, but where no actual harm occurred), making it difficult to effectively assess patient safety for quality improvement. Objective: To develop and assess interrater agreement on a classification system for adverse events reporting that incorporates events in both inpatient and outpatient settings across medical and surgical subspecialties including near miss events. Design, Setting, and Participants: A cross-sectional study in a tertiary care center including 174 patient cases occurring from 2018 to 2020 was carried out. Data were abstracted from a Department of Otorhinolaryngology-Head and Neck Surgery Quality Assurance database. The cases were comprised of near miss and adverse events occurring in adult and pediatric patients in inpatient, outpatient, and emergency department settings. The ratings took place in March and April of 2022. Exposures: Four raters (2 attending physicians and 2 senior resident physicians) were recruited to classify these cases according to 3 classification systems: the National Coordinating Council for Medication Error Reporting and Prevention (NCC-MERP), Clavien-Dindo, and our novel Quality Improvement Classification System (QICS). Main Outcomes and Measures: The primary outcome was overall interrater agreements using Fleiss κ. Results: Across all 4 raters grading 174 cases, the NCC-MERP, Clavien-Dindo, and QICS received a κ score. Fair-to-moderate interrater reliability was observed between the resident and attending physician groups across the 3 classification systems: NCC-MERP (κ = 0.33; 95% CI, 0.30-0.35), Clavien-Dindo (κ = 0.47; 95% CI, 0.43-0.50), and QICS (κ = 0.42; 95% CI, 0.39-0.44). Strong interrater concordance was observed for complications across all scenarios. Conclusion and Relevance: This cross-sectional study found that the new QICS classification scheme was applicable to wide-ranging clinical scenarios with a focus on patient-centered outcomes including near miss events. In addition, QICS allowed for the comparison of patient outcome data in a multitude of settings.

Development and validation of a machine learning ASA-score to identify candidates for comprehensive preoperative screening and risk stratification.

OBJECTIVE: The ASA physical status (ASA-PS) is determined by an anesthesia provider or surgeon to communicate co-morbidities relevant to perioperative risk. Assigning an ASA-PS is a clinical decision and there is substantial provider-dependent variability. We developed and externally validated a machine learning-derived algorithm to determine ASA-PS (ML-PS) based on data available in the medical record. DESIGN: Retrospective multicenter hospital registry study. SETTING: University-affiliated hospital networks. PATIENTS: Patients who received anesthesia at Beth Israel Deaconess Medical Center (Boston, MA, training [n = 361,602] and internal validation cohorts [n = 90,400]) and Montefiore Medical Center (Bronx, NY, external validation cohort [n = 254,412]). MEASUREMENTS: The ML-PS was created using a supervised random forest model with 35 preoperatively available variables. Its predictive ability for 30-day mortality, postoperative ICU admission, and adverse discharge were determined by logistic regression. MAIN RESULTS: The anesthesiologist ASA-PS and ML-PS were in agreement in 57.2% of the cases (moderate inter-rater agreement). Compared with anesthesiologist rating, ML-PS assigned more patients into extreme ASA-PS (I and IV), (p < 0.01), and less patients in ASA II and III (p < 0.01). ML-PS and anesthesiologist ASA-PS had excellent predictive values for 30-day mortality, and good predictive values for postoperative ICU admission and adverse discharge. Among the 3594 patients who died within 30 days after surgery, net reclassification improvement analysis revealed that using the ML-PS, 1281 (35.6%) patients were reclassified into the higher clinical risk category compared with anesthesiologist rating. However, in a subgroup of multiple co-morbidity patients, anesthesiologist ASA-PS had a better predictive accuracy than ML-PS. CONCLUSIONS: We created and validated a machine learning physical status based on preoperatively available data. The ability to identify patients at high risk early in the preoperative process independent of the provider's decision is a part of the process we use to standardize the stratified preoperative evaluation of patients scheduled for ambulatory surgery.

Hypermethylation of a cluster of Krüppel-type zinc finger protein genes on chromosome 19q13 in oropharyngeal squamous cell carcinoma.

