Clinical Trial to Reconfirm the Efficacy and Safety of Cefetamet Pivoxil Treatment in Sinusitis Patients: A Double-Blind, Randomized, Parallel Designed, Multicenter, Active Comparator Study (CASIS Study).

OBJECTIVE: To evaluate the clinical efficacy and safety of cefetamet pivoxil for the treatment of acute bacterial rhinosinusitis in Korean patients compared to treatment with cefdinir. METHODS: A prospective, multicenter, randomized double-blind, comparative study was conducted by the Departments of Otorhinolaryngology-Head and Neck Surgery at 17 hospitals or universities in the Republic of Korea from March 2017 to April 2019. A total of 309 patients were screened and 249 patients participated in the study. RESULTS: Treatment with cefetamet pivoxil for 2 weeks showed 82.4% clinical cure and improvement rates in patients with acute bacterial rhinosinusitis compared to 84.68% in those taking cefdinir for 2 weeks, showing that cefetamet pivoxil administered twice a day for 2 weeks was as effective as cefdinir 3 times a day for 2 weeks for the treatment of acute bacterial rhinosinusitis. The overall adverse reaction rates of both drugs were 10.56% in the cefetamet pivoxil group and 15.49% in the cefdinir group, without serious adverse events or drug reactions. CONCLUSIONS: Cefetamet pivoxil twice a day was as efficacious and safe as cefdinir 3 times a day for the treatment of acute bacterial rhinosinusitis, which suggested that cefetamet pivoxil may be a suitable alternative to cefdinir.

Expression of Estrogen Receptor-alpha in Nasal Polyps and the Effects of Dexamethasone on Estrogen Receptor-alpha Expression in RPMI 2650 Cells.

BACKGROUND: Studies have reported that epithelial cell proliferation may be involved in the pathogenesis of nasal polyps (NPs). Estrogen receptor (ER)-α, one type of ER, is related to anti-inflammatory action and cell survival in certain tissues. In this study, we examined the presence or absence of ER-α in NPs and healthy inferior turbinate mucosae. We also investigated the effect of dexamethasone on ER-α expression, cell viability, and apoptosis in RPMI 2650 cells. METHODS: Immunohistochemical staining and Western blot analysis were conducted to determine the expression of ER-α in 15 NPs and 15 healthy inferior turbinate mucosae. After treating RPMI 2650 cells with dexamethasone, ER-α expression was analyzed using Western blot analysis and cell viability was determined using the MTT assay. Western blot analysis and annexin V-phycoerythrin (PE) staining were used to examine apoptotic cell death. RESULTS: Western blot analysis showed that ER-α expression was upregulated in 13 of the 15 NP tissues. Immunohistochemical staining for ER-α confirmed the results of the Western blot analysis. When RPMI 2650 cells were treated with dexamethasone, both ER-α expression and cell viability were decreased. Furthermore, the treatment of RPMI 2650 cells with dexamethasone increased apoptotic cell death, as shown by increased levels of BAX and cleaved caspase-3, decreased levels of Bcl-2, and an increased percentage of positive annexin V-PE stained cells. CONCLUSION: ER-α expression was higher in NPs than in healthy inferior turbinate mucosae. When RPMI 2650 cells were treated with dexamethasone, ER-α expression was downregulated, cell viability decreased, and apoptosis increased. The decreased cell viability may be related, at least in part, to the decreased ER-α protein levels, which likely contributed to the induction of apoptotic cell death in RPMI 2650 cells.

Clinicopathological and Radiological Features of Chronic Rhinosinusitis with Eosinophilic Mucin in Chungcheong Province of Korea.

