Inflammation is a general defense mechanism conducted by various kinds of chemical mediators, most of which are enzymatically decomposited substance of injured cells. As a rule, the inflammation ceases due to a kind of homeostasis and feedback reaction in a few days, but sometimes such mechanism is deranged and the inflammation enters into the chronic state and occasionally remains through life. A number of factors are working to make the inflammation chronic. In the present paper, several analytical studies were confined to two types of typical chronic inflammation, rheumatoid arthritis (RA) and otitis media with effusion (OME), either clinicopathologically or experimentally.
RA is a chronic inflammation which starts in the joint with systemic background. The articular cavity has a quite limited space among bone-cartilage and is lined by soft interlocking synovial cells. This anatomically confined space makes the inflammatory process slower and complicated because of its less efficient clearing of reactants or by-products of both stimulatory and inhibitory natures. The inflammatory process starts as a result of “type III antigen-antibody reaction” and the destruction of the connective tissue is carried out by the aid of “lysosomal enzyme” released from inflammatory cells such as neutrophils, macrophages and synovial cells. Establishment of a local producing system of rheumatoid immune complexes, which have initially been supplied from circulation, and the “one-way” (post-capillary venule→lymph follicle→IgG production→IC→phagocytosis by M∅ and granulocyte→enzyme [collagenase] release→destruction of hard tissue) process of inflammation in such a limited space are considered to make the inflammation intractable and a vicious closed-circuit of inflammation will occur.
The middle ear is also a very limited closed space in the bone connected to the airway by the auditory tube with isthmus, which is covered by respiratory ciliated epithelia. There are some similarities between RA and OME in their anatomical structure and histopathological patterns; such as lympho-plasmacyte infiltration with follicle, vascular proliferation, inflammatory edema, M∅ infiltration and lining cell reaction. IgG, IgA and occasionally IgE producing plasma cells, goblet cell transformation of ciliated cells and obstruction of the auditory tube by mucin, exudated cells, plasma and desquamated cell debris are characteristic of OME.
Active or passive Arthus' reaction in the middle ear of chinchilla is quite similar to human OME in tympanographic and clinicopathological points of view. Vascular reaction, severe cellular and humoral exudation, desquamation of epithelia, edema, goblet cell transformation of epithelia, obstruction of the auditory tube with mucinous secreta, lymphoplasmacytic cell proliferation and existence of memory and typical tympanographic change; all those changes similar to human OME were experimentally obtainable.
Upon these observations it could be concluded that a similar immuno-inflammatory process takes place in both RA and OME in an anatomically confined, soft tissue lined interosseous space.

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It has been considered that the mucus of the air-passage is a fluid of non-Newtonian flow and closely related to the physiological properties of the airway. In the present study, simulation experiments were conducted on the relationship between the ciliary movement and mucus transport, and on the behavior of the mucus moistening the glottis during phonation. As a result, It was revealed that there were more than two layers of the mucus, each of which showed a series of time delay in the mucociliary transport due to the difference in its viscosity. It was also suggested that the viscosity of the mucus was related to the efficiency of phonation.
In order to further investigate the physical nature of the mucus, a new apparatus called Mucus Rheometer was constructed based on the principles of plate-viscometry and oscillationviscometry for measuring the viscoelasticity of the mucus collected from the airway. The apparatus made it possible to measure the thread-forming ability, yield value and stress relaxation time of the mucus simultaneously with its viscoelasticity. Preliminary use of the apparatus for different types of fluid proved to be promising and its application is expected to provide the physical parameters of the mucus in the airway.

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Chronic sinusitis is one of the representative chronic respiratory inflammatory disease and is similar in some respects to chronic bronchitis. Nasal secretion from chronic sinusitics is an ideal material to study the rheological properties of respiratory fluid because it is readily obtained in large amount without contamination.
Storage modulus (G′) and loss modulus (G″) of nasal secretion from chronic sinusitics were measured using an oscillating sphere magnetic rheometer. Results of the analysis with multiple regression indicate that G′ is closely related to dry weight, sIgA and Ca iron, while G″ is closely related to dry weight, sialomucin and sIgA. Deceleration of nasal mucociliary transport observed in chronic sinusitics could be due to the rheological properties of nasal secretion and in vivo factors, such as decreased periciliary fluid and tethering phenomenon of mucus. Deceleration of nasal mucociliary transport in chronic sinusitics was improved by the treatment such as antral lavage and S-carboxymethylcysteine. This fact indicates that deceleration of nasal mucociliary transport in chronic sinusitics is not a cause of this disease but an effect of chronic sinusitis.

