Nobuhiko Nishino

Larger and more invasive colorectal carcinoma contains larger amounts of plasminogen activator inhibitor type 1 and its relative ratio over urokinase receptor correlates well with tumor size

Considering recent findings that both urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitors (PAIs) are involved in tumor growth through an urokinase‐type plasminogen activator (uPA) activity‐independent mechanism, the relation between the presence of these factors in tumor tissue and the clinicopathologic variables in colorectal carcinoma was reevaluated.

The urokinase type of plasminogen activator in cancer of digestive tracts

The amounts of urokinase (UK) antigen and tissue plasminogen activator (t-PA) antigen were determined in plasma, urine and tissues of patients with cancer of digestive tracts. Urinary levels of UK, but not those of t-PA increased in patients with cancer, and generally decreased after the removal of cancer by operation. Urinary UK levels kept increasing in patients with recurrence of cancer or with metastasis into liver or peritoneum. Plasma levels of t-PA, but not those of UK decreased in patients with cancer. When the amounts of UK were compared in cancer tissues and their adjacent normal mucosal layer, cancer tissues always had higher levels of UK, but t-PA levels were same between tumor tissues and normal mucosa. The results suggest that the type of plasminogen activator was UK-type in cancer of digestive tracts.

Possible role of plasminogen activator inhibitor 2 in the prevention of the metastasis of gastric cancer tissues

The concentrations of urinary type plasminogen activator (u-PA), plasminogen activator inhibitor 1 (PAI-1), and PAI-2 were measured in gastric cancer tissues and adjacent healthy mucosal tissues. Levels of u-PA, PAI-1 and PAI-2 were higher in cancer than in control tissues. PAI-1 levels were higher together with the progression of cancer however there were no differences in u-PA or PAI-2 levels. Tumors with higher PAI-1 and lower PAI-2 levels tend to metastasize to remote lymph nodes. When the numbers of involved lymph nodes were analyzed, tumors with the large number of metastatic lymph nodes showed higher PAI-1 and lower PAI-2 level. No difference was shown in u-PA levels among these groups. These tendencies were more significant in patients with progressed gastric cancer. These results suggest that tumor with higher PAI-2 levels tend to localize or have less tendency to metastasize to lymph nodes. On the other hand PAI-1 was generally higher in tumor with invasion into nearby tissue or with nodal metastasis.

Crohn's Disease of the Esophagus : Report of a Case

We report herein the case of a 27-year-old man with Crohn’s disease of the esophagus. The patient presented with large ulcers in the esophagus for which treatment based on a diagnosis of reflux esophagitis was commenced. Although his symptoms were initially resolved, the ulcers did not improve and he was readmitted to hospital 3 months later for progressive heartburn. An esophagoscopy revealed large ulcers in the esophagus, and a colonoscopy revealed a longitudinal ulcer in the terminal ileum. Histological examination of specimens from the terminal ileum showed severe inflammation without granuloma formation, which led to a diagnosis of Crohn’s disease. The oral administration of prednisolone and salazosulfapyridine controlled his symptoms and the esophageal ulcers were observed to be healing 2 weeks after this treatment was initiated. A review of the English literature revealed only 77 cases of this disease. Isolated esophageal lesions were reported in ten patients (13.0%), none of which were able to be diagnosed as Crohn’s disease preoperatively. Ileocolic lesions developed after esophageal lesions in only five patients (6.5%) including ours. In the remaining 62 patients (80.5%), ileocolic lesions had existed synchronous with or prior to the esophageal lesions. This suggests that ileocolic lesions may often coexist in Crohn’s patients with esophageal lesions, and that examination of the terminal ileum must be performed to confirm a diagnosis of Crohn’s disease of the esophagus.

Measurement of Urinary Trypsin Inhibitor in Urine, Plasma and Cancer Tissues of Patients with Stomach Cancer

Antiserum was obtained from rabbits immunized with a highly purified preparation of urinary trypsin inhibitor (UTI) conjugated with rabbit serum albumin. Anti-UTI antibody did not cross-react with antibody against inter-alpha-trypsin inhibitor (I alpha I) as determined by immunodiffusion against human plasma. A highly sensitive enzyme immunoassay was developed for the determination of UTI-related antigens (UTIR) in plasma, urine and cancer tissues. The level of UTIR correlated with UTI activity in urine. UTIR levels in urine and plasma did not change with age, but UTIR levels were higher in the stomach cancer tissue than in the surrounding stomach mucosa. UTIR levels did not correlate with I alpha I levels in the plasma of patients with stomach cancer, thus the increase was not considered due to the contamination of circulating I alpha I in the cancer tissues.

Synchronous lymphoma and adenocarcinoma occurring as a collision tumor in the stomach: report of a case.

