A Phase II, Multicenter, Randomized, Placebo-Controlled Study of Benralizumab, a Humanized Anti-IL-5R Alpha Monoclonal Antibody, in Patients With Eosinophilic Chronic Rhinosinusitis.

BACKGROUND: Strong eosinophil infiltration in chronic rhinosinusitis with nasal polyp (CRSwNP) is highly associated with recalcitrance and higher nasal polyp recurrence rate after surgery. The prevalence of eosinophilic CRSwNP (ECRS) is increasing in Asian countries including Japan. Benralizumab is a humanized anti-IL-5R alpha monoclonal antibody that depletes eosinophils by antibody-dependent cell-mediated cytotoxicity. OBJECTIVE: To assess the efficacy and safety of benralizumab in patients with ECRS. METHODS: This phase II, randomized, double-blind, placebo-controlled study was conducted in Japan. Patients were randomized 1:2:2 to placebo, a single administration of benralizumab 30 mg, or benralizumab 30 mg every 4 weeks (q4w) for a total of three doses. The primary endpoint was the change in nasal polyp score from baseline at Week 12. RESULTS: Overall, 56 patients were enrolled (placebo, n = 11; benralizumab single dose, n = 22; benralizumab q4w, n = 23). Although the mean total nasal polyp score began to decrease after the initiation of benralizumab treatment, there were no statistically significant differences in change in nasal polyp score from baseline at Week 12 between benralizumab and placebo (placebo, -0.5 ± 0.8; benralizumab single, -0.3 ± 0.8; benralizumab q4w, -0.5 ± 1.5). Post-hoc analysis showed that the administration of benralizumab decreased nasal polyp scores ≥2 points in 42.2% of ECRS patients and that patients with high blood eosinophil levels had a greater tendency to respond to benralizumab treatment. The safety profile was similar to that in previous studies and no unexpected adverse events were noted. CONCLUSION: Although benralizumab did not meet the primary efficacy endpoint, reductions of nasal polyp scores were seen in the benralizumab group compared with the placebo group over the whole study period, especially in patients with high levels of blood eosinophils.

Serum IgG4 as a biomarker reflecting pathophysiology and post-operative recurrence in chronic rhinosinusitis.

BACKGROUND: Type 2 chronic rhinosinusitis (CRS), especially eosinophilic CRS (ECRS), is an intractable upper airway inflammatory disease. Establishment of serum biomarkers reflecting the pathophysiology of CRS is desirable in a clinical setting. As IgG4 production is regulated by type 2 cytokines, we sought to determine whether serum IgG4 levels can be used as a biomarker for CRS. METHODS: Association between the serum IgG4 levels and clinicopathological factors was analyzed in 336 CRS patients. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of serum IgG4 levels that can be used to predict the post-operative recurrence. RESULTS: Serum IgG4 levels were significantly higher in patients with moderate to severe ECRS versus those with non to mild ECRS. The levels were also significantly higher in asthmatic patients and patients exhibiting recurrence after surgery compared to controls. ROC analysis determined that the best cut-off value for the serum IgG4 level to predict the post-operative recurrence was 95 mg/dL. The corresponding sensitivity and specificity were 39.7% and 80.5%, respectively. When we combined the two cut-off values for the serum IgG4 and periostin, patients with high serum levels of either IgG4 or periostin exhibited a high post-operative recurrence (OR: 3.95) as compared to patients having low serum levels of both IgG4 and periostin. CONCLUSIONS: The present results demonstrate that the serum IgG4 level is associated with disease severity and post-operative course in CRS. In particular, the combination of serum IgG4 and periostin could be a novel biomarker that predicts post-operative recurrence.

Periostin as a novel biomarker for postoperative recurrence of chronic rhinosinitis with nasal polyps.

