Kyong-Myong Chon

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.

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.

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.

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.

Histologic changes in the auditory tube mucosa of rats after long-term exposure to cigarette smoke

PURPOSE The aim of the study was to investigate the effect of cigarette smoke on the auditory tube and middle ear mucosa after long-term exposure (4 and 6 months). MATERIALS AND METHODS Fifteen rats were divided into 3 groups. The experimental groups were exposed to cigarette in a smoking chamber for 4 and 6 months (n = 5 each). A control group (n = 5) was placed in the same chamber without exposure to cigarette smoke. Histologic changes of the auditory tube mucosa were observed through light and electron microscopes. Histologic changes of the middle ear mucosa were also observed through light microscopes. RESULTS The histologic changes consisted of a proliferation of goblet cells and an increase of mucus secretion in auditory tube. Squamous metaplasia was paradoxically decreased according to the duration of exposure in auditory tube. The number of goblet cell was gradually increased according to the duration of exposure in the auditory tube and middle ear. CONCLUSIONS Long-term passive smoke directly affects the auditory tube and middle ear mucosa. Histologic changes of auditory tube mucosa consisted of goblet cell proliferation and excessive mucus secretion.

Management of high jugular bulb with tinnitus: transvenous stent-assisted coil embolization.

A 33-year-old woman presented with a right-sided pulsatile tinnitus correlated with her heartbeat and mild right ear hearing disturbance. At the initial physical examination, a dark-purple, pulsating mass from the right tympanic cavity was observed through the inferoposterior portion of the right tympanic membrane. The tympanic membrane was adherent to the promontory and pulsating mass. The tinnitus was eliminated by digital compression of the right jugular vein. A high-resolution computed tomography of the temporal bone revealed a large high jugular bulb with bony dehiscence in the right middle ear. The transfemoral cerebral angiogram showed hypoplasia of the left transverse sinus. The left venous sinus, therefore, was mainly drained into the occipital sinus and then connected to the right sigmoid sinus (88), just distal to the high jugular bulb (Fig I). Considering the dominance of the right venous sinus, we performed a transvenous stent-assisted coil embolization to avoid the risk of increasing intracranial pressure (IICP). A 7-French shuttle sheath Shuttle (Cook Incorporated, Bloomington, IN) was positioned in the right proximal SS via the right femoral vein for easy navigation of the stent delivery system. A 5-French catheter was placed into the right internal carotid artery (ICA) after left femoral puncture allowed the visualization of the high jugular bulb, construction of a roadmap and angiographic monitoring of the procedure. The patient was given intravenous heparin to maintain an activated clotting time between 200 and 300 seconds. A self-expandable stent (Precise RX, Cordis Corporation, Miami Lakes, FL) was placed into the SS over a O.035-in stiff wire (Radiofocus Guide Wire, Terumo Corporation, Tokyo, Japan) that was positioned in the superior sagittal sinus. To cover the neck portion of the high jugular bulb, the stent was placed from the SS to the internal jugular vein (IJV). The microcatheter (Echelon, ev3, Irvine, CA) was then carefully introduced and advanced to the dilated portion of the bulb through the stent mesh. The embolization was performed with electrically detachable polymercoated (Nexus, ev3) and fibered (NXT, ev3) coils. The tinnitus resolved immediately after the embolization. The

Inflammation and apoptosis in malignant transformation of sinonasal inverted papilloma: the role of the bridge molecules, cyclooxygenase-2, and nuclear factor κB.

PURPOSE This study examined the early events in the neoplastic progression of the sinonasal inverted papilloma to squamous cell carcinoma from the viewpoint of chronic inflammation and apoptosis. MATERIALS AND METHODS In total, 118 archival slides stained with hematoxylin and eosin from 45 patients were graded according to histopathology (grades I-IV). Their representative portions were transferred to a tissue microarray, sections of which were stained immunohistochemically for cyclooxygenase-2, p53, bax, bcl-2, and nuclear factor κB. RESULTS Cyclooxygenase-2 expression was positively correlated with histopathologic grade, with higher expression in advanced grades. p53s were detected in all cores from advanced grades (III, IV), but not in early grades (I, II). The expressions of nuclear factor κB, bax, and bcl-2 were not correlated with the grade. CONCLUSIONS A p53 mutation seems be a critical event for the malignant transformation of the sinonasal inverted papilloma. Cyclooxygenase-2-mediated inflammatory signals, activated as a consequence of the p53 mutation, may contribute to promoting the proliferation of the advanced sinonasal inverted papilloma.

The importance of vascular endothelial growth factor in the healing of acute tympanic membrane perforation.

PURPOSE The purpose of this study was to determine the more important growth factor expression between basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in the healing of acute tympanic membrane (TM) perforation. MATERIALS AND METHODS Bilateral perforations of the TM were created in 12 rats. The TM perforations in the right ears were treated with dexamethasone, and left ears were designated as the control group. The TM was examined for the growth factor expression immunohistochemically in the epithelial and fibrous layers according to the rate of TM perforation healing. RESULTS The mean spontaneous healing time of the TM perforations was 11.0 +/- 2.0 days. However, dexamethasone-treated group showed no evidence of closure. The bFGF and VEGF expression were significantly correlated with the rate of healing of acute TM perforations. The VEGF expression was decreased both in the epithelial and fibrous layers, but bFGF expression was decreased only in the epithelial layer in the dexamethasone-treated group. The VEGF was expressed to a lesser degree than bFGF in the dexamethasone-treated group. CONCLUSION Vascular endothelial growth factor is the more specific and important growth factor than bFGF in the healing of acute TM perforation.

Analysis of hepatitis B virus in the cerumen and otorrhea of chronic HBV-infected patients: is there a hepatitis B virus infectivity?

The object of this study was to find out whether cerumen and otorrhea have any infectivity in the transmission of hepatitis B virus (HBV). Background: The HBV infection is a worldwide health problem. It can be transmitted by infected blood or other body fluids through percutaneous or permucosal exposure. Recently, there have been some reports where cerumen can be a potential source of HBV transmission. Methods: This study was performed on 30 chronic hepatitis B patients who tested positive in hepatitis B surface antigen (HBs Ag). Thirty cerumen and 5 otorrhea samples were analyzed. The cerumen and the serum were examined for (HBs Ag) and hepatitis B e antigen (HBe Ag) by using enzyme immunoassay systems. As for HBV DNA detection, quantitative polymerase chain reaction was performed on the serum, cerumen, and otorrhea. Results: Hepatitis B virus DNA was detected in the 20 samples of cerumen (66.7%) and all 5 otorrhea (100%) from 30 patients. The mean values of HBV DNA in cerumen and otorrhea were significantly lower than serum. Hepatitis B virus DNA and HBs Ag were detected with significantly higher rates in the cerumen of patients who are serum HBe Ag positive than negative. However, positive HBe Ag, which implies that it is associated with the increased risk of disease progression and infectivity, was not detected in any of cerumen samples. Conclusion: The cerumen and otorrhea of chronic hepatitis B patients have a low risk of infectivity.