Intra-arterial chemotherapy is useful to improve the prognosis by preserving the functions of eating, swallowing, and speech in oral cancer and pharyngeal cancer. Arterial catheterization was performed via branches of the external carotid artery (the superficial temporal artery, the occipital artery, and the superior thyroid artery) and the femoral artery by using the Seldinger technique . CDDP, CBDCA, Peplomycin, and 5-FU are mainly infused in the artery with or without concurrent radiation therapy. From April 1993, we treated 26cases of pharyngeal cancer (stages I: 2, II: 6, III: 4, and IV: 14) and 32cases of oral cancer (stages I: 7, II: 16, III: 1, and IV: 8) by a combination of intra-arterial infusions of CBDCA or BLM and radiation therapy with or without surgery . The 3-year survival rate by the Kaplan-Meier method was 70% and 88%, respectively.

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Allergic stomatitis apparently caused by allergic reactions to drugs and metals used in dental practice.
Drug eruptions range from minimal, such as maculopapular, urticaria, and fixed drug eruption, to extensive, such as Stevns-Johnson syndrome and toxic epidermal necrosis (Lyell syndrome). Associated fever, malaise, arthralgia, and oral mucosal lesions may extend into the vermilion border of the lip, and erythema exsudativum multiform rapidly coalese, we should be considered the possibility of Stevens-Johnson syndrome and Lyell syndrome.
Clinical diagnosis can be made accurately where characteristic cutaneous lesions are present . In patients with localized oral mucosal lesions without cutaneous lesions, diagnosis is very difficult. They should be carefully questioned regarding topical and oral medications . Prompt therapeutic intervention early on in drug eruptions may limit toxicity, and systematic steroid therapies will speed the rate of healing. Patients with moderate to severe diseases are usually started on predonin 60mg/day.
Dental metal eruptions involve oral mucosa and cutaneous regions, as well as drug eruptions. We observed mucocutaneous diseases such as pigmentation changes (amalgam tattoo), lichen planus, glossodynia, and pustulosis palmaris et plantaris as a result of mercury, copper, nickel, and gold. In each case a patch test was performed and the metal samples were analyzed by an electron probe micro-analyzer (EPMA). After the removal of allergen, the complaints decreased.
A patch test and EPMA both confirmed the diagnosis of dental metal allergy. Patients with uncertain mucocutaneous diseases that are unresponsive to conventional therapy should suspect dental metal allergy.

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urrent aphtha is a disease featured by
(1) A single or a few legions occupying the anterior part of the mouth, tongue, buccal mucosa, and pharyngeal mucosa;
(2) No major symptomes except localized pain;
(3) Lack of tendency to adhere;
(4) Healing generally without scarring after a 1 week interval;
(5) Unknown causes.
The local apperance of the lesion and the clinical course are important for diagnosis.
A local application of steroid ointment is the main treatment. A peroral intake of vitamins, antihistamin, and kampo medications are also reported to be effective.
Some patients may encounter a transformation from recurrent aphtha to Behcet's disease or an intractable recurrent ulcer of the oral cavity and pharynx.

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The relationship of adenoids and the middle ear, particularly the etiological role of the middle ear in the pathogenesis of otitis media with effusion (OME) in children was discussed by reviewing literature and a sequence of our clinical research.
1. Adenoids were considered related to the pathogenesis of OME as a source of inflammation and infection affecting the middle ear instead of as a mass compressing the eustachian tube and impairing middle-ear ventilation.
2. An adenoidectomy was considered to improve inflammatory conditions in the upper respiratory tract represented by sinusitis, and subsequently to partially improve the eustachian tube function in the later stage.
3. A short-term effect of adenoidectomy on OME was reconfirmed, but its long-term effect was the same as tympanostomy tube insertion. The effect of adenoidectomy on refractory OME, such as with hypopneumatized mastoid or organic abnormality in the eustachian tube, was found to be limited.
4. The recommendation of an adenoidectomy was considered when children with OME had sinusitis and/or when their OMEs needed to be cured, for example, their OME accompanied recurrent otitis media.