We previously reported that chronic rhinosinusitis with nasal polyps (CRSwNP) was subdivided into four chronic rhinosinusitis (CRS) subtypes using the JESREC scoring system. We sought to identify the gene expression profile and biomarkers related with CRSwNP by RNA-sequence. RNA-sequencing was performed to identify differentially expressed genes between nasal polyps (NPs) and inferior turbinate mucosa from 6 patients with CRSwNP, and subsequently, quantitative real-time PCR was performed to verify the results. ELISA was performed to identify possible biomarkers for postoperative recurrence. In the RNA-sequencing results, periostin (POSTN) expression was the highest in NP. We focused on POSTN and investigated the protein level of POSTN by immunohistochemistry and ELISA. POSTN was diffusely expressed in moderate and severe eosinophilic CRS using immunohistochemistry, and its staining pattern was associated with the severity of the phenotype of the CRSwNP (P < 0.05). There was a significant difference between the POSTN high/low groups for postoperative recurrence when the cutoff point was set at 115.5 ng/ml (P = 0.0072). Our data suggests that the protein expression level of POSTN was associated with the severity of CRSwNP, and serum POSTN can be a novel biomarker for postoperative recurrence of CRSwNP.

Impact of the early detection of esophageal neoplasms in hypopharyngeal cancer patients treated with concurrent chemoradiotherapy.

AIMS: We examined the risk factors and prognostic factors for synchronous esophageal neoplasia (SEN) by comparing the characteristics of hypopharyngeal cancer (HPC) patients with and without SEN. METHODS: We examined 183 patients who were treated with definitive radiotherapy for HPC. Lugol chromoendoscopy screening of the esophagus was performed in all patients before chemoradiotherapy. RESULTS: Thirty-six patients had SEN, 49 patients died of HPC and two died of esophageal cancer. The patients with SEN exhibited significantly higher alcohol consumption than those without SEN (P = 0.018). The 5-year overall survival (OS) rate of the 36 patients with SEN was lower than that of the other patients (36.2% vs 63.4%, P = 0.006). The SEN patients exhibited significantly shorter HPC cause-specific survival than the other patients (P = 0.039). Both the OS (P = 0.005) and the HPC cause-specific survival (P = 0.026) of the patients with SEN were significantly shorter than those of the patients without SEN in multivariate analysis. Category 4/T1 stage esophageal cancer was treated with concurrent chemoradiotherapy (CCRT), endoscopic treatment or chemotherapy. The 5-year survival rates for esophageal cancer recurrence for CCRT, endoscopic treatment and chemotherapy were 71.5, 43.7 and 0%, respectively. The median (range) survival time (months) of CCRT, endoscopic treatment and chemotherapy was 22.7 (7.5-90.6), 46.44 (17.3-136.7) and 7.98 (3.72-22.8), respectively. CONCLUSION: Advanced HPC patients with SEN might have a poorer prognosis than those without SEN even when the esophageal cancer is detected early and managed appropriately.

Actinomycosis arising from the nasal cavity, with rare fatal progression.

Actinomycosis is a common treatable disease caused by Actinomyces, and generally has a good prognosis. However, we report a fatal case of actinomycosis of the nasal cavity. A 54-year-old man, reporting of left nasal obstruction, swelling and sharp pain around the root of the nose, was referred to our hospital. Histopathological examinations led to a definitive diagnosis of actinomycosis, and oral antibiotics were administered in an outpatient setting. However, the patient discontinued follow-up at the outpatient clinic because of the adverse effects of intravenous delivery, and poor compliance with oral antibiotic therapy led to him receiving a less than adequate dose. Thus, in the absence of sufficient antibiotic treatment, necrosis gradually progressed in the lesion, and the patient died of multiple organ failure and disseminated intravascular coagulation caused by local infection.

Treatment results and prognostic factors for advanced squamous cell carcinoma of the head and neck treated with salvage surgery after concurrent chemoradiotherapy.

BACKGROUND: For primary organ preservation, concurrent chemoradiotherapy (CCRT) is performed for advanced squamous cell carcinoma of the head and neck (SCCHN). In this organ-preservation setting with CCRT, surgery is reserved as a salvage treatment in cases of locoregional failure after CCRT. The purpose of the study was to review our experience with salvage surgery after CCRT for patients with SCCHN and to evaluate the effectiveness and prognostic factors affecting survival. METHODS: The records of patients with stage II-IVB SCC of the larynx, oropharynx, or hypopharynx treated with salvage surgery after CCRT between 1998 and 2012 were reviewed. RESULTS: A total of 645 patients with previously untreated, resectable SCC of the larynx, oropharynx, or hypopharynx received CCRT. Salvage surgery was performed for 78 of 225 patients with residual or recurrent tumors. The 5-year overall survival (OS) and disease-specific survival rates for patients who received salvage surgery were 61.0 and 65.5 %, respectively. Stage IV, poorly differentiated, synchronous double cancer, and surgical complications were significant predictors of unfavorable OS on multivariate analysis. Postoperative complications were observed in 30 patients (38.5 %). CONCLUSIONS: Salvage surgery is the best therapeutic option for failure after CCRT for SCCHN because of its good survival rate, although a high surgical complication rate is seen. Patients with initial stage IV tumors, poorly differentiated SCC, or synchronous double cancer are considered for further adjuvant treatment.

