The role of local ablative therapy in patients with advanced invasive mucinous adenocarcinoma of the lung.

PURPOSE: Invasive mucinous adenocarcinoma (IMA) of the lungs is a rare subtype of lung adenocarcinoma with a limited understanding of its prognosis, particularly in advanced stages. This study aimed to assess the prognosis of patients with advanced IMA by focusing on treatment modalities. METHODS: This single-center retrospective study evaluated 33 patients with IMAs diagnosed with advanced-stage disease or disease progression after curative treatment between 2011 and 2021. The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS). OS and PFS were calculated from the date of the diagnosis of advanced IMA. RESULTS: The study cohort included 13 patients at the initial advanced stage and 20 patients who progressed after curative treatment. Treatment modalities included conventional chemotherapy in 24 patients (72.7%), targeted therapy in seven (21.2%), immunotherapy in 13 (39.4%), and local ablative therapy (LAT) in 13 (39.4%). The median OS was 32 months (95% confidence interval [CI], 2.9-61.0), with LAT significantly associated with improved OS compared to non-LAT treatment (not reached vs. 11.3 months, p = 0.001). However, there was no significant difference in OS based on conventional chemotherapy (p = 0.396), targeted therapy (p = 0.655), or immunotherapy (p = 0.992). In multivariate analysis, LAT remained an independent prognostic factor for OS (hazard ratio, 0.125; 95% CI, 0.026-0.608; p = 0.01). PFS was 8.6 months (95% CI, 3.6-13.7), with no significant differences observed among the treatment modalities. CONCLUSION: Our findings suggest that LAT may provide favorable survival outcomes in patients with advanced IMA.

In vivo comparative assessments on pleural adhesive effects of three commercially available sealants.

Objective: Surgical sealant, which is used for the reinforcement of suture lines, has been widely used in lung-resection surgeries with the aim of reducing postoperative morbidity; however, it may exacerbate surgical-site adhesion, creating the risks of restrictive thoracic movement and a difficult entrance for redo operation. We aimed to assess the pleural adhesive effects of 3 frequently used surgical sealants, (1) fibrin glue (fibrin), (2) a composite of polyethylene glycol and human serum albumin (PEG/HSA), and (3) bioabsorbable polyglycolic acid felt (PGA), in an in vivo setting. Methods: Eighty-one rats were randomly assigned to 3 experimental groups-fibrin, PEG/HSA, and PGA. After intrapleural application of the sealants, the extent and severity of adhesion and inflammation were quantitatively compared among the 3 groups at 2, 4, and 8 weeks. Results: The scores for both the extent and severity of adhesion were significantly greater in the PGA group than the other 2 groups throughout postoperative period (P < .001 for all). Although both scores in the PES/HSA and fibrin groups were 0 at 2 weeks, the fibrin group showed significantly greater scores than the PES/HSA group thereafter (P < .001 for all). Trends in inflammation scores were similar of those of adhesion scores, favoring the PES/HSA group followed by the fibrin group (P < .001 for all). Conclusions: Among 3 commonly used sealants, PEA/HSA showed least degree of adhesion/inflammation compared with fibrin and PGA, whereas PGA demonstrated greatest degrees of adhesion/inflammation throughout a postoperative course of 8 weeks in an in vivo model.

Prognostic impact of limited resection vs. inadequate adjuvant therapy in patients with pathologic stage II or III non-small cell lung cancer: results from the Korean Association of Lung Cancer Registry.

