Towards rainbow portable Cytophone with laser diodes for global disease diagnostics.

In vivo, Cytophone has demonstrated the capability for the early diagnosis of cancer, infection, and cardiovascular disorders through photoacoustic detection of circulating disease markers directly in the bloodstream with an unprecedented 1,000-fold improvement in sensitivity. Nevertheless, a Cytophone with higher specificity and portability is urgently needed. Here, we introduce a novel Cytophone platform that integrates a miniature multispectral laser diode array, time-color coding, and high-speed time-resolved signal processing. Using two-color (808 nm/915 nm) laser diodes, we demonstrated spectral identification of white and red clots, melanoma cells, and hemozoin in malaria-infected erythrocytes against a blood background and artifacts. Data from a Plasmodium yoelii murine model and cultured human P. falciparum were verified in vitro with confocal photothermal and fluorescent microscopy. With these techniques, we detected infected cells within 4 h after invasion, which makes hemozoin promising as a spectrally selective marker at the earliest stages of malaria progression. Along with the findings from our previous application of Cytophone with conventional lasers for the diagnosis of melanoma, bacteremia, sickle anemia, thrombosis, stroke, and abnormal hemoglobin forms, this current finding suggests the potential for the development of a portable rainbow Cytophone with multispectral laser diodes for the identification of these and other diseases.

In vivo liquid biopsy using Cytophone platform for photoacoustic detection of circulating tumor cells in patients with melanoma.

Most cancer deaths arise from metastases as a result of circulating tumor cells (CTCs) spreading from the primary tumor to vital organs. Despite progress in cancer prognosis, the role of CTCs in early disease diagnosis is unclear because of the low sensitivity of CTC assays. We demonstrate the high sensitivity of the Cytophone technology using an in vivo photoacoustic flow cytometry platform with a high pulse rate laser and focused ultrasound transducers for label-free detection of melanin-bearing CTCs in patients with melanoma. The transcutaneous delivery of laser pulses via intact skin to a blood vessel results in the generation of acoustic waves from CTCs, which are amplified by vapor nanobubbles around intrinsic melanin nanoclusters. The time-resolved detection of acoustic waves using fast signal processing algorithms makes photoacoustic data tolerant to skin pigmentation and motion. No CTC-associated signals within established thresholds were identified in 19 healthy volunteers, but 27 of 28 patients with melanoma displayed signals consistent with single, clustered, and likely rolling CTCs. The detection limit ranged down to 1 CTC/liter of blood, which is ~1000 times better than in preexisting assays. The Cytophone could detect individual CTCs at a concentration of ≥1 CTC/ml in 20 s and could also identify clots and CTC-clot emboli. The in vivo results were verified with six ex vivo methods. These data suggest the potential of in vivo blood testing with the Cytophone for early melanoma screening, assessment of disease recurrence, and monitoring of the physical destruction of CTCs through real-time CTC counting.

Noninvasive label-free detection of circulating white and red blood clots in deep vessels with a focused photoacoustic probe.

Blood clotting is a serious clinical complication of many medical procedures and disorders including surgery, catheterization, transplantation, extracorporeal circuits, infections, and cancer. This complication leads to high patient morbidity and mortality due to clot-induced pulmonary embolism, stroke, and in some cases heart attack. Despite the clear medical significance, little progress has been made in developing the methods for detection of circulating blood clots (CBCs), also called emboli. We recently demonstrated the application of in vivo photoacoustic (PA) flow cytometry (PAFC) with unfocused ultrasound transducers for detection of CBCs in small vessels in a mouse model. In the current study, we extend applicability of PAFC for detection of CBCs in relatively large (1.5-2 mm) and deep (up to 5-6 mm) blood vessels in rat and rabbit models using a high pulse rate 1064 nm laser and focused ultrasound transducer with a central hole for an optic fiber. Employing phantoms and chemical activation of clotting, we demonstrated PA identification of white, red, and mixed CBCs producing negative, positive, and mixed PA contrast in blood background, respectively. We confirmed that PAFC can detect both red and white CBCs induced by microsurgical procedures, such as a needle or catheter insertion, as well as stroke modeled by injection of artificial clots. Our results show great potential for a PAFC diagnostic platform with a wearable PA fiber probe for diagnosis of thrombosis and embolism in vivo that is impossible with existing techniques.

Estrogen is involved in hemangioma regression associated with mast cells.