BACKGROUND: Chronic rhinosinusitis (CRS) with eosinophilic mucin is considered rare in Korea. The object of this study was to categorize CRS patients with eosinophilic mucin into several groups and compared the groups based on their clinicopathological and radiological features. METHODS: In total, 105 CRS patients with eosinophilic mucin from four tertiary medical centers which are located at Chungcheong province of Korea were included for this study. The patients were divided into four groups for analysis, based on the presence or absence of an allergy (A) to a fungus or fungal element (F) in the mucin. The following were the four groups: allergic fungal rhinosinusitis (AFRS, A+F+), AFRS-like sinusitis (A+F-), eosinophilic fungal rhinosinusitis (EFRS, A-F+), and eosinophilic mucin rhinosinusitis (EMRS, A-F-). Their clinical manifestation, the presence of associated disease, radiological finding, treatment, and treatment outcome were reviewed and compared. RESULTS: There were no patients in the AFRS-like sinusitis group, 47 patients were assigned to the AFRS group, 27 to the EFRS group, and 41 to the EMRS group. Patients of AFRS group showed a significantly higher association with allergic rhinitis than did the other groups. The mean total serum IgE level in the AFRS patients was significantly higher than in the EFRS and EMRS patients. In the AFRS group and EFRS group, 67.6% and 74.1% had unilateral disease, respectively, in contrast to the EMRS group (4.9%). The mean Hounsfield unit values of the area of high attenuation in the AFRS patients were significantly higher than those in the other groups. CONCLUSIONS: Significant clinicopathological differences existed among the subgroups of CRS with eosinophilic mucin. AFRS tends to be an allergic response to colonizing fungi in atopic individuals. In EFRS, local allergies to fungi might play a role in the disease. EMRS is thought to be unconnected with fungal allergies, and it showed different form compared with the AFRS and EFRS groups.

Bony Changes in a Unilateral Maxillary Sinus Fungal Ball.

OBJECTIVES: In the paranasal sinus fungal ball (SFB), changes that occur in the underlying bone have not been well described. Recently, bacterial coinfection has been reported in patients with paranasal SFB. We evaluated whether bone changes occur in patients with unilateral maxillary SFB, and also how bacteria in an SFB affect the bony wall of the sinus. METHODS: A retrospective study of patients with a unilateral maxillary SFB undergoing endoscopic sinus surgery was conducted from July 2009 to December 2015. Preoperative computed tomography images of the patients were reviewed. Wall thickness (WT) and wall density (WD) of the diseased sinus were measured and compared to the normal sinus. Specimens of the sinus aspirates were obtained during surgery for aerobic and anaerobic cultures. RESULTS: Forty-three patients were included (mean, 55.7 ±â€Š12.8 years). Thirty-one cultures (72.1%) were positive for bacteria. Thickening was evident in the anterior, lateral, and posterior walls of the diseased sinus. The average WT was 1.69 ±â€Š0.45 mm on the diseased sinus and 1.14 ±â€Š0.31 mm on the normal sinus (P < 0.001). In the diseased sinus, the difference in the average WT between the culture-positive and culture-negative groups was not significant (P = 0.44). The average WD on the diseased sinus was higher than that on the normal sinus (P < 0.001). CONCLUSIONS: Osteitic change occurred in most patients with a unilateral maxillary SFB. The presence of bacteria in sinus secretions does not greatly affect the development of osteitic changes in unilateral maxillary SFB.

Superior Branch Palsy of the Oculomotor Nerve Caused by Frontal Sinusitis.

Chronic rhinosinusitis is one of the most common inflammatory diseases with a significant impact on the affected patients. Orbital complications, one of the emergent complications of chronic rhinosinusitis, can be occurred in frontal sinusitis. For early diagnosis and therapy of orbital complications, proper evaluation is essential to prevent loss of vision.Recently, the authors diagnose and treat completely a 60-year-old man with isolated unilateral superior branch palsy of the oculomotor nerve caused by frontal sinusitis. Four days after draining the frontal sinusitis, the patient recovered fully from superior branch palsy of the oculomotor nerve. Frontal sinusitis can cause isolated superior branch palsy of the oculomotor nerve in patients with a history of facial trauma.

Nickel(II)-induced nasal epithelial toxicity and oxidative mitochondrial damage.