Three Cases of Acute Calcific Retropharyngeal Tendinitis.

Acute calcific retropharyngeal tendinitis is an inflammation of the longus coli muscle characterized by the acute onset of neck pain, swallowing pain, and limitations of neck movement. Although symptoms subside spontaneously within one to two weeks, many cases are treated with antibiotics because clinical outcomes are similar to a severe infection of the retropharyngeal area such as a retropharyngeal abscess. We report herein on 3 cases of acute calcific retropharyngeal tendinitis. The first and second cases were hospitalized, had many examinations and were diagnosed retrospectively. The third patient was treated as an outpatient after a CT scan. Typical CT imaging shows prevertebral soft-tissue swelling without ring enhancement, and amorphous calcification just anterior to the atlanto-axial joint, allowing us early diagnosis.

Concurrent Chemoradiotherapy with Docetaxel, Cisplatin and 5-Fluorouracil (TPF) in Patients with Nasopharyngeal Carcinoma.

BACKGROUND/AIM: Several randomized trials have shown that concurrent chemoradiotherapy (CCRT) either with or without adjuvant chemotherapy is more effective than radiotherapy-alone for treating nasopharyngeal carcinoma (NPC). The present study retrospectively evaluated the efficacy and toxicity of CCRT with docetaxel, cisplatin, and 5-fluorouracil (TPF) chemotherapy in patients with NPC. PATIENTS AND METHODS: The study regimen consisted of two cycles of TPF chemotherapy [docetaxel (90 mg/m(2)), cisplatin (60 mg/m(2)), and continuous 5-fluorouracil (600 mg/m(2)/day: 5 days)] during definitive radiotherapy. Radiotherapy was performed 5 days a week with a single daily fraction of 1.8 or 2.0 Gy totalling to 70-Gy doses. A total of 24 patients with NPC were enrolled and evaluated. RESULTS: Treatment completion rate was 70.8%, with an overall response rate of 100%. The 5-year overall survival rate was 82.4%, and 5-year progression-free survival rate was 78.3%. CONCLUSION: CCRT with TPF resulted in excellent survival rates for patients with NPC.

[Intratympanic Steroid Treatment for Severe Idiopathic Sudden Sensorineural Hearing Loss].

Systemic steroid therapy is the only standard drug therapy for severe idiopathic sudden sensorineural hearing loss (ISSHL). We have treated severe ISSHL patients with double combined therapy, intravenous steroids (IVS) and hyperbaric oxygen (HBO). In this study, we retrospectively examined the effects of intratympanic steroids (ITS) by adding it to the double combined therapy. The study subjects were 172 patients with severe ISSHL. Eighty patients (38 men and 42 women) were treated with the double combined IVS and HBO therapy between April, 2007 and July, 2010 (A group: Historical control arm). Ninety-two patients (51 men and 41 women) were treated with triple therapy, combined therapy with IVS and HBO plus ITS, between August, 2010 and October, 2013 (B group: Current protocol arm). Each group was divided into two subgroups; one with a pure-tone average (PTA) between 60 and 89 dB (A1 and B1) and the other with a PTA ≥ 90 dB. A 1, A2, B1, and B2 sub-groups had 56 (29 men, 27 women), 24 (9 men, 15 women), 64 (36 men, 28 women), and 28 (15 men, 13 women) patients, respectively. All patients were treated within 30 days from the onset. There was a statistically significant difference in hearing improvement between the A2 and B2 groups, whereas no significant difference was observed between the A1 and B1 groups. Furthermore, a significant difference was observed in all frequencies but 2 kHz between at the A2 group and B2 group, but not between the A1 and B1 groups. Multivariate logistic analysis revealed that the treatment method (double vs.. triple combined therapies) had the strongest impact on hearing improvement in the ISSHL patients with a PTA ≥ 90 dB. These results indicated that the B2 group demonstrated better hearing improvement than the A2 group and suggested that the addition of the ITS could be effective for profound ISSHL patients with a PTA ≥ 90 dB.