BACKGROUND: Estrogen plays a role in infantile hemangioma (IH) development, but the underlying mechanism remains unclear. This study aimed to assess estrogen and estrogen receptor (ER) localization and expression levels in IH. In addition, the unexpected relationship between mast cells (MCs) and estrogen in human IH was discussed. METHODS: IH (n = 29), vascular malformation (VMs, n = 33) and normal skin (n = 15) specimens were assessed. IH was classified into proliferative (n = 9; age, 3.56 ± 1.01 months), early involuting (n = 10; age, 8.90 ± 2.69 months) and late involuting (n = 10; age, 20.10 ± 4.93 months) groups. Estradiol (E2), ER-a, ER-ß, and tryptase (MC marker) levels were determined immunohistochemically and/or by double immunofluorescence staining. Quantification and localization of tryptase, ER-a, and E2 were assessed for each specimen. RESULTS: ER-a, E2, and tryptase were expressed in the cytoplasm and nucleus of MCs in IH. The IH specimens showed significantly more tryptase, ER-a, and E2 positive MCs (30.6 ± 12.7, 9.7 ± 5.6, and 19.8 ± 8.7 cells/high-power field [HPF], respectively) compared with VM specimens (9.0 ± 9.8, 1.5 ± 2.4, and 2.5 ± 4.1 cells/HPF, respectively) and normal skin (6.1 ± 8.5, 0.5 ± 1.2, and 1.9 ± 3.4 cells/HPF, respectively). Proliferating IH displayed fewer E2 positive MCs (14.0 6.3 cells/HPF) compared with early (22.3 ± 10.2 cells/HPF, P = 0.023) and late (22.4 ± 6.8 cells/HPF, P = 0.006) involuting specimens. In addition, proliferating IH showed fewer tryptase positive MCs (24.7 ± 10.8 cells/HPF) compared with early involuting specimens (35.7 ± 15.3 cells/HPF, P = 0.043). All IH specimens were ER-a positive and ER-ß negative. CONCLUSIONS: E2 and ER-a are expressed on MCs and not on IH endothelial cells. Furthermore, activated MCs may be involved in IH regression.

Cancer patient perspectives regarding preparedness for end-of-life care: A qualitative study.

PURPOSE: The extent to which patients feel prepared for end-of-life (EOL) may be associated with important clinical outcomes. Despite growing interest in the concept of "preparedness," however, there is insufficient information about what cancer patients actually need to feel prepared. Such information is foundational for patient-centered care, theory-building, and instrument development. DESIGN: This qualitative study examined patient perspectives regarding preparedness for EOL care. PARTICIPANTS AND METHODS: In-depth interviews were conducted with patients with advanced malignancies and limited life expectancies. Participants were drawn from a large academic cancer center and had a diverse range of malignancies. Thematic text analysis was used to analyze the data. FINDINGS: Six overarching themes emerged. These included readiness to manage concerns about: (1) EOL planning (e.g., goals of care, location of care); (2) interactions with healthcare providers (e.g., communication, symptom control); (3) interactions with family/friends (e.g., perceived burden, support); (4) emotional well-being (e.g., existential distress, fulfillment); (5) spiritual well-being (e.g., spiritual comfort, congregational support); and (6) financial well-being (e.g., medical expenses, estate planning). CONCLUSIONS: Findings highlight areas that patients themselves regard as critical for a sense of preparedness for EOL care. Participants emphasized broader concerns than those previously construed as facets of patient preparedness, and these domains offer modifiable targets for intervention.

Arteriovenous Malformations of the Head and Neck.

Extracranial arteriovenous malformations (AVMs) are complex vascular malformations to diagnose and treat. They are comprised of congenitally derived arteriovenous shunts with chronic vascular expansion, collateralization, and infiltration of local tissue. Their cause remains unclear, but new genetic and molecular clues are emerging. They may present at any age following an early quiescent period. Diagnosis is based on vascular staining, soft tissue expansion, progressive growth, warmth, and pulsations. Focal lesions can be cured, whereas diffuse AVMs demonstrate highly recidivistic disease. Multimodal therapy with staged interventions can improve treatment outcomes, increase treatment intervals, and control disease. Vigilant follow-up is critical.

Effects of supramaximal balloon dilatation pressures on adult cricoid and tracheal cartilage: A cadaveric study.