Identification of epigenetically affected genes has become an important tool for understanding both normal and aberrant gene expression in cancer. Here we report a whole-genome analysis of DNA methylation profiles in fresh-frozen oropharyngeal squamous cell carcinoma (OPSCC) tissues and normal mucosa samples using microarray technology with patient genomic DNA. We initially compared whole-genome patterns of DNA methylation among 24 OPSCC primary tumors and 24 matched normal mucosal samples. From a survey of 27,578 CpG dinucleotide loci spanning more than 14,000 genes, we identified 958 CpG loci in which measurements of DNA methylation were altered in the primary tumors relative to the normal mucosal samples. These alterations were validated in an independent set of 21 OPSCC patients. A survey of these loci by chromosomal location revealed an abnormally high number of differentially methylated loci on chromosome 19. Many of the loci on chromosome 19 are associated with genes belonging to the Krüppel-type zinc finger protein genes. Hypermethylation was accompanied by a significant decrease in expression of these genes in OPSCC primary tumors relative to adjacent mucosa. This study reports the epigenetic silencing of Krüppel-type zinc finger protein genes on chromosome 19q13 in oropharyngeal cancer. The aberrant methylation of these genes represents a new avenue of exploration for pathways affected in this disease.

Incidence and predictors of case cancellation within 24 h in patients scheduled for elective surgical procedures.

OBJECTIVE: Avoidable case cancellations within 24 h reduce operating room (OR) efficiency, add unnecessary costs, and may have physical and emotional consequences for patients and their families. We developed and validated a prediction tool that can be used to guide same day case cancellation reduction initiatives. DESIGN: Retrospective hospital registry study. SETTING: University-affiliated hospitals network (NY, USA). PATIENTS: 246,612 (1/2016-6/2021) and 58,662 (7/2021-6/2022) scheduled elective procedures were included in the development and validation cohort. MEASUREMENTS: Case cancellation within 24 h was defined as cancelling a surgical procedure within 24 h of the scheduled date and time. Our candidate predictors were defined a priori and included patient-, procedural-, and appointment-related factors. We created a prediction tool using backward stepwise logistic regression to predict case cancellation within 24 h. The model was subsequently recalibrated and validated in a cohort of patients who were recently scheduled for surgery. MAIN RESULTS: 8.6% and 8.7% scheduled procedures were cancelled within 24 h of the intended procedure in the development and validation cohort, respectively. The final weighted score contains 29 predictors. A cutoff value of 15 score points predicted a 10.3% case cancellation rate with a negative predictive value of 0.96, and a positive predictive value of 0.21. The prediction model showed good discrimination in the development and validation cohort with an area under the receiver operating characteristic curve (AUC) of 0.79 (95% confidence interval 0.79-0. 80) and an AUC of 0.73 (95% confidence interval 0.72-0.73), respectively. CONCLUSIONS: We present a validated preoperative prediction tool for case cancellation within 24 h of surgery. We utilize the instrument in our institution to identify patients with high risk of case cancellation. We describe a process for recalibration such that other institutions can also use the score to guide same day case cancellation reduction initiatives.

A comparison of clinically utilized human papillomavirus detection methods in head and neck cancer.

Detection of human papillomavirus (HPV) in head and neck cancer has therapeutic implications. In situ hybridization and immunohistochemistry for p16 are used by surgical pathologists. We compared the sensitivity and specificity of three popular commercial tests for HPV detection in head and neck squamous cell carcinomas with a 'gold standard' HPV PCR assay. A total of 110 prospectively collected, formalin-fixed tumor specimens were compiled onto tissue microarrays and tested for HPV DNA by in situ hybridization with two probe sets, a biotinylated probe for high-risk (HR) HPV types 16/18 (Dako, CA, USA) and a probe cocktail for 16/18, plus 10 additional HR types (Ventana, AZ, USA). The p16(INK4) expression was also assessed using a Pharmingen immunohistochemistry antibody (BD Biosciences, CA, USA). Tissue microarrays were stained and scored at expert laboratories. HPV DNA was detected by MY09/11-PCR, using Gold AmpliTaq and dot-blot hybridization on matched-fresh frozen specimens in a research laboratory. HPV 16 E6 and E7-RNA expression was also measured using RT-PCR. Test performance was assessed by a receiver operating characteristic analysis. HR-HPV DNA types 16, 18 and 35 were detected by MY-PCR in 28% of tumors, with the majority (97%) testing positive for type 16. Compared with MY-PCR, the sensitivity and specificity for HR-HPV DNA detection with Dako in situ hybridization was 21% (95% confidence interval (CI): 7-42) and 100% (95% CI: 93-100), respectively. Corresponding test results by Ventana in situ hybridization were 59% (95% CI: 39-78) and 58% (95% CI: 45-71), respectively. The p16 immunohistochemistry performed better overall than Dako (P=0.042) and Ventana (P=0.055), with a sensitivity of 52% (95% CI: 32-71) and specificity of 93% (95% CI: 84-98). Compared with a gold standard HPV-PCR assay, HPV detection by in situ hybridization was less accurate for head and neck squamous cell carcinoma on tissue microarrays than p16 immunohistochemistry. Further testing is warranted before these assays should be recommended for clinical HPV detection.