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A cooperative, prospective, randomized study to evaluate the effectiveness of preoperative irradiation in curatively resected esophageal carcinoma was performed in 364 cases in eight institutions from August 1982 to November, 1983. Based on the survival curves, postoperative irradiation alone was superior to preoperative plus postoperative irradiation. Because of the progression of the disease and complications after operation, there were many inevaluable cases in this study. However, analysis revealed there was no bias caused by a greater number of unfavorable patients being selectively included in inevaluable cases in the postoperative irradiation only group. Our data question the value of preoperative irradiation being performed in addition to resection plus postoperative irradiation.

An unusual case of pheochromocytoma associated with renal artery stenosis is described. Despite the removal of bilateral adrenal pheochromocytoma, laboratory findings suggested the presence of residual pheochromocytoma and abdominal aortography revealed more pronounced stenosis of the right renal artery. Two months later, the undetected residual pheochromocytoma underwent hemorrhagic necrosis with acute cessation of catecholamine release. Thereafter, the patient's blood pressure decreased to a normal level with marked improvement in hypertensive symptoms. No remaining stenosis was demonstrated on follow up renal angiography. Our case suggests that constant local secretion of catecholamines may be responsible for the development of renal artery stenosis.

A 32-year-old man was admitted to our hospital, complaining of an abdominal mass. An operation disclosed a large tumor, the size of a child's head, in the mesenterium of the transverse colon, with a multiple liver metastasis. A tumor resection was performed and, histologically, the tumor was diagnosed as being a choriocarcinoma. Gynecomastia was not observed. The patient died 2 months after this operation in spite of chemotherapy. An autopsy disclosed metastatic choriocarcinomas in the lungs, the liver, the peritoneum, the stomach, the adrenal glands and in the lymph nodes. The testis was found to be normal by a serial histological examination. Primary advanced adenocarcinoma, which is histologically similar to a choriocarcinoma, was found in the stomach. This case was finally diagnosed as being a gastric adenocarcinoma which showed choriocarcinomatous differentiation at various metastatic sites.

In order to clarify the origin and release mechanism of plasminogen activator in the tracheobronchial secretion of rats, electrophoretic analysis of the secretion and studies on the effects of certain vasoactive drugs on the activator activity in the secretion were carried out. From the results of electrophoretic analysis of the tracheobronchial secretion in non-treated rats, protease inhibitor composed of glycoprotein was not contained in the secretion in contrast to the circulating blood, but a protein of low molecular weight like albumin in the circulating blood was contained in the secretion. Furthermore, after injection of noradrenalin, the blood pressure was temporarily elevated and the fibrinolytic activity of the euglobulin fraction in the circulatory blood was also increased. Subsequent to this elevation of fibrinolytic activity in the circulating blood, the fibrinolytic activity in the tracheobronchial secretion increased. Based on these results, it is suggested that the increase of fibrinolytic activity in the circulating blood was due to increased release of plasminogen activator from the vascular wall, and the increased fibrinolytic activity of the tracheobronchial secretion was caused by a consequent increased transudation of plasminogen activator from the circulating blood into the tracheobronchial lumen.

The distribution and role of tissue plasminogen activator (TA) and proactivator (PA) in various diseases of the nasal and paranasal cavity were investigated. The stronger the inflammatory and proliferative response of the paranasal mucous membrane, the weaker was the fibrinolytic activity of TA. The fibrinolytic activity of PA tended to be stronger than TA activity. It is considered that PA may play an important role in inflammatory enlargement and proliferation of the paranasal mucous membrane, but does not play an important role in carcinogenic enlargement and proliferation of the nasal and paranasal mucous membrane.

Early superficial-type squamous cell esophageal carcinoma is seldom detected by esophagography. Review of the records at the Aichi Cancer Center Hospital revealed seven cases in which serial esophagograms were available to observe the growth pattern and speed of squamous cell esophageal carcinoma from its early superficial to advanced invasive stages. The esophageal carcinomas were found to grow very rapidly longitudinally as well as horizontally compared to gastric carcinomas. The longitudinal growth of the lesion appears to be constant and can be expressed as a linear function of time. Importance of early detection should be stressed in order to improve the poor cure rate of this fast-growing tumor.

In order to predict the possibility of local control of esophageal cancer by radiation therapy, the relationship between the x-ray findings before and after irradiation and the histologic radiation effect obtained from the surgically resected esophagus was analyzed in 130 cases irradiated preoperatively during the period 1971 through 1980. In the superficial or proliferative type in x-ray image before treatment, the local control was obtained in 46.5% of the cases with the dose of 40 Gy, whereas in the ulcerative or infiltrative type, in 21.8%. The barium examination performed after irradiation was more useful to evaluate the radiation effect than that before treatment. In cases with a marked radiation effect after irradiation, the frequency of local control reached 76.9%. On the other hand, the local control remained 11.9% in cases with no or poor radiation effect. The results obtained by the preoperatively irradiated cases were applied to the analysis of 119 cases irradiated radically during the period 1965 to 1980. Almost the same results were also acquired in radically irradiated cases. The degree of radiologic and histologic radiation effect on the primary tumor was closely related to the long-term survival rate of the patient.