BACKGROUND: For patients with stage II and III non-small cell lung cancer (NSCLC), various multi-modality treatments are required. However, depending on the individual conditions of patients, there will be a significant difference in prognosis. Therefore, this study investigated the clinical impact of inadequate treatment (limited surgery and inadequate adjuvant therapy) in patients with NSCLC stage II or III using data from the Korean Association of Lung Cancer Registry (KALC-R) between 2014 and 2016. METHODS: Of the 8,110 new lung cancer cases registered at the Korea Central Cancer Registry in 2014-2016, 721 patients with stage II or III NSCLC were selected and divided into three groups according to differences in cancer treatment methods. In group A, patients underwent standard surgery and completed adjuvant therapy. In group B, patients underwent standard surgery without completing adjuvant therapy. In group C, patients received adjuvant therapy after limited surgery. After performing propensity score matching (PSM) for selected patients, overall survival (OS) and disease-free survival (DFS) rates of the three groups of patients with stage II and III NSCLC patients were then compared. RESULTS: Of the 721 patients with NSCLC, 239, 437, and 45 belonged to groups A, B, and C, respectively. After 1:3 PS matching for groups B and C, the 5-year survival rate of patients with stage II or III NSCLC were 68.0% and 26.7% for groups B and C, respectively and the DFS rate was 59.1% and 16.2% for groups B and C, respectively. CONCLUSIONS: The therapeutic effect of the standard surgery was the best. Although patients received adjuvant therapy, limited resection resulted in a poorer prognosis in compromised patients compared with omitting adjuvant therapy followed by standard surgery. Thus, surgical treatment should be considered in patients who are unable to complete surgical and adjuvant therapy.

Changes in Otitis Media During COVID-19.

OBJECTIVES: During the COVID-19 pandemic, various non-pharmaceutical interventions such as individual hygiene practices like hand washing, social distancing, and mandates for the use of masks in public spaces were implemented to reduce the spread of the disease. Otitis media (OM) is a common infectious disease. How the changed environment due to the COVID-19 pandemic has influenced the prevalence of infectious diseases like OM is not known. This study aimed to investigate how OM prevalence and trends changed during COVID-19 in Korea. METHODS: OM patient data from 2017 to 2021 were extracted from the Health Insurance Review and Assessment Service database. Patients diagnosed with disease code H66 (suppurative and unspecified otitis media) were selected for analysis. Data on OM prevalence, gender, region, medical institution, and number of ventilating-tube prescriptions were analyzed. All age groups were included, and ages were categorized into 5-year ranges. RESULTS: The number of patients diagnosed with the OM disease code decreased continuously from 2017 to 2021 (1 598 205, 1 560 178, 1 520 948, 983 701, and 734 901). The average OM prevalence per 1000 persons decreased by 45.0% from 30.2 in 2017 to 2019 to 16.6 in 2020 to 2021. The change of OM prevalence was greater for the 0 to 5 age group than other age groups. The decrease in average prevalence per 1000 persons was greatest in the 0 to 5 age group (48.6% decrease from 358.2 in 2017-2019 to 184.1 in 2020-2021). The impact of environmental changes on ventilation-tube insertion was smaller than on OM prevalence. The average number of ventilating-tube insertions decreased by 28.1% from 27 311 in 2017 to 2019 to 19 650 in 2020 to 2021. CONCLUSIONS: OM prevalence decreased by 45.0%, and the number of ventilating-tube insertions decreased by 28.1% in Korea during COVID-19.

Management of a Large Hypervascular Apicoposterior Mediastinal Mass Using the Purse-String Suture Technique in Robotic-Assisted Thoracoscopic Surgery: A Case Report.

Complete resection of an apicoposterior mediastinal mass is essential due to the mass effect, which exerts pressure on adjacent organs. Recently, the use of minimally invasive surgery has had many advantages. In this report, we describe a case in which a large apicoposterior mediastinal hypervascular mass was managed using a purse-string suture technique during robotic-assisted thoracoscopic surgery (RATS). The patient, a 77-year-old woman, was diagnosed with a 6.2-cm apicoposterior mediastinal hypervascular solid mass originating from the branches of the right subclavian artery. The patient underwent RATS for treatment. To obtain an adequate view of the apex of the thoracic cavity, a needle aspiration was performed, followed by the application of a purse-string suture technique. This was done to reduce the size of the tumor and to prevent catastrophic events such as seeding or spillage of the cystic mass. The mass was histopathologically diagnosed as a schwannoma. The patient was discharged on the first postoperative day without experiencing any complications.

Which is the More Effective Option for Pleurodesis to Prevent the Recurrence of Malignant Pleural Effusion? Large-Particle Talc or Mistletoe Extract (ABNOVA Viscum Injection).

