IL-22/IL-22R1 signaling regulates the pathophysiology of chronic rhinosinusitis with nasal polyps via alteration of MUC1 expression.

BACKGROUND: IL-22 is an IL-10-family cytokine that regulates chronic inflammation. We investigated the role of IL-22 and its receptor, IL-22R1, in the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: IL-22 and IL-22R1 protein and mRNA expression in NP and in uncinate tissues (UT) from CRS and non-CRS patients was examined using immunohistochemistry and real-time PCR, respectively. Dispersed NP and UT cells were cultured with the Staphylococcus aureus exotoxins, staphylococcal enterotoxin B and alpha-toxin, following which exotoxin-induced IL-22 levels and their association with clinicopathological factors were analyzed. Effects of IL-22 on MUC1 expression and cytokine release in NP cells were also determined. RESULTS: IL-22 and IL-22R1 in NP were mainly expressed in infiltrating inflammatory cells and in epithelial cells, respectively. IL-22 mRNA levels in NP were significantly higher than those in UTs from non-CRS patients whereas IL-22R1 levels were conversely lower in NPs. NP cells produced substantial amounts of IL-22 in response to exotoxins. Exotoxin-induced IL-22 production by NP cells significantly and negatively correlated with the degree of local eosinophilia and postoperative computed tomography (CT) score, whereas conversely it positively correlated with the forced expiratory volume in 1s (FEV1)/forced vital capacity (FVC) ratio. IL-22 significantly enhanced MUC1 mRNA expression in NP cells. IL-22-induced MUC1 mRNA levels were significantly and positively correlated with IL-22R1 mRNA levels in NPs. CONCLUSIONS: These data suggest that imbalance of IL-22/IL-22R1 signaling regulates the pathogenesis of CRSwNP, including local eosinophilia, via alteration of MUC1 expression.

[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.

[Efficacy of intratympanic steroid treatment for idiopathic sudden sensorineural hearing loss after failure of intravenous steroid treatment].

This study investigated the efficacy of intratympanic steroid (ITS) therapy as a salvage treatment for idiopathic sudden sensorineural hearing loss after failure of intravenous steroid (IVS) therapy. Systemic steroid therapy is the only standard drug therapy. However, ethically, we could not simply compare ITS with IVS. Conventionally, we have treated idiopahic sudden sensorineural hearing loss patients after failure of systemic steroid therapy with the double combined therapy IVS and hyperbaric oxygen (HBO), as the salvage modality. We examined the effect of ITS by adding it to the double combined therapy with IVS and HBO. Retrospectively, we clinically examined the effect of double combined therapy with IVS and HBO (A group) for 31 patients (12 men and 19 women) (median age: 54 years) with sudden hearing loss after failure of systemic steroid therapy between June, 2003 and July, 2010. Prospectively, we also examined clinically the effect of triple combined therapy with IVS and HBO, ITS (B group) for 29 patients (17 men and 12 women) (median age: 51 years) with sudden hearing loss after failure of systemic steroid therapy between August, 2010 and April, 2012. In the examination of patients treated within 30 days from the onset, one patient (3.2%) demonstrated remarkable recovery, 6 patients (19.4%) demonstrated mild recovery, while no change was noted in 24 patients (77.4%) in the A group. In the B group, 5 patients (17.2%) demonstrated complete recovery, 3 patients (10.3%) demonstrated remarkable recovery, mild recovery was seen in 14 patients (48.3%), and the remaining 7 patients (24.1%) showed no change. There was a significant difference (p < 0.05) between the A group and the B group. Furthermore, the hearing improvement in group B in five pure tone average was significantly better than in the group A (p < 0.05). We concluded that the B group demonstrated better hearing improvement than the A group. Therefore, ITS could be effective for idiopathic sudden sensorineural hearing loss patients after failure of systemic steroid therapy.

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.

Lung functions of Japanese patients with chronic rhinosinusitis who underwent endoscopic sinus surgery.

