Acquired resistance to immunotherapy and chemoradiation in MYC amplified head and neck cancer.

The proto-oncogene MYC encodes a nuclear transcription factor that has an important role in a variety of cellular processes, such as cell cycle progression, proliferation, metabolism, adhesion, apoptosis, and therapeutic resistance. MYC amplification is consistently observed in aggressive forms of several solid malignancies and correlates with poor prognosis and distant metastases. While the tumorigenic effects of MYC in patients with head and neck squamous cell carcinoma (HNSCC) are well known, the molecular mechanisms by which the amplification of this gene may confer treatment resistance, especially to immune checkpoint inhibitors, remains under-investigated. Here we present a unique case of a patient with recurrent/metastatic (R/M) HNSCC who, despite initial response to nivolumab-based treatment, developed rapidly progressive metastatic disease after the acquisition of MYC amplification. We conducted comparative transcriptomic analysis of this patient's tumor at baseline and upon progression to interrogate potential molecular processes through which MYC may confer resistance to immunotherapy and/or chemoradiation and used TCGA-HNSC dataset and an institutional cohort to further explore clinicopathologic features and key molecular networks associated with MYC amplification in HNSCC. This study highlights MYC amplification as a potential mechanism of immune checkpoint inhibitor resistance and suggest its use as a predictive biomarker and potential therapeutic target in R/M HNSCC.

Racial Disparities in Surgical Management For Early-Stage Laryngeal Squamous Cell Carcinoma and Recurrent Dysplasia.

Objective: The aim of this study is to evaluate the association between race and the treatment of laryngeal dysplasia and early-stage laryngeal squamous cell carcinoma (LSCC). Study design: Retrospective Cohort Study. Setting: Large multispecialty academic medical center. Methods: Patients were treated for laryngeal dysplasia or LSCC between September 2019 and September 2022. A retrospective chart review was conducted to collect demographic and clinical information. Two-sample t tests, chi-square tests, and linear regression models were used to compare characteristics (α = 0.05). Analyses were performed in STATA 17. Results: Sixty-five patients were identified that underwent potassium titanyl phosphate (KTP) transoral laser microsurgery for management of early-stage LSCC (n = 29) or dysplasia (n = 36). The cohort consisted of 23 Black and 42 White patients. No significant difference was found in age, alcohol or tobacco use, rate of adjuvant radiotherapy, stage of disease, nor insurance status between the 2 groups. White patients underwent more procedures to address initial disease and subsequent recurrent dysplasia on average than Black patients (2.52 vs 1.52, P = .02). This remained true after adjusting for demographic and clinical characteristics and insurance status in a linear regression model. While Black patients were more likely to be lost to follow-up than White patients (30.4% vs 9.5%, P = .03), the average number of procedures between the groups still differed significantly (2.63 vs 1.56, P = .04) when controlling for those lost to follow-up. Conclusion: The findings presented here highlight potential inequities that exist for racial minorities at early stages of treatment and in addressing premalignant conditions, which may contribute to the known downstream disparities in laryngeal cancer outcomes.

What Are Vocal Cord Nodules?

This Patient Page describes the symptoms, diagnosis, and treatment of vocal cord nodules.

Exploring Experiences of Traumatic Microaggressions Toward Surgeons and Surgical Residents.

INTRODUCTION: Studies have suggested that experiences of gender and racial discrimination are widespread among surgeons and surgical residents. This study examines the relationship between experienced microaggressions and traumatic stress. METHODS: A one-time, deidentified survey was distributed over email to academic surgical societies. The survey consisted of 35 items including questions on prevalence of microaggressions, perceived job impacts as well as a shortened version of the Trauma Symptoms of Discrimination Scale. Chi-square tests and an independence test for trends were utilized to determine significance. RESULTS: We collected data from 130 participants with majority (81%) having experienced microaggressions in the workplace. On measures of worry (P < 0.001), avoidance (P = 0.012), anxiety (P = 0.004), and trouble relaxing (P = 0.002), racial/ethnic minority surgeons and trainees demonstrated significantly higher scores. With perceived job impacts, significant agreement was seen with occurrences of working harder to prove competence (P = 0.005), gaining patient confidence (P < 0.001), reduced career satisfaction (P = 0.011), work-related negative talk (P = 0.018), and burnout at work due to microaggressions (P = 0.019). Among participants who underwent behavioral modifications, female surgeons were more likely to change their nonverbal communication styles (P < 0.001) and spend more time with patients (P < 0.001). CONCLUSIONS: Experiences of microaggressions are associated with increased anxiety-related trauma symptoms in racial/ethnic minority surgeons and surgical trainees. Additionally, these experiences of microaggression can influence job satisfaction, burnout, career perceptions and workplace behaviors. As the field of surgery becomes more diverse, this study contributes to growing awareness of the role of implicit discrimination in the attrition and retention of racial/ethnic minority surgeons and female surgeons.

