Shigeru Fukase

Treatment of Ranula with Intracystic Injection of the Streptococcal Preparation Ok-432

Intracystic injection of OK-432 was developed as a therapy for operatively difficult lymphangioma (cystic hygroma) and is currently becoming a treatment of first choice for this disease. We tried this therapy in 32 patients with ranula (oral floor type in 21 cases and plunging type in 11 cases). Disappearance or marked reduction of the lesion was observed in 31 patients (97%) who had this therapy, and local scarring did not occur in any patient. As side effects, local pain at the injection site and fever (37°C to 39°C) were observed in almost half of the patients who had this therapy, but such problems resolved within a few days. We treated the initial 4 cases in the hospital for 4 to 5 days, but after the safety of this method had been confirmed, we treated the other 28 cases on an outpatient basis. Thus, we confirmed that intracystic injection therapy with OK-432 is relatively safe and can be used as a substitute for surgery in the treatment of ranulas.

Clinical evaluation of sizofilan as assistant immunotherapy in treatment of head and neck cancer.

Sizofilan (SPG), a simple glucan produced in a culture medium by Schizophyllum commune Feries, was used as an assistant immunotherapy in 15 patients with head and neck cancer. The cumulative 5-year survival rate was 86.7% in the SPG-treated group and 73.4% in the control group. Immunological parameters showed that the SPG group quickly recovered the cellular immunity damaged by radiation, chemotherapy and surgical procedure. SPG was found to be effective as an assistant immunotherapeutic agent in the treatment of head and neck.

Eosinophil and Eosinophil Cationic Protein in Allergic Rhinitis

To evaluate the roles of eosinophils in allergic rhinitis, eosinophil cationic protein (ECP) levels in sera and nasal secretions were measured in 28 patients with allergic rhinitis. In patients, blood eosinophil counts and serum ECP levels were significantly higher than in controls (p < 0.05). However, there was no statistically significant correlation between blood eosinophil count and serum ECP level (r = 0.025). The number of eosinophils and the ECP level in nasal secretion were also measured. In patients, the ECP level increased with the number of eosinophils, and the ECP level in nasal secretion was significantly higher than in controls (p < 0.05). These results suggest that eosinophils and ECP play important roles in allergic rhinitis.

Effects and mechanism of OK-432 therapy in various neck cystic lesions

Abstract Conclusion: Our results confirmed that OK-432 therapy is simple, easy, safe, and effective and can be used as a substitute for surgery in the treatment of benign neck cysts. In OK-432 therapy, inflammatory cytokines may play important roles in shrinkage of the cystic spaces. Objective: The aim of this study was to evaluate the outcome and mechanism of action of OK-432 therapy in benign neck cysts. Methods: We tried OK-432 therapy in 83 patients with benign neck cysts between April 1997 and August 2009. We aspirated as much of the fluid content of each cystic lesion as possible, and then replaced the volume of aspirated fluid with about half the volume of OK-432 solution. We evaluated the mechanism of action of OK-432 in 43 of the patients. The intracystic fluid in the cysts was aspirated before and after OK-432 therapy, and cytokine production in each aspirate was analyzed by ELISA. Results: Disappearance of the lesion was observed in 63 of 83 patients (76%). Marked reduction was observed in 13 of the 83 patients (16%). Partial reduction was observed in two patients (2%) and no response was seen in five (6%). Local discomfort at the injection site and low-grade fever were side effects observed in half of the patients, but such problems resolved within a few days. No local scarring or deformity of the injected sites occurred in any patient. We performed OK-432 therapy on an outpatient basis without hospitalization. Levels of various cytokines, including tumor necrosis factor, interleukin-8, interleukin-6, interferon gamma, and vascular endothelial growth factor, were significantly elevated in each aspirate after OK-42 therapy.

Treatments of various otolaryngological cystic diseases by OK-4321: its indications and limitations.

OBJECTIVES/HYPOTHESIS The aim of this study was to evaluate the indications for, and outcomes and limitations of, OK-432 therapy in various otolaryngological cystic diseases. STUDY DESIGN A retrospective clinical study at Yamagata University School of Medicine and the Fukase Clinic in Japan. METHODS Between April 1996 and November 2009 we tried OK-432 therapy in 148 patients with otolaryngological cystic diseases. In cases of plunging ranulas, lymphangiomas, branchial cleft cysts, thyroglossal duct cysts, thyroid cysts, and cervical lymphocele, we aspirated as much of the fluid content of each cystic lesion as possible, and we then replaced the volume of aspirated fluid with about half the volume of OK-432 solution. RESULTS Disappearance of the lesion was observed in 119 of 148 patients (80%). Marked reduction was observed in 20 of 148 patients (14%). Partial reduction was observed in four patients (3%), and no response was seen in five patients (3%). Plunging ranula, lymphangioma, thyroglossal duct cyst, thyroid cyst, auricular hematoma, and salivary mucocele showed better responses to OK-432 therapy than did branchial cleft cyst. Serious complications with OK-432 therapy were infrequent, and the therapy seemed to have no influence on future surgery. CONCLUSIONS Our results confirmed that OK-432 therapy is simple, easy, safe, and effective and can be used as a substitute for surgery in the treatment of various otolaryngological cystic diseases.

Immunological responses in acute low-tone sensorineural hearing loss and Ménière's disease.

