Doo Hee Han

Radiosurgery of intracranial cavernous malformations.

Summary. Background: The efficacy of radiosurgery in cases of surgically high risk symptomatic cavernous malformations (CMs) for reducing haemorrhagic risk and for seizure control has not been clearly documented and the radiation-induced complications of radiosurgery remain problematic. The authors present a retrospective clinical analysis of 22 cases of CMs treated by radiosurgery. Methods: Twenty-two patients with symptomatic CMs were treated by linear accelerator (LINAC) radiosurgery or Gamma knife (GK) between 1995 and 1998. Medical records including radiological investigations were carefully reviewed to the last follow-up. The mean age of the patients was 34.1 years (12–56) and the male to female ratio was 12:10. Twenty patients reported at least one episode of bleeding and four had undergone microsurgery before radiosurgery. The remaining two patients presented with seizure without evidence of recent haemorrhage. In 16 cases, the CMs were deep-seated, and the others were located in the cerebral hemispheres; four were located at an eloquent area. LINAC radiosurgery using computed tomography scan was performed in 11 cases until May 1997, after which GK radiosurgery using magnetic resonance (MR) image was performed in 11 cases. The volume of the lesion ranged from 0.09 cc to 4.8 cc (mean 1.42 cc) and the mean marginal dose was 16.1 Gy (8–24). The median follow-up period after radiosurgery was 38.3 months (21–67). The rate of haemorrhage, seizure, and neurological deterioration following radiosurgery was analyzed, and the rate of haemorrhage was compared to that seen in natural course reports. Findings: There was one case of haemorrhage during the follow-up period and the seizure was well controlled with anticonvulsants. In the group with prior haemorrhage, the bleeding rate of cavernous malformation after radiosurgery (1.55%/year) was lower than that of pre-radiosurgical period (35.5%/year, t=1.296, P=0.04). Six patients showed neurological deterioration following radiosurgery, however, the neurological deficits persisted in only two of the patients with LINAC. The radiosurgical modality (LINAC vs. GK) showed a possible correlation to radiation induced neurological deficits (P=0.06). On the MR images at the last follow-up, the lesion was decreased in eleven patients, increased in one, and no change was found in 10 cases. The T2 weighted MR images revealed a perilesional high signal change in nine patients. This signal change was not statistically related to lesion size (P=0.236), location (P=0.658), nor radiation dose (P=0.363), but was dependent on the treatment modality (P=0.02). New-enhancing lesion and a new cyst were each found in one case, respectively, during the follow-up. Interpretation: Radiosurgery may be a good alternative option for treatment of surgically high risk CMs. However, the optimal radiosurgical technique, dose adjustment, and proper delineation of the mass are prerequisites. Radiosurgery induced complications are still problematic and post-radiosurgery MR image changes need to be further elucidated.

Hypoxia-inducible Factor 1 Mediates Nasal Polypogenesis by Inducing Epithelial-to-Mesenchymal Transition

RATIONALE Nasal polyposis implies a refractory clinical course in case of chronic rhinosinusitis (CRS). Although hypoxia is believed to be associated with nasal polyposis, little is known about the mechanism underlying polypogenesis. OBJECTIVES To determine if hypoxia drives nasal polyposis by epithelial-to-mesenchymal transition (EMT). METHODS Immunoblotting, immunofluorescence, flow cytometry, and real-time polymerase chain reaction were performed to evaluate EMT and hypoxic markers in human nasal epithelial cells (hNECs) and in sinonasal tissues from patients with CRS with or without polyps. In addition, the effects of hypoxia-inducible factor (HIF)-1α inhibitors on nasal polypogenesis were investigated in a murine model. MEASUREMENTS AND MAIN RESULTS E-cadherin and α-smooth muscle actin (α-SMA) were down-regulated and up-regulated, respectively, in patients with polyps as compared with patients without polyps. Under hypoxia, hNECs transformed to a mesenchymal shape, and demonstrated representative changes in EMT markers; that is, mesenchymal markers (α-SMA, vimentin, and twist) increased but epithelial markers (E-cadherin and β-catenin) decreased. Mechanistically, E-cadherin level was recovered in hypoxia by silencing HIF-1α and decreased in normoxia by expressing HIF-1α. Furthermore, hypoxia was found to down-regulate PP2Ac phosphatase and up-regulate pSmad3, which led to α-SMA induction. In CRS sinonasal specimens, HIF-1α expression was found to correlate with E-cadherin loss and α-SMA expression. Finally, HIF-1α inhibitors suppressed nasal polypogenesis in a murine model. CONCLUSIONS hNECs undergo EMT during hypoxia and this process is critically mediated by HIF-1α and pSmad3. This study shows that hypoxia-induced EMT is likely to contribute to nasal polyposis in CRS, and suggests that HIF-1α be viewed as a therapeutic target for nasal polyposis.

