Randal A. Otto

Sensitivity and specificity of intraoperative recurrent laryngeal nerve stimulation in predicting postoperative nerve paralysis.

Bilateral recurrent laryngeal nerve (RLN) paralysis after thyroidectomy is infrequent, but serious when it occurs. Intraoperative knowledge of the status of the nerve after dissection could potentially provide the surgeon with important decision-making information. The current study examines the sensitivity and specificity of intraoperative stimulation of the RLN during thyroid surgery for predicting postoperative RLN deficits. Eighty-one RLNs in 55 patients were identified to be at risk of injury during thyroidectomy or parathyroidectomy performed between January 1998 and February 2000. Intraoperative determination of RLN function was evaluated with a disposable nerve stimulator (Xomed, Jacksonville, Florida) set at 0.5 mA. Injury was assessed by palpating for a contraction of the posterior cricoarytenoid muscle while the stimulus was applied. Postoperative assessment of RLN integrity was determined by using indirect or direct laryngoscopy to visualize vocal fold mobility. Nine RLNs failed to elicit a posterior cricoarytenoid contraction after nerve stimulation, and 4 RLNs were determined to be deficient in the postoperative evaluation. The calculated sensitivity and specificity were 75% and 92.2% with a positive predictive value of 33.3% and negative predictive value of 98.6%. The RLN injury rate was 4.94%. We conclude that intraoperative RLN stimulation is a relatively safe and useful method of determining what RLN function will be after thyroid or parathyroid surgery.

MANAGEMENT OF THE UNKNOWN PRIMARY CARCINOMA: LONG-TERM FOLLOW-UP ON A NEGATIVE PET SCAN AND NEGATIVE PANENDOSCOPY

The unknown primary carcinoma in the head and neck has been estimated to represent up to 7% of all head and neck carcinomas. In an attempt to identify the occult primary tumor the evaluation of this patient population has included a complete head and neck examination, flexible fiberoptic endoscopy, and imaging with CT/MRI. More recently, positron emission tomography (PET) has been advocated as a tool to detect primary tumors.

The role of positron emission tomography scans in the management of the N-positive neck in head and neck squamous cell carcinoma after chemoradiotherapy

Objective: The objective of this study was to determine the sensitivity, specificity, and predictive value of 18‐fluorodeoxyglucose positron emission tomography (PET) in predicting residual cervical metastatic disease in patients with N‐positive necks undergoing curative radiotherapy and chemoradiotherapy for squamous cell carcinoma (SCC) of the upper aerodigestive tract.

The Endoscopic Management of Zenker Diverticulum: CO2 Laser versus Endoscopic Stapling†

Objective: The purpose of this project was to analyze the endoscopic management of Zenker diverticulum (ZD) using both the CO2 laser and endoscopic stapling techniques. This study compares the two techniques in terms of diverticulum size, onset to oral intake, hospital stay, resolution of symptoms (dysphagia and regurgitation), and complications.

Cochlear microphonics recorded from fetal and newborn sheep

PURPOSE Sounds present within the uterus stimulate the fetal inner ear and central auditory pathway. This study was undertaken to determine the efficiency of transmission of exogenous airborne stimuli to the fetal inner ear. In this way, we may quantify the extent to which the fetal auditory system is isolated from sounds produced outside the mother. MATERIALS AND METHODS Cochlear microphonics were recorded from fetal and newborn sheep to evaluate the extent to which the fetus is isolated from sounds exogenous to the ewe. Electrodes were surgically placed in contact with the round window membrane in nine near-term fetal sheep. Cochlear microphonics were recorded in response to 1/3 octave-band noises (0.125 to 2.0 kHz) delivered through a loudspeaker 1.8 m from one side of the pregnant ewe. Sound pressure levels generated by the noises were simultaneously recorded ex utero with a microphone and in utero with a hydrophone previously sutured to the fetal neck. After cochlear microphonic amplitudes were recorded, the fetus was delivered through an abdominal incision. Recordings were repeated from the newborn lamb. Fetal sound isolation was calculated as the difference between the sound pressure levels that were necessary to evoke equal cochlear microphonic amplitudes from the fetus and from the newborn lamb. RESULTS The sound attenuation observed was variable for all frequencies. The fetus was isolated from external sounds by 11.1 dB for 0.125 kHz, 19.8 dB for 0.25 kHz, 35.3 dB for 0.5 kHz, 38.2 dB for 1.0 kHz, and 45.0 dB for 2.0 kHz. CONCLUSIONS Other investigators have demonstrated that the immature auditory system is more susceptible to damage produced by noise exposure than is the mature auditory system. Low-frequency noise produces damaged cells that later in life code higher frequencies. A possibility of fetal hearing loss produced by intense noise exposure needs more careful evaluation.

