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Stem cells are the base for cell therapy due to their ability to self-renew, differentiate into other cell types, and live throughout the life of an organism. The initial cell therapy was bone marrow transplantation; bone marrow that contains haematopoietic stem cells is transferred from a healthy donor into a sick recipient to transfer the healthy genotype1,2. Stem cell therapy approach may be possible in corals, where there is genotypic variation in heat tolerance that influences survival during increased water temperatures3–5. However, we first need the ability to reliably isolate and transplant stem cells in Hexacorallia, which includes stony corals and sea anemones6. In this work, we used the sea anemone Nematostella vectensis as our model for candidate stem cell transplantation, as it is the only hexacorallian species that has fluorescent-tagged transgenic strains7. We established cell transplantation to show that there are cell populations exhibiting the functional characteristics of stem cells. We showed that a subpopulation of cells from N. vectensis can be transplanted from donor to recipient, are long-lived and self-renewing, can proliferate and differentiate, can integrate into the recipient, and rescue recipient animals treated with lethal doses of a chemotherapeutic agent. Lastly, we showed that this subpopulation can be enriched by sorting, using species non-specific cell markers and that similar subpopulations of cells can be isolated from other hexacorallians, including stony corals. This lays a foundation for the possibility of stem cell-based therapy in species of Hexacorallia.

A surgical technique developed by Dr. Isaac Eliachar in the Section of Laryngotracheal Reconstruction, Cleveland Clinic Department of Otolaryngology, dramatically improves quality of life in patients who require a long-term tracheostoma. This procedure, called “long-term tube-free tracheostomy” (LTTFT), creates a self-sustaining tracheostoma that requires no tracheotomy tubes to maintain patency. The advantages of a tube-free procedure are numerous, and the improvements in quality of life of patients who have successfully undergone this operation are readily noticeable. These benefits include (a) removal of tracheal appliances, such as tracheal tubes, valves, vents, and stents; (b) prevention of tissue damage associated with appliances and a decrease in tissue irritation and formation of granulation tissue; (c) better secretion management, elimination of frequent clogging of tracheal appliances, and need for suction; (d) prevention of aspiration; (e) retention or re-establishment of the functions of sniffing and smelling; and (f) performance of hands-free cough and speech production due to the self-constricting capabilities of the stoma. The purpose of this article is to present the concept of LTTFT as an alternative to standard tracheotomy in select patients. The difference between LTTFT as an alternative to tracheotomy and the impact these differences have upon medical decision-making will be emphasized.

Laryngotracheal trauma may result in lifelong complications or even death if diagnosis or treatment is delayed. Emergency room physicians, trauma surgeons, anesthesiologists, and especially otolaryngologists should maintain a high level of awareness of and suspicion for laryngotracheal trauma whenever a patient presents with multiple trauma in general or with cervical trauma in particular. Although there is some controversy regarding care, treatment in experienced hands will usually result in a favorable outcome. In this article, we review and update the diagnosis and management of acute external laryngotracheal trauma.

Objective/Hypothesis The rotary door flap (RDF) laryngotracheal reconstructive procedure uses a 180° rotation of the sternohyoid muscle into a laryngofissure. Despite excellent clinical results, there are concerns of flap inspiratory prolapse. This study examined RDF stability and the efficacy of ancillary materials in providing additional support. Methods Seventeen dogs underwent endoscopic induction of subglottic stenosis and delayed RDF reconstruction. Animals received 1) traditional RDF (control), 2) RDF with titanium screen implant, 3) RDF with porous polyethylene implant, or 4) RDF with hydroxyapatite cement (HAC) injection. Four weeks postoperatively the flaps were tested for stability. On qualitative assessment, endoscopic visualization was completed with quiet respiration and then following endotracheal tube occlusion. On quantitative assessment, after animals were killed, the RDF segment was isolated and subjected to negative pressure (maximum pressure, −50 mm Hg). The pressure-causing collapse was measured. Results In the traditional RDF animals (control), five of six flaps were stable in vivo and with negative pressures. In the titanium screen, porous polyethylene group, and HAC groups, respectively, four of four, three of four, and two of three flaps were stable in vivo and under negative pressure. Flaps that demonstrated instability had granulation, dehiscence, and poor healing. These occurred in 1 of 6 animals in the traditional RDF group and in 2 of 11 animals in the implant groups. In addition, 13 of 24 animals assigned to the implant groups died, compared with 2 of 8 of those in the traditional RDF group. Conclusions The RDF is stable and maintains the airway under physiological conditions. Support materials did not improve stability, render flap harvest more difficult, or increase morbidity and mortality.

