Surgery in Nasal Polyp Patients: Outcome After a Minimum Observation of 10 Years.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) often requires surgery, but recurrence even after surgery is common. Recurrence rates largely vary in literature and asthma seems to be a comorbid factor. OBJECTIVE: In this study, we aim to estimate disease recurrence during a long-term follow-up, together with the investigation of possible predicting and/or influencing parameters. METHODS: Out of 196 patients operated for CRSwNP between 01/2000 and 01/2006, 133 patients had a follow-up of at least 10 years and could be included. The inflammatory profile at surgery was determined on nasal tissue and sinonasal secretions, and included analysis of eosinophils, eosinophilic-rich mucus (ERM) typically containing Charcot-Leyden crystals (CLC), and fungal hyphae (FH). During follow-up, recurrence, received treatments and comorbidities were collected. RESULTS: Out of the 133 included patients, local eosinophilia was present in 81% and ERM in 60%. Recurrence during follow-up was observed in 62%, and was associated with local eosinophilia and ERM (both p < 0.001). Asthma was present in 28% at inclusion, and 17% developed asthma after surgery during follow-up. The presence of asthma, at inclusion as well as developed during follow-up, was significantly associated with recurrence of CRSwNP (p = 0.001 for group comparison). CONCLUSION: Recurrence after CRSwNP surgery is common when a long-term follow-up is taken into account. ERM detected in sinonasal secretions at surgery seems to be a predictive factor for recurrence and need for revision surgery. Asthma is a frequently found comorbid factor in CRSwNP, develops even at higher age despite surgical treatment for CRSwNP, and is also associated with a higher recurrence rate. Sustained medical care after surgery is mandatory.

Japanese guidelines for allergic rhinitis 2020.

Like asthma and atopic dermatitis, allergic rhinitis is an allergic disease, but of the three, it is the only type I allergic disease. Allergic rhinitis includes pollinosis, which is intractable and reduces quality of life (QOL) when it becomes severe. A guideline is needed to understand allergic rhinitis and to use this knowledge to develop a treatment plan. In Japan, the first guideline was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 8th edition was published in 2016, and is widely used today. To incorporate evidence based medicine (EBM) introduced from abroad, the most recent collection of evidence/literature was supplemented to the Practical Guideline for the Management of Allergic Rhinitis in Japan 2016. The revised guideline includes assessment of diagnosis/treatment and prescriptions for children and pregnant women, for broad clinical applications. An evidence-based step-by-step strategy for treatment is also described. In addition, the QOL concept and cost benefit analyses are also addressed. Along with Allergic Rhinitis and its Impact of Asthma (ARIA), this guideline is widely used for various clinical purposes, such as measures for patients with sinusitis, childhood allergic rhinitis, oral allergy syndrome, and anaphylaxis and for pregnant women. A Q&A section regarding allergic rhinitis in Japan was added to the end of this guideline.

Local Allergic Rhinitis Revisited.

PURPOSE OF REVIEW: Local allergic rhinitis (LAR) represents a diagnostic and therapeutic challenge for clinicians. Even though it affects a considerable number of chronic rhinitis patients and a significant number of articles regarding prevalence, evolution, diagnosis, and treatment have been published, the condition remains still largely unrecognized and therefore misdiagnosed and mistreated. RECENT FINDINGS: LAR is a unique form of chronic rhinitis; it is neither classical allergic rhinitis (AR) nor non-allergic rhinitis (NAR). The symptoms, duration, severity, and complications of LAR are similar to those of AR and can affect adults and children. Thus, a portion of patients diagnosed with NAR or chronic rhinitis of unknown etiology may have LAR. The relationship between LAR inflammation and systemic allergic inflammation is unclear. Patients are frequently misdiagnosed with idiopathic NAR, and distinguishing between both entities is difficult without specific diagnostic tests. Underdiagnosis of LAR has implications on the management of these patients, as they are deprived of allergen immunotherapy (AIT) that has been demonstrated to modulate the immune mechanisms underlying allergic diseases. This review aims to comprehensively summarize the current knowledge on LAR and address unmet needs in the areas of disease diagnosis and treatment.

Consensus guidance of nebulizer therapy for acute rhinosinusitis.

