About

Timothy M. McCulloch is a Professor in the Department of Otolaryngology-Head and Neck Surgery at the University of Wisconsin-Madison. He holds an MD from the University of Nebraska College of Medicine and completed his residency at the University of Washington. Certified by the American Board of Otolaryngology, he specializes in the treatment of head and neck cancer, voice and swallowing disorders, trauma, reconstruction, and skull base surgery. His clinical services include airway dilation, reconstruction procedures, laryngeal and skull base surgeries, and various laser treatments. Dr. McCulloch's research focuses on laryngeal function, voice disorders, dysphagia, trauma, and head and neck cancer treatments. He is recognized as one of the world’s experts on laryngeal electromyography, voice restoration, and high-resolution manometry. As principal investigator for an NIDCD R33 grant, he has developed new clinical capabilities by optimizing high-resolution manometry. His active research includes multisite studies on dysphagia therapy and the impact of radiation therapy, aiming to improve predictive assessments and proactive treatment strategies.

Research topics

• Surgery
• Medicine
• Physical therapy
• Anesthesia
• Mathematics
• Internal medicine
• Intensive care medicine
• Anatomy
• Oncology
• Nursing
• Radiology
• General surgery
• Nuclear medicine
• Family medicine
• Pathology

Selected publications

• PRO-ACTIVE: Results of a pragmatic phase IV randomized trial comparing the effectiveness of prophylactic swallow intervention for patients receiving radiotherapy for head and neck cancer.

  Journal of Clinical Oncology · 2025-06-04 · 1 citations

  article

  LBA12000 Background: Swallowing therapy during radiotherapy (RT) for head and neck cancer (HNC) has gained popularity as a dysphagia mitigation strategy, yet optimal timing and intensity of therapy remains uncertain. The PRO-ACTIVE trial compared the effectiveness of prophylactic and reactive swallowing therapies during RT. We hypothesized that PRO-ACTIVE therapies are more effective than RE-ACTIVE; and, that more intensive PRO-ACTIVE (EAT+EXERCISE) is superior to less intensive PRO-ACTIVE (EAT). Methods: PRO-ACTIVE was an international, multi-site pragmatic phase IV randomized clinical trial (NCT03455608). Eligible, adult patients had functional baseline swallowing and received RT ≥60-Gy for HNC with bilateral neck fields. Prior to RT, patients were randomized 1:2:2 to 1) RE-ACTIVE, 2) PRO-ACTIVE EAT, or 3) PRO-ACTIVE EAT+EXERCISE arms and followed for 1 year. RE-ACTIVE received weekly monitoring with therapy only if/when dysphagic, and PRO-ACTIVE arms received bi-weekly therapy pre- and during RT. The primary endpoint was feeding tube (FT) use in days from the end of RT to 1 year. Secondary endpoints were patient-reported and clinician-graded outcomes. Adjusted linear regression compared FT days per intention-to-treat with a gate-keeper approach to test hypotheses in hierarchical order with 80% power to detect a small effect size (≥.21 SD) with type 1 error probability of 0.5 (two-sided). Results: 952 patients from 13 institutions were randomized to RE-ACTIVE (n=196), PRO-ACTIVE-EAT (n=377) or PRO-ACTIVE-EAT+EXERCISE (n=379). 21 (2.2%) patients exited before intervention, thus, 931 were retained for analysis. The majority had stage I/II disease (552/931, 59.3%), oropharyngeal tumors (647/931, 69.5%), and p16+ and/or HPV+ disease (680/931, 73.0%). Baseline function was excellent (499/931 (53.5%) grade 0 dysphagia, mean [SD] MDADI 86 [14]). All patients received curative intent RT (median 70 Gy), 706/931 (75.8%) with chemotherapy, and 105/931 (11.3%) with primary site surgery. 364 of 931 (39.1%) required a FT with 34.4 (SD 75.9) mean days of use. Adjusted FT days at 12-months did not meaningfully differ by pro- and re-active timing (∆5.4 days, 95% CI -6.5 to 17.2, p=0.37) or EAT versus EAT+exercise intensity (∆5.9 days, 95% CI -3.8 to 17.6, p=0.21). Swallowing-related QOL, diet, weight/BMI, and dysphagia symptoms did not differ meaningfully by arm. Conclusion: FT utilization was lower than expected and secondary measures of swallowing outcomes were favorable across all arms of the PRO-ACTIVE trial reflecting relative effectiveness of EAT and exercise therapies regardless of timing or intensity of therapy delivery during RT for HNC. As a pragmatic trial, we are robustly powered to examine heterogeneous treatment effects in subgroup analyses and image-based swallowing metrics as critical next steps. Clinical trial information: NCT03455608 .