OBJECTIVES/HYPOTHESIS: Cricoid fracture is a serious concern for balloon dilatation in airway stenosis. Furthermore, there are no studies examining tracheal rupture in balloon dilatation of stenotic segments. The aim of this study was to evaluate the effect of supramaximal pressures of balloons on the cricoid and tracheal rings. STUDY DESIGN: Prospective cadaveric study. METHODS: Seven cadaveric laryngotracheal complexes of normal adults with intact cricothyroid membranes were acquired. Noncompliant vascular angioplasty balloons (BARD-VIDA) were used for dilatation. The subglottis and trachea were subjected to supramaximal dilatation pressures graduated to nominal burst pressure (NBP) and, if necessary, rated burst pressure (RBP). Larger-diameter balloons, starting from 18 mm size to 24 mm, were used. Dilatations were maintained for 3 minutes. RESULTS: The cricoid ring was disrupted by larger-diameter balloons (22 mm and 24 mm) even at lower pressures (less than NBP) in six cases. Tracheal cartilages were very distensible, and external examination after supramaximal dilatation (24 mm close to RBP) revealed no obvious cartilage fractures or trachealis tears. Histopathological examination revealed sloughing of mucosa in the areas corresponding to balloon placement, but no microfractures or disruption of the perichondrium of tracheal ring cartilages. CONCLUSIONS: These results indicate that the cricoid is vulnerable to injury from larger balloons even at lower dilatation pressures. The tracheal cartilages and the membranous wall of the trachea remained resilient to supramaximal dilatation and larger balloons. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:1304-1309, 2018.

Real-Time Label-Free Embolus Detection Using In Vivo Photoacoustic Flow Cytometry.

Thromboembolic events are one of the world's leading causes of death among patients. Embolus or clot formations have several etiologies including paraneoplastic, post-surgery, cauterization, transplantation, or extracorporeal circuits. Despite its medical significance, little progress has been made in early embolus detection, screening and control. The aim of our study is to test the utility of the in vivo photoacoustic (PA) flow cytometry (PAFC) technique for non-invasive embolus detection in real-time. Using in vivo PAFC, emboli were non-invasively monitored in the bloodstream of two different mouse models. The tumor-free mouse model consisted of two groups, one in which the limbs were clamped to produce vessel stasis (7 procedures), and one where the mice underwent surgery (7 procedures). The melanoma-bearing mouse model also consisted of two groups, one in which the implanted tumor underwent compression (8 procedures), and one where a surgical excision of the implanted tumor was performed (8 procedures). We demonstrated that the PAFC can detect a single embolus, and has the ability to distinguish between erythrocyte-rich (red) and leukocyte/platelet-rich (white) emboli in small vessels. We show that, in tumor-bearing mice, the level of circulating emboli was increased compared to tumor-free mice (p = 0.0013). The number of circulating emboli temporarily increased in the tumor-free control mice during vessel stasis (p = 0.033) and after surgical excisions (signed-rank p = 0.031). Similar observations were noted during tumor compression (p = 0.013) and after tumor excisions (p = 0.012). For the first time, it was possible to detect unlabeled emboli in vivo non-invasively, and to confirm the presence of pigmented tumor cells within circulating emboli. The insight on embolus dynamics during cancer progression and medical procedures highlight the clinical potential of PAFC for early detection of cancer and surgery-induced emboli to prevent the fatal thromboembolic complications by well-timed therapy.

Elevated Expression of Matrix Metalloproteinase-9 not Matrix Metalloproteinase-2 Contributes to Progression of Extracranial Arteriovenous Malformation.

Extracranial arteriovenous malformations (AVMs) are rare but dangerous congenital lesions arising from direct arterial-venous shunts without intervening capillaries. Progressive infiltration, expansion, and soft tissue destruction lead to bleeding, pain, debilitation and disfigurement. The pathophysiology of AVMs is not well understood. Matrix Metalloproteinases (MMPs) are thought to play an important role in pathologic processes underlying many diseases. This study investigates the expression of MMP-9 and MMP-2 in aggressive extracranial AVMs. The differential expression of MMP-9 and its regulatory factors is also examined. Herein we demonstrate that mRNA and protein expressions of MMP-9, but not MMP-2, are significantly higher in AVM tissues compared to normal tissues. The serum level of MMP-9, but not MMP-2, is also elevated in AVM patients compared to healthy controls. MMP-9/neutrophil gelatinase-associated lipocalin (NGAL) complex is also significantly increased in AVM tissues. The MMP-9/ tissue inhibitor of metalloproteases-1 (TIMP-1) complex presents as a major form detected in normal tissues. The increased and aberrant expression of MMP-9 and specific MMP-9 forms may help explain the constitutive vascular remodeling and infiltrative nature of these lesions. Specific MMP-9 inhibitors would be a promising treatment for AVMs.

