Eui-Kyung Goh

Effects of Cisplatin, 5-Fluorouracil, and Radiation on Cell Cycle Regulation and Apoptosis in the Hypopharyngeal Carcinoma Cell Line

In head and neck cancer including hypopharyngeal cancer, cisplatin and 5-fluorouracil (5-FU) usually have been used as neoadjuvant chemotherapeutic agents. We investigated the effects of cisplatin, 5-FU and radiation on p53 protein expression and cell responses (cell cycle arrest and/or apoptosis) in the hypopharyngeal carcinoma cell line (PNUH-12; mutant type p53). PNUH-12 cells were treated with cisplatin, 5-FU and radiation. The changes in the cells were assessed by a cell cytotoxicity assay, Western blotting (p53 and p21WAF1/CIP1 proteins), a DNA fragmentation assay, propidium iodide (PI) staining and DNA flow cytometry. The expression of p53 protein was increased after treatment with cisplatin and 5-FU, but not radiation. The expression of p21WAF1/CIP1 protein was increased only after treatment with 5-FU, not cisplatin or radiation. With cisplatin and radiation, we observed apoptosis both by DNA fragmentation and PI staining and increased S phase in cisplatin and G2 phase in radiation by DNA flow cytometry. But, with 5-FU, we could not observe apoptosis by DNA fragmentation and PI stain but only an increased G1 phase by DNA flow cytometry. In PNUH-12, radiation induced p53-independent apoptosis and p21WAF1/CIP1-independent G2-phase cell cycle arrest. Cisplatin induced p53-dependent apoptosis and p21WAF1/CIP1-independent S-phase cell cycle arrest and 5-FU induced p53 and p21WAF1/CIP1-dependent G1-phase cell cycle arrest, not apoptosis. Cisplatin and 5-FU induced p53-dependent pathways, but radiation p53-independent pathway. The cell responses by cisplatin, 5-FU and radiation were all different pathways.

Autologous cartilage injection for the patulous eustachian tube

The eustachian tube (ET) is normally closed, but it opens temporarily during swallowing. Patients with a patulous ET (PET) have various aural symptoms such as aural fullness, autophony, and hearing their own breathing. These symptoms are caused by abnormal transmission of sound from the pharynx to the middle ear via an open ET with little attenuation. We introduce a novel injection technique for the treatment of PET using autologous cartilage. This procedure is minimally invasive and has been successfully used to treat PET in 2 patients.

Topical inhalant steroid (budesonide, Pulmicort nasal) therapy in intubation granuloma.

Intubation granuloma of the larynx is an iatrogenic disease which is induced by endotracheal intubation. It has basically been managed by conservative medical treatment with observation. Surgical excision can be considered as a last resort due to the high recurrence rate which subjects the patients to repeated anaesthesia. The purpose of this study is to evaluate the therapeutic effect of topical steroid in intubation granuloma, comparing the results of conservative medical treatment with, or without, surgery (Group I, 14 patients) and inhalant therapy with topical budesonide (Group II, 20 patients). In Group I, complete disappearance of granuloma occurred in six cases within a year (42.8 per cent) with conservative therapy only. Microlaryngeal surgery was performed on the eight cases of persisting granuloma after conservative therapy for a year, resulting in two cases of recurrence. In Group II, the granuloma disappeared completely in 85 per cent within six months and in 95 per cent within 12 months without any remarkable side-effects. We concluded that intubation granuloma of the larynx could be treated with topical inhalant steroid as the first choice of therapy rather than other medical treatment or surgical intervention.

