Robert M. Brody

Objective: To review the landscape of cloud‐native analytics platforms and large language models (LLMs) applied to surgical outcomes research; to present the development of an automated head and neck free flap outcomes database as a reference implementation for using lakehouse architectures in the development of clinical databases. Data Sources: PubMed and Embase from January 2018 through June 2026. Methods: A scoping review of PubMed and Embase was conducted using five searches combining data architecture (e.g., “data lakehouse,” “cloud‐native”), clinical text extraction (“natural language processing,” “LLM”) surgical outcomes (“postoperative,” “surgical outcome”), and domain‐specific databases (“free flap,” “microvascular reconstruction,” “automated”). Studies were reviewed if they described database development incorporating automated outcomes classification. Results: Of 311 studies identified, five studies included elements of incremental processing, pattern‐matching‐gated LLM classification, or fault‐tolerant parallel processing for prospective database maintenance. No implementation examples combined all architectural characteristics. We present the development of a production database for microvascular surgery that automatically identifies free flap cases, collects and analyzes operative notes, validates cohort membership through LLM reasoning, and classifies outcomes across multiple dimensions (flap type, indication, flap failure, hardware complications, bony complications, etc.), all operating incrementally as new cases enter the electronic health record and existing cases are updated. Conclusion: We describe what appears to be the first data lakehouse‐based automated surgical database applied to otolaryngology, detail architectural decisions required for production, and identify critical unresolved challenges including LLM validation standards, data access barriers, and the translation of clinical domain expertise into computational logic. Level of Evidence: N/A.

Human papillomavirus–associated oropharyngeal squamous cell carcinoma (HPV⁺ OPC) is driven by viral E6 and E7 oncoproteins, which disrupt G1 checkpoint control and impose selective dependency on WEE1-mediated G2/M regulation. While this vulnerability confers sensitivity to WEE1 inhibition, its immunologic consequences remain poorly defined, and the challenge of eliciting antitumor immunity without compromising immune fitness has limited clinical translation. Here, we show that WEE1 inhibition elicits durable antitumor immunity in immunocompetent models of HPV⁺ OPC. Using murine and human preclinical systems, we demonstrate that the WEE1 inhibitor azenosertib (ZN-c3) mediates tumor control through both cell-autonomous cytotoxicity and immune-dependent mechanisms requiring T cells and conventional dendritic cells. Mechanistically, HPV⁺ tumor cells are deficient in STING signaling and fail to mount canonical type I interferon responses. Instead, tumor cell–intrinsic cGAS drives immune activation through STING-competent host cells within the tumor microenvironment, revealing a non-cell-autonomous relay that circumvents viral immune evasion. Intermittent WEE1 inhibition preserves T cell fitness while maintaining antitumor efficacy, and mice achieving complete responses develop immunologic memory capable of rejecting tumor rechallenge. These findings establish intermittent WEE1 inhibition as an immune-permissive therapeutic strategy that enables antigen-specific T cell responses in HPV-driven malignancies and provides a mechanistic rationale for combination with immunotherapy.

Free flap procedures are important components of reconstructive surgery in otolaryngology, plastic surgery, and maxillofacial surgery. This research investigates trends in utilization, charges, and Medicare reimbursements for free flap procedures performed across these specialties. CMS Medicare Physician & Other Practitioners Data (2013‐2022) were analyzed using CPT codes 15757 and 20969 for free skin flaps and osteocutaneous flaps, respectively. Trends in procedure utilization, average charges, average reimbursements, and charge‐to‐reimbursement ratios (CRRs) were assessed across these specialties. A total of 4920 free flap procedures were reported between 2013 to 2022. Otolaryngology utilization increased by 73.6% while plastic and maxillofacial surgery volumes remained stable. Otolaryngology reimbursements and charges showed significant declines while the CRR remained stable around 7.65 (0.58). Plastic and maxillofacial surgery exhibited the greatest CRRs in 2022 at 9.54 and 8.87, respectively. These data demonstrate the evolving finances of free flap procedures, laying the groundwork for further investigation and discussion.