The guidance deals with the recommended applications, procedures, and safety management of nebulizer therapy for acute rhinosinusitis. In Japan, nebulizer therapy for sinusitis has been covered by public health insurance since 1958 and has been commonly carried out nationwide. The Japan Society for Infection and Aerosol in Otorhinolaryngology and the Oto-Rhino-Laryngological Society of Japan set up a working group to draw up a consensus guidance on nebulizer therapy for acute rhinosinusitis. The device for nebulizer therapy are classified into jet, ultrasound, and mesh types. In Japan, cefmenoxime hydrochloride (CMX) was approved for use in nebulizer therapy since 1996. The widening of the obstructed lesions such as large polyps prior to nebulizer therapy were recommended. The numbers of times of nebulizer therapy is recommended for three times in a week for at least for 2 weeks (cure rate: 68%, eradication ratio: 48%). Concerns should be pay for the changes of activity of medicine due to the mixing and bacterial contamination. Pseudomonas cepacia growing in a short even in both saline and distilled water leads to contamination at high concentrations by 2 days. Nebulizer therapy is an effective treatment based on a drug delivery system (DDS) to the nasal and paranasal cavities. The therapy effectively increases the local drug concentration by promptly and uniformly delivering drugs to a targeted local site. The therapy is safe with less systemic absorption and with few adverse reactions.

Clinical Applications for Tissue Engineering in Rhinology.

Tissue engineering implies a number of established techniques in several fields in medicine. A thorough review of current clinical applications for tissue engineering in rhinology is addressed. Current status, as well as, published in vivo studies is presented. Moreover, relevant clinical applications and future perspectives of tissue engineering are demonstrated. There is a lack of high quality clinical studies in the literature regarding the role of tissue engineering in the rhinology field. Further research is needed to translate this concept from bench to bedside.

Sublingual Immunotherapy Attenuates Nasal Symptoms Upon Allergen Exposure in Murine Allergic Rhinitis Model via an Induction of IL-10 producing T cells in Submandibular Lymph Node.

OBJECTIVE: Sublingual immunotherapy has been considered to be a painless and effective therapeutic treatment of patients with allergic rhinitis. Its mechanism of action has been elucidated, but there are still controversies among many reports between clinical efficacy and laboratory data. Therefore, its mechanism of action needs to be investigated further by using promising animal models such as rodents and monkeys. MATERIALS AND METHODS: Bearing this in mind, in our present study, we successfully constructed an effective murine model for sublingual immunotherapy (SLIT) in allergic rhinitis in which mice were sublingually administered ovalbumin (OVA), followed by intraperitoneal (ip) sensitization and intranasal (i.n.) challenge of OVA. RESULTS: To summarize our experimental data, nasal symptoms such as sneezing and nasal rubbing of sublingually treated mice were significantly attenuated in accordance with lower specific IgE antibodies in sera. Histological analysis of eosinophil recruitment in nasal mucosae reveals less allergic inflammation in sublingually treated mice. Interleukin-10 (IL-10) production and IL-10-specific mRNA gene expression of cultured submandibular lymph node (SMLN) cells with OVA, obtained from sublingually treated mice, were significantly higher than those of mice without sublingual treatment. CONCLUSION: These results demonstrate that sublingually introduced antigens can actually attenuate nasal symptoms in a murine allergic rhinitis model upon allergen exposures. Furthermore, our immunological data might indicate an important role of IL-10 producing T cells in SMLN to control nasal allergic reaction.

Differentiating Rhinitis in the Paediatric Population by Giving Focus on Medical History and Clinical Examination.

Chronic rhinitis is defined as an inflammation of the nasal epithelium, and is characterized by the presence of two or more specific nasal symptoms including obstruction, rhinorrhea, sneezing, and/or itching for at least 12 weeks. In childhood, this clinical entity is very common and carries a significant socioeconomic burden. The impact on the physical, social, and psychological well-being of family cannot be underestimated. Rhinitis is an umbrella term which includes different phenotypes of rhinitis with distinct underlying pathophysiologic mechanisms. In most cases the diagnosis of rhinitis is rather straightforward; however, sometimes when based on clinical symptomatology, characterization may be challenging. Herein, we provide guidance for getting all the data needed for the differential diagnosis of rhinitis based on medical history and clinical examination.

Regulation of Interaction between the Upper and Lower Airways in United Airway Disease.