  PublisherDOI

• Defining Pharyngeal and Upper Esophageal Sphincter Disorders on High‐Resolution Manometry‐Impedance: The Leuven Consensus

  Neurogastroenterology & Motility · 2025-04-09 · 6 citations

  articleOpen access

  INTRODUCTION: The Leuven Consensus provides a classification scheme for the diagnosis of pharyngeal and upper esophageal sphincter (UES) motor disorders using metrics derived from pharyngeal high-resolution manometry-impedance (P-HRM-I). METHODS: Twenty-six experts with broad multidisciplinary backgrounds contributed their knowledge and experience to this initiative via a formal deliberative Delphi process. Guidance on a swallow assessment protocol as well as diagnostic criteria for UES dysfunction and pharyngeal contractile dysfunction is provided. RESULTS: For UES dysfunction, the stepwise evaluation of UES and intrabolus pressure metrics under increasing bolus volume and/or viscosity conditions is used to confirm failure of manometric relaxation and opening of the UES region. For pharyngeal contractile dysfunction, the evaluation of contractile metrics is used to define pharyngeal hypocontractility or hypercontractility. CONCLUSION: These recommendations complement routine instrumental investigations and provide a standardized process, criteria, and nomenclature for P-HRM-I assessment of patients reporting symptoms of oropharyngeal dysphagia.

  PublisherOA PDFDOI

• Timely resection of juvenile nasopharyngeal angiofibroma following embolization for uncontrolled acute epistaxis case report

  SAGE Open Medical Case Reports · 2025-08-01

  articleOpen access

  Uncontrolled epistaxis in patients with juvenile nasopharyngeal angiofibroma requires prompt intervention. When embolization is required, neovascularization can occur, making expedited surgical resection essential. We conducted a single-institution, retrospective review of one patient. This case study details the patient's clinical presentation and his preoperative, intraoperative, and postoperative course. We present the management of a 14-year-old male with a juvenile nasopharyngeal angiofibroma, who 3 days after initial evaluation at our institution, developed uncontrolled epistaxis requiring embolization at an outside hospital before transfer back to our institution for further management. He initially presented to an outside emergency department with acute epistaxis refractory to medical treatment. He was subsequently transferred to another facility for embolization. After successful embolization, he was transferred to our institution and underwent surgical resection within 48 h. A combined transnasal endoscopic and transmaxillary approach was used for excision. Pathological analysis confirmed the diagnosis of juvenile nasopharyngeal angiofibroma. Twenty-four months after post-embolization and resection, the patient remains asymptomatic with no evidence of recurrence on magnetic resonance imaging. This case report highlights the potential need to develop a clinical tool to risk stratify juvenile nasopharyngeal angiofibroma patients at risk for uncontrolled epistaxis. It also underscores the importance of timely transfer from resource-limited settings to centers capable of coordinating interventional radiology and surgical resection within 48 h of embolization.

  PublisherDOI

• Internal Superior Laryngeal Nerve Injections Through the Piriform Sinus for Laryngeal Neurosensory Disturbances: A Prospective Analysis

  Annals of Otology Rhinology & Laryngology · 2025-05-28 · 1 citations

  article

  Objective: Internal superior laryngeal nerve (iSLN) injections demonstrate short term improvements in patients with laryngeal neurosensory disturbances (ie, chronic refractory cough and globus pharyngeus) that can require multiple injections. A more targeted iSLN injection approach could provide greater effectiveness. This study prospectively evaluated whether transnasal endoscopic iSLN injections that target the internal iSLN as it transverses the piriform sinuses was effective at treating laryngeal neurosensory disturbances. Methods: This was a prospective cohort analysis performed at a single tertiary care center. Patients with laryngeal neurosensory disturbances underwent transnasal endoscopic iSLN injections bilaterally using triamcinolone-40 mg/mL. Demographics, clinical history, and exam findings were recorded, along with post-injection complications. The primary outcomes were the Leister Cough Questionnaire (LCQ), Reflux Symptom Index (RSI), and the Voice Handicap Index-10 (VHI-10) collected at pre-injection, 3-weeks post-injection, and 2-months post-injection that were examined with linear mixed modeling. Results: Eighteen patients with laryngeal sensory disturbances (11 with chronic cough and 7 with globus sensation) underwent the procedure. There were significant improvements in LCQ scores (all greater than 1.3 points) and RSI scores (all greater than 7-point improvement) at both 3-week and 2-month timepoints ( P < .05). When stratified into globus sensation patients alone, there was significant improvements in LCQ at 3 weeks (3.92 points, P = .02) as well as across both 3-week and 2-month timepoints (14 points, P < .001; 7.4 points, P = .04). There were no aspiration events or major complications. Conclusions: Targeted transnasal endoscopic iSLN injections of the piriform sinus mucosa appears to be a safe and effective way of treating laryngeal neurosensory disturbances. The technique provides a visual target for injection of the iSLN which may allow for exploration of alternative neuromodulating medicines for use in this patient population.