Characterization of a chronic cough in cerebellar ataxia, neuropathy, vestibular areflexia syndrome.

Objectives: Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a common cause of late-onset ataxia that often presents with chronic cough. This study is the first to characterize the CANVAS cough both objectively and subjectively. Methods: A cross-sectional study of 13 patients was conducted. Medical records and available esophagram, modified barium swallow study, esophageal manometry, and video laryngostroboscopy data were reviewed. Leicester cough questionnaire (LCQ) and Eating Assessment Tool-10 were administered to evaluate quality of life (QoL) impairments and dysphagia symptoms, respectively. CANVAS history questionnaire was developed to characterize the clinical course. Results: 92% of patients endorsed chronic cough that preceded gait instability by a median of 16 years. Cough was dry (67%), disturbed sleep (75%), triggered by various factors, including talking, eating, and dry/spicy foods, did not respond to standard reflux therapy, and inconsistently responded to neuromodulators and superior laryngeal nerve injections. Despite perceived cough severity worsening or remaining constant in most patients, no correlation was found between cough duration and total LCQ scores. Patients reported significantly more negative social QoL impacts compared to physical QoL impacts. Ataxia duration and years of cough before ataxia symptoms were directly and inversely correlated with total LCQ scores, respectively. Imaging data revealed esophageal dysmotility (71%), vestibular penetration (57%), vestibular aspiration (14%), supraglottic compression (63%), vocal fold lesions/atrophy (50%), and arytenoid erythema (38%). Conclusion: Chronic cough is a hallmark presenting symptom in CANVAS with predominantly psychosocial QoL effects and unrecognized laryngeal alterations. In cases of idiopathic, refractory chronic cough, genetic testing for CANVAS should be considered, especially in association with sensory, cerebellar, and/or vestibular involvement. Level of evidence: VI.

Assessment of Demographic Changes of Workforce Diversity in Otolaryngology, 2013 to 2022.

Importance: Given the growth of minoritized groups in the US and the widening racial and ethnic health disparities, improving diversity remains a proposed solution in the field of otolaryngology. Evaluating current trends in workforce diversity may highlight potential areas for improvement. Objective: To understand the changes in gender, racial, and ethnic diversity in the otolaryngology workforce in comparison with changes in the general surgery and neurosurgery workforces from 2013 to 2022. Design, Setting, and Participants: This cross-sectional study used publicly available data from the Accreditation Council for Graduate Medical Education and the Association of American Medical Colleges for 2013 to 2022, and included medical students and trainees in all US medical residency programs and allopathic medical schools. Main Outcomes and Measures: Average percentages of women, Black, and Latino trainees during 2 intervals of 5 years (2013-2017 and 2018-2022). Pearson χ2 tests compared demographic information. Normalized ratios were calculated for each demographic group in medical school and residency. Piecewise linear regression assessed linear fit for representation across time periods and compared rates of change. Results: The study population comprised 59 865 medical residents (43 931 [73.4%] women; 6203 [10.4%] Black and 9731 [16.2%] Latino individuals; age was not reported). The comparison between the 2 study intervals showed that the proportions of women, Black, and Latino trainees increased in otolaryngology (2.9%, 0.7%, and 1.6%, respectively), and decreased for Black trainees in both general surgery and neurosurgery (-0.4% and -1.0%, respectively). In comparison with their proportions in medical school, Latino trainees were well represented in general surgery, neurosurgery, and otolaryngology (normalized ratios [NRs]: 1.25, 1.06, and 0.96, respectively); however, women and Black trainees remained underrepresented in general surgery, neurosurgery, and otolaryngology (women NRs, 0.76, 0.33, and 0.68; Black NRs, 0.63, 0.61, and 0.29, respectively). The percentage of women, Black, and Latino trainees in otolaryngology all increased from 2020 to 2022 (2.5%, 1.1%, and 1.1%, respectively). Piecewise regression showed positive trends across all 3 specialties. Conclusions and Relevance: The findings of this cross-sectional study indicate a positive direction but only a modest increase of diversity in otolaryngology, particularly in the context of national demographic data. Novel strategies should be pursued to supplement existing efforts to increase diversity in otolaryngology.