In probing the underlying mechanisms of nickel(II)-induced cytotoxicity on nasal epithelium, we investigated the effects of nickel(II) acetate on nasal epithelial RPMI-2650 cells. Nickel(II) elicited apoptosis, as signified by pyknotic and fragmented nuclei, increased caspase-3/7 activity, and an increase in annexin V binding, hypodiploid DNA, and Bax/Bcl-2 protein ratio. Nickel(II)-induced G2/M arrest was associated with up-regulation of p21(WAF1/CIP1) expression, decrease in phosphorylation at Thr(161) of Cdc2, and down-regulation of cyclin B1. Associated with these responses, ROS generation and mitochondrial depolarization increased in a nickel(II) concentration-dependent fashion. Pretreatment with N-acetylcysteine (NAC) attenuated these changes. p53 reporter gene assay and analyses of p53, Puma, Bax, and Bcl-2 protein levels indicated that NAC inhibited nickel(II)-induced activation of p53-mediated mitochondrial apoptotic pathway. Collectively, our study provides evidences that nickel(II) may induce oxidative damage on nasal epithelium in which antioxidant NAC protects cells against nickel(II)-induced apoptosis through the prevention of oxidative stress-mediated mitochondrial damage.

Cellular proliferation and angiogenesis in nasal polyps of young adult and geriatric patients.

BACKGROUND: Cellular proliferation and angiogenesis are associated with pathophysiology of nasal polyposis (NP). In a previous report, we showed that patient age is a predictive factor of surgical outcomes among patients with chronic rhinosinusitis and NP, and that geriatric patients exhibit better outcomes than pediatric and adult patients. We postulated that better outcomes in the geriatric population may be secondary to decreased proliferation and angiogenesis within polyps. Therefore, we evaluated the cellular proliferation and angiogenesis in young adult and geriatric patients with NP. This was a prospective case-control study. METHODS: Twenty patients were divided into 2 groups according to age (20 to 30 years vs ≥65 years of age). NP tissues were sampled during endoscopic sinus surgery and processed for immunohistochemistry. Cellular proliferation was evaluated with proliferating cell nuclear antigen and Ki67, and angiogenesis was assessed with vascular endothelial growth factor. We also compared objective surgical outcomes using endoscopy scores. RESULTS: Immunohistochemical analysis revealed significantly higher expression and positive reactivity of proliferating cell nuclear antigen and Ki67 in the polyps of young adults than in those of geriatric patients, whereas the expression of vascular endothelial growth factor was similar between the 2 groups. Endoscopy scores were better in the geriatric group. CONCLUSION: Geriatric patients have a lower cellular proliferative ability than young adults, and angiogenesis does not significantly differ between the 2 age groups. Cellular proliferation seems to be the cause of the different surgical outcomes between the 2 age groups, whereas angiogenesis has no significant influence on the postoperative course.

Long-term efficacy of inferior meatal antrostomy for treatment of postoperative maxillary mucoceles.

PURPOSE: Transnasal endoscopic marsupialization has replaced the conventional Caldwell-Luc operation for managing postoperative maxillary mucoceles. Inferior meatal antrostomy (IMA) may be an easier and more effective method than middle meatal antrostomy (MMA) because of anatomical and structural changes of the maxillary sinus. We evaluated the long-term efficacy and technical simplicity of both methods. METHODS: This study included 21 and 32 patients who underwent MMA and IMA, respectively. They were diagnosed with a unilateral postoperative maxillary mucocele, and medical records were reviewed for history, clinical presentation, radiographic findings, surgical intervention, complications, and outcomes. During follow-up, the size of the opening and stenosis or obstruction of the antrostomy site were evaluated. RESULTS: Preoperative symptoms and mean follow-up period were similar in both groups. All patients in the IMA group received the operation as planned, whereas in four MMA patients, the attempt to create an opening failed because of thick bones and anatomical changes from the previous operation; in these patients, IMA was performed. The opening remained large enough for ventilation and drainage between the mucocele and the nasal cavity in both groups. There were no major complications, such as profuse bleeding, wound infection, or orbital or nasolacrimal duct injury. CONCLUSIONS: Although both surgical procedures seem to be effective for managing postoperative maxillary mucoceles, IMA is easier to perform, and no instances of failure to create antrostomy openings occurred. We recommend IMA as the surgical technique of choice, but providing an opening of sufficient size is necessary to ensure long-term efficacy.

Overexpression of angiomotin in sinonasal inverted papilloma.