Early Compliance and Efficacy of Sublingual Immunotherapy in Patients with Allergic Rhinitis for House Dust Mites

Objectives Sublingual immunotherapy (SLIT) has recently received much attention around the world as a treatment for allergic rhinitis. This study aimed to investigate the efficacy and adverse effects of SLIT in Korean patients with allergic rhinitis caused by house dust mites. The treatment compliance and the patient satisfaction with SLIT were also assessed. Methods The patients who were sensitized to Dermatophagoides pteronyssinus and Dermatophagoides farinae and who started SLIT between November 2007 and July 2008 were included in this study. The symptom questionnaires, which included items on rhinorrhea, sneezing, nasal obstruction, itchy nose, olfactory disturbance, eye discomfort and sleep disturbance, were obtained before and 6 months after SLIT. The patient satisfaction and the adverse effects were also investigated. Results One hundred forty-two patients started SLIT and 98 of them continued SLIT for 6 months or more. Ninety-two of the 98 patients completed the questionnaires. The duration of receiving SLIT was 9.8 months on average (range, 6 to 13 months). All the symptoms of allergic rhinitis were improved with SLIT. Forty-five percent of the patients were satisfied for SLIT, while 12% were unsatisfied. The incidence of adverse effects was 12% during maintenance therapy, although it was 48% during the up-dosing phase. The drop-out rate of SLIT was 31.0%. Conclusion The subjective symptoms were improved with SLIT in Korean patients with allergic rhinitis for house dust mites. Yet the drop out rate was high despite of the symptomatic improvement.

Clinical and immunologic effects of sublingual immunotherapy on patients with allergic rhinitis to house-dust mites: 1-Year follow-up results

Background There have been no data on sublingual immunotherapy (SLIT) in Asian patients with allergic rhinitis (AR) sensitized to house-dust mites (HDMs). This study aimed to investigate the efficacy and immunologic change after 12 months of SLIT in Korean patients. Methods Fifty-eight patients, who had AR caused by Dermatophagoides pteronyssinus and Dermatophagoides farinae and who completed 12 months of SLIT were included. Symptom scores were evaluated before and after 12 months of SLIT, and medication scores were assessed throughout the study. Peripheral blood eosinophil counts, eosinophil cationic protein (ECP), total IgE, and specific IgE were also evaluated. Results All of the symptoms of AR were significantly improved with reduced medication scores. In addition, there were significant decrements in peripheral blood eosinophil counts and ECP (p = 0.025 and p = 0.048, respectively). Specific IgE for D. farinae slightly increased (p = 0.019), whereas specific IgE for D. pteronyssinus and total IgE did not change significantly. Thirty-six (62%) of 58 patients were in the effective response group. Although not statistically significant, findings in the study showed that the effective response group had a tendency to have higher ECP levels before SLIT than the ineffective response group (p = 0.056). Conclusion SLIT improved the symptoms and medication scores in Korean patients with AR from HDM. Laboratory parameters including eosinophil counts, ECP, and specific IgE for D. farinae seemed to be modified after 1-year SLIT. A high ECP level may be a useful parameter to predict the effectiveness of SLIT and select the patient for the treatment.

