One hundred and seventy cancerous lesions observed among 159 esophagectomised specimens were systematically investigated with histochemical staining methods in addition to the ordinary hematoxylin-eosin staining. About 2/3 of them, 113 lesions, were entirely consisted of the squamous elements, regardless with pearl-formation or not, Group 1. On the contrary, the remaining 57 lesions (33.5%) showed foci of esophageal gland-like transformation, Group 2. Those lesions were specified by constituent epithelia with esophageal glandular epithelia-like characteristics; positive for epithelial mucin, secretory component and S-100 protein. Such esophageal gland-like structures could be demonstrated exclusively in cancerous foci penetrated through the lamina muscularis mucosa. Those 113 lesions of the Group 1 did not show any such transformation even by the meticulous examination of the whole lesion by the step sectioning. Those lesions of the Group 2 had a distinct tendency of the perpendicular mural penetration and submucosal extention than the horizontal mucosal involvement, giving rise a characteristic appearance resembling to submucosal tumors. On the contrary, those of the Group 1 showed an ordinary mural extension pattern corresponding to the extent of mucosal involvement, so-to-speak, a typical features of common esophageal cancer. No outstanding difference in biological behaviours could be obviated between two groups so far examined; survival rate, lymph node metastasis, vascular permeation, intraepithelial extension, etc.
Sixteen cases of resected gastric lymphoma were classified into 3 groups based on the easiness of the diagnosis; mucosa associated lymphoid tissue lymphoma (MALToma) 4 cases, superficial type lymphoma 5 cases and ulcerative (mass forming) type lymphoma 7 cases. Sixty seven of pre-operative biopsy reports and 44 biopsy specimens were analyzed. Although lymphoma cells retrospectively obtained in 92%, 69% and 88% of biopsy specimens, the definite diagnosis was only made in 7%, 24% and 38% of endoscopic biopsy. Mean AgNOR number per nucleus in resected specimens were as follows; chronic inflammation 1.20±0.02, MALToma 1.39±0.23, superficial lymphoma 2.44±0.50 and ulcerative lymphoma 3.44±0.55. They correlated well to proliferating cell nuclear antigen positive rates (r=0.776, p<0.01). Supposing that lesions showing 2.0 or more AgNOR dots in biopsy specimens are lymphoma, diagnostic rate improves to 69% in superficial lymphoma and to 88% in ulcerative lymphoma. Biopsy specimens from MALToma never showed 2.0 or more AgNOR dots. These results suggest that application of AgNOR to the biopsy diagnosis is useful in superficial and ulcerative lymphoma and has limitation in MALToma of the stomach.
We studied cell kinetics of colo-rectal neoplasms using PCNA (the auxiliary protein of DNA polymerase-δ) immunohistochemistry. We analized the distribution pattern of PCNApositive cells on normal colon mucosa, adenoma (6 cases) and cancer (early: 33 cases, advanced: 6 cases). PCNA positive index (PI) was calculated as the percentage of PCNA positive tumor cells in relation to the total number (about 1000) of the tumor cells. PCNA positive indices were 30% in normal colon mucosa, 49% in adenoma and 72% in cancer, respectively. There were statistically significant differences between three mean values (p<0.01). In normal colon mucosa PCNA positive cells are localized at the lower part of mucosa, but, in adenoma, they are found at the more upper part of mucosa too. In cancer, PCNA positive cells were localized diffusely and their immunoreactivity is higher than those of the normal mucosa and adenoma. In conclusion, our results suggests that the ratio of PCNA positive cells almost equivalents to growth fraction, and is correlated with the histological grading of colo-rectal tumor, but not correlated with depth of carcinoma. It is presumed that carcinoma has a higher ratio of PCNA positive cells than adenoma, and therefore carcinoma has higher proliferating cell density than adenoma.
We evaluated the usefulness of percutaneous biopsy under sonographic control and histological examination in the early diagnosis of hepatocellular carcinoma (HCC) in comparison with CT and angiography. 121 patients in whom hepatic nodules 3cm or smaller in size were found by ultrasound as suspected HCC underwent percutaneous biopsy, CT and angiography. 118 patients were finally diagnosed as HCC. Correct diagnosis of HCC was obtained by each modality in relation to tumor size as follows: 87.3% by histological examination, 55.1% by CT, 52.5% by angiography. However, the diagnostic capability of these modalities for HCC 1.5cm or smaller in size was as follows: 88.5% by histological examination, 34.6% by CT, and 23.1% by angiography. Cytology using a biopsy specimen was performed in 26 patients and it showed a positivity of 61.5%. In conclusion, for a definitive diagnosis of small HCC 1.5cm or less in size, the current imaging modalities have some limitations. On the other hand, percutaneous biopsy and histological examination are the most reliable and indispensable for making a definite diagnosis of small HCC.