BACKGROUND: Although inverted papilloma (IP) is one of the most common sinonasal tumors, its etiology and factors associated with tumor progression have not been fully determined. Generally, tumorigenesis or tumor growth requires angiogenesis to feed tumor cells. Angiomotin is a recently discovered protein that regulates migration and tubule formation in endothelial cells. It has been reported that angiomotin affects angiostatin (circulating inhibitor of angiogenesis), resulting in promotion of angiogenesis. Thus, we evaluated the expression and distribution of angiomotin in sinonasal IP, compared to normal control tissue. METHODS: The study included 10 subjects with sinonasal IP and 5 normal controls. Ethmoid sinus mucosa obtained during reduction of blowout fractures was used as a normal control. Reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, immunohistochemistry, and Western blot analysis were used to assess the expression, intensity, and distribution of angiomotin in tissues. RESULTS: Positive bands for angiomotin were seen in all specimens by RT-PCR. The expression level of angiomotin was significantly upregulated in IP tissues versus normal sinus mucosa by real-time PCR. Immunohistochemistry revealed positive reactions on endothelial cells of capillaries and small vessels within the tumor and normal tissues, but the positivity was significantly stronger in IP. Western blot analysis showed that expression levels of angiomotin were increased in IP compared to normal sinus mucosa. CONCLUSION: Angiomotin, a novel protein in angiogenesis, was overexpressed in IP. Although it is not an etiological or initiating factor in tumor development, it seems to be associated with progression and growth of IP via promoting angiogenesis.

Effect of cold-water cooling of tonsillar fossa and pharyngeal mucosa on post-tonsillectomy pain.

PURPOSE: Post-tonsillectomy pain is a notable concern and thermal injury produced by electric surgical devices is considered a main cause. Intraoperative cooling of the tonsillar fossa and pharyngeal mucosa with cold water has effectively reduced postoperative pain, but no studies have fully evaluated the effects of this technique with a proper study design. We assessed mucosal cooling in two groups of patients undergoing the same surgical technique by a single surgeon, with one group receiving cold-water cooling and the other group as a control. METHODS: Forty patients who underwent monopolar electrocautery tonsillectomy were randomly assigned to two groups (n = 20 for each group). Group 1 received cooling of the tonsillar fossa and pharyngeal mucosa with 4 °C saline just after removal of each tonsil whereas Group 2 did not receive cooling. Postoperative pain was recorded on operation day and 1, 2, 4, 7, and 10 days postoperatively. Post-tonsillectomy pain, return to normal diet, and incidence of postoperative bleeding were compared between the groups. RESULTS: Post-tonsillectomy pain on 6 selected days and overall pain during the 10-day follow-up period were significantly lower in Group 1. However, return to normal diet and incidence of postoperative bleeding did not differ significantly between the groups. CONCLUSIONS: Intraoperative application of cold water after tonsillectomy significantly reduced postoperative pain. We recommend cooling the tonsillar fossa and pharyngeal mucosa with cold water during tonsillectomy to easily and effectively reduce post-tonsillectomy pain.

Effect of prostaglandin e2 on vascular endothelial growth factor production in nasal polyp fibroblasts.

PURPOSE: Angiogenesis is involved in the pathogenesis of chronic rhinosinusitis with nasal polyps. We aimed to investigate the effects of prostaglandin E2 (PGE2) on vascular endothelial growth factor (VEGF) production, the role of E-prostanoid (EP) 4 receptors, and the signal transduction pathway mediating VEGF production in nasal polyp-derived fibroblasts (NPDFs). METHODS: Eight primary NPDF cultures were established from nasal polyps, which were incubated with or without PGE2. Reverse transcription-polymerase chain reaction amplification of EP receptors (EP1, EP2, EP3, and EP4) and immunofluorescence staining for VEGF production were performed. VEGF production via the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) and phosphatidylinositol 3-kinase (PI3K) pathways was evaluated by enzyme-linked immunosorbent assay. RESULTS: All EP receptors were expressed in NPDFs. PGE2 significantly increased VEGF production concentration- and time dependently, and VEGF production was regulated by an EP4 receptor. Activation of intracellular cAMP regulated VEGF production. VEGF production was decreased by PKA and PI3K inhibitors via intracellular cAMP. CONCLUSIONS: PGE2 stimulates VEGF production via the EP4 receptor in NPDFs. These results indicate that PGE2-induced VEGF production is mediated, at least partially, through cAMP-dependent signaling pathways. Therapies targeting the EP4 receptor may be effective in inhibiting the development of nasal polyps.