The concept of united airway disease comprises allergic rhinitis (AR) with asthma, and eosinophilic chronic rhinosinusitis (ECRS) with asthma. It embodies a comprehensive approach to the treatment of upper and lower airway inflammation. The treatment of upper airway inflammation reduces asthma symptoms and decreases the dose of inhaled corticosteroids (ICS) necessary to treat asthma. However, little is known about the mechanisms of interaction between upper and lower airway inflammation. Here we review these mechanisms, focusing on neural modulation and introduce a novel therapeutic approach to united airway disease using a fine-particle ICS. Our understanding of the relationship between the upper and lower airways and its contribution to T helper 2 (Th2)-skewed disease, such as AR and/or ECRS with asthma, has led us to this novel therapeutic strategy for a comprehensive approach to the treatment of upper airway inflammation with asthma.

Eosinophilic Upper Airway Inflammation in a Murine Model Using an Adoptive Transfer System Induces Hyposmia and Epithelial Layer Injury with Convex Lesions.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a refractory upper airway disease, accompanied mainly by eosinophilia and/or asthma. In addition, the disease correlates with a high rate of hyposmia, following a marked infiltration of eosinophils into the inflamed site, the paranasal sinus. Although eosinophils are known to contribute to the development of hyposmia and CRSwNP pathology, the underlying mechanisms remain unclear. This study aimed to investigate whether eosinophilic upper airway inflammation induces hyposmia and CRSwNP in a murine model using an adoptive transfer system. METHODS: To induce eosinophilic rhinosinusitis, splenocytes, including a high proportion (over 50%) of activated eosinophils (SPLhEos), were collected from interleukin-5 transgenic mice following double intraperitoneal injections of antigens, such as ovalbumin, house dust mite, or fungus. Activated SPLhEos with corresponding antigens were then transferred into the nasal cavity of recipient mice, which were sensitized and challenged by the corresponding antigen four times per week. Olfactory function, histopathological, and computed tomography (CT) analyses were performed 2 days after the final transfer of eosinophils. RESULTS: Hyposmia was induced significantly in mice that received SPLhEos transfer compared with healthy and allergic mice, but it did not promote morphological alteration of the paranasal sinus. Pathological analysis revealed that epithelial layer injury and metaplasia similar to polyps, with prominent eosinophil infiltration, was induced in recipient tissue. However, there was no nasal polyp development with interstitial edema that was similar to those recognized in human chronic rhinosinusitis. CONCLUSIONS: This study supports the previously unsuspected contribution of eosinophils to CRS development in the murine model and suggests that murine-activated eosinophilic splenocytes contribute to the development of hyposmia due to more mucosal inflammation than physical airway obstruction and epithelial layer injury with convex lesions.

Antihistamines for Allergic Rhinitis Treatment from the Viewpoint of Nonsedative Properties.

Antihistamines targeting the histamine H1 receptor play an important role in improving and maintaining the quality of life of patients with allergic rhinitis. For more effective and safer use of second-generation drugs, which are recommended by various guidelines, a classification based on their detailed characteristics is necessary. Antihistamines for first-line therapy should not have central depressant/sedative activities. Sedative properties (drowsiness and impaired performance) are associated with the inhibition of central histamine neurons. Brain H1 receptor occupancy (H1RO) is a useful index shown to be correlated with indices based on clinical findings. Antihistamines are classified into non-sedating (<20%), less-sedating (20⁻50%), and sedating (≥50%) groups based on H1RO. Among the non-sedating group, fexofenadine and bilastine are classified into "non-brain-penetrating antihistamines" based on the H1RO. These two drugs have many common chemical properties. However, bilastine has more potent binding affinity to the H1 receptor, and its action tends to last longer. In well-controlled studies using objective indices, bilastine does not affect psychomotor or driving performance even at twice the usual dose (20 mg). Upon selecting antihistamines for allergic rhinitis, various situations should be taken into our consideration. This review summarizes that the non-brain-penetrating antihistamines should be chosen for the first-line therapy of mild allergic rhinitis.

OK-432 Administration Inhibits Murine Allergic Rhinitis at the Induction Phase, through the Macrophage Activation with TLR2 Signaling Pathway.

