Bernhard G. Weiss

Early Oral Tongue Squamous Cell Carcinoma: Sampling of Margins From Tumor Bed and Worse Local Control

IMPORTANCE Positive margins are associated with poor prognosis among patients with oral tongue squamous cell carcinoma (SCC). However, wide variation exists in the margin sampling technique. OBJECTIVE To determine the effect of the margin sampling technique on local recurrence (LR) in patients with stage I or II oral tongue SCC. DESIGN, SETTING, AND PARTICIPANTS A retrospective study was conducted from January 1, 1986, to December 31, 2012, in 5 tertiary care centers following tumor resection and elective neck dissection in 280 patients with pathologic (p)T1-2 pN0 oral tongue SCC. Analysis was conducted from June 1, 2013, to January 20, 2015. INTERVENTIONS In group 1 (n = 119), tumor bed margins were not sampled. In group 2 (n = 61), margins were examined from the glossectomy specimen, found to be positive or suboptimal, and revised with additional tumor bed margins. In group 3 (n = 100), margins were primarily sampled from the tumor bed without preceding examination of the glossectomy specimen. The margin status (both as a binary [positive vs negative] and continuous [distance to the margin in millimeters] variable) and other clinicopathologic parameters were compared across the 3 groups and correlated with LR. MAIN OUTCOMES AND MEASURES Local recurrence. RESULTS Age, sex, pT stage, lymphovascular or perineural invasion, and adjuvant radiation treatment were similar across the 3 groups. The probability of LR-free survival at 3 years was 0.9 and 0.8 in groups 1 and 3, respectively (P = .03). The frequency of positive glossectomy margins was lowest in group 1 (9 of 117 [7.7%]) compared with groups 2 and 3 (28 of 61 [45.9%] and 23 of 95 [24.2%], respectively) (P < .001). Even after excluding cases with positive margins, the median distance to the closest margin was significantly narrower in group 3 (2 mm) compared with group 1 (3 mm) (P = .008). The status (positive vs negative) of margins obtained from the glossectomy specimen correlated with LR (P = .007), while the status of tumor bed margins did not. The status of the tumor bed margin was 24% sensitive (95% CI, 16%-34%) and 92% specific (95% CI, 85%-97%) for detecting a positive glossectomy margin. CONCLUSIONS AND RELEVANCE The margin sampling technique affects local control in patients with oral tongue SCC. Reliance on margin sampling from the tumor bed is associated with worse local control, most likely owing to narrower margin clearance and greater incidence of positive margins. A resection specimen-based margin assessment is recommended.

Betahistine metabolites, Aminoethylpyridine, and Hydroxyethylpyridine increase cochlear blood flow in guinea pigs in vivo

Abstract Objective: Betahistine is a histamine-like drug that is used in the treatment of Ménières disease. It is commonly believed that betahistine increases cochlear blood flow and thus decreases the endolymphatic hydrops that is the cause of Ménières. Despite common clinical use, there is little understanding of the kinetics or effects of its metabolites. This study investigated the effect of the betahistine metabolites aminoethylpyridine, hydroxyethylpyridine, and pyridylacetic acid on cochlear microcirculation. Design: Guinea pigs were randomly assigned to one of the groups: placebo, betahistine, or equimolar amounts of aminoethylpyridine, hydroxyethylpyridine, or pyridylacetic acid. Cochlear blood flow and mean arterial pressure were recorded for three minutes before and 15 minutes after treatment. Study sample: Thirty Dunkin-Hartley guinea pigs assigned to one of five groups with six guinea pigs per group. Results: Betahistine, aminoethylpyridine, and hydroxyethylpyridine caused a significant increase in cochlear blood flow in comparison to placebo. The effect seen under aminoethylpyridin was greatest. The group treated with pyridylacetic acid showed no significant effect on cochlear blood flow. Conclusion: Aminoethylpyridine and hydroxyethylpyridine are, like betahistine, able to increase cochlear blood flow significantly. The effect of aminoethylpyridine was greatest. Pyridylacetic acid had no effect on cochlear microcirculation.