Atypical primary meningioma in the nasal septum with malignant transformation and distant metastasis.

BACKGROUND: Primary extracranial meningiomas (PEMs) originating from the nasal septum are extremely rare, as are extracranial metastases of meningiomas. CASE PRESENTATION: A 44-year-old male presented with a 2-month history of left-side nasal obstruction and frequent episodes of epistaxis. A friable mass originating from the nasal septum was resected completely via an endoscopic endonasal approach. According to WHO criteria, the tumor was diagnosed as an atypical meningioma radiologically and histopathologically. Two years later, a tumor recurred at the primary site with the same histopathological findings, and the patient was given local external radiotherapy (6840 cGy in 38 fractions). Two months after this local recurrence, a left anterior chest wall mass and a left parietal area scalp mass were observed. The subcutaneous mass was resected and showed histological evidence of malignant transformation. Several months after the last operation, the patient died. CONCLUSIONS: We describe the clinical, radiological, and bio-pathological features of this unique case and review the literature on atypical PEMs originating in the nasal septum. To our knowledge, this is the first reported case of an atypical PEM originating from the nasal septum that recurred with malignant transformation and extracranial metastasis.

Surgical results of endoscopic dacryocystorhinostomy and lacrimal trephination in distal or common canalicular obstruction.

OBJECTIVES: To evaluate the surgical outcomes of endoscopic dacryocystorhinostomy followed by canalicular trephination and silicone stenting in patients with distal or common canalicular obstructions. METHODS: The medical records of 29 patients (31 eyes) from January 2001 to December 2009 who underwent endoscopic dacryocystorhinostomy followed by canalicular trephination and silicone tube insertion for the treatment of distal or common canalicular obstructions were retrospectively reviewed. The level of obstruction was confirmed by intraoperative probing. The outcome of the surgery was categorized as a complete success, partial success, or failure according to the functional and anatomic patency. RESULTS: The average age of the patients was 52 years. The duration of silicone intubation ranged from 4 to 11 months with an average of 5.7±1.6 months. The follow-up period after stent removal ranged from 4 to 15 months with an average of 8.2±3.3 months. Complete success was achieved in 25 out of 31 eyes (80.6%), partial success in 4 out of 31 eyes (12.9%), and failure in 2 out of 31 eyes (6.5%). CONCLUSION: Endoscopic dacryocystorhinostomy followed by canalicular trephination and silicone stent intubation may be safe and considered as an initial treatment of patients with distal or common canalicular obstructions.

The inhibitory effect of honokiol, a natural plant product, on vestibular schwannoma cells.

OBJECTIVES/HYPOTHESIS: As the molecular biology of vestibular schwannoma (VS) is better understood, new means of targeting the pathways involved for intervention in schwannoma cells are being developed. Honokiol, a bioactive constituent of Magnolia officinalis, has attracted attention due to its diverse biological effects. This study was conducted to determine the inhibitory effect of honokiol on schwannoma cell proliferation. METHODS: HEI 193 cells were used to investigate the growth-inhibitory effects of honokiol. Cell proliferation was assessed by MTT assays. Apoptosis was measured by flow cytometry analysis and immunofluorescence staining including Hoechst 33342 and TUNEL. Western blot analysis was used to assess the potential inhibition of extracellular signal-regulated kinase (ERK) and AKT signaling by honokiol. RESULTS: Honokiol exhibited significant antiproliferative activity in a dose-dependent manner on HEI 193 cells. Significant apoptosis was detected on schwannoma cells with 7 mg/mL(IC50) honokiol. Western blot analysis showed significant inhibition of ERK phosphorylation. CONCLUSIONS: Honokiol, a low molecular weight natural product, inhibits cell proliferation and promotes apoptosis in schwannoma cells by targeting the ERK pathway. Our data suggest that honokiol can be evaluated as a chemotherapeutic agent for VS.