OK-432, a preparation of a low-virulence strain (Su) of Streptococcus pyogenes (Group A) killed by a penicillin and lyophilized, is a stiff inducer of Th1 cytokines, and exerts anti-cancer effects in tumor-bearing mice. OK-432 has been reported to consist of many bacterial components, such as peptidoglycan, M-protein, etc. However, it is yet to be ascertained which bacterial component induces T helper 1 (Th1) responses. For the last decade, Toll-like receptor (TLR) family proteins are well elucidated to play a role in recognizing bacterial components and inducing interleukin (IL)-12 from macrophages. Above all, peptidoglycan seems to be the agonist of TLR2 rather than the obverse. In our present study, the role of TLR2 for the recognition of OK-432 by macrophages and the effects of OK-432 are examined on murine allergic rhinitis model. Interestingly, results show IL-12 production by macrophages derived from TLR2 knock-out (ko) mice was significantly decreased, in comparison with that of macrophages derived from wild-type mice. Moreover, in TLR2 ko mice, no regulatory effect of OK-432 was observed on an allergic rhinitis model. These data indicate that TLR2 signaling is involved in regulating OK-432-induced anti-T helper 2 (Th2) immunity, and may offer a new prophylactic and therapeutic approach using OK-432 to downregulate allergic disorders, such as allergic rhinitis.

Acute suppurative thyroiditis caused by thyroid papillary carcinoma in the right thyroid lobe of a healthy woman.

BACKGROUND: The thyroid gland is resistant to microbial infection, because of its organ characteristics such as encapsulation, iodine content, and rich blood supply. Therefore, acute suppurative thyroiditis (AST), as a bacterial infection of the thyroid gland, is rarely seen. AST typically takes places on the left side the neck region in children, because of the coincidence of the left piriform sinus fistula, as a most common route of infection. AST is also usually seen in immunocompromised hosts. Herein, we report a rare case of AST in the right thyroid lobe of adult woman without any immunocompromised condition. CASE PRESENTATION: A 59-year-old woman was introduced to our hospital for the further examination with fever, sore throat, and right anterior neck swelling. The patient appeared not to be immunodeficient. Neck ultrasonography showed a 47-mm, hypoechoic, heterogeneous nodule with ill-defined margins and irregular form, suggesting a right thyroid malignant nodule. Fine needle aspiration (FNA) biopsy specimen revealed numerous number of neutrophils in the background without nuclear atypia. Based on the clinical course and cytology, AST was confirmed to be diagnosed. Complete response was obtained by an intravenous administration of antimicrobial agents within a week. Image findings such as CT scan did not show any piriform sinus fistula. Four months later, neck ultrasonography showed a significant decrease in size of the nodule in the right thyroid gland to 27 mm, but the lesion still resembled a malignant nodule. So, FNA was repeated again and cytological examination confirmed papillary thyroid carcinoma (PTC). The patient subsequently underwent total thyroidectomy and bilateral level D1 lymph node dissection. Histological findings revealed a 20-mm PTC in the right lobe with sternothyroid muscle invasion of the tumor. CONCLUSIONS: This report represents a rare case of AST associated with PTC on the right side of thyroid gland, found in a healthy adult woman. The reason why AST coincided with malignant thyroid tumor is unclear. We have to take it into our account that malignant tumor may exist in the background when AST is identified on the right side of thyroid gland with a healthy subject.

Fibrous encapsulation of the peritoneal catheter in peritoneal shunt: Case report.

BACKGROUND: The authors report a case of fibrous encapsulation of the peritoneal catheter, which caused peritoneal shunt malfunction, and has not previously been researched well as a complication of peritoneal shunts. CASE DESCRIPTION: A 69-year-old woman who had undergone a lumboperitoneal (LP) shunt for communicative hydrocephalus following subarachnoid hemorrhage caused by a ruptured aneurysm was identified with malfunction of the LP shunt system by dementia and gait disturbance. Hydrocephalus was revealed on computed tomography (CT). Under a laparoscopy, the intraabdominal peritoneal catheter was observed to be obstructed by fibrous encapsulation covering it like a long white stocking. Although the fibrous encapsulating tissue was excised by laparoscopy forceps, a ventriculoperitoneal shunt device was replaced with a new peritoneal catheter. The histopathological diagnosis of the surgically resected encapsulating tissue was the fibrous tissue with a few inflammation cells and a layer of lining cells surrounding some part of it. In the immunohistochemical study, a layer of lining cells surrounding the fibrous tissue showed immunohistochemically positive staining for calretinin. CONCLUSION: The fibrous encapsulation would be formed by peritoneal reaction to a peritoneal catheter as a foreign body by these histopathological and immunohistochemical analyses.