Rapid sequence tandem intubation to navigate a subglottic obstruction.

Emergency airway management requires matching the appropriate intubation tools to anticipated obstacles. Video laryngoscopy and flexible endoscopy are often used for difficult airways. Here we describe a case where neither method alone was anticipated to be sufficient. A 53-year-old female with an obstructing lung mass required intubation for a mixed type 1 and 2 respiratory failure. Chest x-ray revealed a tortuous subglottic obstruction. The patient could not be temporized on maximized non-invasive airway support. These factors made tandem intubation, sequentially using video laryngoscopy and flexible endoscopic intubation, an appropriate intubation strategy. In this case report we describe the rationale and technique for a rapid sequence tandem intubation.

Laryngotracheal Resection After B-Raf Proto-oncogene Inhibition for Anaplastic Thyroid Carcinoma.

Anaplastic thyroid carcinoma is a rare but aggressive neoplasm that often presents as advanced inoperable disease. Patients with B-Raf proto-oncogene (BRAF) v600e mutated anaplastic thyroid carcinoma who receive neoadjuvant dabrafenib/trametinib have improved rates of microscopically margin-negative resection and durable locoregional control. However this has not been evaluated in the setting of tracheal resection and primary reconstruction. Here we demonstrate the safety and efficacy of laryngotracheal resection and reconstruction after dabrafenib/trametinib for locoregionally advanced BRAF v600e mutated anaplastic thyroid carcinoma.

Right Vocal Cord Paralysis Caused by Histoplasmosis: A Case Report.

OBJECTIVES: Histoplasma capsulatum is a prevalent dimorphic fungus, reaching an exposure rate of 90% in endemic areas such as the Midwest and Central United States. We report an unusual presentation of dysphonia due to right vocal cord paralysis caused by mediastinal lymphadenopathy from histoplasmosis. METHODS: A 73-year-old male presented to an otolaryngology clinic with 4 months of hoarseness. Flexible strobolaryngoscopy demonstrated right vocal cord paralysis in lateral position and a full length glottic gap. Computerized tomography (CT) scan showed enlargement of a right paratracheal node. RESULTS: A lymph node biopsy was obtained and showed histoplasmosis. He was treated with a 3-month course of pozaconazole. He then received a vocal cord medialization injection 2 months after symptom onset, which produced favorable improvement of his symptoms at 8-month follow up. CONCLUSIONS: One other case report in the literature has reported left vocal cord paralysis related to histoplasmosis. This first case of right vocal cord paralysis was extremely unusual and is not often included in the differential diagnosis of vocal cord paralysis.

Surgical Treatment Strategies for Laryngeal Chondrosarcomas: A Single Institution Investigation.

OBJECTIVES/HYPOTHESIS: Laryngeal chondrosarcomas are rare malignancies with a spectrum of presentations due to varying size, local extension, and biological behavior. Moreover, these neoplasms have differing effects on respiration, phonation, and deglutition. Consequently, it is valuable to assess endoscopic and transcervical treatment strategies. STUDY DESIGN: Retrospective case series. METHODS: A retrospective review was done from 2001 to 2020; 25 patients were identified with laryngeal chondrosarcomas. Their tumor pathology and treatment were analyzed. RESULTS: All 25 chondrosarcomas were in the posterior cricoid and arose in proximity to at least one cricoarytenoid joint: 23 of 25 grade I-II (low-mid), one of 25 grade II-III (mid-high), and one of 25 grade III (high). Some tumor was left in 23 of 25 to preserve cricoarytenoid-joint function. There were no known disease-specific deaths (~8-year median follow-up). Final surgical treatment in 24 of 25 was: 13 of 25 transcervical partial laryngectomy, 7 of 25 transoral-endoscopic removal, 4 of 25 total laryngectomy, and 1 of 25 observation. CONCLUSIONS: In this series, unresected intercurrent disease with laryngeal chondrosarcomas was not life-threatening. Therefore, disease was typically left in the posterior cricoid region to preserve mobility of at least one cricoarytenoid joint. This philosophy employed an ultra-function-sparing conservation approach that preserved and/or restored optimal voice, airway patency and swallowing. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:169-176, 2022.

Multi-disciplinary management of patients with benign airway strictures: A review.