BACKGROUND: Chronic rhinosinusitis (CRS), which is clinically classified into CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP), shows considerable geographic differences and heterogeneity. Eosinophilic (E) CRS with nasal polyps (ECRSwNP) has a higher degree of disease severity and higher frequency of comorbid asthma. Epidemiologic studies in different ethnic populations have improved understanding of the pathophysiology of the disease. Here we report the clinical characteristics of Japanese patients with medically refractory CRS undergoing endoscopic sinus surgery (ESS). METHODS: We recruited a total of 210 CRS patients and assessed them by nasal endoscopy, the Lund-Mackay score using computed tomography (CT), peripheral eosinophilia and smoking status. We also examined the comorbidity of asthma, effects of age and lung functions in the patients. RESULTS: In this study, 13% of CRSwNP patients and 20% of CRSwNP patients with peripheral blood eosinophilia exhibited obstructive lung dysfunction (FEV1/FVC <70%) despite the absence of an asthma diagnosis. Among elderly nonsmoker patients (≥ 60 years) who had never been diagnosed with asthma, 50% of CRSwNP patients with peripheral blood eosinophilia showed decreased FEV1/FVC <70%. CONCLUSIONS: Our findings suggest that asthma is under-diagnosed in CRS patients who undergo ESS, especially the elderly. Although the association between CRS and asthma has been recognized, increased attention to the comorbidity of obstructive airway diseases such as asthma is still needed for management of medically refractory CRS.

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.

[A case report: a repeated cerebrospinal fluid otorrhea].

Cerebrospinal fluid (CSF) otorrhea, leakage of CSF through the ear structures, may occur from a traumatic or operative defect in the skull, tumor, cholesteatoma, or congenital anomalies. A case of repeated CSF otorrhea is uncommon. In this report, we presented a case of a repeated CSF otorrhea which occurred a decade after the first middle ear surgery for chronic otitis media. The first CSF leakage, which might have been due to bone defects in the tegmen at the first middle ear sutgery, was surgically repaired using a transmastoid approach. However, CSF leakage with a meningoencephalocele occurred again 8 years after our first surgery for the CSF and the fistula was repaired using a transmiddle cranial fossa approach. Although 2 years have passed since the surgery, the CSF leakage has not recurred.

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.

Randomized controlled phase II comparison study of concurrent chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil versus CCRT with cisplatin, 5-fluorouracil, methotrexate and leucovorin in patients with locally advanced squamous cell carcinoma of the head and neck.

We compared concurrent chemoradiotherapy (CCRT) with docetaxel, cisplatin (CDDP), and 5-fluorouracil (5-FU) (TPF) with CCRT with CDDP, 5-FU, methotrexate and leucovorin (PFML) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) in terms of safety and efficacy on survival. A total of 100 patients were enrolled. The TPF group received CCRT with the TPF regimen [docetaxel (50 mg/m(2): day 1), CDDP (60 mg/m(2): day 4), and continuous 5-FU infusion (600 mg/m(2)/day: days 1-5)]. In the PFML group, patients received CCRT with the PFML regimen [CDDP (60 mg/m(2): day 4)], continuous 5-FU infusion (600 mg/m(2)/day: days 1-5), methotrexate (30 mg/m(2): day 1) and leucovorin (20 mg/m(2)/day: days 1-5)]. Both groups received 2 cycles of chemotherapy during definitive radiotherapy. The total radiation dose was between 66.6 and 70.2 Gray. The overall response rates after CCRT were 98 with 90% of a pathologically complete response (pCR) in the TPF group and 94 with 77% in the PFML group. For grade 3/4 adverse events, mucositis was more frequent in the PMFL group, and the TPF group showed a higher incidence of hematological toxicity. CCRT with TPF or PMFL for advanced SCCHN was tolerable and produced excellent survival rates.

Phase I/II study of s-1 plus cisplatin combination chemotherapy in patients with advanced/recurrent head and neck cancer.

OBJECTIVE: The objectives of this study were to determine the maximum tolerated dose (MTD) and recommended dose (RD) of S-1 plus cisplatin (CDDP) and to evaluate safety and efficacy using the defined RD in advanced/recurrent head and neck cancer (HNC). METHODS: S-1 was administered orally at 40 mg/m(2) twice daily for 14 consecutive days, and CDDP was infused on day 8 at a dose of 60 and 70 mg/m(2). Each course was repeated every 4 weeks. RESULTS: A total of 38 patients were registered, 10 patients for the Phase I study and an additional 28 patients for the Phase II study. Although no dose-limiting toxicity (DLT) was observed in the CDDP 60 mg/m(2) (Level 1) group, two of six patients in the CDDP 70 mg/m(2) (Level 2) group exhibited DLT (fatigue/diarrhea). The MTD was not achieved in the Phase I study. Level 2 was therefore determined as the RD. In the Phase II study, 34 patients, including 6 patients from the Phase I study, were evaluated. At the termination of treatment, the confirmed response rate was 44.1% (15/34, 95% CI: 27.4-60.8). The best response rate without an adequate duration time was 67.6% (95% CI: 51.9-83.4). The median survival period was 16.7 months, and the 1-year survival rate was 60.1%. The main toxicities of Grade 3 or above were anorexia (26.5%), nausea (14.7%), neutropenia/thrombocytopenia (11.8%) and anemia/fatigue (8.8%). CONCLUSIONS: This is considered to be an effective regimen with acceptable toxicities for HNC.