In order to clarify the physicochemical property of tissue plasminogen activator (TA), tissue extracts of human paranasal mucous membrane and pig heart were studied by the biochemical techniques. The studies by gel filtration revealed that two plasminogen activators of different molecular weight were present in the extract of human paranasal mucous membrane. The existence of tissue plasminogen activator with a low molecular weight (LMW-TA) has not previously been reported. This molecular weight of this compound was lower than that of cytochrome c. On the other hand, the molecular weight of tissue plasminogen activator from pig heart (PH-TA) was similar to that of ovalbumin, about 46,000 daltons, as estimated by Sephadex G-150 gel filtration. From the physicochemical property of LMW-TA, it is suggested that the LMW-TA from paranasal mucous membrane with chronic sinusitis was produced by proteases, i.e. trypsin-like enzyme, present in the mucous membrane with chronic inflammation.

It has been shown that large amounts of fibrinolytic enzyme are contained in tissue extracts of the paranasal mucous membrane in patients with chronic sinusitis. However, the fibrinolytic enzyme in the tissue extracts has not yet been characterized by biochemical techniques. In the present study, proactivator was differentiated from tissue plasminogen activator with low molecular weight in extracts of the paranasal mucous membrane and the existence of the proactivator was thus demonstrated in tissue extracts. By analogy with the proactivator in antrochoanal polyps, this proactivator may play an important role in the proliferation and enlargement of the paranasal mucous membrane.

Five parameters of blood coagulation and fibrinolysis, viz., levels of fibrinogen, fibrinolytic activity of euglobulin, fibrinogen and/or fibrin-degradation products (FDP), antiplasmin activity, and antithrombin activity, were measured in patients with cancer of the head and neck, and the results were compared with those of healthy adults. The fibrinogen content in cancer was significantly increased (p less than 0.001), the fibrinolytic activity of euglobulin significantly enhanced (p less than 0.001), the antiplasmin activity significantly reduced (p less than 0.05), the antithrombin activity significantly reduced (p less than 0.001), and the FDP level slightly increased, although the difference was not significant. The importance of the coagulation and fibrinolytic system in cancer of the head and neck is discussed.

A 58-year-old woman presented an unusual variant of bronchial carcinoid. A tumor measuring 20 x 25 mm was recognized upon gross examination in the upper lobe of the right lung. Microscopically, the tumor consisted of large polyhedral cells with a pseudoglandular arrangement similar to pheochromocytoma cells. Immunohistochemically, the tumor cells contained serotonin, S-100 protein and neuron-specific enolase. Thus, we consider this neoplasm to be a large cell variant of bronchial carcinoid which, to our knowledge, has not been described in the literature.

We succeeded in differentiating the proactivator (PA) in tissue extract of paranasal mucous membrane with chronic sinusitis by the gel filtration technique. Furthermore, the results demonstrated that PA in the tissue extracts of the paranasal mucous membrane with chronic sinusitis and antrochoanal polyp was unrelated to the antigenicity of plasminogen. In particular, it was clarified that the tissue extract of antrochoanal polyp as a source of PA was not related to the antigenicity of plasminogen.

Some 218 resected cases and 43 autopsied cases after resection during the last 13 years were analyzed with regard to the mode of recurrence and survival. Several factors were investigated with the following results. 1) Extensive clearance of upper mediastinal lymph nodes during radical surgery may reduce the incidence of tumor recurrence. It is preferable to remove the cervical lymph node, however, after positive metastasis to cervical lymph node. 2) Beginning in 1981, interstitial brachytherapy of 192Ir seed assemblies using afterloading techniques was administered to two patients with esophageal carcinoma infiltrating the aorta and four patients infiltrating the trachea and main bronchus which were not completely resected in either case due to invasion of adjacent organs. No significant difference in life-prolongation was observed, but it may have been effective for prevention of localized recurrence in cases with aortic infiltration and with infiltration of the trachea and bronchus. 3) From 1984, eleven patients with recurrent squamous cell esophageal carcinoma were treated with combination chemotherapy sandwiched with irradiation (CDDP/5FU-RT-CDDP/5FU). Eight patients (73%) had complete or partial response, and six patients survived over one year after combination chemotherapy sandwiched with irradiation. Combination chemotherapy sandwiched with irradiation appears to be effective in the treatment of patients with recurrent squamous cell carcinoma of the esophagus. Toxic effects are moderate and manageable.