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We examined the clinical usefulness of the tonsillar provocation test in a patient with pustulosis palmoplantaris (PPP). To determine the usefulness of this test, we discussed the following: 1) its diagnostic value as a focal test, 2) referral to a dermatologist for the diagnosis of focal infection, 3) an explanation to the patient concerning tonsillar focal infection.
It has already been reported by the Committee for the standardization of diagnostic criteria for tonsillar focal infection that the test may have poor low diagnostic value as a focus test.
We investigated its reliability with regard to the prognosis of tonsillectomy by using an increasing ratio of WBC or neutrophil as new parameters besides the current standard. The results showed that it had insufficient diagnostic value.
However, to reassure dermatologists and patients, it is believed that some clinical tests of this kind should still be done in the approach to otolaryngeal problems.
With these clinical matters being considered, this test seems to be helpful for diagnosing tonsillar focal infection until a more useful provocation test is developed.

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The key for the surgical treatment of tumors of the tongue base is to select the optimum approach to the pharyngeal portion of the tongue. Three approaches to the tongue base where the tumor was located were shown in the VTR symposium at the 11th annual meeting of the Japan Society of Somato-pharyngology. One approach was an oropharyngeal microsurgical enucleation with CO2 laser irradiation for a branchiogenic cyst at the valeculla. The others were a lateral pharyngotomy with a pull-through procedure of the tongue for SCC of the tongue base and a mandibular swing approach for an oropharyngeal carcinoma that recurred at the tonsil and extended to the pharyngeal portion of the tongue and the posterior wall of the pharynx.
The complete removal of lesions at the pharyngeal portion of the tongue is highly important to selecting an optimum approach that can gain a wide operative field and to observing and resecting the tongue base from the lateral view, especially in cases of malignant lesions.

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We report two kinds of reconstructive methods following segmental resection of the mandible because of intraoral malignancy: the scapular osteocutaneous flap and the fibular osteocutaneous flap.We choose either of these methods according to the condition of defect. The former has a characteristic enabling its bone flap to be made bipedicled, and an osteotomy within the flap is safely possible. So it is suitable for a repair to be made in the curved front part of the mandible. As for the fibular flap, osteotomy may injure the blood circulation in the bone flap, which is less than that of the scapular bone flap.The 3-dimensional relationship between bone flap and skin flap is more restricted in the fibular flap than in the scapular flap.The skin flap adheres closely to the bone flap in the fibular flap.However, the great advantage of the fibular flap is the shortness of total operating time, since its harvestiing procedure can be done simultaneously with tumor ablation. Our first choice for reconstruction is the flbular flap if the defect condition permits. We employ the scapular flap only in irreplaceable cases.
Two illustrative cases are presented. Case 1 is a 56-year-old male patient who suffered cancer of the oral floor. Bilateral neck dissection, total glossectomy, laryngectomy, and segmental resection of the front part of the mandible were carried out. We performed reconstructive surgery by using scapular osteocutaneous flap.Osteotomy within the bone flap was done to make a natural curvature of the front part of the mandible. Case 2 is a 51-year-old female patient who suffered an osteosarcoma in her left mandible and a segmental mandibulectomy from the left No .5 tooth to the condylar head was done. We reconstructed the partial body and total ramus of the mandible by using fibular osteocutaneous flap.

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Apoptosis is a mechanism involved in physiological cell death, as opposed to necrosis, which is pathological cell death. In the immune system, especially, apoptosis plays an important role in the removal of autoimmune lymphocyte clones in the thymus and bone marrow. Recent studies have provided suggestive information that B cells, which produce antibodies with low affinity to antigen or that fail to receive a signal of activation from T cells, may be removed by apoptosis in the lymphoid follicles which provides the site of maturation for B cells. Because of this information, we carried out an immunohistological investigation of human tonsils to identify the stages of B cell differentiation involving apoptosis, of antigen special relationships with follicular dendritic cells, and of functional T cells engaging in important in relation to antigen presentations. As a result, apoptotic cells scattered mainly in the dark and basal light zones in the lymphoid follicle, especially in the basal light zone. On the other hand, apoptotic cells were sparse in the apical light and mantle zones in the lymphoid follicle and outside it. Many B cells in the dark zone were positive for Ki-67 antigen and were in the mitotic phase of the cell cycle. Moreover, B cells had already begun to mature for antigen affinity in this zone. These findings suggest that apoptosis in the dark zone operates in response to excessive propagation of B cells and also removes low-affinity antibody-producing B cells and non functional B cells produced as a result of somatic point mutation in the immunoglobulin variable region genes. In the basal light zone, however, they were almost Ki-67 negative. This zone contained many activated T cells and immunocomplex-bearing follicular dendritic cells. Based on these findings, apoptosis in this zone is presumed to concern the selection in the stage of antigen affinity maturation. B cells in the apical light zone were found to express differentiated antigen CD23 and activated antigen CD86. Many activated T cells were also present in this zone. Therefore, this zone may be where selected B cells, which produce high-affinity antibodies to antigen, differentiate to memory B cells or preplasma cells that will leave the lymphoid follicle.