Intracordal injection of autologous auricular cartilage in the paralyzed canine vocal fold

OBJECTIVE: Vocal fold augmentation by injectable material under direct visual control is an easy and simple operation. However, when autologous fat or bovine collagen is used, resorption creates a problem. And autologous fascia is debating about absorption now days. This study is to evaluate the histology of minced and injected autologous auricular cartilage and fat graft in the augmentation of unilateral vocal fold paralysis using a canine model. METHOD: Nine dogs were operated. At first, a piece of auricular cartilage was harvested from ear and minced into tiny chips with a scalpel, and a piece of fat tissue was harvested from inguinal area and minced into tiny chips with a scalpel. Cutting off a section of the recurrent nerve paralyzed the right vocal fold. The minced cartilage and fat-paste (0.2 mL) was injected using a pressure syringe into the paralyzed thyroarytenoid muscle under direct laryngoscopy. Two animals were sacrificed at 3 days, three at 3 weeks, two at 3 months, one at 6 months, and one at 12 months. Each dog underwent laryngectomy and serial coronal sections of paraffin blocks from the posterior part of the vocal fold were made. RESULTS: There was no significant complication perioperatively and during follow-up. There was acute inflammatory findings in the graft at 3 days and 3 weeks. The injected cartilage remained in the larynx until 12 months. CONCLUSION: The autologous auricular cartilage graft is well tolerated and may be very effective material for volumetric augmentation on paralyzed vocal cord.

Factors Associated with Postoperative Delirium after Major Head and Neck Surgery

Postoperative delirium (POD) is an acute change in cognitive status characterized by fluctuating consciousness and is associated with high incidences of morbidity, high complication rates, and long hospitalizations. This study was performed to determine the incidence of POD and the perioperative risk factors in order to predict which patients have an increased risk and thus to prevent POD after major head and neck surgery. The authors retrospectively evaluated 341 patients who underwent laryngectomy or the Commando (combined operation of mouth, mandible, and neck dissection) procedure at Pusan National University Hospital from January 1986 through July 2001. Postoperative delirium developed in 13.8% of the patients who underwent laryngectomy (42 of 304) and 13.5% of the patients who underwent the Commando procedure (5 of 37). A multivariate analysis showed that older age, hypertension, low postoperative 02 saturation, and decreased postoperative hemoglobin levels were risk factors for POD (p < .05). Postoperative delirium is preventable, and its incidence can be decreased by predicting these risk factors during the preoperative and postoperative periods.

Acute otitis media–induced petrous apicitis presenting as the Gradenigo syndrome: successfully treated by ventilation tube insertion

Petrous apicitis has traditionally been treated with aggressive surgical methods. However, recent reports describe good results with more conservative medical treatment and minimal surgical intervention. We report a case of petrous apicitis presenting as the Gradenigo syndrome treated by ventilation tube insertion. We recommend aggressive surgical intervention for patients who failed to respond to conservative therapy including ventilation tube insertion.

Histologic Evaluation of Intracordal Autologous Cartilage Injection in the Paralyzed Canine Vocal Fold at Two and Three Years

OBJECTIVE: Intracordal injection for vocal fold augmentation is easy and simple and does not require a cervical skin incision. We reported previously on the 1-year results of injected autologous auricular cartilage for volumetric augmentation in paralyzed canine vocal cord. This study evaluates the long-term histomorphologic results of injected autologous auricular cartilage for the augmentation of the paralyzed canine vocal fold at 2 and 3 years. STUDY DESIGN AND SETTING: A prospective trial of autologous cartilage augmentation of vocal cord in animal model. Five dogs were operated on. A piece of auricular cartilage was harvested from the ear and minced into tiny chips with a scalpel. Fat was harvested from inguinal area and minced with a scalpel. The minced cartilage and fat-paste (0.2 ml) was injected using a pressure syringe into the paralyzed thyroarytenoid muscle using direct laryngoscopy. Three animals were sacrificed at 2 years, two at 3 years. Each subject underwent laryngectomy and serial coronal sections of paraffin blocks from the posterior vocal fold were made. RESULTS: There was no significant complications perioperatively or postoperatively. The injected cartilage that seemed to have lost viability existed in the vocalis muscles until 36 months. Fibrotic change was exhibited in the surrounding injected cartilage. There were no differences between 2 and 3 years in histomorphologic results of the injected cartilage. CONCLUSION: The autologous auricular cartilage graft is well tolerated and may be a very effective material for long-term volumetric augmentation in the paralyzed vocal cord.