Cocaine, lidocaine, tetracaine: which is best for topical nasal anesthesia?

The quality of nasal anesthesia obtained with three local anesthetic solutions (4% cocaine, 2% lidocaine in oxymetazoline, and 1% tetracaine in oxymetazoline) was evaluated in a randomized study.Each local anesthetic mixture was applied to the nasal septum of healthy volunteers using medication-soaked pledgets. Measurements of anesthetic effect (sensation threshold and pain perception) were made with Semmes-Weinstein monofilaments. Measurements were performed prior to local anesthetic application and 10 and 70 min after local anesthetic application. Subjects had greater increases in sensation threshold with tetracaine than with lidocaine or cocaine at both 10 and 70 min (P < 0.05). Subjects had greater decreases in pain perception with tetracaine than with lidocaine or cocaine at both time intervals (P < 0.05). Tetracaine mixed with oxymetazoline appears to be a superior topical anesthetic for nasal procedures. (Anesth Analg 1995;81:724-7)

Intraoperative 186Re-Liposome Radionuclide Therapy in a Head and Neck Squamous Cell Carcinoma Xenograft Positive Surgical Margin Model

Purpose: Positive surgical margins in advanced head and neck squamous cell carcinoma (HNSCC) have a well-documented association with an increased risk of locoregional recurrence and significantly poorer survival. Traditionally, unresectable tumor is treated with postoperative radiotherapy and/or chemotherapy. However, these therapeutic options can delay treatment and increase toxicity. The potential value of intraoperative injection of liposomal therapeutic radionuclides as a locoregional, targeted therapy in unresectable advanced HNSCC was assessed in a nude rat xenograft positive surgical margin model. Experimental Design: The therapeutic effects of β-emission rhenium-186 (186Re) carried by liposomes into the tumor remnants in a nude rat squamous cell carcinoma xenograft model were studied. Following the partial resection of tumor xenografts, the animals were intratumorally injected with 186Re-labeled or unlabeled (control) neutrally charged or positively charged 100-nm-diameter liposomes. Tumor size, body weight, hematology, and toxicity were monitored for 35 days posttherapy. Results: The neutral (n = 4) and cationic (n = 4) liposome control groups showed an increase in tumor growth of 288.0 ± 37.3% and 292.2 ± 133.7%, respectively, by day 15. The 186Re-neutral-liposome group (n = 8) and the 186Re-cationic-liposome group (n = 8) presented with an average final tumor volume of 25.6 ± 21.8% and 28.5 ± 32.2%, respectively, at the end of the study (day 35). All groups showed consistent increases in body weight. No significant systemic toxicity was observed in any of the animals. Conclusions: With excellent tumor suppression and minimal side-effect profile, the intraoperative use of liposomal therapeutic radionuclides may play a role in the management of positive surgical margins in advanced HNSCC.