Differential expression of periostin in the nasal polyp may represent distinct histological features of chronic rhinosinusitis.

OBJECTIVE: Chronic rhinosinusitis (CRS) is thought to be a multifactorial disease, and it is classified into a number of subtypes according to clinicohistological features. Periostin, a 90-kDa secreted protein, was reported to exist in nasal polyps (NPs) associated with CRS. We compared the expression of periostin with the degree of eosinophilic infiltration as well as tissue remodeling. MATERIALS AND METHODS: Tissue samples were collected from 28 patients of CRS with NPs, and clinicohistological features were evaluated. The pattern of periostin expression was assessed immunohistochemically. RESULT: Two patterns of periostin expression was observed in nasal polyps: "diffuse type", in which periostin was expressed throughout the lamina propria starting just below the basement membrane, and "superficial type", in which the protein was detected only in the subepithelial layers between the basement membrane and the nasal gland. The average infiltrated eosinophil count in the diffuse type was significantly higher than that in the superficial type (diffuse type 360.5±393.0 vs. superficial type 8.46±13.81, p=0.001). Tissue remodeling was observed in 17 (85.0%) of the 20 diffuse-type nasal polyps, but only in one (12.5%) of the eight superficial-type nasal polyps (p<0.001). CONCLUSION: At least two distinct patterns of periostin expression were observed in the nasal polyps associated with CRS in accordance with the heterogeneous mechanisms underlying the pathogenesis of CRS with NPs.

Phase II study of concurrent chemoradiotherapy with S-1 in patients with stage II (T2N0M0) squamous cell carcinoma of the Pharynx or Larynx.

OBJECTIVE: The goals of treatment for head and neck cancer are cure and organ-function preservation. For organ preservation, primary treatment via radiotherapy alone is thought to be insufficient for Stage II squamous cell carcinoma of the larynx, oropharynx or hypopharynx. The objective of the present study was to investigate the efficacy and safety of concurrent chemoradiotherapy with S-1 for patients with Stage II squamous cell carcinoma of the pharynx or larynx for primary organ preservation. METHODS: Previously untreated patients with Stage II squamous cell carcinoma of the larynx, oropharynx or hypopharynx received three courses of S-1 (40 or 50 mg twice a day; 2 weeks of administration followed by 1 week of rest every 3 weeks) during conventional radiotherapy (a single daily fraction of 1.8 Gy) to a total dose of 70.2 Gy. The primary endpoint was the local control rate at 3 years. RESULTS: From August 2009 to October 2012, 37 patients were evaluated for the study. The overall response rate was 100%. The 3-year local control rate was 89.0% (95% confidence interval, 78.9-99.2%), and the 3-year overall survival rate was 97.2% (95% confidence interval, 91.8-100%). Mucositis and dermatitis in the radiation field were the most common acute adverse events observed. The rates of Grade 3 mucositis and dermatitis were 27 and 35%, respectively. No patients experienced Grade 4 acute adverse events. The treatment completion rate was 89.2%. CONCLUSION: Concurrent chemoradiotherapy with S-1 was safe and effective in improving local control for Stage II squamous cell carcinoma of the pharynx or larynx.

Temporary facial nerve dysfunction after parotidectomy correlates with tumor location.

OBJECTIVE: To investigate the clinical factors associated with temporary facial nerve dysfunction (TFND) following surgery for benign parotid gland tumors. METHODS: We reviewed the records of 175 patients with benign parotid gland tumors who underwent partial parotidectomy at Yokohama City University Medical Center in Japan. TFND was found in 33 patients (18.9%). We used two hypothetical lines in magnetic resonance imaging (MRI) images to define the tumor location (upper/lower or anterior/posterior) in the parotid gland. We then studied the associations of TFND with the following clinical factors: patient age, tumor size, histopathological diagnosis, and the location of the tumor within the parotid gland (superficial lobe/deep lobe; upper part/lower part; and anterior part/posterior part). RESULTS: Tumors located in the upper parts, anterior parts or the deep lobes of the parotid gland had statistically higher incidences of TFND compared with tumors located in the lower parts, posterior parts or the superficial lobe (P<0.001, <0.001, <0.01, respectively). The odds ratio for the risk of TFND was significantly high if tumors were located in the upper parts, the anterior parts or the deep lobes with stepwise multivariate regression analysis. The other factors, including patient's age, tumor size, histopathology of the tumor, and inadequate surgeon's experience, were not apparent risks for TFND. CONCLUSIONS: Parotid gland tumors located in the upper parts, the anterior parts or the deep lobes had a higher risk of TFND. The two hypothetical lines we used were shown to be useful to define the tumor location, eventually the risk of TFND.