Histologically benign airway strictures are frequently misdiagnosed as asthma or COPD and may present with severe symptoms including respiratory failure. A clear understanding of pathophysiology and existing classification systems is needed to determine the appropriate treatment options and predict clinical course. Clinically significant airway strictures can involve the upper and central airways extending from the subglottis to the lobar airways. Optimal evaluation includes a proper history and physical examination, neck and chest computed tomography, pulmonary function testing, endoscopy and serology. Available treatments include medical therapy, endoscopic procedures and open surgery which are based on the stricture's extent, location, etiology, morphology, severity of airway narrowing and patient's functional status. The acuity of the process, patient's co-morbidities and operability at the time of evaluation determine the need for open surgical or endoscopic interventions. The optimal management of patients with benign airway strictures requires the availability, expertise and collaboration of otolaryngologists, thoracic surgeons and interventional pulmonologists. Multidisciplinary airway teams can facilitate accurate diagnosis, guide management and avoid unnecessary procedures that could potentially worsen the extent of the disease or clinical course. Implementation of a complex airway program including multidisciplinary clinics and conferences ensures that such collaboration leads to timely, patient-centered and evidence-based interventions. In this article we outline algorithms of care and illustrate therapeutic techniques based on published evidence.

Surgeon Positioning During Awake Laryngeal Surgery: An Ergonomic Analysis.

OBJECTIVES: While it is acknowledged that otolaryngologists performing microlaryngeal surgery can develop musculoskeletal symptoms due to suboptimal body positioning relative to the patient, flexible laryngoscopy and awake laryngeal surgeries (ALSs) can also pose ergonomic risk. This prospective study measured the effects of posture during ergonomically good and bad positions during laryngoscopy using ergonomic analysis, skin-surface electromyography (EMG), and self-reported pain ratings. STUDY DESIGN: Prospective cohort study. METHODS: Eight participants trained in laryngoscopy assumed four ergonomically distinct standing positions (side/near, side/far, front/near, front/far) at three different heights (neutral-top of patient's head in line with examiner's shoulder, high-6 inches above neutral, and low-6 inches below neutral) in relation to a simulated patient. Participants' postures were analyzed using the validated Rapid Upper Limb Assessment (RULA, 1 [best] to 7 [worst]) tool for the 12 positions. Participants then simulated ALS for 10 minutes in a bad position (low-side-far) and a good position (neutral-front-near) with 12 EMG sensors positioned on the limbs and torso. RESULTS: The position with the worst RULA score was the side/near/high (7.0), and the best was the front/near/neutral (4.5). EMG measurements revealed significant differences between simulated surgery in the bad and good positions, with bad position eliciting an average of 206% greater EMG root-mean-squared magnitude across all sampled muscles compared to the good posture (paired t-test, df = 7, P < .01), consistent with self-reported fatigue/pain when positioned poorly. CONCLUSION: Quantitative and qualitative measurements demonstrate the impact of surgeon posture during simulated laryngoscopy and suggest ergonomically beneficial posture that should facilitate ALSs. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:2752-2758, 2021.

Vocal Hygiene in Collegiate Singers-Does Formal Training Relate to Practices?

BACKGROUND: Vocal hygiene is vitally important for protecting vocal quality and promoting vocal longevity. It includes adequate hydration, avoidance of environmental irritants, and refraining from phonotraumatic behaviors such as screaming, excessive talking, and throat clearing. Formal singing training in addition to enhancing singing techniques, is also assumed to promote good vocal hygiene. Consequently, we investigated whether collegiate singers with formal training are more likely to practice good vocal hygiene habits than untrained collegiate singers. METHODS: We completed a prospective cohort study, where collegiate singers at Stanford University were voluntarily enrolled in an annual vocal health clinic. Full laryngeal exams were performed and demographic information, formal vocal training status, and information on vocal hygiene habits were obtained through questionnaires. The results were then analyzed by grouping singers as "untrained" if less than 1 year of formal training, and "trained" if greater than a year. RESULTS: A total of 82 singers were included for analysis, with 49 (59.8%) having greater than one year of formal training. Trained singers were more likely to employ a primary musical singing style of classical or operatic singing compared to untrained singers who were more likely to utilize "R&B" (P < 0.001). No significant differences were found between groups for hydration practices (P = 0.20), caffeine consumption (P = 0.73), warm up practices (P = 0.08), and phonotraumatic behaviors. Alcohol consumption, smoking tobacco, marijuana, e-cigarette usage was similar between groups. Overall, 11% of our sample reported intermittent less than daily marijuana use, with one singer reporting daily consumption. None of the singers in this sample used e-cigarettes. These rates are noticeably lower than the agematched United States population. Perceptions of cigarettes, marijuana, electronic cigarettes, alcohol, and caffeine were also the same between groups, with the vast majority of singers perceiving these agents as harmful to the voice (64%-100% depending on the agent). No laryngeal pathology was identified during laryngeal examination of any singers. CONCLUSIONS: Vocal hygiene habits are similar between trained and untrained collegiate singers. This likely relates to a desire for vocal longevity irrespective of prior training. This may dispel the long-held assumption that formal training was necessary to develop good vocal habits. We do however, present a very homogenous, highly educated sample of collegiate singers from Stanford University, having significantly less at-risk behavior than their aged-matched counterparts in the general US population. A lack of laryngeal pathology despite extensive vocal demands may also be reflective of good vocal hygiene habits.