Contribution of interleukin 17A to the development and regulation of allergic inflammation in a murine allergic rhinitis model

BACKGROUND Interleukin (IL) 17A, a key cytokine of T(H)17 cells, is a well-known proinflammatory cytokine. Despite the important role of T(H)17 cells in acute airway inflammation, the role of IL-17A in allergic rhinitis (AR) remains unclear. OBJECTIVE To investigate the role of IL-17A in the allergic response in AR. METHODS Wild-type BALB/c and IL-17A-deficient mice were immunized intraperitoneally and were challenged intranasally with ovalbumin. Allergic symptom scores, eosinophil infiltration, serum IgE level, and the levels of several cytokines in nasal lavage fluid and splenocyte supernatants were analyzed. RESULTS IL-17A levels increased significantly more in ovalbumin-sensitized wild-type mice than in the negative control group. IL-17A-deficient mice showed a significant decrease in allergic symptoms, serum IgE levels, and eosinophil infiltration into the nasal mucosa compared with wild-type mice. IL-17A-deficient mice also showed decreased histamine and cysteinyl leukotriene release. Bone marrow-derived mast cells from IL-17A-deficient mice showed significantly lower degranulation and secretion of tumor necrosis factor α. Moreover, IL-17A deficiency attenuated the IL-5 level in nasal lavage fluid and its production in response to ovalbumin but did not increase interferon γ production and its level in nasal lavage fluid. In addition, secretion of IL-17A from spleen cells induced the expression of proinflammatory cytokine messenger RNA in macrophages. The mean level of proinflammatory cytokines, including tumor necrosis factor α and IL-17, decreased in IL-17A-deficient mice. CONCLUSION These results suggest that IL-17A may partly contribute to the development of nasal allergic inflammation in an AR animal model and regulate AR via the activation of proinflammatory cytokines and modulation of T(H)2 cytokine.

Sleep Magnetic Resonance Imaging as a New Diagnostic Method in Obstructive Sleep Apnea Syndrome

Although precise localization of obstruction sites in the upper airway during sleep is essential in subjects with obstructive sleep apnea syndrome (OSAS), no gold standard diagnostic method has been established. This study aimed to evaluate the dynamic collapse inside the upper airway by using cine magnetic resonance imaging (MRI), also called sleep MRI.

Endoscopic Versus Traditional Craniofacial Resection for Patients with Sinonasal Tumors Involving the Anterior Skull Base

Objectives With the advent of microdebriders and image guidance systems, endoscope-assisted surgery is now more widely used for the treatment of tumors involving the base of the skull. The aim of this study was to analyze the clinical features of tumors involving the anterior skull base and to evaluate the treatment outcomes according to the surgical approach, which included the traditional craniofacial resection (TCFR) and the endoscopic craniofacial resection with craniotomy (ECFR). Methods Forty-six patients who underwent craniofacial resection from 1989 through 2006 at Seoul National University Hospital and Seoul National University Bundang Hospital were included in this study. Demographics, histology, surgical management, surgical outcomes, complications, and morbidity were analyzed. Results The number of malignant and benign lesions was 40 and 6 cases respectively. The most common diagnosis was olfactory neuroblastoma occurring in 41% of the cases followed by squamous cell carcinoma and malignant melanoma. Thirty-six patients underwent TCFR, while ECFR was performed with or without adjunctive chemotherapy or radiotherapy in 10 patients. The overall five-year survival rate for patients with malignant tumors of the anterior skull base was 47.4%. Out of 19 patients with olfactory neuroblastomas, 10 patients had TCFR and six among them died of their disease. Nine patients underwent ECFR, and none of them died of their disease. The ECFR group had lower morbidity and cosmetic deformity than did the TCFR group. Conclusion The ECFR may be considered as an alternative option for the treatment of selected tumors with anterior skull base invasion. This approach offers the advantages of avoiding facial incisions with comparable treatment results.

No packing versus packing after endoscopic sinus surgery: pursuit of patients' comfort after surgery.