Japanese guidelines for allergic rhinitis 2017.

Like asthma and atopic dermatitis, allergic rhinitis is an allergic disease, but of the three, it is the only type I allergic disease. Allergic rhinitis includes pollinosis, which is intractable and reduces quality of life (QOL) when it becomes severe. A guideline is needed to understand allergic rhinitis and to use this knowledge to develop a treatment plan. In Japan, the first guideline was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 8th edition was published in 2016, and is widely used today. To incorporate evidence based medicine (EBM) introduced from abroad, the most recent collection of evidence/literature was supplemented to the Practical Guideline for the Management of Allergic Rhinitis in Japan 2016. The revised guideline includes assessment of diagnosis/treatment and prescriptions for children and pregnant women, for broad clinical applications. An evidence-based step-by-step strategy for treatment is also described. In addition, the QOL concept and cost benefit analyses are also addressed. Along with Allergic Rhinitis and its Impact of Asthma (ARIA), this guideline is widely used for various clinical purposes, such as measures for patients with sinusitis, childhood allergic rhinitis, oral allergy syndrome, and anaphylaxis and for pregnant women. A Q&A section regarding allergic rhinitis in Japan was added to the end of this guideline.

Contemporary Use of Corticosteroids in Rhinology.

PURPOSE OF REVIEW: Exogenously administered corticosteroids are widely used today in the field of rhinology. Allergic rhinitis (AR), non-allergic rhinitis (NAR), acute rhinosinusitis (ARS), chronic rhinosinusitis with (CRSwNP) and without (CRSsNP) nasal polyps, and autoimmune disorders with nasal manifestations are common diseases treated effectively with intranasal and oral glucocorticoids. We focus on physiological pathways, therapeutic benefits, indications, contra-indications, and side effects of glucocorticoid utilization in the treatment of rhinologic disorders such as AR, NAR, ARS, CRSsNP, and CRSwNP. RECENT FINDINGS: Second-generation intranasal steroid (INS) agents have pharmacokinetic characteristics that minimize their systemic bioavailability, resulting in minimum risk for systemic adverse events. Several studies have demonstrated the symptomatic efficacy of both intranasal and oral corticosteroids in ARS. Moreover, intranasal and systemic steroid administration has been repeatedly proven beneficial in the conservative and perioperative management of CRSwNP. For patients with AR, there is no need for oral steroids, with the exception of severe cases, as there is lack of superiority to INS. SCUAD patients challenge currently available treatment schemes, underlining the importance of research in the field. Corticosteroids' effectiveness in the treatment of various rhinologic disorders is indisputable. However, their characteristics, and potential side effects, make a clear consensus for utilization difficult.

Short treatment time and excellent treatment outcome in accelerated hyperfractionated radiotherapy for T1 glottic cancer.

Accelerated hyperfractionated radiotherapy was performed as treatment for patients with T1 glottic cancer, and its utility was evaluated based on treatment outcomes and adverse effects. Fifty-eight men who had undergone radiotherapy were retrospectively reviewed. Tumor classification was Tis in 4 patients, T1a in 38, and T1b in 16. Histological examination revealed squamous cell carcinoma in 55 patients. Travel time from home to hospital was 0-1 hour for 24 patients, 1-2 hours for 9, and >2 hours for 25. Laser vaporization was performed prior to radiotherapy in 38 patients, and 19 patients received concurrent chemotherapy with an agent such as S-1. Patients were irradiated twice daily using an irradiation container. Most patients received a dose of 1.5 Gy/fraction up to a total of 60 Gy. The median overall treatment time was 30 days, with a median observation period of 59.6 months. A complete response was observed in all patients. The 5-year overall survival, disease-free survival, and local control rates were 97.2%, 93.2%, and 97.8%, respectively. Although grade 3 pharyngeal mucositis was observed in 2 patients, there were no other grade 3 or higher acute adverse events. As late toxicity, grade 2 laryngeal edema and grade 1 laryngeal hemorrhage were observed in 1 patient each, but no serious events such as laryngeal necrosis or laryngeal stenosis were observed. In conclusion, this treatment method brings excellent outcome and will substantially reduce the treatment duration among patients who need to stay at nearby hotels while undergoing treatment at hospitals in rural areas.