Cadmium-induced up-regulation of aldo-keto reductase 1C3 expression in human nasal septum carcinoma RPMI-2650 cells: Involvement of reactive oxygen species and phosphatidylinositol 3-kinase/Akt.

Cadmium is a well-known toxic metal and occupational exposure to it is associated with lung cancer. In probing the possible non-genotoxic molecular targets of cadmium-induced nasal toxicity, we performed an mRNA differential display analysis for cadmium-treated human nasal septum carcinoma RPMI-2650 cells. Cadmium (≥ 0.5 µM) inhibited the cell proliferation. The intracellular ROS levels were induced by cadmium treatment. In addition, cadmium elicited the AKR1C3 expression. The cadmium-induced increase in AKR1C3 protein levels was suppressed by N-acetylcysteine (NAC) and, to a lesser extent, PI3K inhibitor (Ly294002). Cells pretreated with Ly294002 were more resistant to cadmium toxicity than control. The increase in AKR1C3 protein level was accompanied by an increase in the nuclear transcription factor Nrf2. Overall, our data suggest that cadmium-induced ROS cause up-regulation of AKR1C3 expression, at least partially via the activation of PI3K-related intracellular signaling pathways, and Nrf2 activation, thereby contributing to an adaptive intracellular response to cadmium toxicity.

Changes in the maxillary sinus volume and the surgical outcome after the canine fossa puncture approach in pediatric patients with an antrochoanal polyp: results of a minimum 3-year follow-up.

BACKGROUND: An antrochoanal polyp (ACP) originates from the maxillary antrum and simple excision results in high recurrence rates. Canine fossa puncture (CFP) has been proposed as an alternative method of accessing the entire maxillary antrum. To investigate the long-term effects of the CFP approach on changes in the maxillary sinus volume in pediatric patients with an ACP, we compared the sinus volume on the operated and normal sides, using preoperative computed tomography (CT), and postoperative CT performed at least 3 years after the procedure. The surgical outcomes were also assessed using endoscopic and CT findings. METHODS: Seven patients met the inclusion criteria and the ACP was removed via the CFP approach. After a mean follow-up period of 43.9 months, we compared the changes in the maxillary sinus volume between the operated and normal sides, using the pre- and postoperative CT data. RESULTS: No contractures or decrease in the maxillary sinus volume on the diseased side were observed in any of the patients on postoperative CT, and the average volume of both maxillary sinuses was greater on postoperative CT compared with the preoperative scans. None of the patients showed evidence of recurrence on the endoscopic and CT examinations. CONCLUSION: CFP did not affect the maxillary sinus volume in pediatric patients with an ACP and led to a successful surgical outcome in all of the patients. Based on these results, we recommend CFP as a safe, effective method for the treatment of ACP.

Comparison of Conventional Excision via a Sublabial Approach and Transnasal Marsupialization for the Treatment of Nasolabial Cysts: A Prospective Randomized Study.

OBJECTIVES: Surgical excision via a sublabial approach is considered the standard treatment for nasolabial cysts. Although transnasal marsupialization has been proposed as an alternative method, no prospective study has compared the effectiveness of these techniques. We thus compared the surgical procedure, operating time, postoperative pain, complications, and recurrence rate between the two surgical methods. METHODS: Twenty patients diagnosed with nasolabial cysts were allocated randomly into two groups according to the surgical technique. In the sublabial approach group, the cysts were excised completely using a sublabial approach, while in the transnasal marsupialization group, the cysts were marsupialized transnasally under the guidance of nasal endoscopes. The pure operating time was measured and postoperative pain was evaluated using a visual analog scale. Complications after the procedure were assessed and recurrence was determined according to the clinical symptoms and postoperative radiologic findings. RESULTS: The transnasal marsupialization group had significantly shorter operating times, less postoperative pain, lower complication rates, and shorter duration of side effects than the sublabial approach group. No recurrence occurred in either group after a 1-yr follow-up period. CONCLUSION: Although both methods are effective for treating nasolabial cysts, the transnasal marsupialization of nasolabial cysts has many benefits over the conventional sublabial approach. Therefore, we propose that transnasal marsupialization be the treatment of choice for nasolabial cysts.