Objectives/Hypothesis Objectives of the current study were as follows: 1) to determine whether a self-sustaining, tube-free tracheostomy with unaided speech capability can be achieved, 2) to propose new surgical techniques to enhance voluntary constriction of a tube-free tracheostoma to improve cough and speech production, and 3) to explain the mechanism involved in unaided speech after long-term tracheostomy. The hypotheses were that long-term, tube-free tracheostomy could minimize the unwanted effects of conventional tube-dependent tracheotomy; that surgical shunting of the trachea to the skin surface can be established through a short, skin-lined, self-supporting, nostril-like opening; and that patients could generate speech and cough without the need to occlude the stoma or use stents and/or one-way valves if such a long-term tube-free tracheostoma were established. Study Design A prospective study of tube-free tracheostomy intended to establish unaided cough and speech. Methods Thirty-five patients who underwent long-term flap tracheostomies between 1992 and 1999 with the prospective intent of establishing a self-sustaining stoma without the need for tubes or stents were reviewed. The patients were trained to intentionally constrict the stoma for production of unaided speech and cough. The pertinent techniques developed for successful achievement of these characteristics are presented and reviewed. A new surgical technique using a local tendinous muscular sling was designed to further improve the efficacy of stomal constriction. Results A tube-free stoma was successfully established in all 35 patients. Eighteen patients achieved effective intentional constriction of the stoma and thereby were capable of unaided speech production. Four patients required an additional new surgical sling procedure to optimize unaided cough and speech production. Thirteen patients achieved only limited unaided speech production, but were satisfied to do nothing further. Conclusions New surgical techniques and postoperative management to create a modified tube-free tracheostomy with self-constricting capabilities can enable production of effective cough and near-normal generation of unaided speech. In this manner, the airway can be secured with little or no voice compromise.

This research investigated the histopathologic and migratory properties of injectable alternatives for vocal fold medialization. Thirteen dogs underwent sectioning of the recurrent laryngeal nerve followed by vocal fold injection with 1 of 4 substances: Teflon, autologous fat, silicone suspension, or hydroxyapatite cement. Six months later, the animals were painlessly sacrificed and histopathologic analysis of the larynx and regional lymph nodes was performed. Although regional lymph node migration was noted, Teflon injection resulted in minimal vocal fold inflammatory reaction. Vocal folds injected with autologous fat exhibited persistence of fat at the injection site without significant inflammation or migration. Silicone suspension caused a localized giant cell reaction without regional lymph node migration, and 1 study subject died secondary to acute inflammation with critical respiratory compromise. Hydroxyapatite cement was well tolerated without inflammation or migration. This pilot study indicates that a wide range of possible substances for vocal fold medialization exist. Many of these may produce results superior to those obtained with Teflon and are thus far untested.

Objectives/Hypothesis: Early topical application of mitomycin to a laryngotracheal lesion may prevent or reduce laryngotracheal stenosis (LTS). Study Design: Prospective controlled animal study. Methods: LTS was induced in 60 dogs randomly assigned to four groups. Controls received an immediate topical application of normal saline. The suction-control group received an immediate application of normal saline followed by suction of secretions on day 2. The mitomycin group received immediate application of 0.7 mL mitomycin (0.2 mg/mL). The repeat-mitomycin group received an immediate application of mitomycin and a second application on day 2, after secretions were suctioned. The laryngeal lumens were measured endoscopically at baseline, day 12, and day 21. Animals were euthanatized if stenosis approximated 95% or at day 21. Results: All dogs in the mitomycin groups survived to day 21, compared with 12 in the suction group and only 2 controls. No side effects of mitomycin were observed. At day 21, surviving controls had 85% and 95% stenosis. In the mitomycin group, median stenosis was 27% (interquartile range, 29% to 42%); in the repeat-mitomycin group, 30% (22% to 40%); and in the suction-control group, 84.5% (72.5% to 93.5%). The mitomycin group differed significantly from controls on day 12 (median difference = 85%, 95% CI = 80%-94%, P < .0001) and day 21 (difference = 63.9%, 95% CI = 58%-85%, P = .031). Conclusion: A single topical application of mitomycin significantly reduces the severity of LTS in dogs. Reapplication after 2 days does not improve results. Prospective clinical studies are warranted to assess the efficacy in humans.