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The upper respiratory tract is at the uppermost end of the respiratory organ and is one of the most common sites of infection. Especially, we repeatedly encounter infections of the palatine tonsil in our daily clinical work.
In this paper, we examined the experimental and clinical research on palatine tonsil in Japan for the past 10 years. Excellent experimental and clinical research has been performed in Japan during this time.
We also investigated bacteria isolated from cases of acute lacunar tonsillitis from 1993 to 1997 and compared the findings with data from 1988. The results indicated no differences in the isolated bacteria from these two investigations. The ratio of Methicillin-resistant S. aureus (MRSA) isolated was low, but that of Penicillin G insensitive (resistant) S. pneumoniae [PI (R) SP] has been increasing recently.
The reports on bacteria isolated from peritonsillar abscess have also been summarized. The data indicate that we must pay attention to detecting anaerobes correctly. They were detected in more than half the cases. Among anaerobes, Peptococcus, Peptostreptococcus, and Bacteroides were the major bacteria isolates.
We studied normal bacterial flora of the palatine tonsil in subjects without otolaryngological disease ranging in age from newborn to 84 years. We found that normal flora started to develop 3 hours after birth in the neonatal palatine tonsil. The ratios of gram-positive bacteria and gram-negative bacteria detected decreased with aging. The detected ratio of anaerobes increased with advancing age.
We also studied the bacterial biofilm of the palatine tonsil. We examined 86 tonsils from habitual angina patients who underwent tonsillectomies. We found that S. pyogenes-producing biofilm survived even under conditions of an above-minimal inhibitory concentration of Cephotiam. We stress that we must pay attention to how antibacterial agents we use.

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IgA is the predominant immunoglobulin effector molecule of mucosal immunity functioning as the first line of specific immunological defense against many microbial pathogens. However, IgA causes IgA nephropathy, which was reported to perhaps be associated with colonization with Haemophilus parainfluenzae (HP). In this study we investigated whether tonsillar mononuclear cells from patients with IgA nephropathy produce HP-specific IgA and/or IgA-related cytokines by stimulation with the components of HP outer membranes (OMHP). As a result of this study, HP-specific IgA was predominately induced by the tonsillar mononuclear cells of IgA nephropathy, compared with those from chronic tonsillitis.The production of IL-10 and TGF-βwas enhanced by stimulation with OMHP in tonsillar mononuclear cells from IgA nephropathy. These results suggested that local infection of HP and HP-specific IgA induction in the tonsil may be associated with the pathogen in IgA nephropathy.

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Diseases resulting from tonsillar focal infection have attracted great interest by physicians, pediatrists, orthopedists, and dermatologists.
In 1978, we reported data on these disorders obtained from dermatological departments of medical schools in Japan.
We have again sent out questionnaires to physicians, pediatrists, orthopedists, and dermatologists, using a similar method, to acquire knowledge about the treatment of related disorders . The present data were from replies from 57 orthopedic, 51 dermatologic, 77 medical, and 38 pediatric departments in Japan.
In this report, many diseases were referred to secondary diseases, possibly a result of focal infection, thus indicating the variety of these diseases.
And their problem would be important for otorhinolaryngologists to investigate.