Antiemetic effects of granisetron and dexamethasone combination therapy during cisplatin-containing chemotherapy for head and neck cancer: dexamethasone dosage verification trial.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) remains a significant problem for patients and is associated with a substantial deterioration in quality of life; appropriate use of antiemetic drugs is crucial in maintaining the quality of life in patients undergoing chemotherapy. METHODS: This randomized, crossover trial evaluated the antiemetic efficacy and safety of 8 mg per day (low-dose) and 16 mg per day (standard-dose) dexamethasone, in combination with the 5-HT(3) receptor antagonist granisetron, in 36 patients receiving cisplatin (CDDP)-containing chemotherapy for head and neck cancer. Following chemotherapy, the antinausea/vomiting inhibition rate for each dexamethasone dose was measured. RESULTS: During the 24-h period following administration of chemotherapy (acute phase), the antinausea/vomiting inhibition rates (no nausea and no episodes of vomiting) for 8 mg and 16 mg dexamethasone were comparably high (58.3% and 63.8%, respectively; P = 0.8092). Similar results were seen on days 2-5 following chemotherapy. Efficacy during the acute phase, based on the number of instances of vomiting and degree of nausea, was also comparably high for the two dexamethasone doses (overall efficacy rates were 94.4% and 88.8%, respectively, for 8 mg and 16 mg dexamethasone; P = 0.7637). Both doses maintained an 80% or higher response rate until day 3, and neither dose produced severe side effects. CONCLUSION: The results suggest that granisetron and dexamethasone combination therapy is useful in controlling acute and delayed nausea and vomiting induced by CDDP-containing chemotherapy for head and neck cancer. Furthermore, 8 mg and 16 mg dexamethasone have equivalent antiemetic efficacy.

Analysis of feasibility and toxicity of concurrent chemoradiotherapy with S-1 for locally advanced squamous cell carcinoma of the head and neck in elderly cases and/or cases with comorbidity.

PURPOSE: The aim of this study was to evaluate the feasibility and toxicity of concurrent chemoradiotherapy (CCRT) with S-1 in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) in elderly cases and/or cases with comorbidity. METHODS: Fifty eligible patients with stage III (15 cases) or stage IV (35 cases) SCCHN were treated with CCRT. Thirteen cases had an advanced age of over 75 years and 37 cases had comorbidity. Definitive radiotherapy was delivered up to a total dose of 66-70.2 Gy. The patients received two courses of oral S-1 (40 or 50 mg twice a day [80 or 100 mg/day]) for 2 weeks followed by 1 week of rest while receiving CCRT. RESULTS: All the patients received the planned radiotherapy and at least one course of S-1. Grade 3 mucositis occurred in 20% of the patients (10/50). Grade 3 neutropenia occurred in 12% (6/50) and leukocytopenia occurred in 6% (3/50) of the cases. Pathologically, the complete response rates were 93% in stage III and 54% in stage IV. CONCLUSION: Concurrent chemoradiotherapy with S-1 is a safe, well-tolerated and effective regimen for locally advanced SCCHN in elderly cases and/or cases with comorbidity.

[A study of surgical procedures for inverted papilloma in the nasal cavity and paranasal sinuses].

Inverted papilloma, although benign, recurs frequently and may become malignant, making definitive initial resection extremely important. We evaluated surgical procedures for recurrence and sites, with special reference to management of the orbital plate of the ethmoid and lacrimal bones, in 24 patients (32 cases) with inverted papilloma of the nasal cavity and paranasal sinuses undergoing surgical resection from 2000. Nine of the 32 showed recurrence, all around the ethmoid orbital plate. Up to 2002, recurrence was noted in 7 of 17 cases (41%), so we changed surgical selection criteria. Since 2003, we have conducted partial and combined excision of the orbital plate of the ethmoid and lacrimal bones (extended operation of the extranasal ethmoid and frontal sinuses) in cases in which tumors adhered to the orbital plate, noting recurrences in only 2 of 15 cases (13%). A number of reports advocate endoscopic sinus surgery to minimize invasiveness for inverted papilloma, but partial and combined excision of the orbital plate is indispensable, in progressive inverted papilloma cases to reduce recurrent.