PURPOSE: Routine confirmatory testing of p16+ oropharyngeal cancers (OPCs) for human papillomavirus (HPV) mRNA is nonstandard despite evidence that negative confirmatory tests are common and may indicate poor prognosis. This study aimed to evaluate the utility of confirmatory testing by assessing the etiologies and prognostic significance of negative HPV mRNA tests in a surgically treated cohort of p16+ OPCs enriched for recurrence-prone tumors. METHODS: Fifty tumors that later recurred (cases) and 50 cured tumors (controls) were matched for key clinical features. Patients were predominantly White males with a median age of 62 years. Confirmatory testing was performed with a clinically used E6/E7 RNA in situ hybridization assay (RNAScope). RNA sequencing (RNAseq) was used to define true HPV positivity and profile HPV mRNA levels. HPV genotypes and integration were evaluated by sequencing HPV DNA and detecting HPV-host fusion mRNAs, respectively. RESULTS: Positive p16 was 100% specific for high-risk HPV mRNA expression. Content of HPV types, lineages, and sublineages did not differ significantly between cases and controls. Cases contained more frequent HPV integration based on increased HPV-host mRNA fusions ( P < .0007). False-negative confirmatory assays, which occurred in 6% (n = 6) of the cohort, were equally distributed between groups and not prognostic of survival. False negatives included three tumors containing HPV types absent from the RNAScope probe set and an episomal tumor with E6/E7 mRNA below the detection threshold by RNAseq. CONCLUSION: HPV RNAScope appears unlikely to detect HPV status misclassification or be prognostic in typical p16+ OPCs treated surgically in the United States. Confirmatory RNAScope can produce misleading false negatives in this population through various mechanisms and should be used selectively rather than routinely.

Objective: To investigate the impact of clinical surveillance, primary radiotherapy, and primary surgery on overall survival (OS) in laryngeal carcinoma in situ (Cis). Methods: The 2006–2020 National Cancer Database was queried for adults with a biopsy‐proven diagnosis of laryngeal Cis. Multivariable binary logistic and Cox proportional hazards regression models were implemented. Results: Of 3567 unique patients satisfying inclusion criteria, 514 (14.4%) underwent clinical surveillance, 1074 (30.1%) underwent primary radiotherapy, and 1979 (55.5%) underwent primary surgery. Receiving treatment at an academic/research facility was associated with higher odds of undergoing primary surgery compared to primary radiotherapy. Among 646 patients undergoing primary surgery with known pT classification and margins, 570 (76.6%) had pTis and NSM and 174 (23.4%) had pT1 and/or PSM. 5‐year OS of clinical surveillance, primary radiotherapy, and primary surgery was 73%, 81%, and 86%, respectively ( p < 0.001). Patients undergoing primary surgery with invasive or residual disease (i.e., pT1 and/or PSM) had similar 5‐year OS as those without (84% vs. 88%, p = 0.057). Compared with primary radiotherapy, clinical surveillance (aHR 1.29, 95% CI 1.06–1.57, p = 0.003) was associated with worse OS, and primary surgery (aHR 0.80, 95% CI 0.69–0.92, p = 0.003) was associated with higher OS. Conclusion: Primary surgery is associated with higher OS than clinical surveillance and primary radiotherapy among patients with laryngeal Cis. Level of Evidence: 4.

Objectives: Treatment of patients with head and neck squamous cell carcinoma of unknown primary (CUP) is challenging. Given the relative rarity of this condition and the recent use of primary transoral robotic surgery (TORS) in modern diagnostic and treatment algorithms, long‐term oncologic outcomes are unclear. The objectives were to evaluate oncologic outcomes of patients treated with TORS for management of CUP. Methods: This retrospective case series was conducted at a tertiary care academic medical center from 2010 to 2021. All patients with HPV‐mediated CUP who underwent TORS‐assisted endoscopy were included. CUP was defined as biopsy‐proven squamous cell carcinoma in a cervical lymph node with uncertain primary location following standard‐of‐care clinical and radiologic assessment. Primary outcomes were recurrence‐free survival and overall survival. Secondary outcomes included usage of radiation and chemotherapy. Results: In total, 157 patients were included in the study. Median follow‐up time was 62 months. Primary tumor was identified in 88% of patients. Surgery alone was performed in 21%, although adjuvant therapy was recommended but declined in 13%. Adjuvant radiation was completed in 46% and adjuvant chemoradiation in 33%. Two‐thirds of patients avoided chemoradiation. Overall survival was 94% and recurrence‐free survival was 92% at 5 years. Conclusion: In the largest reported experience to date of TORS‐assisted management of CUP, we demonstrate that this approach facilitates a high rate of identification of occult mucosal malignancies and can eliminate the need for chemotherapy and potentially radiation therapy in select patients without compromising excellent oncologic and functional outcomes. Level of Evidence: 4.

