Based on a thorough knowledge of the breast cancer biology, surgical management of breast cancer has become more conservative. Most of the previous prospective randomized studies also showed that extended radical mastectomy did not improve survival of the patients. However, several reports suggested that a small number of patients with axillary node-negative and parasternal node-positive had a higher survival rate after extended radical mastectomy compared to radical mastectomy. The means to obtain this information is at present not satisfactory. Therefore, several authors avocate the limited usefulness of extended radical mastectomy in a staging operation. Even in these surgical procedures, combination with systemic therapy is essential.

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We investigated the long-term prognosis of the hepatitis C virus carriers with normal or near normal liver enzyme, who were positive for anti-HCV at blood center or regular medical check between 1988 and 1992.
The number of the cases were 35 (15 men, 20 women) and the age ranged between 25 and 66 years old (average 48.4±11.5). Follow-up period was 6 to 156 months (average 27.8±29.2 including the data. before a first visit to our hospital). The results were as follows; 1) Most of the cases (19 of 20 cases, 95%) who were positive for anti -HCV and HCV-RNA had abnormal histological findings. 2) There were three cases positive for anti-HCV and HCV-RNA whose transaminase urgently elevated after showing the normal values for over 10 years. So, HCV carriers should be followed up regularly for a long period to detect early the elevation of ALT. 3) There were four cases positive for anti-HCV and negative for HCV-RNA, among them two cases seemed to be false positive or past infection of HCV because ZTT and ALT (≤23) were entirely normal over 12 months and value of optical density was very low, and the other two cases seemed to be mismatching of the primer for PCR because of continuous slight elevation of ALT.

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We investigated the incidence of peptic ulcer, cancer and surgical history, which should always be taken into account when examining and treating chronic pancreatitis. From 1972 to 1992 we examined 154 patients with chronic pancreatitis at National Kyushu Cancer Center. Peptic ulcer and cancer were found in 14.3% and 14.9%, respectively. Surgery had been performed on 63.0%; pancreatectomy in 14.3% and gastrectomy in 9.7%. Chronic pancreatitis cases with peptic ulcer showed high incidences of decreased pancreatic bicarbonate secretion and moderate or advanced ERP abnormality. Additionally alcoholic pancreatitis was found more often in cases with peptic ulcer than those without, although the differences were not significant. Chronic pancreatitis was diagnosed at around the same age, at which peptic ulcer was found, but cancer was discovered much later. Pancreatectomy and exploratory celiotomy for suspected pancreatic cancer were performed in 9.1% and 5.8% of all the chronic pancreatitis patients, respectively. These results show that history of peptic ulcer and cancer plus the patients' surgical history must be kept in mind when examining and treating chronic pancreatitis patients.

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In order to evaluate precisely the blood coagulation and fibrinolytic state of hematologically malignant diseases, we measured plasma levels of D-dimer, thrombin-antithrombin III complex (TAT), plasm-α₂ plasmin inhibitor complex (PIC) and plasminogen activator inhibitor-1 antigen (PAT-1 antigen) by ELISA in 6 patients with acute myelocytic leukemia (AML) and in 6 patients with malignant lymphoma (ML) before and after chemotherapy.
The mean plasma levels of TAT, D-dimer, PIC and PAT-1 antigen before therapy were 6.42±2.77ng/ml, 406.11±237.54ng/ml, 1.31±0.54μg/ml and 51.09±39.0ng/ml, respectively. These values were significantly higher than those in normal controls. The mean plasma levels of D-dimer, TAT and PIC at 24-48 hours after chemotherapy were remarkably higher than those before chemotherapy.
The PAI-1 antigen levels were not changed at all after therapy.
In most patients with AML, the plasma levels of D-dimer, TAT and PIC were clearly increased at 24-48 hours after chemotherapy, but not in patients with ML. One patient with NHL who had remarkably higher levels of D-dimer, TAT and PIC than other patients with ML died of pulmonary embolism. In conclusion, anticoagulant therapy must be neccesary for patients with higher levels of D-dimer, TAT and PIC.