Background: Malignant pleural effusion affects many patients with advanced cancer. When chemotherapy or radiotherapy fails to relieve malignant pleural effusion and related symptoms, drainage and pleurodesis can help. Although surgical talc pleurodesis is the most widely used method, Viscum album, which has been recently used in surgical or bedside procedures, has demonstrated significant results and is as effective as talc. This study aimed to determine the most effective agent and procedure. Methods: Between January 2015 and July 2022, chemical pleurodesis was performed in 137 patients with malignant pleural effusion, using a V. album surgical procedure in 48, a V. album bedside procedure in 55, and a talc surgical procedure in 34 patients. We reviewed patients' clinical responses and disease progression after chemical pleurodesis. Results: The success rate was not significantly different among the V. album surgical procedures (91.7%), V. album bedside procedures (83.6%), and talc surgical procedures (91.2%). However, the total drainage amount and tube insertion duration in both Viscum groups were more effective than those in the talc group. Furthermore, the bedside Viscum group showed significantly lower post-pleurodesis pain scores than the other 2 groups. Conclusion: According to our results, talc and V. album can be considered ideal agents for chemical pleurodesis. However, Viscum pleurodesis showed safer outcomes in terms of ensuring quality of life than talc. Additionally, the bedside Viscum group showed significantly lower pain scores than the other groups. Hence, patients for whom surgical procedures are inappropriate can undergo bedside Viscum pleurodesis without diminishing the therapeutic effect.

BRAF V600E Mutation of Non-Small Cell Lung Cancer in Korean Patients.

Background and Objectives: BRAF mutational status in resected non-small cell lung cancer (NSCLC) in the Korean population is poorly understood. We explored BRAF (particularly BRAF V600E) mutational status among Korean patients with NSCLC. Materials and Methods: This study included 378 patients with resected primary NSCLC who were enrolled from January 2015 to December 2017. The authors obtained formalin-fixed paraffin-embedded (FFPE) tissue blocks and performed peptide nucleic acid (PNA)-clamping polymerase chain reaction (PCR) for detecting BRAF V600, real-time PCR for detecting BRAF V600E, and immunohistochemical analyses using the mutation-specific Ventana VE1 monoclonal antibody. For positive cases in any methods mentioned above, direct Sanger sequencing was additionally performed. Results: The PNA-clamping method revealed the BRAF V600 mutation in 5 (1.3%) of the 378 patients. Among these five patients, real-time PCR, direct Sanger sequencing detected BRAF V600E mutations in three (0.8%) patients. Thus, two cases showed differences in their PNA-clamping and the others. Direct Sanger sequencing of PNA-clamping PCR product was performed for two cases showing negative results on direct Sanger sequencing; both contained BRAF mutations other than V600E. All patients harboring BRAF mutations had adenocarcinomas, and all patients with V600E mutation exhibited minor micropapillary components. Conclusions: Despite the low incidence of the BRAF mutation among Korean patients with NSCLC, lung adenocarcinoma patients with micropapillary components should be prioritized in terms of BRAF mutation testing. Immunohistochemical staining using Ventana VE1 antibody may serve as a screening examination for BRAF V600E.

Endotracheal suture through extending tracheostoma for post-tracheostomy tracheal laceration: a case report.

BACKGROUND: Tracheal laceration is very rare but can be life-threatening if proper treatment is not provided. The general concept for the management of tracheal laceration is surgical repair through cervical incision or via thoracotomy. However, in the case of tracheal laceration after tracheostomy, tracheostoma could be extended to avoid urgent surgical repair and additional incision. CASE PRESENTATION: A 30-year-old Asian woman suffered intracerebral hemorrhage. Tracheostomy was necessary for prolonged ventilator care. While tracheostomy was performed, the posterior tracheal wall was torn. After observing that, we reinserted endotracheal tube through the oral orifice. Following bronchoscopy showed torn posterior tracheal wall. The tearing wound was 5-6 cm in length, from the middle to distal parts of the trachea. We used minimally invasive procedure for extending the already existing tracheostoma. CONCLUSIONS: In the case of tracheal laceration related to tracheostomy, a new incision is not necessary because the tracheal opening already exists. Using the extended tracheostomy technique, tracheal laceration can be repaired by endotracheal suture method.

Early Diagnosis and Intervention Are Needed for a Reasonable Prognosis of Thromboangiitis Obliterans.