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Twenty patients with mucoepidermoid carcinoma of the parotid glands, treated in our clinic from 1966 to 1998, were reviewed with attention to clinical features, histopathological grading of malig nancy, and prognosis. Those patients misdiagnosed as having benign lesions had primary tumors of T1-2 in size and low or intermediate in pathological malignancy. They underwent typical partial parotidectomy with preservation of facial nerves. Postoperative irradiation was performed only when the surgical margin proved to be insufficient. Recurrence occurred in none of these patients. Those with T3-4 in size were easily diagnosed as malignant lesions, and they commonly underwent total or extended total parotidectomy with facial nerve resection and postoperative irradiation. In this group of patients, no one with low-or intermediate-grade tumor experienced local recurrence or metastasis. Only one patient with high-grade carcinoma who underwent tumor removal with the preservation of facial nerves died of intracranial invasion after local recurrence. These results suggest that appropriate surgical resection according to the pathological grading and extent of the tumor is most important, and it is an urgent issue to be clarified accurate preoperative grading of mucoepidermoid carcinoma be made.

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We presented cases of mucoepidermoid carcinoma (MEC) of major salivary glands, and reviewed the results of treatment. Twelve cases are reviewed, 10 occurring in the parotid gland and 2 in the submandibular gland. Low-grade MEC occurred in six patients who remain alive and free of disease. High-grade MEC occurred in six patients who, except for one, also remain alive and free of disease though the observation period in these cases are all less than three years. Since the histopathological grading of MECs in the major salivary glands correlates well with prognosis and overall survival, it is very important to diagnose their gradings, and the choosing of types of operations for MECs should be based on them. The facial nerve is basically resected in high-grade MEC, and preserved in a lowgrade type. Radical neck dissection is indicated in a high-grade MEC, and supraomohyoid neck dissection with level V is performed in a low-grade MEC. Adjuvant radiation therapy was performed when the surgical margin was inadequate in a low-grade MEC and in all cases of high-grade MECs.

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Mucoepidermoid carcinoma is typically managed by surgery as the primary treatment modality. The low-grade histology patients can be treated effectively with surgery. Since the long-term prognosis of high-grade mucoepidermoid carcinoma is very poor; an adjuvant setting of radiotherapy and/or chemotherapy should be the treatment of choice. We studied the effects of radiotherapy and chemotherapy on this tumor by analyzing questionnaires, reviewing literature, and analyzing our cases. The indications of postoperative radiotherapy are high-grade histology, inadequate surgical margins, perineural invasion, large tumors, and nodal disease. Salvage radiotherapy can be a treatment of choice for an unresectable case. The role of combining chemotherapy with radiotherapy was not evaluated.
The role of the chemotherapy for this disease is only as an adjuvant setting, except for a recurrent and/or an advanced inoperable lesion.
Mucoepidermoid carcinoma may respond to chemotherapy in the manner of squamous cell carcinomas. Platinum programs may provide useful palliation for selected patients with these cancers, but the impact on survival is now negligible. CDDP plus ADM plus EX seems to consistently produce the best results.

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The effect of tonsillectomy on specific immune responses for nontypeable Haemophilus influenzae was investigated. Tonsil tissues, nasopharyngeal secretions, and epithelial cells of palatine tonsils were obtained and cultured from 32 patients with chronic tonsillitis or tonsillar hypertrophy (mean age, 18; range, 3 to 66) who underwent tonsillectomy. Mononuclear cells were isolated from the tonsils, and the numbers of P6-specific antibody secreting cells were determined by ELISPOT assay. Before and 1 month after tonsillectomy, we determined antibody titers against P6 in nasopharyngeal secretions and sera by ELISA, concentrations of cytokines in nasopharyngeal secretions by using ELISA kits, nd incidence of P6-specific intracellular cytokines producing CD4⁺T cells in peripheral blood by flow cytometry. Nontypeable Haemophilus influenzae was cultured frequently, especially in young children, from the epithelial cells and from tonsil tissues and nasopharyngeal secretions. The presence or absence of nontypeable Haemophilus influenzae inside the epithelial cell did not exert particular influence on the number of P6-specific antibody secreting cells of the tonsil. The incidence of nontypeable Haemophilus influenzae detected in the nasopharyngeal secretion decreased after the tonsillectomy. However, significant differences were not observed in P6-specific antibody titers in the nasopharyngeal secretion and sera, in concentrations of cytokines in the nasopharyngeal secretion, or in the ratio of Thl and Th2 phenotypes of CD4⁺T cells that produce P6-specific intracellular cytokines in peripheral blood. These findings suggest that a tonsillectomy may be effective in eliminating nontypeable Haemophilus influenzae from the upper aerodigestive tract and that it may not result in depressed P6-specific immune responses.

