Kaoru Umeyama

The detection of human pancreatic cancer‐associated antigen in the serum of cancer patients

A radioimmunoassay (RIA) test for human pancreatic cancer‐associated antigen (Span‐1) was developed to evaluate the diagnosis of various gastrointestinal disorders. Serum Span‐1 in normal subjects ranged from 5 to 275 U/ml, with a mean of 58.8 U/ml (±58.7, standard deviation). All control subjects had levels of less than 400 U/ml. Study subjects, 93% with pancreatic cancer, 59% with hepatobiliary cancers, 23% with gastric cancers, and 13% with colonic cancers had serum Span‐1 levels greater than 400 U/ml. Sensitivities of Span‐1, CA 19‐9, and Dupan‐2 for pancreatic cancer were 94%, 85%, and 38% respectively. Span‐1 in patients with Stage I pancreatic cancer showed a 50% positive rating but CA 19‐9 and Dupan‐2 showed only 0% and 25%. Although a positive rating of these three antibodies increased in advanced cases, Span‐1 showed the highest positive rating. Span‐1 reacted with colonic cancer tissues with Lewisa−b− phenotype. However, none of these tissues did not react against CA 19‐9. From these results, Span‐1 has a good predictive value for detecting pancreatic cancer compared with CA 19‐9 and Dupan‐2.

Pathology of the Liver in “Idiopathic Portal Hypertension” Associated with Autoimmune Disease

The histopathology of the liver in idiopathic portal hypertension (IPH) associated with autoimmune disease (15 cases), was examined and compared with that of IPH without autoimmune disease (31 cases). It was found that hepatic histopathology was heterogeneous in the cases with autoimmune disease. That is, the hepatic histopathology in 7 cases was similar to that of classic IPH without autoimmune disease, and the remaining 8 cases disclosed unusual lesions such as focal non suppurative cholangitis, nodular parenchymal hyperplasia, moderate portal inflammation, and intrahepatic ductopenia. These unusual lesions, which frequently coexisted in the same case, were not typical ones for making other diagnoses such as primary biliary cirrhosis or nodular regenerative hyperplasia of the liver. These findings suggest that unusual histologic lesions in the livers of IPH patients with autoimmune disease may represent an accentuated immunologic reaction inherent in IPH, or that such cases may be an abortive or incomplete form of primary biliary cirrhosis or nodular regenerative hyperplasia of the liver. Acta Pathol Jpn 39: 586‐592, 1989.

Serum elastase I levels in pancreatic disease.

The radioimmunoassay for human elastase I used in this study is accurate, sensitive, and specific, which we have confirmed. The assay can be done within 4 hours, which is important for clinical purposes. A total o 103 subjects were examined, and levels of 99 to 370 ng/dl (mean 200) in normal human sera were determined. The serum elastase levels in acute, acute relapsing, and chronic relapsing pancreatitis were significantly higher than normal. Although serial determinations returned to normal within 5 days after the onset of the attack, they decreased gradually and remained high on the 7th, 10th, and 11th days in patients who still had residual signs of pancreatitis. The values in patients with chronic pancreatitis and various other diseases were normal. The values in patients with acute pancreatitis were significantly higher than in those with hyperamylasemia of nonpancreatic origin. Twelve of 19 patients with pancreatic cancer had abnormal serum elastase levels; this was especially true in patients with cancer of the pancreatic head. We believe that the measurement of serum elastase levels by radioimmunoassay will become a useful diagnostic method for pancreatic disease in the future.