Coronavirus Disease-19: Challenges Associated with the Treatment of Head and Neck Oncology and Laryngology Patients in the Coronavirus Disease-19 Era.

This review explores the changes to practice associated with COVID-19 for providers treating patients with head and neck cancer and laryngeal pathology. The aim of the review is to highlight some of the challenges and considerations associated with treating this patient population during the pandemic. Additionally, it seeks to discuss some of the areas of concern related to ramping up clinical volume.

A Preliminary Study of Vocal Health Among Collegiate A Cappella Singers.

OBJECTIVE: Collegiate a cappella groups have grown significantly in popularity and prominence; however, there have been few studies that evaluate the vocal health of this subgroup of young singers. The objective of this preliminary study was to conduct a multiparametric evaluation of the vocal health characteristics of a sample of collegiate a cappella singers. We further tested whether differences in vocal health assessments exist between a cappella singers with and without vocal training and trained collegiate singers who do not participate in a cappella groups. STUDY DESIGN: Point prevalence study. METHODS: Forty-one collegiate singers participated in this study. Participants were divided into the following three groups: trained singers (TS), trained a cappella singers (ATS), and untrained a cappella singers (AUS). Participants were administered a set of surveys to assess self-perception of singing voice health and perceived access and attitudes toward voice-related health care. Acoustic and laryngoscopic assessments of participant's speaking and singing voice was performed and validated vocal health questionnaires administered as a means to objectively evaluate for the presence of voice problems. RESULTS: Overall, 87.5% of the ATS and 60% of the AUS groups reported experiencing problems with their singing voice. However, no vocal abnormalities were detected during laryngoscopic and acoustic assessments. Furthermore, minimal differences between any of the measured vocal health parameters were observed between the TS, ATS, and AUS groups. CONCLUSION: Collectively, a high percentage of collegiate a cappella singers with and without vocal training report singing voice problems. However, our sample of a cappella singers did not have increased singing voice problems as compared to vocally trained collegiate singers not in a cappella groups. We did find that a cappella singers may be more inclined to seek information about maintaining a healthy singing voice from their fellow musicians as opposed to singing teachers or other voice health professionals. Singing teachers, otolaryngologists, and speech-language pathologists may need to play a more active role in educating a cappella singers regarding maintaining good vocal health.

Treatment of early-stage laryngeal cancer: A comparison of treatment options.

Over the course of the last several decades, the treatment options for early laryngeal cancers (T1 and T2) have evolved; however, simultaneously the mortality rate has increased. As larynx preservation approaches have become the standard of care, the selection of the proper treatment modality has become paramount. Radiation therapy or transoral laser microsurgery are the most common options for treatment of these early lesions. Oncologic and functional outcomes are considered equivalent between the two modalities for early glottic cancers; however, no direct comparisons exist for robust analysis. In terms of larynx preservation, there also is not compelling data favoring one treatment option or another. For early stage lesions, the goal for any larynx-sparing technique, either radiation or surgery, should be the intent to cure with single modality treatment and minimal short- and long-term toxicity. This article is designed to create a frame of reference for managing early stage disease with respect to lesions of the glottis and supraglottis while weighing treatment implications from an oncologic, functional, and cost perspective.

Detecting oropharyngeal carcinoma using multispectral, narrow-band imaging and machine learning.