Quality of life in patients after resection of pT3 lateral tongue carcinoma: Microvascular reconstruction versus primary closure

Controversy exists regarding the functional advantages of free flap reconstruction after partial glossectomy as compared to primary closure.

Histaminergic H3-Heteroreceptors as a Potential Mediator of Betahistine-Induced Increase in Cochlear Blood Flow.

Objective: Betahistine is a histamine-like drug that is considered beneficial in Ménières disease by increasing cochlear blood flow. Acting as an agonist at the histamine H1-receptor and as an inverse agonist at the H3-receptor, these receptors as well as the adrenergic α2-receptor were investigated for betahistine effects on cochlear blood flow. Materials and Methods: A total of 54 Dunkin-Hartley guinea pigs were randomly assigned to one of nine groups treated with a selection of H1-, H3- or α2-selective agonists and antagonists together with betahistine. Cochlear blood flow and mean arterial pressure were recorded for 3 min before and 15 min after infusion. Results: Blockage of the H3- or α2-receptors caused a suppression of betahistine-mediated typical changes in cochlear blood flow or blood pressure. Activation of H3-receptors caused a drop in cochlear blood flow and blood pressure. H1-receptors showed no involvement in betahistine-mediated changes of cochlear blood flow. Conclusion: Betahistine most likely affects cochlear blood flow through histaminergic H3-heteroreceptors.

Surgical margins and oncologic results after carcinoma of the external auditory canal

External auditory canal cancer is rare and carries a poor prognosis. To date, only a few studies provide evidence for clinical decision making in multimodal treatment.

Coated collagen patches for closure of pharyngo-cutaneous fistulas.

After laryngectomy or lateral pharyngotomy for treatment of laryngeal or hypopharyngeal cancer the occurrence of a pharyngo-cutaneous fistula is a challenging complication. Especially after previous radiotherapy and expanded surgical resections of mucosa the management is demanding. Besides the prolonged hospital stay, increased treatment costs and reduced quality of life, a delayed adjuvant treatment follows the development of a fistula. Treatment strategies range from conservative procedures comprising parenteral nutrition, antibiotics and local wound care to primary surgical closure or reconstructive tissue transfer. We report three cases of using the fibrin/thrombin-coated collagen patch TachoSil(®) as a solitary or adjuvant strategy in surgical treatment. In one patient primary closure of the fistula was achieved by transoral application of the collagen patch. In the other cases a not tension free primary suture was strengthened by the adjuvant use of TachoSil(®). The healing process was rapid and straightforward in all patients. The use of TachoSil(®) may be indicated in between conservative treatment strategies and reconstructive surgery. After occurrence of a fistula the healing process is intended to be accelerated by primary closure with TachoSil(®) or by sealing of a primary suture.

Two-Photon Microscopy Allows Imaging and Characterization of Cochlear Microvasculature In Vivo

Impairment of cochlear blood flow has been discussed as factor in the pathophysiology of various inner ear disorders. However, the microscopic study of cochlear microcirculation is limited due to small scale and anatomical constraints. Here, two-photon fluorescence microscopy is applied to visualize cochlear microvessels. Guinea pigs were injected with Fluorescein isothiocyanate- or Texas red-dextrane as plasma marker. Intravital microscopy was performed in four animals and explanted cochleae from four animals were studied. The vascular architecture of the cochlea was visualized up to a depth of 90.0 ± 22.7 μm. Imaging yielded a mean contrast-to-noise ratio (CNR) of 3.3 ± 1.7. Mean diameter in vivo was 16.5 ± 6.0 μm for arterioles and 8.0 ± 2.4 μm for capillaries. In explanted cochleae, the diameter of radiating arterioles and capillaries was measured with 12.2 ± 1.6 μm and 6.6 ± 1.0 μm, respectively. The difference between capillaries and arterioles was statistically significant in both experimental setups (P < 0.001 and P = 0.022, two-way ANOVA). Measured vessel diameters in vivo and ex vivo were in agreement with published data. We conclude that two-photon fluorescence microscopy allows the investigation of cochlear microvessels and is potentially a valuable tool for inner ear research.