Effects of cerulein on the normal pancreas and on experimental pancreatic carcinoma in the Syrian golden hamster

The effects of cerulein on normal pancreas and on N-nitrobis (2-hydroxypropyl) amine (BHP)-induced experimental pancreatic carcinoma in Syrian golden hamsters were studied. Twenty hamsters received a subcutaneous injection of cerulein (20 μg/kg) twice daily for 10 days. The 10 control hamsters received normal saline (1 ml/kg). The results showed that when cerulein was injected subcutaneously for 10 days, pancreatic weight and amylase increased. DNA and the pancreatic weight/DNA ratio were also increased significantly in treated hamsters compared with controls (p <0.02 versus p <0.01). These results indicated that chronic cerulein injection had hypertrophic and hyperplastic effects. DNA synthesis, as measured by histoautoradiography of tritiated thymidine-labeled tissue, increased in pancreatic acinar cells (p <0.01) and increased slightly in islet cells and in ductal cells. Tritiated thymidine uptake in the pancreas of the treated group indicated a rather selective exocrine gland incorporation by acinar rather than ductal cells. Sixty hamsters received a subcutaneous injection of BHP (500 mg/kg) once a week, while 63 hamsters received BHP (500 mg/kg) plus cerulein (20 pg/kg). Twenty-seven hamsters received cerulein (20 μg/kg) alone. All animals were killed from 8 to 27 weeks later, and no cancer-bearing hamsters were observed during the eighth and ninth week following administration. From the 10th to 14th weeks after administration of BHP and cerulein, 87.9% (13 of 15) had tumors compared with 18.7% (3 of 16) after BHP alone (p <0.01). One of three and two of 13 tumors were adenoma. The earliest appearance of cancer, including carcinoma in situ and intraductal carcinoma, was at the 14th week after the administration of BHP alone and the 10th week after BHP and cerulein. During the 10th to the 14th weeks after administration of BHP and cerulein, cancer was found in 73.3%, which was statistically higher than after the administration of BHP alone (12.5%; p <0.01). All tumors were of exocrine origin in both groups. There were no special differences in histology, and no tumors were observed in cerulein-treated hamsters. This study has shown that cerutein stimulates pancreatic growth, especially acinar cell hyperplasia, and augments the carcinogenicity of N-nitrobis (2-hydroxypropyl) amine in the hamster pancreas.

Yellow nail syndrome associated with mental retardation in two siblings

Two siblings with yellow nail syndrome and mental retardation are described. In addition to nail changes, the younger brother was found to have congenital lymphoedema and idiopathic pleural effusion, and the elder brother, lymphoedema praecox. They had in common a history of respiratory tract infections. Their intelligence quotient as measured by the Suzuki‐Binet tests was 30% and 70%, respectively.

The possibility of diagnosing small pancreatic cancer (less than 4.0 cm) by measuring various serum tumor markers. A retrospective study

Comparative studies measuring various tumor markers such as SPan‐1, CA 19‐9, carcinoembryonic antigen (CEA), DUPAN‐2, and elastase I were done in 74 patients with small pancreatic cancer including 23 cases of T1 pancreatic cancer (tumor size less than 2.0 cm) and 51 cases of T2 pancreatic cancer (tumor size between 2.1 to 4.0 cm), retrospectively. Although the mean value of these tumor markers in T1 and T2 pancreatic cancer were higher than those of the control cutoff levels, their sensitivities were different. In T1 pancreatic cancer, 13 of 23 cases (56.5%) of SPan‐1 and 14 of 23 cases of (60.7%) of CA 19‐9 had levels above normal. Although the numbers of patients were small, sensitivities of CEA, DUPAN‐2, and elastase I were 30.8%, 22.2%, and 28.6%, respectively. In T2 pancreatic cancer, 41 of 51 cases (80.4%) of SPan‐1 and 40 of 51 cases (78.4%) of CA 19‐9 showed higher levels than normal, but only 46.9% of CEA, 40.0% of DUPAN‐2, and 52.6% of elastase I were positive. The overall sensitivities in small pancreatic cancer (less than 4.0 cm) were 73% for SPan‐1 and CA 19‐9 but were less for CEA, DUPAN‐2, and elastase I. These results indicate that even small pancreatic cancers release detectable pancreatic cancer‐associated antigens in serum in more than 70% of cases, especially SPan‐1 and CA 19‐9. The measurement of these two tumor markers makes it possible to detect small pancreatic cancers after using imaging diagnostic procedures.