Background: Thromboangiitis obliterans (TAO) poses a higher risk of amputation than atherosclerosis obliterans. It is characterized by onset at a relatively young age. There are currently no clear treatment guidelines for TAO other than smoking cessation. In this study, we aimed to identify factors that could influence a favorable prognosis of TAO. Methods: From January 2009 to December 2019, we retrospectively reviewed the initial symptoms, characteristics, treatments, and disease course of 37 patients (45 limbs) with TAO. Logistic regression analysis was performed to investigate factors affecting the course of symptoms that persisted or worsened despite treatment. Results: Patients' mean age was 37.2±11.4 years, and all patients were men. The mortality rate was 0% during the follow-up period (76.9±51.1 months). All patients were smokers at the time of diagnosis, and 19 patients (51.4%) successfully quit smoking during treatment. When comparing the Rutherford categories before and after treatment, 23 limbs (51.1%) showed improvement, the category was maintained in 11 limbs (24.4%), and 11 limbs (24.4%) worsened. Symptom persistence or exacerbation despite treatment was associated with a higher initial Rutherford category (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.04-2.42; p=0.03) and a higher score of the involved below-knee artery at the time of diagnosis (OR, 2.26; 95% CI, 1.10-4.67; p=0.03). Conclusion: The degree of disease progression at the time of diagnosis significantly affected patients' prognosis. Therefore, early diagnosis and intervention are important to improve the course of TAO.

Acute limb ischemia after minimally invasive cardiac surgery using the ProGlide: A case series.

BACKGROUND: We report two cases of acute femoral artery occlusion following the use of ProGlide in minimally invasive cardiac surgery and insertion of large-bore catheters through the common femoral artery. This will add to the existing body of literature by highlighting the possible complications associated with the use of ProGlide and reiterate that the use of the sono-guided ProGlide skill will reduce the incidence of these complications. CASE SUMMARY: A 78-year-old man underwent minimally invasive cardiac surgery for severe aortic valve stenosis. After the operation, the puncture site of the common femoral artery was closed using ProGlide. The next morning, after regaining consciousness, he complained of pain, motor weakness (grade 2), and coldness in the right lower extremity. A 65-year-old man underwent minimally invasive cardiac surgery for a large secundum atrial septal defect (5 cm × 5 cm). After the operation, the puncture site of the common femoral artery was closed using ProGlide. After extubation, the patient complained of paresthesia of the right thigh. Both the patients underwent emergency surgery for acute occlusion of the common femoral artery. CONCLUSION: If the sono-guided ProGlide skill is used, complications can be prevented, and ProGlide can be safely used.

Effects of Inhalation versus Total Intravenous Anesthesia on Postoperative Pulmonary Complications after Anatomic Pulmonary Resection.

BACKGROUND: No consensus exists regarding whether volatile anesthetics are superior to intravenous anesthetics for reducing postoperative pulmonary complications (PPCs) in patients undergoing general anesthesia for surgery. Studies of this issue focused on anatomic pulmonary resection are lacking. This study compared the effects of total intravenous anesthesia (TIVA) versus volatile anesthesia on PPCs after anatomic pulmonary resection in patients with lung cancer. METHODS: This retrospective study examined the medical records of patients with lung cancer who underwent lung resection at our center between January 2018 and October 2020. The primary outcome was the incidence of PPCs, which included prolonged air leak, pneumonia, acute respiratory distress syndrome, empyema, atelectasis requiring bronchofiberscopy (BFS), acute lung injury (ALI), bronchopleural fistula (BPF), pulmonary embolism, and pulmonary edema. Propensity score matching (PSM) was used to balance the 2 groups. In total, 579 anatomic pulmonary resection cases were included in the final analysis. RESULTS: The analysis showed no statistically significant difference between the volatile anesthesia and TIVA groups in terms of PPCs, except for prolonged air leak. Neither of the groups showed atelectasis requiring BFS, ALI, BPF, pulmonary embolism, or pulmonary edema after PSM. However, the length of hospitalization, intensive care unit stay, and duration of chest tube indwelling were shorter in the TIVA group. CONCLUSION: Volatile anesthetics showed no superiority compared to TIVA in terms of PPCs after anatomical pulmonary resection in patients with lung cancer. Considering the advantages of each anesthetic modality, appropriate anesthetic modalities should be used in patients with different risk factors and situations.

Risk Factors Associated with Difficult Reversal of Heparin by Protamine Sulfate in Cardiopulmonary Bypass: An Ignored Issue.