OBJECTIVE: To determine if multispectral narrow-band imaging (mNBI) can be used for automated, quantitative detection of oropharyngeal carcinoma (OPC). STUDY DESIGN: Prospective cohort study. METHODS: Multispectral narrow-band imaging and white light endoscopy (WLE) were used to examine the lymphoepithelial tissues of the oropharynx in a preliminary cohort of 30 patients (20 with biopsy-proven OPC, 10 healthy). Low-level image features from five patients were then extracted to train naïve Bayesian classifiers for healthy and malignant tissue. RESULTS: Tumors were classified by color features with 65.9% accuracy, 66.8% sensitivity, and 64.9% specificity under mNBI. In contrast, tumors were classified with 52.3% accuracy (P = 0.0108), 44.8% sensitivity (P = 0.0793), and 59.9% specificity (P = 0.312) under WLE. Receiver operating characteristic analysis yielded areas under the curve (AUC) of 72.3% and 54.6% for classification under mNBI and WLE, respectively (P = 0.00168). For classification by both color and texture features, AUC under mNBI increased (80.1%, P = 0.00230) but did not improve under WLE (below 55% for both models, P = 0.180). Cross-validation with five folds yielded an AUC above 80% for both mNBI models and below 55% for both WLE models (P = 0.0000410 and 0.000116). CONCLUSION: Compared to WLE, mNBI significantly enhanced the performance of a naïve Bayesian classifier trained on low-level image features of oropharyngeal mucosa. These findings suggest that automated clinical detection of OPC might be used to enhance surgical vision, improve early diagnosis, and allow for high-throughput screening. LEVEL OF EVIDENCE: NA. Laryngoscope, 2514-2520, 2018.

Selection for mechanical advantage underlies multiple cranial optima in new world leaf-nosed bats.

Selection for divergent performance optima has been proposed as a central mechanism underlying adaptive radiation. Uncovering multiple optima requires identifying forms associated with different adaptive zones and linking those forms to performance. However, testing and modeling the performance of complex morphologies like the cranium is challenging. We introduce a three-dimensional finite-element (FE) model of the cranium that can be morphed into different shapes by varying simple parameters to investigate the relationship between two engineering-based measures of performance, mechanical advantage and von Mises stress, and four divergent adaptive zones occupied by New World Leaf-nosed bats. To investigate these relationships, we tested the fit of Brownian motion and Ornstein-Uhlenbeck models of evolution in mechanical advantage and von Mises stress using dated multilocus phylogenies. The analyses revealed three performance optima for mechanical advantage among species from three adaptive zones: bats that eat nectar; generalized insectivores, omnivores and some frugivores; and bats that specialize on hard canopy fruits. Only two optima, one corresponding to nectar feeding, were consistently uncovered for von Mises stress. These results suggest that mechanical advantage played a larger role than von Mises stress in the radiation of New World Leaf-nosed bats into divergent adaptive zones.

Upregulation of IL-1ß, IL-6, and CCL-2 by a novel mouse model of pancreatic ischemia-reperfusion injury.

BACKGROUND: Little is known about the immunologic events surrounding pancreatic ischemia-reperfusion injury (IRI) because of a lack of established experimental models. The purpose of this study was to develop a mouse model for pancreatic IRI to serve as a basis for the immunologic characterization of pancreatic organ damage at transplantation. METHODS: Reversible ischemia was surgically induced by vascular isolation of the distal pancreas for 0, 10, 20, or 30 min. Mice receiving laparotomy without clamping served as sham-operated controls. After reperfusion, mice were serially assayed for biochemical and histologic evidence of inflammation, proinflammatory cytokine and chemokine production, and inflammatory gene upregulation. RESULTS: After induction of pancreatic IRI, serum amylase and lactate dehydrogenase peaked at 6 hr and returned to baseline by 120 hr after injury in all groups. Mice undergoing 30 min of IRI demonstrated the greatest biochemical evidence of inflammation. Histologic scoring similarly demonstrated marked inflammation in mice subjected to 30-min IRI compared with controls. Serum cytokine/chemokine analysis demonstrated significant upregulation of granulocyte colony-stimulating factor, interferon γ, tumor necrosis factor α, interleukin (IL)-2, IL-1ß, IL-6, chemokine (C-C motif) ligand-2, chemokine (C-C motif) ligand-5, chemokine (C-X-C motif) ligand-1, and macrophage inflammatory protein 2. A similar upregulation of ccl2, il1b, il6, fos, hspa1a, hspd1, and cd14 gene expression was detected by real-time polymerase chain reaction analysis of pancreatic tissue. CONCLUSIONS: This novel model of distal pancreatic IRI in the mouse demonstrates time-limited pancreatic inflammation and injury by histologic and biochemical indices. Inflammation may be, in part, a result of the immunologic effects of IL-1ß, IL-6, and CCL-2. This model provides a method by which immunologic mechanisms of pancreatic IRI can be elucidated.