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To evaluate the effects and toxicities of Imipenem/Cilastatin sodium (IPM/CS) to the severe infections of granulocytopenia in hematological diseases and cancers in children, multinstitioal studies were conducted from September, 1990 through April, 1992.
A total of 60 episodes of infection were treated with the drug, and overall effectiveness was 48/60, 80.096. The rate of effectiveness in the patients with positive Endospecy Test was 90.0%. Between the two groups, one which had received other antibiotics previously, and the other without antecedent administration of antibiotics, there was no statistically significant difference.
Only 3 patients developed nausea, vomiting and/or diarrhea, and 2 other patients showed abnormal liver function tests; nevertheless they recovered soon after the drug was stopped. Consequently, we could conclude that IPM/CS is an effective antibiotic for the severe infections of hematological diseases as well as cancers in children. However, not a few strains of Meticillin-Resistant-Staphylococcus-aureus which were recently isolated at our hospital, showed resistance against IPM/CS. The administration of this drug must be strictly controlled.

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In vitro antimycobacterial activity and blood concentration after administration of tosufloxacin (TFLX) were studied to evaluate it's therapeutic potential against mycobacterial infections. In this study, the actual count method was adopted to measure the minimal inhibitory concentration (MIC) using Ogawa egg medium.
In vitro antimycobacterial activity of TFLX was much lower than that of ofloxacin. It was supposed that TFLX has a weak therapeutic potential against mycobacterial infections except for mycobacterium fortuitum or mycobacterium scrofulaceum infection considering blood concentration of this drug.

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The change of NK activity with aging was studied by using fluorimetric assay. NK cell subsets were also examined by measurement of expression of membrane antigens, CD16, CD56 and CD57. NK activity and all of NK subsets, especially CD57⁺ and CD16^- CD57⁺, tended to increase with aging. NK activity showed high positive relationship with CD16⁺ and CD16⁺ CD57⁺, but no relationship with CD16^- CD57⁺ subset.
The tendency of increase of NK activity with aging seemed to be due to the increase of proportion of CD16⁺ subset.

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The relationship between the two outstanding pathologic hallmarks of Alzheimer's disease, intracellular neurofibrillary tangles and extracellular amyloid deposits, is still a mystery. Tangles are partly characterized by argentophilicity and Alz-50 positivity, while amyloid deposits are characterized by accumulations of beta-amyloid precursor protein (APP). We hypothesized that a disturbance of axoplasmic flow may be the common pathogenic mechanism linking these main two pathological entities. To test this hypothesis, we injected kainic acid, colchicine, or aluminum salts into rat brain as independent methods of damaging neuron and interfering with axoplasmic flow. We then examined brain sections by silver staining and by immunohistochemical staining for APP and Alz-50. With each injection, affected neurons accumulated APP within hours and showed Alz-50 immunopositivity as well as an argentophilic reaction. After several days, APP immunoreactivity was seen extraneurally, some within phagocytosing reactive microglia. These results support the hypothesis that an interference with axoplasmic flow could link cytoskeletal abnormalities and APP accumulation.

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We studied 49 patients with T₃ and T₄ progressive oral cancer and recurrent cancer undergoing immediate oral reconstruction surgery involving microvascular anastomosis after resection in the 9 years between November 1983 and October 1992. They included 14 T₃ patients, 20 T₄ patients, and 18 patients with recurrence. The primary site was the tongue in 26 cases, the floor of mouth in 10 cases, the buccal mucosa in eight cases, the mandibular gingiva in six cases, the palate in one case, and the mandible in one case The free flaps used for reconstruction included forearm flaps, jejunum, rectus abdominis musculocutaneous flap, and scapular flaps, and the take rate of these grafted free flaps was 94.2%. The 5-year-survival rate was 72.5% in T3 patients, 63.7% in T₄ patients, and 50.8% in patients with recurrence, which were good results. The 18 cancer deaths includep six due to the primary cancer, nine due to cervical lymph node metastasis, and three due to distant metastasis. Deaths due to the primary cancer were decreased in this series and control of the primary was finally achieved in 43 out of 49 patients. These results indicate that in patients with progressive oral cancer, the role of reconstruction is important when the defect left after tumor resection can be filled surgically.