Comorbidities and factors associated with endoscopic surgical outcomes in adult laryngotracheal stenosis.

This study which is a retrospective chart review aims to characterize the comorbidities associated with adult laryngotracheal stenosis and evaluate the relationship of these with stenosis grade, length, surgical interventions, and surgical intervals. Patients' demographics, medical and surgical comorbidities, grade of stenosis, quantity and degree of balloon dilations, dilation intervals, open airway procedures, and tracheotomy status were recorded from 2002 to 2012, at a tertiary voice and airway center. Surgical outcomes were evaluated in relation to patient comorbidities, stenosis quality, and surgical procedures. A total of 101 patients with laryngotracheal stenosis were examined with female patients comprising 71 % of the population. Seventeen patients (16.8 %) had idiopathic stenosis. Number of balloon dilations ranged from 0 to 24 (mean = 3.3). The average time between dilations was 38.4 weeks (range = 1.14-215.8 weeks). The patients with idiopathic stenosis were found to have a lower grade (p = 0.0066). Fifty-two patients (51.5 %) received a tracheotomy at one point during their management. The 14 patients (13.9 %) who remained tracheotomy dependent had a body mass index (BMI) of >30. No statistically significant correlation was found when the patients' age, BMI and comorbidites were compared with the grade of stenosis, number of balloon dilatations needed and other surgical interventions. On the other hand, interval in between surgeries was found to be longer in patients without an intubation history, and in idiopathic SGS (p = 0.004, p = 0.015, respectively). There was no significant relationship between surgical interval and gender, BMI, length of stenosis, grade (p = 0.059, p = 0.47, p = 0.97, p = 0.36, respectively). Airway stenosis in adults is complicated by the presence of multiple comorbidities. Better understanding of the etiology could aid in the prevention of the injury before it forms.

Dual mTOR inhibitor MLN0128 suppresses Merkel cell carcinoma (MCC) xenograft tumor growth.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. Pathologic activation of PI3K/mTOR pathway and elevated expression of c-Myc are frequently detected in MCC. Yet, there is no targeted therapy presently available for this lethal disease. Recently, MLN0128, a second-generation dual TORC1/2 inhibitor is shown to have therapeutic efficacy in preclinical studies. MLN0128 is currently in clinical trials as a potential therapy for advanced cancers. Here we characterize the therapeutic efficacy of MLN0128 in the preclinical setting of MCC and delineate downstream targets of mTORC1/2 in MCC cellular systems. MLN0128 significantly attenuates xenograft MCC tumor growth independent of Merkel cell polyomavirus. Moreover, MLN0128 markedly diminishes MCC cell proliferation and induces apoptosis. Further investigations indicate that senescence does not contribute to MLN0128-mediated repression of xenograft MCC tumor growth. Finally, we also observe robust antitumor effects of MLN0128 when administered as a dual therapy with JQ1, a bromodomain protein BRD4 inhibitor. These results suggest dual blockade of PI3K/mTOR pathway and c-Myc axis is effective in the control of MCC tumor growth. Our results demonstrate that MLN0128 is potent as monotherapy or as a member of combination therapy with JQ1 for advanced MCC.

In Vivo Long-Term Monitoring of Circulating Tumor Cells Fluctuation during Medical Interventions.

The goal of this research was to study the long-term impact of medical interventions on circulating tumor cell (CTC) dynamics. We have explored whether tumor compression, punch biopsy or tumor resection cause dissemination of CTCs into peripheral blood circulation using in vivo fluorescent flow cytometry and breast cancer-bearing mouse model inoculated with MDA-MB-231-Luc2-GFP cells in the mammary gland. Two weeks after tumor inoculation, three groups of mice were the subject of the following interventions: (1) tumor compression for 15 minutes using 400 g weight to approximate the pressure during mammography; (2) punch biopsy; or (3) surgery. The CTC dynamics were determined before, during and six weeks after these interventions. An additional group of tumor-bearing mice was used as control and did not receive an intervention. The CTC dynamics in all mice were monitored weekly for eight weeks after tumor inoculation. We determined that tumor compression did not significantly affect CTC dynamics, either during the procedure itself (P = 0.28), or during the 6-week follow-up. In the punch biopsy group, we observed a significant increase in CTC immediately after the biopsy (P = 0.02), and the rate stayed elevated up to six weeks after the procedure in comparison to the tumor control group. The CTCs in the group of mice that received a tumor resection disappeared immediately after the surgery (P = 0.03). However, CTC recurrence in small numbers was detected during six weeks after the surgery. In the future, to prevent these side effects of medical interventions, the defined dynamics of intervention-induced CTCs may be used as a basis for initiation of aggressive anti-CTC therapy at time-points of increasing CTC number.