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The morphological expression of the immune response of the palatine tonsils obtained from patients with pustulosis palmaris et plantaris (PPP) was investigated by morphometry in conjunction with immunohistochemistry. As a result, the most remarkable findings of the tonsils in PPP were the highfrequency appearance (69.2%) of multinucleated giant cells and the formation of secondary T nodules with atrophy of the lymph follicles, which suggests an intensely advanced stage of cellular immune response within the tonsils. In the relation between histological findings and prognosis after tonsillectomy, the formation of secondary T nodules and atrophy of the lymph follicles were not observed in the tonsils of noneffective cases in PPP. This result indicates that the histological findings may be useful in predicting the effects of tonsillectomy on PPP. Furthermore, many cutaneous lymphocyte antigenpositive lymphocytes were observed in the secondary T nodules of tonsils in PPP. This makes us think that the possibility of some T lymphocytes that infiltrate in the early skin lesion of PPP might be tonsillar T lymphocytes.

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We studied the usefulness of a tonsillar provocation test on the prediction of the long-term effect of tonsillectomy in patients with IgA nephropathy. Fifty-three patients (25 males and 28 females) with IgA nephropathy were followed up for more than 5 years after tonsillectomies. The average age at the operations was 28.8 years old. The average follow-up period was 8 years and one month.
Fourteen (26.4%), 49 (92.5%), and 51 (96.2%) of the 53 patients showed clinical remission, stable renal function, and renal survival, respectively, 5 years after the tonsillectomies. In 71.7% of the patients, one or more parameters of the tonsillar provocation test was positive. Patients showing positive revealed lower clinical remission rates and stable renal function rates than those showing negative results. On the other hand, patients with mild renal lesions based on renal biopsy showed a significantly higher stable renal function rate than those with severe renal lesions. No statistically significant difference was noted in the clinical remission rate and the stable renal function rate between positive and negative patients against any parameter of the tonsillar provocation test.

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A loss of heterozygosity (LOH) and a replication error (RER) in squamous cell carcinoma of the tongue were studied by using 8 microsatellite markers. LOH at 3p and/or 9p was observed in 5 out of 18 samples (28%) that could be evaluated from the 30 tongue cancer specimens examined. No significant difference was found between the survival rates of patients with LOH positive tumors and those of patients with LOH negative tumors. RER was detected in 7 out of 29 samples (24%) that could be evaluated, at one to five loci. The number of patients with RER positive tumors was higher in the younger group (under 45) than in the older group (over 45) (p=0.018). The frequency of RER was not correlated with the clinical stage of the patient and tumor size; however, it was apparently high in the N1 cases. The survival rates of the patients with RER negative tumors was significantly low compared with that of patients with RER positive tumors (p<0.05), and the prognoses of the patients with RER positive tumors were obviously good with no recurrent tumors. The amount of alcohol consumption by patients with RER positive tumors was significantly lower than that of patients with RER negative tumors (p=0.002), and the amount of smoking was also lower among patients with RER positive tumors.
These results indicate that the allelic loss of 3p and/or 9p is not apparently correlated with the malignant transformation of tongue cancers; however, the presence of RER is a prognostic factor independent of other clinicopathological factors. Moreover, it is likely that an intrinsic factor such as DNA mismatch error or instability of the genome is correlated with the carcinogenesis of a subgroup of tongue cancers besides environmental factors such as tobacco and alcohol.

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This report deals with dysphagia brought about by surgical treatment of cancers in the oral cavity, the pharynx, and the larynx, Seven cases of dysphagia after surgery of the cancers were referred to us for the rehabilitation from 1988 to 1998, of which two were presented and rehabilitation for dysphagia after surgery was discussed. The number of cases with dysphagia after surgery in the oral cavity, pharynx and larynx were fewer than that of cerebral vascular disorders in our hospital. This resulted the central nervous system controlling deglutition is intact in the cases of the cancers and that the disorders by the surgery being easily compensated. In cancers when the dysphagia resulted from the surgery is expected to be harder during the surgery, the surgery for dysphagia or laryngectomy is performed simultaneously. The rehabilitation for dysphagia after the cancer surgery should be performed under the management of cancers in the institutes where the surgery was performed.

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