Junichi Ishitoya

Yokohama City University, Yokohama, Kanagawa, Japan

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Publications (36)28.47 Total impact

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    ABSTRACT: Chronic rhinosinusitis (CRS) can be classified into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays more intense eosinophilic infiltration and presence of Th2 cytokines. Mucosal eosinophilia is associated with more severe symptoms, and often requires multiple surgeries because of recurrence; however, even in eosinophilic CRS (ECRS), clinical course is variable. In this study, we wanted to set objective clinical criteria for the diagnosis of refractory CRS. This was a retrospective study conducted by 15 institutions participating in the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC). We evaluated CRS patients treated with endoscopic sinus surgery (ESS), and risk of recurrence was estimated using Cox proportional hazard models. Multiple logistic regression models and receiver operating characteristics curves were constructed to create the diagnostic criterion for ECRS. We analyzed 1716 patients treated with ESS. To diagnose ECRS, the JESREC scoring system assessed unilateral or bilateral disease, presence of nasal polyps, blood eosinophilia, and dominant shadow of ethmoid sinuses in computed tomography (CT) scans. The cutoff value of the score was 11 points (sensitivity: 83%, specificity: 66%). Blood eosinophilia (>5%), ethmoid sinus disease detected by CT scan, bronchial asthma, aspirin and non-steroidal anti-inflammatory drugs intolerance were associated significantly with recurrence. We subdivided CRSwNP in non-ECRS, mild, moderate, and severe ECRS according to our algorithm. This classification was significantly correlated with prognosis. It is notable that this algorithm may give useful information to clinicians in the refractoriness of CRS before ESS or biopsy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Allergy 05/2015; DOI:10.1111/all.12644 · 6.00 Impact Factor
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    Allergology International 02/2015; 50(2). DOI:10.1016/j.alit.2014.10.006
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    ABSTRACT: IgG4-related disease is a syndrome characterized by hyper-IgG4 gamma-globulinemia and infiltration of tissues by IgG4+plasma cells. Although glucocorticoid therapy can improve both the symptoms and serum IgG4 concentrations, differential diagnosis from other similar disorders is necessary. We report the cases of 5 patients who presented with swelling of the salivary glands and elevated serum IgG4 concentrations, and were suspected as having IgG4-related disease. Of the 5 patients, 2 were histopathologically diagnosed as having IgG4-related disease, the diagnosis remained unclear due to a lack of biopsy findings in 2 patients, and the remaining 1 patient was diagnosed as having malignant lymphoma after follow-up for 3 years. To obtain a definitive diagnosis, histopathological examination may have to be performed several times.
    Practica Otologica 01/2015; 108(5):359-365. DOI:10.5631/jibirin.108.359
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    ABSTRACT: 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.
    Auris Nasus Larynx 09/2014; 42(2). DOI:10.1016/j.anl.2014.09.003 · 1.00 Impact Factor
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    ABSTRACT: 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.
    Nippon Jibiinkoka Gakkai Kaiho 06/2014; 117(6):802-8. DOI:10.3950/jibiinkoka.117.802
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    ABSTRACT: 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.
    Auris Nasus Larynx 05/2014; 41(5). DOI:10.1016/j.anl.2014.05.001 · 1.00 Impact Factor
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    ABSTRACT: 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.
    Allergology International 11/2013; 63(1). DOI:10.2332/allergolint.13-OA-0579
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    ABSTRACT: 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.
    Nippon Jibiinkoka Gakkai Kaiho 03/2013; 116(3):161-4. DOI:10.3950/jibiinkoka.116.161
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    ABSTRACT: 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). 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. 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. 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.
    Anticancer research 02/2012; 32(2):681-6. · 1.87 Impact Factor
  • Junichi Ishitoya, Yasunori Sakuma
    Arerugī = [Allergy] 05/2011; 60(5):535-45.
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    ABSTRACT: 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. 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. 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%). 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.
    Auris, nasus, larynx 03/2011; 38(5):583-8. DOI:10.1016/j.anl.2011.01.007 · 1.00 Impact Factor
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    ABSTRACT: 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.
    Cancer Chemotherapy and Pharmacology 09/2010; 66(4):729-36. DOI:10.1007/s00280-009-1217-0 · 2.57 Impact Factor
  • Junichi Ishitoya, Yasunori Sakuma, Mamoru Tsukuda
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    ABSTRACT: 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.
    Allergology International 09/2010; 59(3):239-45. DOI:10.2332/allergolint.10-RAI-0231
  • Nihon Kikan Shokudoka Gakkai Kaiho 01/2010; 61(1):8-14. DOI:10.2468/jbes.61.8
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    ABSTRACT: 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). 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. 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%). This is considered to be an effective regimen with acceptable toxicities for HNC.
    Japanese Journal of Clinical Oncology 11/2009; 40(3):214-21. DOI:10.1093/jjco/hyp153 · 1.75 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    International Journal of Clinical Oncology 09/2009; 14(4):337-43. DOI:10.1007/s10147-008-0874-z · 2.17 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    Cancer Chemotherapy and Pharmacology 03/2009; 64(5):945-52. DOI:10.1007/s00280-009-0946-4 · 2.57 Impact Factor
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    ABSTRACT: 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.
    Nippon Jibiinkoka Gakkai Kaiho 09/2008; 111(8):581-7. DOI:10.3950/jibiinkoka.111.581
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    ABSTRACT: Early glottic carcinoma has a good prognosis compared to other head and neck carcinomas, but we must aim for larynx preservation in the treatment. Regarding T1N0, larynx preservation rates are favorable even with radiotherapy alone. However for T2N0, the treatment strategies differ in each institution, and larynx preservation rates range from 72% to 85%, and are not high enough. We conducted a study to determine the efficacy of the concurrent chemoradiotherapy with S-1 for T2N0 glottic carcinoma. In this study, 12 patients with T2N0 glottic type laryngeal squamous cell carcinoma enrolled from the year 2004 to 2006, received one reduction dose of S-1 (80 or 100 mg/day) with concomitant irradiation with a total dose of 60-70 Gy (2.0 Gy/fr). The 2-week administration of S-1 followed by one-week rest was repeated during irradiation. In terms of adverse events of Grade 3 and above, Grade 3 mucositis and dermatitis were found in 2 patients each, but there was no cancellation nor interruption of S-1 or irradiation. All patients achieved pathological CR at the time of evaluation after the primary treatment, and no recurrences have been seen yet in any of the primary sites. Concurrent chemoradiotherapy with S-1 showed efficacy in T2N0 glottis carcinoma. Further investigation of this treatment with long-term follow up results is warranted.
    Gan to kagaku ryoho. Cancer & chemotherapy 06/2008; 35(5):789-92.