Objective--The autoimmune response appears to play an important role in some types of acute sensorineural hearing loss. Endolymphatic hydrops associated with fluctuating hearing loss has also been suggested to be caused by an immunological mechanism. Acute low-tone hearing loss (ALHL) associated with Ménières disease (MD) is characterized by fluctuating hearing loss, and its etiology is thought to involve endolymphatic hydrops. The aim of this study was to attempt to determine the etiology of ALHL in MD. Material and methods--A flow cytometer was used to analyze intracellular cytokine levels in peripheral blood from 19 patients with ALHL and 26 patients with MD and the data compared to those obtained from age- and gender-matched healthy volunteers. Results--The patients with ALHL showed significantly increased levels of Th1 subsets (interferon-gamma-producing helper T cells) as compared to those in normal controls. The levels of Th2 (IL-4-producing helper T cells) subsets did not differ from those in the control group and thus Th1 predominated in ALHL patients. The patients with MD showed significantly increased natural killer cell activity but no Th1 dominance. These patients had no obvious systemic or local disease except in the inner ear. Conclusion--An abnormality of the Th1/Th2 balance in ALHL and increased natural killer cell activity in MD are thought to relate to inner ear disorder. These results are consistent with the possibility that the etiology of ALHL and MD involves an immune response.

Serum levels of soluble adhesion molecules ICAM-1, VCAM-1 and E-selectin in patients with Wegener's granulomatosis

OBJECTIVE To examine the role of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), and soluble E-selectin (sE-selectin) in the pathogenesis of Wegeners granulomatosis (WG) and the values of measuring serum levels of these soluble adhesion molecules for monitoring disease activity during follow-up, a total of 24 serum samples from 16 patients with WG were studied. METHODS The serum concentrations of soluble adhesion molecules (sICAM-1, sVCAM-1 and sE-selectin) and cytokines (tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6)) of patients with WG were measured by ELISA. RESULTS The serum levels of sICAM-1 were significantly elevated in active WG and correlated with disease activity. At the time of relapse, a significant increase of sICAM-1 was also observed. The serum levels of TNF-alpha and IL-6 were also significantly elevated in active WG. CONCLUSION These findings suggest that sICAM-1 plays an important role in the pathogenesis of WG and may be used as an additional parameter of disease activity.

Treatment of auricular hematoma by OK-432

Objectives: Intralesional injection therapy with OK-432 was developed as a therapy for operatively difficult lymphangioma (cystic hygroma) and is currently becoming a first-choice treatment for this disease. The aim of this article was to evaluate the outcome and complications of the treatment of patients with auricular hematoma by OK-432 therapy. Study Design: Case series with planned data collection. Setting: Yamagata University School of Medicine. Subjects and Methods: We tried this therapy in 21 patients with auricular hematoma between January 2001 and February 2009. We injected OK-432 solution into the lesion with a 27-gauge needle to prevent the leak of the agent out of the hematoma. We performed this treatment on an outpatient basis without hospitalization. Results: Disappearance or marked reduction of the lesion were observed in all patients who had this therapy, and local scarring and deformity of the auricle did not occur in any patients. As for side effects, local pain at the injection site and fever (37°C-38°C) were observed in a few of the patients who had this therapy, but such problems resolved within a few days. Conclusion: These results may allow us to speculate that intralesional injection therapy with OK-432 is simple, easy, safe, and effective and can be used as a substitute for surgery in the treatment of auricular hematoma.

Treatment of salivary mucocele of the lower lip by OK-432

OBJECTIVE The aim of this paper was to evaluate the outcome and complications of the treatment of patients with salivary mucocele by intralesional injection therapy with OK-432. METHODS We tried OK-432 therapy in 20 patients with salivary mucocele. We injected OK-432 solution into the lesion with a 27-gauge needle to prevent any leakage of the agent from the mucocele. RESULTS Disappearance of the lesion was observed in 16 of 20 patients. Marked reduction was observed in 4 of 20 patients. No local scarring or deformity of the lower lip occurred in any patients. As side effects, local discomfort at the injection site was observed in two of the patients, but such problems resolved within a few days. We performed this treatment on an outpatient basis without hospitalization. CONCLUSION Our results confirmed that OK-432 therapy is simple, easy, and relatively safe, and can be used as a substitute for surgery in the treatment of salivary mucocele.

Increase of Th2 and Tc1 cells in patients with Kimura's disease

OBJECTIVE A Th1/Th2 cytokine imbalance with a predominance of Th2 cytokines has been suggested to be of pathogenic importance in Kimuras disease. METHODS To evaluate the role of Th1/Th2 cytokines in Kimuras disease, the subsets of Th1, Th2, Tc1 and Tc2 cells from patients with Kimuras disease were examined by intracellular cytokine flow cytometry. The expressions of IL-5, eotaxin and RANTES in the lesions were investigated by RT-PCR. RESULTS The population of Th2 and Tc1 cells in Kimuras disease was significantly increased compared with these cells in control (p<0.05). Th1 and Tc2 cells in Kimuras disease were not significantly increased compared with control subjects. The titers of IgE and the number of Th2 cells were correlated. The expression of IL-5 and RANES was observed in the lesions of patients with Kimuras disease. CONCLUSION These results indicate that the predominance of Th2 and Tc1 cells might contribute to the mechanism in pathogenesis of Kimuras disease.