Disruption of BRD4 at H3K27Ac-enriched enhancer region correlates with decreased c-Myc expression in Merkel cell carcinoma.

Pathologic c-Myc expression is frequently detected in human cancers, including Merkel cell carcinoma (MCC), an aggressive skin cancer with no cure for metastatic disease. Bromodomain protein 4 (BRD4) regulates gene transcription by binding to acetylated histone H3 lysine 27 (H3K27Ac) on the chromatin. Super-enhancers of transcription are identified by enrichment of H3K27Ac. BET inhibitor JQ1 disrupts BRD4 association with super-enhancers, downregulates proto-oncogenes, such as c-Myc, and displays antitumor activity in preclinical animal models of human cancers. Here we show that an enhancer proximal to the c-Myc promoter is enriched in H3K27Ac and associated with high occupancy of BRD4, and coincides with a putative c-Myc super-enhancer in MCC cells. This observation is mirrored in tumors from MCC patients. Importantly, depleted BRD4 occupancy at the putative c-Myc super-enhancer region by JQ1 correlates with decreased c-Myc expression. Thus, our study provides initial evidence that super-enhancers regulate c-Myc expression in MCC.

BET protein inhibitor JQ1 attenuates Myc-amplified MCC tumor growth in vivo.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin currently with no cure. In this study, we have first demonstrated that c-Myc overexpression is common in MCC. By targeting c-Myc, bromodomain inhibitors have demonstrated antitumor efficacy in several preclinical human cancer models. Thus, we interrogated the role of c-Myc inhibition in MCC with c-Myc amplification by using the BET inhibitor JQ1. We have uncovered that c-Myc can be regulated by JQ1 in MCC cells with pathologic c-Myc activation. Moreover, JQ1 potently abrogates c-Myc expression in MCC cells and causes marked G1 cell-cycle arrest. Mechanistically, JQ1-induced cell-cycle arrest coincides with downregulation of cyclin D1 and upregulation of p21, p27, and p57, whereas JQ1 exerts no effect on apoptosis in MCC cells. Further knockdown of p21, p27, or p57 by shRNA partially protects cells from JQ1-induced cell-cycle arrest. In addition, c-Myc knockdown by shRNA generates significant cell-cycle arrest, suggesting that c-Myc overexpression plays a role in MCC pathogenesis. Most importantly, JQ1 significantly attenuates tumor growth in xenograft MCC mouse models. Our results provide initial evidence, indicating the potential clinical utility of BET protein inhibitors in the treatment of MCC with pathologic activation of c-Myc.

Loss of cytokeratin 20 and acquisition of thyroid transcription factor-1 expression in a merkel cell carcinoma metastasis to the brain.

Merkel cell carcinoma (MCC) is recognized by its morphologic features and by its classic immunophenotypic properties. Although MCCs demonstrating nonclassic immunoreactivities have been described, a case documenting a change in immunophenotype during the course of disease progression has not been previously reported. We report a case of MCC that initially demonstrated cytokeratin 20 positivity but lost expression in subsequent metastases. Likewise, thyroid transcription factor-1 was initially negative in the tumor but expression was present in metastatic lesions.

Real-time monitoring of circulating tumor cell release during tumor manipulation using in vivo photoacoustic and fluorescent flow cytometry.

BACKGROUND: Circulating tumor cells (CTCs) form metastases in distant organs. The purpose of this research was to determine if tumor manipulation could enhance cancer cell release from the primary tumor into the circulatory system. METHODS: Nude mice were inoculated with melanoma or breast cancer cells. The implanted tumor underwent compression, biopsy, complete resection, or laser treatment. CTCs were monitored in the bloodstream using in vivo photoacoustic and fluorescence flow cytometry. RESULTS: We discovered that pressure, biopsy, and laser treatment can dramatically increase CTC counts (up to 60-fold), whereas proper tumor resection significantly decrease CTC counts. CONCLUSION: Standard medical procedures could trigger CTC release that may increase the risk of metastases. This finding suggests the guidance of cancer treatment and likely diagnosis by real-time monitoring of CTC dynamics followed by well-timed treatment to reduce CTCs in the blood. In vivo detection of intervention-amplified CTCs could be used for early diagnosis of a small tumor, which is undetectable with conventional methods.