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As we consider the public hospitals in our country as clusters in terms of their scales, the group of National Hospitals and Sanatoriums will be certainly ranked well with those of University Hospitals, Red-cross and Saiseikai Hospitals, and local community hospitals.
The University Hospitals make their raison d'être for education and research works, The Red-cross and Saiseikai Hospitals take part in the medical services lined with the nature of social welfares. The local community hospitals put more emphasis on the regional health care services including emergency cases. What should be, then, the raison d'être or purpose of National Hospitals? In answering to this question, we may refer that the National Cancer Center, the National Cardiovascular Center, and the National Center of Neurology and Psychiatry have established their highly admirable reputation as pioneers of the specific medical fields and will continue to be the leading medical institutions both domestically and internationally.
However, nearly all the National Hospitals and Sanatoriums fall one step behind the Red-cross Hospitals or the local community hospitals not only in the regional health activities but also in the emergency medical services. They seem to be somehow passe, mere government-attached facilities or affiliated hospitals of the universities. They appeared to be dominated by the University Hospitals in the aspects of medical research works and even personnel and educational administration.
In 1985, the Medical Service Law was amended to start the regional medical plans and to regulate available numbers of beds in each prefecture based on the population. Furthermore, according to the second Amendment of the Medical Service Law in 1992, the National Hospitals, the nature of which is between the wings of “hospitals for highly specialized medical service” and “hospitals for long-term medical service ” are enforced to clarify its functional status, performance and future respect.
So far as National Hospitals are concerned to be medical service organizations, they should not be deviated or aloof from any regional medical activeties. On the other hand, they should have some different characteristics from the regional medical facilities in order to play the leading roles for the advanced medical care. They should also pursue for the role of guiding the related regional medical service. What then are they actually involved in? The environmental conditions around the regional medical services have been increasingly changed since the last few years, and the medical business has been severely deteriorated. Under such circumstance, the time has come to a crucial point at which the National Hospitals must decide on what a role it has to play in the regional medical services, and what kind of philosophy and principle it has to abide by at the stage of entering the coming 21st century.
The most important point of stepping forward practically for this object may be found in the making of one model national hospital, which will achieve its own innovation and to which direction is to be destined. Preparations for obtaining consensus among the national hospitals and for stepwise planning are required as a matter of urgency.
In this symposium, Mr. Ito, the Director of the Health Planning Division in the Health Policy Bureau of the Ministry of Health and Welfare, mentioned as one of the medical planners, that the drastic reorganization of the National Hospitals and Sanatoriums will be expected to play a supplementary role in the secondary medical area in each prefecture. From the standpoint of a system planner, Mr. Sueyoshi, the Director of the Division of Human Environment Research at the Mitsubishi General Research Institute, advised that first of all National Hospitals should establish a definite geopolitical goal for several service areas such as “Kinki region”, “Hokkaido region” and so o

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There have been many cases of herpes simplex esophagitis found in autopsies, only but a few cases where this disease was detected in a patient. In ourpresent case, an 81 year old female was admitted with complaints of nausea and anorexia.
She was not given any immunosuppressant, nor did she receive nasogastric intubation. An upper gastrointestinal endoscopic examination showed multiple small punchedout ulcers with swollen margins in the middle portion of the esophagus, while an esophageal biopsy specimen revealed ballooning change and intranuclear inclusion (full type).
Histochemical study with monoclonal antibody to herpes simplex virus verifyed the diagnosis of herpes simplex esophagitis.
So far, in Japan, there have been, in the literatures, a total of 11 cases of herpes simplex esophagitis found in endoscopic examination, including our present case. Of these, four cases had malignant tumor as, underlying disease, one received an immunosuppressant after renal transplantation, two had hiatus hernia, and four had nasogastric intubation. However, there were three cases in which no clear underlying diseases were observed. Therefore, in performing endoscopy, it is important to pay a careful attention to possible presence of herpes simplex esophagitis.