  PublisherDOI

• Survival outcomes of locoregionally advanced papillary thyroid carcinoma

  International Journal of Otorhinolaryngology and Head and Neck Surgery · 2025-07-25

  articleOpen accessSenior author

  Background: PTC carries an overall excellent prognosis. Most patients with PTC have small and asymptomatic disease. This raises the question whether overall rates overestimate the survival of those with advanced disease. We use our institutional data to report disease-free and overall survival of patients with locoregionally advanced PTC. Methods: A retrospective study of 92 patients who underwent a total thyroidectomy from 2002 to 2019 at a single institution. Features of locoregionally advanced disease were defined as extra thyroid extension, primary tumor size ≥4 cm, or cervical nodal involvement. These and additional clinical and histological features were analyzed for association with recurrence and disease-free survival. Results: Twenty-six patients had recurrence of disease. Patients with ETE, nonspecific cervical nodal involvement, or tumor size ≥4 cm had no significant increase in recurrence (p=0.2554, 0.1886, 0.2278, respectively). Patients with nodal metastasis to lateral neck compartment had a significant increase in recurrence (p=0.0434). 5-year overall survival was 95%. Conclusion: PTC has an excellent prognosis even in the presence of advanced locoregional disease. However, lateral neck nodal involvement is associated with higher rates of recurrence and may be an indicator for more aggressive management.

  PublisherOA PDFDOI

• Correlation Between Peak Upper Esophageal Sphincter and Pharyngeal Pressures in Patients With Dysphagia

  Laryngoscope Investigative Otolaryngology · 2025-10-01

  articleOpen access

  ABSTRACT Objective The upper esophageal sphincter (UES) serves multiple functions in the management of the upper aerodigestive tract. Prior investigations have defined the roles of UES resting and nadir pressures in normal swallowing. The distinctly high‐amplitude UES peak pressures, a patterned feature of pressure propagation in the transition from the pharynx to the esophagus on high‐resolution manometry (HRM), have not been characterized beyond normative data reports. This study investigated the relationship between peak UES and pharyngeal pressures at the velopharyngeal and tongue base regions in both patients with dysphagia and healthy controls. Methods Sixty‐three adult patients with dysphagia underwent pharyngeal HRM to obtain peak measures of velopharyngeal, tongue base region, and UES pressures. Age‐ and sex‐matched healthy controls were analyzed for comparison. Results UES peak pressures in patients with dysphagia showed no significant correlation with velopharyngeal or tongue base region pressures ( p > 0.05). In contrast, UES peak pressures were positively correlated with velopharyngeal ( r = 0.525, p < 0.001) and tongue base ( r = 0.415, p = 0.001) region peak pressures in healthy subjects. Velopharyngeal region pressures showed a significant correlation with tongue base region pressures in both patients with dysphagia ( r = 0.377, p = 0.002) and healthy subjects ( r = 0.406, p = 0.001). Conclusions Pharyngeal and UES peak pressures are correlated in healthy subjects; loss of this relationship in patients with dysphagia indicates that UES peak pressures may be influenced by factors independent of pharyngeal contractile responses and bolus‐related sensory feedback. Level of Evidence 4.

  PublisherOA PDFDOI

• Bilateral internal superior laryngeal nerve injections for unexplained chronic cough

  American Journal of Otolaryngology · 2024-12-19 · 3 citations

  articleOpen access

  OBJECTIVE: Internal Superior laryngeal nerve (iSLN) injections with steroids and anesthetic for Unexplained Chronic Cough (UCC) was initially described as a unilateral injection. This study reports the safety profile and patient-reported outcomes of concurrent bilateral iSLN injections for UCC. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary center. METHODS: A chart review from 2018 to 2023 was performed for patients with UCC who underwent bilateral iSLN injections. Demographics, clinical history, and physical exam findings were recorded, along with any post-injection complications. The primary outcome was patient-reported percent improvement in cough symptoms. Nonparametric statistical analyses were performed to examine whether treatment effectiveness differed based on (a) duration of cough, (b) whether an upper respiratory illness (URI) preceded the start of the cough, (c) had undergone prior speech therapy or (d) neuromodulator treatment for cough, (e) laterality of symptoms, and (f) demonstrated abnormal flexible laryngoscopy/stroboscopy findings. RESULTS: 12 UCC patients underwent a median of 2 injections (Interquartile Range (IQR): 1-5.5 injections) for a total of 42 injections). There were no aspiration events and only 3 self-limited minor complications. 75 % of patients reported improvement with at least one of their injections with a median percentage response of 73 % (IQR: 26-89 %) and a reported median duration of response of 2.2 months (IQR: 1.2-3.2 months). Nonparametric testing revealed greater responses to injection in patients with abnormal flexible laryngoscopy/stroboscopic findings with their initial injection (p ≤0.02). CONCLUSION: Bilateral concurrent iSLN injections are a safe and effective way of treating UCC that may require fewer visits to effectively treat UCC.