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Nobody can deny that lubrication is one of the factors which influences the phonatory function of the larynx. However, no notable studies on the mechanism of lubrication have ever been carried out. This study is an effort to clarify how the larynx is lubricated.
In the present study, it is revealed that the secretory fluid from the tracheal and subglottic spaces passes instantly through the glottis at the moment of the onset of phonation. Thus, the initiation of the lubrication is accomplished. The fluid from the subglottis is then mixed with the supraglottic fluid which comes mainly from the ventricular gland. A lubricant column is bilaterally made by the mixed fluid on the upper surface of the vocal folds. This lubricant column is rotating perpendicularilly to the free edge of the folds. The lubricant column may lubricate the folds which vibrate during phonation. At the end of phonation, the column decomposes and mostly flows backward to the subglottis. By this flow, the glottis is lubricated again.
In this paper, the results mentioned above were discussed and analyzed from the viewpoint of phonodynamics.

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Local immunity of the respiratory tracts was evaluated in patients with chronic bronchitis who were retired workers of Okunojima Poison Gas Factory. Proteins of IgA system were measured in the serum, sputum and saliva. Low levels of IgA and secretory IgA in the sputum were shown in the cases with severe respiratory infection, with high levels of serum IgA and polymeric IgA. It was concluded that the low levels of sputum IgA in the cases of respiratory infection were caused by the disturbance of secretory component synthesis.

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1) Some enzymes suggested to be related to physiological activities of tracheal fluid were investigated by chemical and histochemical methods.
2) Materials were the tracheal fluid obtained from patients with tracheostoma, and the bronchi resected from patients with lung cancer.
3) Protease was not detected in all specimen of tracheal fluid, whereas protease-positive cells were found in the bronchial wall.
4) Amylase of high concentration was detected in all the specimen and the isozyme pattern was of salivary gland type. Amylase-positive cell was the serous gland cell.
5) Lipase was negative or of low grade.
6) Phospholipase A of high concentration was detected in tracheal fluid, the concentration of which was higher than that in the peripheral respiratory tract fluid. Phospholipase A was observed histochemically at bronchial surface. Phospholipase C was not detected.

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When an abnormal increase of sputum is noted, expectoration plays a major role in the treatment of respiratory diseases. Expectorants, transfusion and physical therapy are three main means for facilitating expectoration. We divide expectorants according to Nagaoka's classification into 4 groups: Mucolytic agent, Mucoregulator, Mucolubricant and Mucospissic agent.
Since our patients were almost all bronchial asthma cases, transfusion was carried out with 300ml of 5% glucose (or fructose) solution and with aminophylline (5mg/kg). The expectoration effect of transfusion was 60% in bronchial asthma cases.
As a physical therapy, we have applied interferential wave therapy. When two electrodes of slightly different frequency (4kHz) are applied on the chest and back each, an interferential wave (70Hz±50%) is obtained, which is expected to produce 1/3 subharmonic resonnance in the ciliary motion. As a result, it leads to enhanced expectoration, and also stabilizes the smooth muscle and autonomic nervous system. The safety of this treatment applied to bronchial asthma patients has been confirmed through our trials, and the rate of success on expectoration was 64.3% in single application.
By applying the interferential therapy, we obtained the improvement in pulmonary function test results (FEV_1.0, PFR and R. r). In the case of combining transfusion and interferential therapy, it proved favorable to apply interferential therapy first.