The precancerous state in the gallbladder disorders is an interesting problem in oncology. We studied the DNA synthetic potency by using BrdU-anti BrdU monoclonal antibody in vitro method in patients who underwent cholecystectomy with various gall bladder disorders. The results (BrdU labeling indeces; mean±SD) were as follows; (1)carcinoma; 4.8±1.9%, (2)adenoma; 3.3±2.9%, (3)dysplasia; 3.5±1.3%, (4)control; 0.4±0.3%. (5)abnormal pancreatico-choledocho-ductal junction; 0.4±0.2% (the surrounding portions of carcinoma and dysplasia). BrdU L.I. was the greatest in carcinoma and the second geatest in dysplasia and adenoma. It is suggested that dysplasia and adenoma are the precancerous states in gallbladder disorders. While, in the cell types of carcinoma, the L.I. was the greatest in undifferentiated type, followed by tubular type and papillary type was the smallest.
To clarify differential points of angiographic findings, cystic angiograms of 46 patients with various gallbladder diseases were studied. In cases of gallbladder carcinoma, the angiographic findings differed in degree of the depth of cancer invasion and the shape of tumor. Abnormal findings in arterial phase were seen even in some cases of early carcinoma and tumor stains were clearly seen in all cases except for cases of superficial type of early carcinoma. In cases of cholecystitis, the findings on the degree of inflammation and wall thickening of the gallbladder varied. It was important for differential diagnosis between carcinoma and inflammation of the gallbladder to fully understand reciprocal relation of arterial and venous phase of the cystic angiogram. In cases of adenomyomatosis of the gallbladder, dilatation and tortuosity of the branches of the cystic artery and an increase of vasucularity in the thickened wall were chracteristic. Faint tumor stains were seen in some cases of cholesterol polyps of the gallbladder, which indicates that malignancy should not be diagnosed based only on the presence of such stains.
In order to clarify the interaction of hormones which exert various effects on the exocrine pancreas, we investigated the effect of cholecystokinin (CCK) and secretin on subsequent insulin binding to pancreatic acini and cultured AR42J cells derived from azaserine-induced acinar cell carcinoma of the pancreas. CCK at concentrations of 100pM-lOnM inhibited subsequent 125I-insulin binding to pancreatic acini. 12-O-tetradecanoylphorbol 13-acetate (TPA) inhibited 125I-insulin binding whereas A23187 had little effect, suggesting that the in-hibitory effect of CCK is mediated by protein kinase C. On the other hand, 100pM-10nM secretin had no effect on subsequent 125I-insulin binding to pancreatic acini, although higher concentrations of forskolin and 8 bromoadenosine 3', 5'-cyclic monophosphate inhibited 125I-insulin binding. In addition, secretin exerted no potentiating effect on the inhibitory effect of CCK on 125I-insulin binding to pancreatic acini. Based on these results, we further investigated the effect of CCK and TPA on subsequent 125I-insulin binding to AR42J cells. In this carcinoma cell line, inhibitory effect of CCK and TPA on insulin binding was completely abolished. The present results suggest, therefore, that hormonal interaction may play an important role in the regulation of exocrine pancreatic function including acinar cell growth.
We studied on the effect of combined use of CR1505 with UFT for the subcutaneously transplanted pancreatic cancer induced by BOP (N-nitrosobis (2-oxopropyl) amine) in the Syrian golden hamsters. The tumor growth in the group treated with both CR1505 and UFT was significantly inhibited compared with that in the group treated with only CR1505 or UFT. Labelling index judged by BrdU immunohistochemistry in the group with the combined use was significantly lower than that in the group with the single use. The differences of the body weights and blood analysis were not obscured in the both groups. Moreover, the concentrations of 5-FU and FT207 in tumors were not different between them. These results suggest that a new therapy of the combined use with CR1505 and UFT for the pancreatic cancer should be effective.