Renal function in experimentally induced acute pancreatitis in dogs: How it is affected by the nephrotoxic substance in pancreatic exudate from ascitic fluid

Renal failure occurring in dogs during experimental acute pancreatitis and the effect on renal function of intravenous injections of ascitic fluid which accumulated during the acute pancreatitis were studied. Five hours after the induction of acute pancreatitis, the accumulation of 200 to 400 ml of ascitic fluid, and an elevation in hematocrit as well as a decreased mean arterial pressure were observed, which suggested hypovolemia due to plasma loss. At the same time, the renal blood flow, glomerular filtration rate, and urinary output decreased significantly. Hypovolemia was observed to be the main cause of renal failure in accordance with previous reports. When the sterile ascitic fluid was injected into healthy dogs, temporary hypotension was observed without changes in the hematocrit. However, the renal blood flow, glomerular filtration rate and urinary output decreased, together with an elevation in renal vascular resistance, even after the hypotension had returned to normal. This study shows that renal failure associated with acute pancreatitis occurred mainly as a direct result of hypovolemia but also that the sterile ascitic fluid contained nephrotoxic substances which were suspected to be unrelated to vasoactive substances or protease. Their removal is therefore necessary for the treatment and prevention of renal failure complicating acute pancreatitis.

Clinico-histochemical studies on type 4 carcinoma of the stomach—With special reference to mucopolysaccharides and sialic acid in tumor tissue

One hundred and twenty-one patients with gastric cancer of Borrman IV (type 4) were classified into two types according to the macroscopic appearance of their tumors, namely, those tumors with giant folds (type G, n=84) and those without giant folds (type P, n=37). A large percentage of the cases in both type groups had advanced stage carcinoma. Type G was found to be predominant in young women and the incidence of high-grade lymph node metastasis was higher in type G than in type P. Histochemically, it was shown that the tumor interstitium of type G contained obviously many more acid mucopolysaccharides (AMPS) than the localized Borrman II (type 2) gastric cancer, which was used as a control. The results of enzymatic digestion tests suggested that the amounts of hyaluronic acid, chondroitin sulfate, and sialic acid were greater in type G than in type P or the localized type, the differences involved being marked between type G and the localized type.

An analysis of the DNA ploidy patterns of gastric cancer

This article deals with DNA measurements by fluorometry of nuclei in 33 freshly obtained specimens and in 109 fixed specimens of gastric cancer in Japanese patients. Histograms of the DNA measurements can be classified into four types (Ia, Ib, II, III). The nuclear DNA patterns had definite, if not significant, correlations with clinical and histologic parameters. For example, 88.2% of the cases classified as Type III were advanced stage disease, whereas early stage cases were predominant in Type Ia. Type II and III were frequently found in hepatic, peritoneal, and lymph node metastasis. The rate of occurrence of polyploid cells was significantly higher in the group with hepatic or lymph node metastasis than in the other group without metastasis. The results of this study show that fluorometric measurement of nuclear DNA is considered one method of determining the biological activity of gastric cancer cells.

Carcinoembryonic antigen-like activity in gastric juice and plasma in patients with gastric disorders

Carcinoembryonic antigen (CEA)-like activity in gastric juice and plasma was examined in patients with gastric disease. There was no statistical difference in plasma CEA in normal subjects and in patients with benign gastric cancer. However, four patients with advanced gastric cancer, one with stage III and three with stage IV disease had a very high plasma CEA level. There was significant differences in CEA-like activity in gastric juice in patients with benign gastric disease and early gastric cancer (p less than 0.01) and patients wih benign and advanced gastric cancer (p less than 0.001). These results suggest that measurement of CEA-like activity in gastric juice is a useful adjunct to the diagnosis of early malignant changes in the stomach.