We report herein the rare case of a 71-year-old man who was initially operated on under the diagnosis of advanced gastric cancer, but was subsequently found to have synchronous lymphoma and early adenocarcinoma of the stomach, confirmed by postoperative pathological examination. The patient had a history of lymphoma of the left tonsil, and histologically the gastric lymphoma was observed to be of the non-Hodgkins, diffuse, large-cell type. Conversely, the gastric cancer was early well-differentiated tubular adenocarcinoma of type 0-IIa, according to the Japan Gastroenterological Endoscopy Society classification. The two tumors had collided at the fornix. The relationship between these two tumors is analyzed and the most appropriate methods of diagnosis and treatment are discussed.

p53 Overexpression and Proliferative Activity Do Not Correlate with Lymph Node Metastasis in Early Gastric Cancer

We investigated p53 overexpression and the proliferative activity of the primary lesion as well as the clinicopathological features of 75 patients with gastric cancer invading the submucosa (sm cancer), of whom 14 (18.7%) had lymph node metastasis. Among the clinicopathologic features studied, only lymphatic invasion by the primary tumor was related to lymph node metastasis. There was no relationship between immunohistochemical staining for p53 protein or Ki-67 and lymph node metastasis. The p53-positive rate was 35.7 and 57.1% in patients with and without metastasis, respectively, while the mean Ki-67 labeling index was 38.9 and 38.1%, respectively. Our results suggest that p53 mutation or the proliferative activity of sm cancer do not influence lymph node metastasis, even though p53 mutation may enhance the proliferative activity and metastatic potential of advanced gastric cancer.

Relationship of p53 and Vascular Endothelial Growth Factor Expression to Clinicopathological Factors in Human Scirrhous Gastric Cancer

Although scirrhous cancer has the highest malignant potential among various types of gastric cancer, its pathogenesis is still unclear. The relationship between expression of p53 or vascular endothelial growth factor (VEGF) and clinicopathological variables was investigated by immunohistochemical analysis of archival specimens from 40 patients with scirrhous gastric cancer. Staining for p53 and VEGF was observed in the nuclei and cytoplasm of the tumor cells, respectively. There was no significant association between expression of p53 or VEGF and sex, age, depth of invasion, lymph node metastasis or histological stage. Peritoneal dissemination was the most frequent mode of recurrence, and the depth of tumor invasion was a crucial factor. The recurrence rate was 83.9% (26/32) in patients with serosal invasion, whereas it was 22.2% (2/9) in patients without serosal invasion. Only 7 out of 40 patients (17.5%) survived without recurrence. Among them, the VEGF-positive rate was 14.3% (1/7), whereas it was 52.6% (10/19) in the patients with recurrence. There was no correlation between p53 and VEGF staining. These findings suggest that the progression of scirrhous gastric cancer may be promoted by VEGF overexpression, which is not upregulated by p53 mutation.

Esophageal Intramural Pseudodiverticulosis with Mallory-Weiss Syndrome : Report of a Case

A 62-year-old man with a chief complaint of coughing up blood was revealed to have Mallory-Weiss syndrome with arterial bleeding by gastrointestinal endoscopy at the esophagogastric junction, and two teardrop-shaped fissures were found longitudinally extending into the muscle layer. Endoscopic treatment with ethanol injection and the administration of a thrombin solution spray failed to control the arterial bleeding. Hemostasis was finally archived by suturing the fissures under an open laparotomy. A postoperative barium esophagogram showed multiple flask-shaped outpouchings in the thoracic esophagus, and a diagnosis of esophageal intramural pseudodiverticulosis (EIPD) was thus made. EIPD is usually accompained with esophageal strictures but esophageal bleeding is rare.

Postoperative changes in plasma tissue-type plasminogen activator and type I plasminogen activator inhibitor

To clarify the changes which occur postoperatively in intravascular fibrinolysis, plasma levels of tissue-type plasminogen activator (t-PA) antigen, the total plasminogen activator inhibitor type-1 (PAI-1) antigen, and the t-PA-PAI-1 complexes were assayed in this study. Blood samples were taken the morning before surgery, then at 0, 12, 24, 36, 60, 108, and 156h postoperatively in ten patients who underwent radical surgery for thoracic esophageal cancer. The plasma levels of the t-PA and total PAI-1 antigens, and the t-PA-PAI-1 complexes were then measured by enzyme immunoassay. The plasma t-PA and total PAI-1 levels increased significantly in the immediate postoperative period, the percent increase of the latter being much greater than that of the former. Moreover, the calculated free t-PA antigen level was decreased throughout the postoperative period, suggesting postoperative hypofibrinolysis. The platelet count and neutrophil elastase level were significantly correlated with the free t-PA antigen level atr = 0.630,P < 0.001, andr = -0.447,P < 0.01, respectively. The results of this study indicated that postoperative hypofibrinolysis caused by the increased synthesis of PAI-1 may enhance postoperative hypercoagulability, and this may lead to the development of organ damage. Thus, the concentration of the PAI-1 antigen may be a potentially important index for the prediction of postoperative illness.