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A case of cellular leiomyoma of the stomach was reported. The patient was a 66-year-old female who was admitted to our hospital for endoscopic examination of the stomach as a minute examination of mass survey by fluoroscopic examination of the stomach. Endoscopy revealed an chicken egg-sized submucosal tumor with a couple of bridging folds in the upper gastric corpus, but histological study of biopsy specimens taken from it revealed no definite diagnosis. Considering the possbility of malignancy, total gastrectomy with R₂ curettage was performed. The operative specimen demonstrated a welldefined submucosal tumor at the lesser curvature of the upper gastric corpus, measuring 4.5×3.5×2.5cm, with bridging folds. Histopathologically, the tumor was found to be cellular leiomyoma of the stomach with no lymphnode metastasis. Postoperative course was uneventful.
It is now considered that cellular leiomyoma may derive from a multipotential gastric stromal stem cell that is capable of differentiating towards smooth muscle although its morphogenesis is not completely resolved. We should know the correct biologic behavior of cellular leiomyoma different from other smooth muscle tumors. The most popular and reliable thought is that the combination of an increased mitotic rate and large tumor size is indicative of malignant potential.

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A 74-year-old female patient had taken 250mg of fulfenamic acid aluminium (FFAA) three times a day for gonarhrisis and two weeks later, abdominal pain, diarrhea bloody stool were obserbed. And she was admitted to our hospital.
A barium enema examination showed many diverticles in the descending colon. On the colonoscopic examination performed at the time of admission, edema and reddish mucosa with hemorrhage in the descending colon were noticed. Stool cultures were negative for bacterial and fungal pathogens. FFAA was discontinued and her symptoms disappeared. Lymphocyte stimulation test for FFAA was negative.
Three years before, she had had the same symptoms, when she had taken 250mg of FFAA three times a day for 3 months. Discontinuation of taking the FFAA resulted in the disappearance of the symptoms. A tentative diagnosis of hemorrhagic colitis associated with FFAA was made. So far, hemorrhagic colitis associated with FFAA has been reported in three cases including the present one until the year 1990. We discussed our case, compared with 15 cases of hemorrhagic colitis associated with mefenamic acid.

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A 36-year-old man was referred to our hospital for the treatment of pulmonary tuberculosis. He had hyperpigmentation of skin and mucosa. Serum electrolytes were normal on admission, but hyponatremia was found after the common cold symptoms. His serum cortisol level and urine 17-OHCS were normal. Serum ACTH level was elevated. ACTH stimulation test was low response. He was diagnosed as partial Addison's disease. On diagnosis, no abnormal findings were found on adrenal glands by computed tomography. After three months, bilateral adrenal enlargement was demonstrated. Enlarged adrenal glands slowly regressed in size and CT value was elevated. And calcifications was found in adrenal glands after four years.

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Four patients with hyperkalemia and mild azotemia were investigated. The hyperkalemia was inappropriate to the extent of renal function and ascribed to the primary defect of renin-aldosterone secretion. In a patient with SLE, hyperkalemia was corrected by administration of predonin. In case 2, hyperkalemia produced complete A-V block. Treatment with Kayexalate resulted in normalization of potassium level and electrocardiogram. In case 3 with hypertension, continuous treatment with Kayexalate was necessary to keep the potassium level within normal ranges. In a patient with rheumatoid arthritis, the association of hyperkalemia with non-steroidal anti-inf Iamatory drug is confirmed.

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The patient was a seven-year-old girl who underwent heart transplantation because of progressive congestive heart failure resulting from a familial dilated cardiomyopathy. Her parents were second cousins and her brother died of dilated cardiomyopathy. Her symptoms of congestive heart failure began four months before the transplantation and they gradually became worse. Left ventricular ejection fraction was 10% by an echocardiogram. Her condition of NYHA IV was not improved by the administration of catecholamines. She was transported to the Primary Children's Medical Center in Utah. U.S.A. on July 22, 1991 in an emergency condition for the purpose of receiving heart transplantation. Despite the addition of amrinone and increased catecholamines, she became semicomatose due to ischemic liver injury on July 24, 1991. A donor became available on July 25, 1991 and the transplantation was done. Cardiac ischemic time was 97 minutes. She had moderate rejection on the 20th postoperative day and mild rejection on the 79th and 149th postoperative days. She has had no significant infectious diseases. She returned to Japan and has been in elementary school. The annual examination of her transplanted heart showed neither stenosis nor occlusion in her coronary angiogram. The use of steroid was discontinued at the 20th postoperative month and she has been receiving cyclosporine and azathioprine as an immunosuppressive regimen.

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