Background This study was designed to evaluate the necessity of postoperative nasal packing and to find factors relevant in determining if nasal packing was required after endoscopic sinus surgery (ESS). Methods From January 2007 through June 2007, 64 consecutive patients who underwent ESS were evaluated. The decision whether or not to perform nasal packing depended on the surgeons judgment of the bleeding after surgery. Demographic characteristics, medical history, disease extent, surgical procedures, and subjective and objective amount of intraoperative bleeding were analyzed. Postoperative symptoms and endoscopic findings were evaluated also. Results Forty-eight (75%) of the 64 patients included in this study did not have nasal packing after ESS. One patient from the no-packing group needed nasal packing postoperatively because of persistent nasal bleeding. Symptom scores of nasal obstruction and postnasal drip on the 1st postoperative day were lower in the no-packing group. In unilateral ESS cases, subjectively estimated blood loss and mucosal inflammation scores were lower in the no-packing group. It was observed that preoperative steroid use was more frequent in the packing group. All other parameters did not show significant differences between the two groups. Conclusion Nasal packing can be safely used less frequently to help the patients experience less discomfort after ESS. The need for nasal packing after ESS can be decided by judicious estimation of bleeding during and after the surgery.

Variability of offending allergens of allergic rhinitis according to age: optimization of skin prick test allergens.

Purpose This study evaluates offending allergens in patients with allergic rhinitis (AR) according to age that establish a minimal panel for skin prick test (SPT) allergens required to identify if a patient is sensitized. Methods We retrospectively analyzed SPT results according to age to determine the minimum test battery panel necessary to screen at least 93%-95% of AR patients. Allergic skin tests (common airborne indoor and outdoor allergens) were performed on 7,182 patients from January 2007 to June 2011. All patients were classified into 9 groups according to age; subsequently, we investigated offending allergens by age group. Results A total of 5,032 (70.1%) patients were found sensitized to at least one of the 55 aeroallergen extracts tested. The annual ranking of offending allergens was not significantly different from each other over the past 5 years. House dust mites (HDM) were the most prevalent allergens ranked from first to third for all 5 years. The allergens in the minimum test panel differed slightly among all age groups; in addition, the types of sensitized allergen sources were more diverse in the older versus younger age group. HDM covered a larger proportion of the sensitized allergens in the younger age group versus the older age group. Testing with 5 allergens (Dermatophagoides farinae, Tetranychus urticae, oak, mugwort and cockroach) adequately identified over 90% of the sensitized patients. Conclusions A SPT with around 5-7 allergens adequately detected most of the sensitization in the majority of the age groups in Korea. However, this study suggests that physicians perform the SPT with appropriately selected allergens in each age category for the screening of AR.

Efficacy of sublingual immunotherapy with house dust mite extract in polyallergen sensitized patients with allergic rhinitis

BACKGROUND It is suggested that polysensitized patients might not benefit from specific allergic rhinitis immunotherapy as much as monosensitized patients, although further research on this subject is needed. OBJECTIVE To compare the efficacy of sublingual immunotherapy (SLIT) with standardized house dust mite extract in monosensitized and polysensitized patients with allergic rhinitis. METHODS Patients who were sensitized to house dust mites and treated with SLIT for house dust mites for at least 1 year between November 2007 and March 2010 were studied. The monoallergen sensitized group was defined as patients who were sensitized to Dermatophagoides pteronyssinus and/or Dermatophagoides farinae (n = 70). The polyallergen sensitized group was defined as patients who were simultaneously sensitized to house dust mites and other allergens (n = 64). A standardized extract of house dust mites was used for immunotherapy. Antiallergic medication and the total nasal symptom score (TNSS), including rhinorrhea, sneezing, nasal obstruction, and itchy nose, were evaluated before and 1 year after SLIT. RESULTS This study enrolled 134 patients. The TNSS improved significantly after SLIT in both groups, whereas the change in the TNSS did not differ significantly between the groups. The antiallergic medication scores also decreased significantly in both groups, but there was no significant difference between the groups. CONCLUSIONS In polysensitized allergic rhinitis patients, SLIT for D pteronyssinus and/or D farinae produced improvements in both nasal symptoms and rescue medication scores comparable to those in monosensitized patients, regardless of other positive allergens. SLIT for D pteronyssinus and/or D farinae should be considered in polysensitized allergic rhinitis patients.