Objective: Hypoalbuminemia (HA) is a proxy for malnutrition that has been associated with postoperative complications in several surgical subspecialties. This study investigates the association between pre‐operative HA and complications following major salivary gland (MSG) resection.Methods: Patients undergoing outpatient, elective MSG resection were extracted from the 2005 to 2020 National Surgical Quality Improvement Program database. Demographics and comorbidities were compared between HA (preoperative serum albumin < 3.5 g/dL) and non‐HA cohorts. To determine associations between albumin status and postoperative complications, univariate and multivariable binary logistic regression analyses were performed.Results: A total of 5774 patients undergoing MSG resection were included, of which 321 (5.6%) had preoperative HA. HA was associated with older age on univariate analysis (65.2 vs. 60.2 years, p < 0.001). Multivariable analysis found HA to be independently associated with any surgical complication (OR 2.03, 95% CI 1.09–3.56, p = 0.019) and length of stay (LOS) ≥ 90th percentile (OR 1.58, 95% CI 1.04–2.38, p = 0.032).Conclusion: Preoperative HA may be a poor prognostic factor associated with an increased risk of surgical complications and prolonged LOS among patients undergoing MSG resection.Level of Evidence: 4.

Importance: Laryngeal cancer has undergone a complex evolution in incidence, management, and standards of care over the past 20 years. Disease‐wide demographic and survival risk factors have yet to be elucidated.Objective: Examine incidence, management, and survival trends in laryngeal cancer from 2000 to 2019.Design, Setting, and Participants: The Surveillance, Epidemiology, and End Results database was utilized to identify age‐adjusted incidence rates (AAIRs) of laryngeal squamous cell carcinoma (LSCCa) from 2000 to 2019. Joinpoint regression was conducted to identify annual percentage changes (APCs). Chi‐squared analysis was used to find changes in demographic, clinicopathologic, and treatment changes over the study period. Finally, univariate Kaplan–Meier and COX multivariate regressions were conducted to identify survival differences.Results: There were 46 266 cases of LSCCa identified between 2000 and 2019 with AAIR of 2.7 per 100 000 person‐years with APC of −2.6% [95% CI: −2.8% to 2.4%]. These rates have largely been down‐trending among demographic substratifications. Age at initial diagnosis has been increasing (64.6 → 66.0, p < 0.001). Higher median household income was associated with lower AAIR (35 000 5.3; > $75 000 2.2) and increased annual percentage decrease (< $35 000, −1.1%*; > $75 000, −3.2%*). There were no other clinically significant differences in demographic and clinicopathologic trends although persistent demographic differences were noted. Late T‐stage at diagnosis has increased over the study period (T3, 18% → 23%, p < 0.001). Treatment with primary chemoradiotherapy has increased significantly (20.0% → 27.0%, p < 0.001). On univariate analysis, there were no significant differences in survival; however, on multivariate analysis, there has been a progressive improvement in disease‐specific and overall survival over 5‐year bins. Late‐stage disease had a progressive improvement in survival with each treatment period on both univariate and multivariate analysis.Conclusions and Relevance: There has been a progressively significant decrease in age‐adjusted incidence of LSCCa with increased utilization of primary chemoradiotherapy. When adjusted for associated characteristics, there has been a continuing improvement in survival over the study period, primarily in late‐stage disease.

Background: The geriatric nutritional risk index (GNRI) is a tool to assess preoperative nutritional status that can be calculated simply based on height, weight, and serum albumin. This study assesses the utility of GNRI in predicting postoperative complications in patients undergoing major head and neck cancer (HNC) surgery.Methods: Retrospective review of the 2016–2020 National Surgical Quality Improvement Program database. Patients were categorized into GNRI > 98 (normal nutritional status), GNRI 92–98 (moderate malnutrition status), and GNRI < 92 (severe malnutrition status). Univariable and multivariable binary logistic regression analyses were performed.Results: Sixteen thousand seven hundred eight‐nine patients undergoing HNC resection were included. On multivariable analysis, moderate and severe malnourishment based on GNRI remained significantly associated with any surgical complication, any medical complication, any complication, Clavien‐Dindo grade IV complications, and 30‐day mortality.Conclusions: GNRI may have utility as a potentially modifiable preoperative prognostic factor that can be optimized to improve complications and mortality following HNC resection.Level of Evidence: Level 4.