Setup and characterization of a human head and neck squamous cell carcinoma xenograft model in nude rats

OBJECTIVE: To develop and characterize a new head and neck cancer animal model. STUDY DESIGN: A human head and neck squamous cell carcinoma (HNSCC) xenograft model in nude rats was established via subcutaneous inoculation of a human-origin HNSCC cell line, SCC-4. The tumor was evaluated for growth characteristics, pathologic features by hematoxylin-eosin (HE) staining, and immunohistochemistry of epidermal growth factor receptor (EGFR). 2-[18F] fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET) imaging characteristics were studied too. RESULTS: A new HNSCC animal model was successfully established. Tumor sizes reached about 1 cm3 on day 15 after tumor cell inoculation. HE staining pathology has confirmed that this tumor is a typical SCC. EGFR immunohistochemistry demonstrated this tumor model to be strongly EGFR positive. 18F-FDG PET study has shown that 18F-FDG accumulated in tumors. CONCLUSIONS: This study has demonstrated that this tumor model is an appropriate HNSCC tumor model for animal studies on HNSCC.

Induced telomerase activity in primary aortic endothelial cells by low-LET γ-radiation is mediated through NF-κB activation

Our objective was to understand the mechanism through which cells that initially survive irradiation could acquire survival advantage. In this study, we show evidence that low-linear energy transfer gamma-radiation can induce telomerase enzyme activity in primary aortic endothelial cells, and that an upstream regulator, nuclear factor kappa B (NF-kappaB), controls this activation. Telomeric repeat amplification protocol (TRAP) assay showed that cells exposed to a dose of 2 Gy induce telomerase activity. Subsequent analysis revealed that radiation-induced telomeric activity is regulated at the transcriptional level by triggering activation of the promoter of the telomerase catalytic subunit, telomerase reverse transcriptase (TERT). A mechanistic study revealed that NF-kappaB becomes functionally activated upon radiation exposure and mediates the upregulation of telomerase activity by binding to the kappaB-binding region in the promoter region of the TERT gene. More significantly, elimination of the NF-small ka, CyrillicB recognition site on the telomerase promoter or inhibition of NF-small ka, CyrillicB by ectopically expressing the inhibitor protein IkappaBalpha mutant (Ismall ka, CyrillicBalpha(S32A/S36A))) compromises radiation-induced telomerase promoter activation. Consistent with the notion that NF-kappaB mediates gamma-ray-induced telomerase responses, TRAP assay revealed that ectopically expressed IkappaBalpha(S32A/S36A)) also attenuated telomerase enzyme activity. These findings indicate that NF-kappaB activation following ionizing radiation exposure may elicit a survival advantage by upregulating and maintaining telomerase activity.

Intraoperative therapy with liposomal drug delivery: retention and distribution in human head and neck squamous cell carcinoma xenograft model.

The focus of this study is to investigate the retention and biodistribution of technetium-99m ((99m)Tc) labeled liposomes in a human head and neck squamous cell carcinoma (HNSCC) positive surgical margin animal xenograft model. Positive surgical margin (with margin<1mm) in HNSCC is associated with significant higher mortality and recurrence rate when compared to clear margin. An immediate intraoperative application of liposome-carried therapeutic agents may treat the residual disease intraoperatively and improve long term survival in these patients. To understand the feasibility of this intraoperative therapy in HNSCC, the in vivo behavior of liposomes after intraoperative administration of (99m)Tc-labeled liposomes using non-invasive nuclear imaging was investigated in an animal xenograft model. Neutral and cationic (99m)Tc-labeled liposomes of 100 nm, 1 microm and 2 microm in diameter (6 study groups with 4 rats per study group) were injected into a nude rat HNSCC positive surgical margin xenograft model. Intratumoral, locoregional, and systemic retention and distribution of the (99m)Tc-liposomes were determined using non-invasive nuclear imaging and post-mortem organ distribution. The (99m)Tc-liposomes demonstrated high locoregional retention rate of 55.9+/-3.7% to 72.9+/-2.4% at 44 h after intraoperative injection to allow significant radiation to the surgical cavity if therapeutic radionuclides were used. Overall, the cationic liposomes demonstrated higher intratumoral retention rate, and the neutral liposomes showed greater retention in the paratumoral cavity (p<0.05 respectively). In conclusion, intraoperative therapy with liposome carried radionuclide drug delivery system carries great potential in treating unresectable HNSCC, and further study using therapeutic radionuclide should be explored.