Guidelines for the treatment of head and neck venous malformations.

Venous malformation is one of the most common benign vascular lesions, with approximately 40% of cases appearing in the head and neck. They can affect a patient's appearance and functionality and even cause life-threatening bleeding or respiratory tract obstruction. The current methods of treatment include surgery, laser therapy, sclerotherapy, or a combined. The treatment of small and superficial venous malformations is relatively simple and effective; however, the treatment of deep and extensive lesions involving multiple anatomical sites remains a challenge for the physicians. For complex cases, the outcomes achieved with one single treatment approach are poor; therefore, individualized treatment modalities must be formulated based on the patient's condition and the techniques available. Comprehensive multidisciplinary treatments have been adapted to achieve the most effective results. In this paper, based on the national and international literature, we formulated the treatment guidelines for head and neck venous malformations to standardize clinical practice. The guideline will be renewed and updated in a timely manner to reflect cutting-edge knowledge and to provide the best treatment modalities for patients.

Expression of endoglin (CD105) and endothelial nitric oxide synthase in head and neck arteriovenous malformations.

IMPORTANCE: Endoglin (CD105) and endothelial nitric oxide synthase (eNOS) assist in regulating vascular development. Variation in expression of these factors is linked to errors in vascular growth and remodeling in invasive lesions. OBJECTIVE: To clarify the role of endoglin and eNOS in the growth of extracranial head and neck arteriovenous malformations (AVMs), an invasive and high-flow vascular anomaly. DESIGN AND SETTING: Immunohistochemistry and Western blot study at an academic research center. SPECIMENS: Frozen and formalin-fixed paraffin-processed human AVMs (n = 14) were examined for expression of CD105 and eNOS. Expression in infantile hemangiomas (n = 9) and in normal skin with subcutaneous tissue (n = 9) was used for comparison. MAIN OUTCOME MEASURES: Quantitative assessment and localization of CD105 and eNOS protein expression were performed on each specimen by immunohistochemistry and Western blot analysis. Protein expression levels were compared with ß-actin level and were semiquantitatively assessed. RESULTS: Abundant CD105 protein was found in AVMs but was not present in infantile hemangiomas or normal skin with subcutaneous tissue. Expression of eNOS protein in AVMs and infantile hemangiomas was similar (P = .20) and was significantly greater than that in normal skin with subcutaneous tissue (P < .001 and P = .008, respectively). Immunohistochemistry demonstrated that CD105 and eNOS are predominantly located in AVM vascular endothelial cells. CONCLUSIONS AND RELEVANCE: CD105 and eNOS are present and significantly expressed in head and neck AVMs. Expression of CD105 and eNOS may have an important role in the angiogenesis and vascular remodeling of AVMs. CD105 can be used as a specific marker for AVM endothelial cells.

Herpes simplex infection of the larynx requiring laryngectomy.

Herpes simplex virus infection of the larynx is an exceedingly rare clinical entity, most frequently reported in the pediatric population or in immunocompromised adults. We present a 62-year-old woman presented with neck pain, hoarseness, crepitus over the larynx, and what appeared to be a necrotic mass of the right true vocal cord on laryngoscopy. Due to near-complete destruction of the cartilaginous framework of the larynx, a total laryngectomy was performed. The final pathology report showed squamous mucosal changes consistent with herpes simplex infection, confirmed by immunohistochemical staining. Though herpes simplex laryngitis is uncommon, this case shows the potential for herpes simplex to cause extensive damage and compromise airway patency when left untreated.

First bite syndrome: case report of 3 patients treated with botulinum toxin and review of other treatment modalities.

BACKGROUND: First bite syndrome is an unexpected yet relatively common complication of surgeries involving the parapharyngeal space. It can have a significant effect on both the quality of life and physical health of affected patients. This study presents 3 cases of first bite syndrome treated with botulinum toxin and a review of the current literature on available treatment modalities for first bite syndrome. METHODS: Three patients with first bite syndrome were injected with 75 units of botulinum toxin into affected parotid glands, focusing on areas of greatest first bite pain. RESULTS: Two of 3 patients experienced complete relief of symptoms for 4 to 6 months. The third patient had significant decrease in pain at 4-month follow-up. CONCLUSIONS: Many treatments for first bite syndrome have been attempted including: dietary modification, pharmacological treatments, and surgical treatments. However, few have been successful. Botulinum toxin is a safe and effective treatment for this life altering and difficult to treat first bite syndrome.