Concurrent chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF) in patients with locally advanced squamous cell carcinoma of the head and neck.

OBJECTIVE: Compared with radiotherapy alone, concurrent chemoradiotherapy significantly improves survival rates for patients with squamous cell carcinoma of the head and neck. The aim of this study was to retrospectively evaluate the efficacy, toxicity and long-term prognosis of concurrent chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil chemotherapy. METHODS: A total of 140 patients were enrolled and evaluated. Patients were received two cycles of docetaxel, cisplatin and 5-fluorouracil chemotherapy (docetaxel [50 mg/m(2): Day 1], cisplatin [60 mg/m(2): Day 4] and continuous 5-fluorouracil [600 mg/m(2)/day: Days 1-5]) during definitive radiotherapy. RESULTS: The overall response rate was 97.1%. The 3 and 5-year overall survival rates were 83.3 and 79.2%, respectively. The 3 and 5-year disease-specific survival rates were 84.2 and 80.0%, respectively. Among patients with laryngeal or hypopharyngeal carcinoma, the 5-year laryngectomy-free survival rate was 64.9%. CONCLUSIONS: Concurrent chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil showed excellent survival and organ preservation rates for the patients with locally advanced squamous cell carcinoma of the head and neck.

Treatment results and prognostic factors for advanced squamous cell carcinoma of the larynx treated with concurrent chemoradiotherapy.

OBJECTIVE: To review our experience with concurrent chemoradiotherapy (CCRT) for patients with advanced resectable squamous cell carcinoma (SCC) of the larynx and to evaluate the factors affecting survival and larynx preservation. STUDY DESIGN: Retrospective study. SUBJECTS AND METHODS: The records of 102 patients with stage III or IV resectable SCC of the larynx treated with CCRT between February 1994 and March 2009 were reviewed. Of 102 patients, 59 were treated with high-dose regimens, including cisplatin, 5-fluorouracil (5-FU), methotrexate, and leucovorin or docetaxel, cisplatin, and 5-FU, and 43 were treated with low-dose regimens, including carboplatin and uracil-tegafur or S-1. Radiotherapy was delivered 5 days a week using a single daily fraction of 1.8­2.0 Gray (Gy), to a total dose of 66.0­70.2 Gy. Overall survival (OS), disease-specific survival (DSS), and DSS with larynx preservation were estimated using Kaplan­Meier methods. The log-rank test and Cox proportional hazards regression were used to identify significant prognostic factors for DSS and DSS with larynx preservation. RESULTS: The 5-year OS and DSS for all patients treated with CCRT were 63.9 and 70.7 %, respectively. The 5-year DSS with larynx preservation was 54.1 %. On multivariate analysis, N stage, synchronous multiple primary cancers, and the contents of chemotherapy were significant predictors of OS for patients undergoing CCRT; T stage, N stage, and the contents of chemotherapy were significant prognostic factors for larynx preservation. CONCLUSION: The treatment method including the indication for CCRT may be determined by the contents of the chemotherapy and the T and N stages of laryngeal SCC. It is important to diagnose multiple synchronous primary cancers before CCRT.

Comparison of concurrent chemoradiotherapy versus induction chemotherapy followed by radiation in patients with nasopharyngeal carcinoma.