A 9 year old Japanese girl was admitted complaining of left hypochondrial pain and a large upper left abdominal tumor. There were no clinical or laboratory signs of hormonal abnormality. Intravenous pyelography showed marked compression and deformity of the kidney by a tumor. This tumor was excised together with the left kidney. The pathological diagnosis was adrenocortical carcinoma. Postoperatively, the child was given neither irradiation nor chemotherapy. Twenty-one months after the surgery, there was a hepatic metastasis, and she died 40 months after surgery from a combination of hepatic metastases and local tumor recurrence.

For the purpose of verifying the effectiveness of peplomycin, one of the derivatives of bleomycin, against carcinoma of the esophagus and the safety of it, the analysis of the data for total 113 cases collected from 25 institutions in Japan was made. The results are as follows. It was effective in 19 out of 74 evaluable cases of carcinoma of the esophagus (25.7%). In case of treatment with peplomycin alone, it was effective in 6 out of 39 cases (15.4%). In case of the combination treatment with peplomycin and some other therapy, it was effective in 13 out of 35 cases (37.1%). As for the side effects, the incidence of fever was the highest in both the cases of peplomycin alone and the combination treatment such as 39.6% and 37.0%, respectively. Anorexia, nausea, vomiting, respiratory symptoms and tiredness were found in relatively many cases. In the clinical laboratory tests, the vital capacity after the treatment tended to be lower than that before the treatment, but there was little change in the hematological tests, pulmonary function test and renal function test.

In order to clarify the pathophysiological significance of the fibrinogen (FgDP)-protamine complex, the interaction between fibrinogen and protamine sulphate was studied in vitro and in vivo. Using the electrophoretic technique, an attempt was made to determine whether the complex could be detected in vitro and in the circulating blood. From the present studies, it has been clarified in in vitro experiments that the slower mobility of two peaks on immunoelectrophoresis represented a complex of protamine sulphate and fibrinogen (FgDP). Furthermore, the peak of slower mobility on crossed immunoelectrophoresis appeared in the circulating blood of a rabbit receiving administration of excess protamine sulphate. That is, in vivo experiments showed that a complex of protamine sulphate and fibrinogen (FgDP) could be detected in the circulating blood.

We report a case of intramural giant gallstone. Cholangiography revealed narrowing of the neck of the gallbladder due to a hemispherical prominence. At cholecystectomy, a giant gallstone 2.1 cm in diameter which was located in the submucosa of a hemispherical prominence at the neck of the gallbladder, was found. Although the usual sizes of intramural gallstones mentioned in previous reports have ranged from 2 to 5 mm in diameter, the stone found in our case is, as far as we know, the largest intramural gallstone yet reported.

A phase II study of Vindesine for esophageal carcinoma was carried out cooperatively by 10 Japanese institutions. Fifty patients were enrolled in the study over a year and ten months. Four patients could not be evaluated because less than 4 weeks had elapsed since their preceding therapy. There were one complete remission and five partial remissions among the 46 remaining patients, a response rate of 13.0%. The patient experiencing the complete remission is still alive more than 24 months after treatment. The main side effects were depilation, anorexia, stomatitis and leukopenia. Thrombocytopenia and elevations of blood urea nitrogen and creatinine were not marked. There was no mortality connected with the administration of Vindesine. It was concluded that Vindesine is useful in the treatment of esophageal carcinoma as a single agent.

Previous reports have shown that fibrinolytic activity was increased in the circulatory blood of rabbits with Arthus tonsillitis. In this study, t-AMCHA was administered intravenously to rabbits, in order to clarify its role as an antiplasminic agent in the control of Arthus tonsillitis. First, to establish the proper method of administration of t-AMCHA and the quantity to be administered, a preliminary estimation was made of the requisite concentration of t-AMCHA in the circulating blood and tonsillar tissue. Then macroscopic observations and histopathological studies were performed on the tonsils of rabbits with Arthus tonsillitis after t-AMCHA administration at various doses. Finally, after injection of the antiplasminic agent, estimations were made of the plasma fibrinolytic activity in the blood of the rabbits under study. It was decided that administration of t-AMCHA at 3-hourly intervals could maintain a constant concentration of the substance in the tonsillar tissue. The marked hyperaemia and bleeding which were observed macroscopically and histopathologically at 1-2 days after the onset of tonsillitis, disappeared from the parenchyma of the tonsils and pharyngeal tissue surrounding the tonsils in the group receiving regular injections of t-AMCHA at 3-hourly intervals. After estimating certain parameters of the fibrinolytic system in the blood, it was found that fibrinolytic activity decreased and whole plasmin was not consumed as a result of the administration of t-AMCHA during the early stage of tonsillitis. The process of Arthus tonsillitis can thus be controlled by the administration of the antiplasminic agent.