  PublisherDOI

• Imatinib plus Cetuximab as a Window of Opportunity Clinical Trial in Head and Neck Cancer

  International Journal of Radiation Oncology*Biology*Physics · 2024-03-14 · 1 citations

  article
  PublisherDOI

• Safety and toxicity of Iopofosine I 131 (CLR 131) with external beam radiation therapy in recurrent or metastatic head and neck cancer: results of a phase 1 single-centre, open-label, single-arm, dose escalation and dose expansion study

  EBioMedicine · 2024-12-12 · 3 citations

  articleOpen access

  BACKGROUND: Re-irradiation of recurrent head and neck cancer (HNC) is often limited by tumour adherence to critical structures and/or radiation tolerance of critical normal tissues. Iopofosine I 131 (CLR 131) is a targeted small molecular phospholipid ether (PLE) drug conjugate that delivers iodine-131 selectively to tumour cells. We conducted a phase 1, single-centre, open-label study to determine whether CLR 131 given with reduced dose of external beam radiation therapy (EBRT) would be tolerable and feasible. METHODS: All participants received previous curative intent treatment with radiotherapy as primary or adjuvant treatment. Eligible participants demonstrated uptake of CLR 131 as indicated via single photon emission CT/CT (SPECT/CT) imaging following CLR 131 test dose. Participants received two therapeutic doses of CLR 131 (days 1 and 8) with SPECT/CT imaging performed to quantitate the biodistribution of CLR 131. Participants subsequently received EBRT to achieve the designated radiation dose (60-70 Gy). The primary endpoint was safety. This trial was registered with ClinicalTrials.gov, NCT04105543, and enrolment and follow-up are complete. FINDINGS: Twelve participants completed treatment with CLR 131 and EBRT. Eight participants experienced grade 4 non-DLT haematologic toxicities (2 anaemia, 8 leukopenia, 5 thrombocytopenia) at least probably attributed to CLR 131, consistent with the expected toxicity profile. Haematologic toxicities occurred during weeks 6-8 from the first dose of CLR 131 and resolved within three weeks without sequelae. There were no treatment-related grade 3-4 non-haematologic toxicities. INTERPRETATION: CLR 131 in combination with EBRT did not confer any safety concerns, and was tolerable in participants with recurrent/metastatic HNC. Myelosuppression was consistent with the known toxicity profile of CLR 131. FUNDING: National Institutes of HealthP50 DE026787, National Cancer InstituteP30 CA014520, National Institutes of Health1UL1TR002373, Cellectar, NCT04105543.

  PublisherDOI

• A protocol for stakeholder engagement in head and neck cancer pragmatic trials

  BMC Cancer · 2024-09-05

  letterOpen access

  Meaningful engagement with stakeholders in research demands intentional approaches. This paper describes the development of a framework to guide stakeholder engagement as research partners in a pragmatic trial proposed to evaluate behavioral interventions for dysphagia in head and neck cancer patients. We highlight the core principles of stakeholder engagement including representation of all perspectives, meaningful participation, respectful partnership with stakeholders, and accountability to stakeholders; and describe how these principles were operationalized to engage relevant stakeholders throughout the course of a large clinical trial.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R21DC011130

  NIH · $398k · 2013

• High Resolution Manometry: A Novel Pattern Recognition Method for Dysphagia

  NIH · $1.6M · 2011–2017

Frequent coauthors

• Ernest A. Weymuller

  University of Washington

  69 shared

• Robert A. Sofferman

  University of Vermont Medical Center

  66 shared

• K. Thomas Robbins

  Southern Illinois University Carbondale

  65 shared

• Jonathan Harris

  64 shared

• William R. Wilson

  University of Auckland

  64 shared

• Paul A. Levine

  64 shared

• Robert A. Weisman

  University of California, San Diego

  64 shared

• Parvesh Kumar

  Norfolk and Norwich University Hospital

  64 shared

Education

• MD

  University of Nebraska College of Medicine

  1985

Awards & honors

• Best Doctors in America Award, Otolaryngology