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At present, sputology is applied to the followig items.
1. Researches on the characteristic physicochemical properties of the sputum in various respiratory diseases, particularly in chronic bronchitis and in bronchial asthma.
2. Researches on the relationship between rheological properties and chemical constituents of the sputum.
3. Researches on the relationship between rheological properties and ciliary transport rate of the sputum.
4. Evaluations on the pharmacological effects of expectorants and of anti-asthmatic drugs in a scientifically acceptable way.
Up to date, the author obtained the following results.
1. The mean concentration of fucose in sputa collected from patients with chronic bronchitis was significantly (P<0.01) higher than those of bronchial asthma.
2. Sputa collected from patients with bronchial asthma showed a tendency to higheralbumin concentration compared with those of chronic bronchitis.
These results (1 & 2) highly suggested that while bronchial secretory component is predominant in sputum of patients with chronic bronchitis, serum component is predominant in sputum of patients with bronchial asthma.
3. The mean yield value and spinnability of sputa collected from patients with chronic bronchitis was higher compared with those of bronchial asthma.
4. Sputa collected from patients with bronchial asthma during clinical exacerbation showed a tendency to lower ciliary transport rate on frog palate compared with those of during clinical improvement.
The author proposes the new category of expectorant drug “mucoregulators”. This is an agent which lubricates the airway wall by augmenting the output of respiratory tract fluid including surface active material and reduces the adhesiveness between mucus and tracheobronchial epithelial surface.
For the advance of pathophysiological researches on respiratory diseases, a new approach based on sputology should be developed.

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Some regulatory substanses in the nasal fluid were investigated in patients with chronic sinusitis and nasal allergy. Protease and protease inhibitor activities were measured by ³H-casain as substrate. Protease, α₁-Antitrypsin and α₂-macroglobulin activities were high in chronic sinusitis but low in nasal allergy. Trypsin inhibitor activities were higher in nasal allergy compared with chronic sinusitis.
Lipoxygenase metabolites were extracted from the nasal fluids and measured by means of high pressure liquid chromatography (HPLC). SRS-A was extracted from the nasal fluid of chronic sinusitis, and all SRS-A's except LTE₄ were detected from the fluid of nasal allergy. A large amount of LTB₄, 5HETE, 12HETE and 15HETE were found in the nasal fluid of chronic sinusitis.

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In our department, 149 patients with advanced cancer of the aero-digestive tract have been treated with chemotherapy for the past 7 years. The clinical effect of chemotherapy was analysed in these cases according to primary lesion, neck metastasis and distant metastasis. The results obtained revealed that a multidisciplinary treatment incorporated with a neo-adjuvant chemotherapy consisting of vincristine, methotrexate and peplomycin or cisplatin and peplomycin was very useful.
Meanwhile, even in cases failed in surgery and/or radiotherapy, survival time was much prolonged by chemotherapy not only in poor status but also at the level possible to make a home life.
The clinical effect of chemotherapy against distant metastasis was very disappointing but there is a possibility of its improvement only for lung metastasis. At present, we don't have any reliable chemotherapy against distant metastasis, so that it is very important to prevent a metastasis by means of neo-adjuvant chemotherapy or adjuvant chemotherapy, especially in cases of nasopharyngeal and hypopharyngeal carcinoma in which distant metastasis often occurs.

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Management of advanced cases of malignant tumors arising from the tracheo-esophageal region yields various problems. This article describes the general role and practical application of the pre- and postoperative irradiation (RT) into tracheo-esophageal malignancies. In T₃ hypopharyngeal carcinoma, preoperative RT with 4, 000cGy/4w followed by surgery yielded the comparable results (50% 5 year survival) to T_1-2N₀ cases with radical RT. RT seemed to play a significant role in the management of hypopharyngeal carcinoma. In carcinoma of the esophagus the role of postoperative RT to upper mediastinum and lower neck has been established for n(-) cases after surgery. The local control is hard to be obtained with only external RT (50%), however, significant improvement has been achieved with the intracavitary irradiation with low- or high-dose-rate sealed sources. In managing the anaplastic carcinoma/malignant lymphoma of the thyroid, it is important to determine the treatment plan according to histology, operability and adjuvant radio/chemotherapy. Over 50% 5-year survival is obtained in small cell ca./malignant lymphoma, in definite contrast to that of as low as 10% in pleomorphic/giant cell carcinoma. Additional recent developments are mentioned to control advanced local areas, such as hyperthermia and multidisciplinary treatment.