PURPOSE: The study aimed to evaluate the efficacy of concurrent chemoradiotherapy (CCRT) with platinum-based chemotherapy as a primary treatment for nasopharyngeal carcinoma (NPC) and to further compare the results of CCRT with these of neoadjuvant chemotherapy (NAC) followed by radiotherapy (RT). PATIENTS AND METHODS: Before 1998, 21 patients with NPC received NAC followed by RT (NAC-RT). Between 1999 and 2008, a total of 25 NPC patients received CCRT. The CCRT group received a regimen including docetaxel (50 mg/m(2), day1), cisplatin (CDDP, 60 mg/m(2), day4) and continuous 5-fluorouracil (5-FU) infusion (600 mg/m(2), day 1-5), the TPF regimen, or a regimen including CDDP (60 mg/m(2), day4), continuous 5-FU infusion (600 mg/m(2), day 1-5), methotrexate (MTX, 30 mg/m(2), day 1) and leucovorin (LV, 20 mg/m(2), day 1-5), PFML regimen. The CCRT group received 2 cycles of chemotherapy during definitive RT. The NAC group of patients received a PFML regimen. RESULTS: The overall response rate after CCRT was 96%. The 3-year and 5-year disease-specific survival rates were 75.6% and 60.1%, respectively. In patients receiving NAC-RT, the 3-year and 5-year disease-specific survival rates were 84.1% and 67.3%, respectively. There was no difference observed in terms of survival rates between the group receiving CCRT and that receiving NAC-RT. CONCLUSION: CCRT with the TPF or PFML regimen was tolerable, and the NPC patients receiving this treatment showed excellent survival rates. In comparison to the group receiving NAC-RT, CCRT had no advantage in terms of the survival rate. In the future, the control of distant metastasis might play an important role in improving the survival rate of patients with advanced NPC receiving CCRT.

New clinical diagnostic criteria for eosinophilic chronic rhinosinusitis.

OBJECTIVE: Chronic rhinosinusitis is a heterogeneous disease. Most cases of chronic rhinosinusitis with nasal polyp(s) (CRSwNP) in Western countries show a strong tendency for recurrence after surgery and pronounced eosinophil infiltration in the nasal polyps. The prevalence of CRSwNP with pronounced eosinophilic inflammation is steadily increasing and is classified as eosinophilic chronic rhinosinusitis (ECRS) in Japan. However, less than 50% of CRSwNP patients in Japan and East Asia show such features. Since the treatment strategy of ECRS differs from that of non-ECRS, clinical diagnostic criteria that distinguish ECRS from non-ECRS are needed. METHODS: A total of 124 patients with CRSwNP patients who underwent endonasal sinus surgery were classified as ECRS or non-ECRS according to their clinical characteristics and the clinical features of the two groups were compared. Computed tomography (CT) images of the sinuses were graded according to the Lund-Mackay system. We also graded CT images of the olfactory cleft. Blood examination findings, sinus CT images and asthma complications were analyzed by multivariate logistic regression. Clinical findings that were significantly different between ECRS and non-ECRS were analyzed by receiver operating characteristic curves to determine optimal predictors of ECRS. RESULTS: Blood eosinophilia, asthma complications and CT image scores were significantly different between ECRS and non-ECRS. In particular, increased blood eosinophil percentage and CT image scores for the posterior ethmoid and the olfactory cleft showed good accuracy as predictors of ECRS. A combination of the cut-off values for three predictors (increased blood eosinophil percentage above the normal range, olfactory cleft score ≥1 and posterior ethmoid score ≥1) indicated high accurate diagnostic ability (sensitivity, 84.6%; specificity, 92.3%). CONCLUSION: A set of three clinical findings can differentiate ECRS from non-ECRS with high accuracy, even when these findings are assessed in regular outpatient clinics.

Eosinophilic chronic rhinosinusitis in Japan.

Chronic rhinosinusitis is a heterogeneous disease. In Europe and the United States, it has recently been divided into two subgroups: chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP). The majority of CRSwNP cases have a strong tendency to recur after surgery and show eosinophil-dominant inflammation. However, this definition has proved difficult to apply in Japan and East Asia, because more than half of the CRSwNP cases do not exhibit eosinophil-dominant inflammation in these areas of the world. In Japan in the 1990s, refractory CRSwNP to the standard treatment was focused on in clinical studies and the term "eosinophilic chronic rhinosinusitis" (ECRS) was introduced to identify this subgroup of chronic rhinosinusitis in 2001. ECRS is different from non-ECRS in terms of many clinical features: symptom appearance, occurrence site of nasal polyps, CT scan findings, the histology of nasal polyps, blood examination findings, clinical course after surgery, and co-morbid asthma, etc. In this review, we describe these clinical features and mention how to make a clinical diagnosis of ECRS as well as how to treat it. Finally, we discuss the pathophysiology of ECRS. The concept of ECRS in Japan would be applicable for CRSwNP in other countries including Europe and the United States.