BACKGROUND: The aim of this study was to evaluate risk factors associated with difficult heparin reversal by protamine after cardiopulmonary bypass. METHODS: Data from 120 consecutive patients who underwent open heart surgery from 2009 to 2017 were retrospectively reviewed. Patients were divided into 2 groups: (1) those in whom complete heparin reversal was achieved after a single infusion of protamine (group A, n=89); and (2) those who required more protamine for heparin reversal (group B, n=31). RESULTS: Female sex, prolonged bypass time (>200 min), long aortic cross-clamping time (>120 min), and a lowest rectal temperature <26°C were significant predictors of difficult heparin reversal. Larger amounts of fresh frozen plasma and platelet concentrate were transfused in group B than in group A. CONCLUSION: Surgeons' efforts to reduce operative time and avoid deep hypothermia may be helpful for increasing the likelihood of easy heparin reversal, especially in female patients.

Clinical Value of Intraoperative Flow Measurements of Brachiocephalic Arteriovenous Fistulas for Hemodialysis.

BACKGROUND: The aim of this study was to analyze the clinical outcomes of autogenous brachiocephalic arteriovenous fistulas and to investigate the factors associated with 1-year patency after initiation of hemodialysis. METHODS: We retrospectively reviewed the medical records of 41 patients who underwent surgery to create an autogenous brachiocephalic arteriovenous fistula between January 2015 and December 2017, received hemodialysis at the same hospital for longer than 1 year, and were monitored for their vascular access status. Intraoperative flow was measured using transit-time ultrasonography. RESULTS: The 1-year primary and secondary patency rates were 61% (n=25) and 87.8% (n=36), respectively. The functional group (subjects who required no intervention to maintain patency within the first year after hemodialysis initiation) displayed a significantly higher median intraoperative flow rate (450 mL/min) than the non-functional group (subjects who required intervention at least once regardless of 1-year patency) (275 mL/min) (p=0.038). Based on a receiver operating characteristic curve analysis, all patients were additionally subdivided into a high-flow group (>240 mL/min) and a low-flow group (≤240 mL/min). The high-flow group included a significantly greater number of functional brachiocephalic arteriovenous fistulas than the low-flow group (74.2% vs. 20%, respectively; p=0.007). CONCLUSION: Transit-time flow, as measured with intraoperative transit-time ultrasonography, was associated with patency without the need for intervention at 1 year after initiation of hemodialysis.

Cardiac Autotransplantation with Concurrent Pneumonectomy for Complete Resection of Primary Cardiac Intimal Sarcoma.

Primary cardiac sarcoma is rare, and intimal sarcoma is an extremely rare and highly lethal disease. We report a case of a 62-year-old woman who was incidentally diagnosed with a primary cardiac sarcoma originating from the left atrial appendage and extending to the left superior pulmonary vein. The location of the tumor was very complicated, posing a major challenge for complete resection. We successfully performed complete resection of the cardiac sarcoma via cardiac autotransplantation with left pneumonectomy. The patient recovered uneventfully, without any adjuvant therapy as of 6 months postoperatively. Autotransplantation of the heart may be suggested as a reasonable surgical option for extensive left atrial tumors.

Bronchogenic cysts mimicking thymoma in the anterior mediastinum.

Bronchogenic cysts are commonly located in the middle mediastinal compartment as fluid-filled cysts and thymoma is one of the most common neoplasms in the anterior mediastinum in adult cases. For two cases of asymptomatic, incidentally discovered anterior mediastinal soft tissue mass in adults, we planned to perform complete thymectomy with minimally invasive techniques based on the guidelines of International Thymic Malignancy Interest Group. Their pathological finding revealed cystic lesions lined by ciliated epithelium and this supported the diagnosis of bronchogenic cyst rather than thymic neoplasm. We report the two cases of resected bronchogenic cysts which were in the unusual location of anterior mediastinum with uncommon radiological feature.

Association Between Hearing Loss and Postural Instability in Older Korean Adults.