Histologic changes in the eustachian tube mucosa of rats after short-term exposure to cigarette smoke.

Objective and Background: It is generally accepted that cigarette smoke is a major risk factor for middle ear disease. However, the literature is void of articles addressing the direct relationship between cigarette smoke exposure and middle ear disease. Furthermore, there are many conflicting opinions concerning the role of cigarette smoke in the pathogenesis of middle ear disease. The purpose of this study was to evaluate the effects of cigarette smoke on the Eustachian tube mucosa. Materials and Methods: Thirty healthy 150 to 230 g Sprague Dawley rats with normal middle ears were used. The animals were divided into six groups of five. Five experimental groups (N = 5 each) were exposed to a domestic cigarette (This®, tar 7.0 mg, nicotine 0.75 mg) every 30 minutes (total 2.5 hours, 5 cigarettes total) on a daily basis in a smoking chamber for 1, 2, 4, 6, or 8 weeks. A control group (N = 5) was placed in the same chamber without exposure to cigarette smoke. After exposure, the animals were sacrificed and cross sections of the Eustachian tubes were prepared. Histologic changes of the Eustachian tube mucosa were observed through light and electron microscopes. Results: Loss of cilia, goblet cell depletion, and squamous metaplasia of the Eustachiann tube mucosa were observed following exposure to smoke. The one- and two-week exposure groups demonstrated the greatest decrease in goblet cell counts. The eight-week exposure group showed recovery from this decrease. Squamous metaplasia was observed in all experimental groups and was most prominent in the eight-week exposure group. Conclusion: These findings suggest that cigarette smoke directly affects Eustachian tube mucosa in the early stages of exposure. Some of the mucosal changes, however, were reversed during the latter stages of exposure. A mechanism different from that which occurs in the nasal cavity and trachea may be activated in the Eustachian tube after exposure to passive smoke. The protective function of the Eustachian tube may play some role in this mechanism.

Closure of large tracheocutaneous fistula using turn-over hinge flap and V-Y advancement flap.

Tracheocutaneous fistula is a frequent sequel of long-term tracheostomy or tracheal fenestration. Closure of fistula is complicated by the presence of extensive scar tissue, mucopurulent secretions, and tension from insufficient advancement of adjacent soft tissue. We report two successfully closed cases of large tracheocutaneous fistulae using a hinge flap and a V-Y advancement flap.

The prognostic value of telomerase expression in peripheral blood mononuclear cells of head and neck cancer patients

Objective:This study investigates the expression of telomerase in the peripheral blood mononuclear cells (PBMCs) of head and neck cancer patients and the relationship between the telomerase expression in PBMCs and clinicopathological features with prognosis. Methods:Peripheral blood samples were collected from 100 head and neck squamous cell cancer patients and 20 normal control group. The telomerase activity in peripheral blood mononuclear cells was measured by telomerase rapid amplification protocol (TRAP) assay using TRAPeze telomerase detection kit. Pearson &khgr;2 test was used to analyze the correlation of telomerase expression with clinicopathologic parameters. Kaplan-Meier method and Cox proportional hazards model were used for prognostic analysis. Results:Regarding the expression of telomerase in PBMCs of patients, 73 out of 100 (73.0%) were found to be positive, and the remaining 27 cases (27.0%) were negative. The difference to the telomerase expression of PBMCs in the normal and cancer patients was significant (P < 0.001). The expression of telomerase in PBMCs of patients was significant correlated with T classification (P = 0.005), N classification (P = 0.002), and AJCC stages (P < 0.001). On multivariate analysis, N classification (P = 0.007), AJCC stages (P = 0.02), and telomerase expression (P = 0.017) showed independent factors associated with poor survival. Conclusion:The detection of telomerase expression in PBMCs of head and neck cancer patients is a simple and very useful molecular marker for the progression and prognosis of head and neck cancer.