Cochlear Pericytes Are Capable of Reversibly Decreasing Capillary Diameter In Vivo After Tumor Necrosis Factor Exposure

OBJECTIVE The aim of this work was to evaluate the effect of tumor necrosis factor (TNF) and its neutralization with etanercept on the capability of cochlear pericytes to alter capillary diameter in the stria vascularis. METHODS Twelve Dunkin-Hartley guinea pigs were randomly assigned to one of three groups. Each group was treated either with placebo and then placebo, TNF and then placebo, or TNF and then etanercept. Cochlear pericytes were visualized using diaminofluorescein-2-diacetate and intravasal blood flow by fluorescein-dextrane. Vessel diameter at sites of pericyte somas and downstream controls were quantified by specialized software. Values were obtained before treatment, after first treatment with tumor necrosis factor or placebo and after second treatment with etanercept or placebo. RESULTS Overall, 199 pericytes in 12 animals were visualized. After initial treatment with TNF, a significant decrease in vessel diameter at sites of pericyte somas (3.6 ±4.3%, n = 141) compared with placebo and downstream controls was observed. After initial treatment with TNF, the application of etanercept caused a significant increase (3.3 ±5.5%, n = 59) in vessel diameter at the sites of pericyte somata compared with placebo and downstream controls. CONCLUSION We have been able to show that cochlear pericytes are capable of reducing capillary diameter after exposition to TNF. Moreover, the reduction in capillary diameter observed after the application of TNF is revertible after neutralization of tumor necrosis factor by the application of etanercept. It seems that contraction of cochlear pericytes contributes to the regulation of cochlear blood flow.

Drug-induced Defibrinogenation as New Treatment Approach of Acute Hearing Loss in an Animal Model for Inner Ear Vascular Impairment

OBJECTIVE Disturbance of cochlear microcirculation is considered to be the final common pathway of various inner ear diseases. Hyperfibrinogenemia causing increased plasma viscosity is a known risk factor for sudden sensorineural hearing loss and may lead to a critical reduction of cochlear blood flow. The aim of this study was to evaluate the effect of a substantial reduction of plasma fibrinogen levels by drug-induced defibrinogenation for the treatment of acute hearing loss in vivo. METHODS Acute hearing loss was induced by hyperfibrinogenemia (i.v. injection of 330 mg/kg BW fibrinogen), using a guinea pig animal model. Parameters of cochlear microcirculation and hearing thresholds were quantified by intravital microscopy and evoked response audiometry. After obtaining baseline values, the course of hearing loss and disturbances of microcirculation were investigated under influence of intravenous defibrinogenation therapy (ancrod), corticosteroid, or placebo treatment, using 5 animals/group. RESULTS Acute hyperfibrinogenemia caused hearing loss from 10 ± 7 to 26 ± 10 dB SPL at baseline. Drug-induced reduction of fibrinogen levels showed a significant increase of cochlear microcirculation (1.6-fold) and recovered hearing threshold (11 ± 6 dB SPL). Placebo or corticosteroid treatment had no effect on hearing loss (35 ± 7 dB SPL and 32 ± 18 dB SPL, respectively). CONCLUSION Acute hyperfibrinogenemia resulted in hearing loss. Drug-induced reduction of elevated fibrinogen levels caused an increase in cochlear blood flow and a decrease in hearing thresholds. Placebo or corticosteroid treatment had no effect. Reduction of plasma fibrinogen levels could serve as a clinical treatment option for acute hearing loss.

Transoral laser microsurgery for treatment for hypopharyngeal cancer in 211 patients

The oncologic and functional outcome of transoral laser microsurgery (TLM) for primary treatment of hypopharyngeal cancer was examined in a multimodal treatment concept.