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Among the resected cases of esophageal cancer, the cancer have involved the neighboring visceral organs in 25 to 30%. Five year survival rate was 30% in such cervical esophageal carcinoma with invasion neighboring visceral organs and less than 2% in such thoracic esophageal carcinoma. As for invaded visceral organs, larynx-trachea was involved in 60% of cervical carcinoma, but aorta, lung and trachea-bronchus were involved in 54%, 16% and 13% of thoracic esophageal carcinoma, respectively. As for the clinical result of the thoracic esophageal carcinoma, five-year survival rate of the cases invaded to aorta was 4.2%, but none of the cases invaded to trachea or lung survived over 2 years. Studying on the outcome of non-resection cases according to their causes of non-resectability, the cases which could not be resected due to general condition showed 4.7% of five-year survival rate, but the cases due to the condition of carcinoma showed less than 0.5%, furthermore, there was no two year survivor among the cases involved the respiratory tract. Therefore, by the name of “isolation surgery”, we would like to advocate a method of no-touching to the primary lesion but dissecting the surrounding lymph nodes as much as possible and performing the post-operative therapy to the primary lesion intensively. And we reported a case treated with “isolation surgry” in the paper.

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It is very important to have a complete remission for the treatment of advanced lung cancer by chemotherapy. The effect of chemotherapy, especially complete response, can be expected in small cell lung cancer, but not in non-small cell lung cancer. In forty-one cases of small cell lung cancer the alternative COMP-VAN chemotherapy was used since 1981 (COMP: cyclophosphamide, vincristine, methotrexate, procarbazine, VAN: VP-16-213, adriamycin, AC NU). The response rate of the COMP-VAN regimen was 86% that included 42% complete remission. The complete response and survival rate in patients with limited disease were much higher than in patients with extensive disease. In limited disease patients there were no significant differences in response rate and in survival between chemotherapy alone and chemotherapy plus radiation group. A decreasing tendency of CNS metastasis was observed in prophylactic cranial irradiation received group after complete remission by COMP-VAN therapy. For prolonging disease free survival or curability in advanced small cell lung cancer a completely complete response in initial induction chemotherapy using some trial, for instance, drug sensitivity test due to tumor stem cell assay or monoclonal antibody cytotoxic drug conjugate is necessary with maintenance immunotherapy and sometimes with radiation for consolidation or prophylaxis.

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Terminal cancer patients have many pains such as physical, mental, social and spiritual. It is important to organize the team consisting of physicians, nurses, social workers, pastors, paramedical staff to control those pains. The functions of the team are as follows:
1. The organized evaluation of the patient's psychological state.
2. The approach to the family.
3. To help the attending physician.
4. Mutual help among team members.
5. Carrying out the agreed upon plan of action.
6. To encourage each one to carry out his own job.
7. The organized evaluation of the conditions of the patient and the family.
By means of realizing the reasons why people are afraid of cancer and the psychological process of the dying patient, the author concludes that having an understanding attitude toward a dying patient is more necessary than having an encouraging attitude.

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The treatment of early carcinoma is done in any hospital according to the standardized policy: however, advanced carcinoma must be treated in different way according to the doctor's ability.
The author's therapeutic policy is as follows. In advanced laryngeal carcinoma, total laryngectomy with radical neck dissection is the first choice and followed by radiation with immunochemotherapy. Radiation therapy is always done with an application of Vitamin A and 5FU (FAR-therapy). For poor-risk patients, intravenous hyperalimentation (IVH) is employed before surgery. In advanced hypopharyngeal carcinoma, IVH with radiation is always done before laryngopharyngoesophagectomy which is carried out under full exposure of the thoracic inlet after removal of the sternal manubulium. Reconstruction of the cervical esophagus is secondarily carried out with tubed skin graft; meanwhile, the postoperative radiation is done in the situation of open pharyngeal and esophageal stomas.

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