Background A phase III randomized comparison of radiotherapy alone versus combination chemotherapy and concurrent continuous-course radiotherapy was performed at the Cleveland Clinic Foundation. Methods Between March 1990 and June 1995, 100 patients with resectable stage III and IV squamous cell head and neck cancer were randomized to either Arm A: radiotherapy alone, 68–72 Gy at 1.8–2.0 Gy per day; or to Arm B: the identical radiotherapy with concurrent chemotherapy. Chemotherapy consisted of 5-fluorouracil, 1000 mg/m2/day, and cisplatin 20 mg/m2/day, both given as continuous intravenous infusions over 4 days beginning on day 1 and day 22 of the radiotherapy. At 50–55 Gy, patients were clinically reassessed. If a response was evident, radiotherapy was completed. In non-responding patients, however, radiotherapy was terminated and surgery recommended. After completion of all treatment, salvage surgery was performed, if possible, for any residual primary or nodal disease or for any subsequent locoregional recurrence. Results Except for an overrepresentation of T1 patients on Arm A, the treatment arms were equivalent. Toxicity was greater in the patients on Arm B with a higher incidence of grade III and IV neutropenia, thrombocytopenia, cutaneous reaction, and mucositis. Feeding tubes were also required more often, and weight loss was greater on the chemotherapy arm. No toxic deaths occurred. With a median follow-up of 36 months, the Kaplan-Meier 3-year projections of relapse-free survival are 52% for Arm A and 67% for Arm B (p = .03), and the likelihood of developing hematogenous metastases is 21% for Arm A and 10% for Arm B (p = .04). Although overall survival is not significantly different, overall survival with successful primary site preservation was 35% for Arm A and 57% for Arm B (p = .02). This difference remains statistically significant in the subsets of patients with laryngeal and hypopharyngeal primaries but not in patients with oropharyngeal primaries. Conclusions Continuous-course radiotherapy and concurrent combination chemotherapy is an intensive, toxic but tolerable treatment regimen, which, when compared with radiotherapy alone, can produce an improvement in relapse-free survival, a decrease in distant metastases, and an improvement in overall survival with successful primary site preservation. © 1997 John Wiley & Sons, Inc. Head Neck19: 567–575, 1997.

Background. Treating the neck after organ-preservation treatment with radiotherapy or chemoradiotherapy can be problematic. Methods. To develop management guidelines, we reviewed the results of a 100-patient phase-3 trial that had compared outcome after radiotherapy alone with outcome after chemoradiotherapy for head and neck cancer. Patients were randomly assigned to receive radiotherapy alone or concurrent chemoradiotherapy. After completing therapy, patients were reassessed, and surgery was recommended for persistent disease at the primary site or neck and for all patients with stage N2-3 neck nodes regardless of clinical response. Results. Of the 47 patients with stage NO-1, 43 had a complete response (CR); of the 18 N1 patients, all but 4 had a CR. One of these 4, as well as 5 others among the N0-1 patients, underwent neck dissection (n = 6). No disease was found on pathologic examination, and no patient had neck recurrence. Of the remaining 41 N0-1 patients, 3 had disease progression and received no further therapy. Of the 38 others, 4 had neck recurrence, with 3 recurring at the primary site. Of the 53 with stage N2-3, 23 had less than a complete response (

Surgical treatment of Zenker's diverticulum is controversial because many different procedures exist. We retrospectively reviewed 87 consecutive patients surgically treated for Zenker's diverticulum at a tertiary care institution from 1976 through 1993. Four surgical procedures were performed: cricopharyngeal myotomy alone (n = 16), excision (hand-sewn) plus myotomy (n = 51), excision (stapler) plus myotomy (n = 11), and diverticulopexy plus myotomy (n = 9). There were three surgical mortalities (3.5%) and a complication rate of 24%. Eighty patients (92%) were available for follow up. Sixty-eight patients (78%) reported excellent relief of symptoms, 10 (13%) reported improvement with occasional symptoms, and two (3%) described persistent dysphagia. No statistical difference in complication rate was found among surgical groups (P = 0.15). Myotomy alone patients had worse outcomes (P = 0.04) compared with the other surgical groups. Median follow-up was 7.5 months.