Importance: Hearing loss is one of the most frequently occurring sensory disabilities worldwide. The association between hearing loss and postural instability in an older population remains to be studied. Objective: To determine whether the odds of postural instability increase with the degree of hearing loss and to suggest criteria for hearing rehabilitation for postural instability. Design, Setting, and Participants: This cross-sectional population-based study of 3864 participants 40 years and older with hearing loss used data from 2010 through 2012 in the fifth edition of the Korea National Health and Nutrition Examination Survey, a nationwide survey of South Korea. Pure tone audiometry was performed on both the left and right sides and each hearing grade of each side was classified into 1 of 3 subcategories: normal hearing, mild hearing loss, or moderate hearing loss (moderate hearing loss or worse). Postural instability was defined as the failure to remain standing on a foam pad surface with feet 10 cm apart with arms folded and hands cupping the elbows and eyes closed. A binomial logistic regression model was used to assess the association between hearing loss and postural instability. Data were analyzed from August 18, 2019, to September 2, 2019. Exposures: Age-related hearing loss defined as a threshold of 26 dB or more. Main Outcomes and Measures: The degree of hearing loss and postural instability. Results: Of the 3864 participants included in the study, the mean (SD) age was 57.8 (11.3) years and 2135 (55.2%) were women. Female sex was associated with higher odds of postural instability compared with male sex (odds ratio [OR], 1.65; 95% CI, 1.12-2.42, adjusted for age and hearing status), and the odds of postural instability increased with every 1 year increase in age (OR, 1.13; 95% CI, 1.10-1.16, adjusted for sex and hearing status). Unilateral or bilateral mild hearing loss was not associated with an increase in the odds of postural instability, but moderate hearing loss present on at least 1 side was associated with an increase in the odds of postural instability: unilateral moderate hearing loss group (OR, 2.71; 95% CI, 1.12-6.10, adjusted for age and sex), one mild and the other moderate hearing loss group (OR, 2.18; 95% CI, 1.16-4.09, adjusted for age and sex), and bilateral moderate hearing loss group (OR, 2.34; 95% CI, 1.27-4.33, adjusted for age and sex). Conclusions and Relevance: Aging, female sex, and having hearing loss were associated with postural instability in this analysis. Moderate or worse hearing loss present on at least 1 side was associated with increased odds of postural instability. Future research in this area is warranted to identify more precise interrelationships and preventive measures.

All-trans retinoic acid regulates TGF-ß1-induced extracellular matrix production via p38, JNK, and NF-κB-signaling pathways in nasal polyp-derived fibroblasts.

BACKGROUND: All-trans retinoic acid (ATRA), a derivative of vitamin A, is known to have anti-fibrogenic effects and regulates cell proliferation and differentiation. Therefore, these abilities of ATRA may influence tissue remodeling in the upper airway. The aims of the present study were to investigate the effects of ATRA on the myofibroblast differentiation, extracellular matrix (ECM) production, cell migration, and collagen gel contraction and to determine the molecular mechanisms of ATRA in TGF-ß1-induced nasal polyp-derived fibroblasts (NPDFs). METHODS: NPDFs were isolated from nasal polyp. Cytotoxicity was evaluated by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide assay. TGF-ß1-induced fibroblasts were pretreated with ATRA. The expression levels of alpha-smooth muscle actin (α-SMA), collagen type 1, fibronectin, phospho-mitogen-activated protein kinase, and p-p50 (nuclear factor-kappaB [NF-κB]) were measured by Western blot analysis, real-time polymerase chain reaction, and/or immunofluorescence staining. Cell migration was analyzed with cell migration scratch assay and Transwell migration assay. Collagen contractile activity was measured using a collagen gel contraction assay. RESULTS: ATRA had no significant cytotoxic effect in NPDFs. Expression levels of α-SMA, collagen type 1, and fibronectin stimulated by TGF-ß1 were significantly downregulated in the ATRA-pretreated fibroblasts. TGF-ß1-induced cell migration and collagen gel contraction were significantly inhibited by ATRA pretreatment. ATRA also significantly inhibited phosphorylation of c-Jun N-terminal kinase (JNK), p38, and p50 in TGF-ß1-induced NPDFs, but did not inhibit phosphorylation of extracellular signal-related kinase (ERK). CONCLUSION: ATRA downregulated myofibroblast differentiation, ECM production, cell migration, and collagen gel contraction via p38, JNK-dependent NF-κB-signaling pathways in TGF-ß1-induced NPDFs. The findings suggest that ATRA could serve as a novel therapeutic agent to ameliorate nasal polyp development.