Carcinoma-associated expression of core 2 beta-1,6-N-acetylglucosaminyltransferase gene in human colorectal cancer: role of O-glycans in tumor progression.

Recently, it was demonstrated that an increased level of NeuNAc alpha2-3Gal beta1-4(Fuc alpha1-3)GlcNAc beta-R (sialyl Le(x)) and NeuNAc alpha2-3Gal beta1-3(Fuc alpha1-4)GlcNAc beta-R (sialyl Le(a)) expression on the surface of colorectal cancer cells is positively correlated with progression of the disease. It has not been determined, however, which type of glycans, N- or O-glycans, is more closely associated with progression when cancer cells express those oligosaccharides. To address this problem, we have examined expression of sialyl Le(a) and sialyl Le(x), those oligosaccharides in O-glycans, and core 2 beta-1,6-N-acetylglucosaminyltransferase (C2GnT) transcripts in colorectal cancer specimens from 46 patients and compared those results with clinicopathological variables. C2GnT is a glycosyltransferase that is responsible for the core 2 branch, which is critical for biosynthesis of sialyl Le(a) and sialyl Le(x) in O-glycans. Sialyl Le(a) and sialyl Le(x) were determined by immunohistochemistry, and C2GnT transcripts were detected by reverse transcription-PCR. Sialyl Le(a) or sialyl Le(x) in O-glycans was assessed by combining immunohistochemistry for sialyl Le(a) or sialyl Le(x) with reverse transcription-PCR for C2GnT. Sialyl Le(a), detected on cancer cells in 74% of patients, was well correlated with lymph node metastasis, whereas sialyl Le(a) and sialyl Le(x) in O-glycans, which were specifically detected in cancer tissues of 50 and 61% of patients, respectively, were closely associated with lymphatic and venous invasion. In addition, C2GnT, which was specifically detected in cancer tissues of 63% of patients, was closely correlated with the vessel invasion, as well as depth of tumor invasion. These results strongly suggest that sialyl Le(a) and sialyl Le(x) in O-glycans and C2GnT, expressed in cancer cells, may play important roles in tumor progression through vessel or direct invasion.

The relationship between drinking status and serial changes of pancreatographic findings in patients with suspected early chronic alcoholic pancreatitis.

Twenty-two patients (mean age, 48.5 years) suspected of early chronic alcoholic pancreatitis, who had ductal changes mainly in the side branches, were followed by serial endoscopic retrograde pancreatography (ERP). Follow-up ranged from 1.1 to 11.9 years (mean, 5.4). Serial ERP revealed deterioration in six patients (27%), five of whom had outflow disturbance of the main pancreatic duct. On the other hand, five patients presented slight progressive changes restricted to the side branches and the remaining 11 patients showed no change. None of the 12 patients who abstained from drinking showed a deterioration of their pancreatogram. The deterioration of clinical symptoms was less frequently seen in patients with abstinence (5/12) than in those who continued drinking (10/10). This study suggests that a ductal abnormality mainly in the side branches may be an early sign of chronic alcoholic pancreatitis. Outflow disturbance of the main pancreatic duct might play an important role in the progression of the pancreatogram to an advanced stage. Abstinence is associated with a high probability of stabilization of both clinical symptoms and ductal changes.

Comparative study of CA242 and CA19-9 in chronic pancreatitis.

CA242 has been proved to be useful in the diagnosis of pancreatic cancer. The aim of the present study was to clarify the mechanisms contributing to the high specificity of CA242 as compared with CA19-9 resulting from scarce serum elevation of this antigen in patients with chronic pancreatitis by correlating serum levels and endoscopic retrograde choledocho-pancreatography (ERCP) findings and by immunohistochemical analysis. Serum CA19-9 levels were significantly elevated in patients with calcification and with main pancreatic duct (MPD) stenosis or obstruction. On the other hand, serum CA242 levels showed no significant elevation in patients with such factors. Even though such pathological conditions were considered to lead to the stagnation of pancreatic juice, serum CA242 levels seemed to be less affected than serum CA19-9 levels. Immunohistochemical studies of chronic pancreatitis tissues revealed that CA242 was expressed less frequently and less intensely than CA19-9, and the difference in expression was more prominent in the centroacinar cells and terminal ductules. From the results of the present study, it is conceivable that CA242 is less influenced by the stagnation of the pancreatic juice than CA19-9 because of the low levels of expression in ductal systems, which results in the release of this antigen into the circulation in lower amounts than that of CA19-9.

Comparative study of CA242 and CA19-9 for the diagnosis of pancreatic cancer.

A comparative study of a new tumour marker, CA242, and CA19-9 was conducted with special reference to their diagnostic usefulness in pancreatic cancer. CA242 showed sensitivity similar to that of CA19-9 for overall cases and early cases (stage I tumour) of pancreatic cancer. For other malignancies, the positive rates of CA242 were lower than those of CA19-9 except for colorectal cancer. An important characteristics of CA242 was that it was only slightly and infrequently elevated in the sera of patients with benign diseases such as chronic pancreatitis, chronic hepatitis and liver cirrhosis. This characteristic was more apparent in the patients with benign obstructive jaundice, indicating that the serum level of this marker was scarcely affected by cholestasis. Using cut-off levels corresponding to a 90% specificity, the clinical results obtained with CA242 in the diagnosis of pancreatic cancer were similar to those obtained with CA19-9, except that CA19-9 was falsely negative in some patients with early-stage pancreatic cancer. These findings suggest the usefulness of this marker for screening pancreatic cancer in patients on their first hospital visit. However, CA242 was found to be influenced by the Lewis blood group system. This unfavourable result is attributed to the C241 catcher antibody of this assay system, which has almost the same epitope specificity as the C50 and the NS19-9 monoclonal antibodies. In conclusion, CA242 is superior to CA19-9 in diagnosing pancreatic cancer by virtue of its higher specificity.

Long-term survival of a patient with bile duct carcinoma by endoscopic biliary drainage.

An 80-yr-old female presented with obstructive jaundice. Endoscopic retrograde cholangiopancreatography showed a carcinoma in the middle extrahepatic bile duct, and a biliary endoprosthesis was inserted. Exfoliative cytology of the bile and forceps biopsy of the tumor revealed a papillary adenocarcinoma. Surgical resection could not be done because of her cardiovascular complications, and neither chemotherapy nor radiotherapy was administered. Stents were exchanged and cleaned 21 times because of occlusion and cholangitis. Subsequent serial cholangiogram showed a slow growth of the papillary tumor, but local invasion to the adjacent organs or distant metastasis was not observed. The patient survived for 7 yr and 6 months after insertion of the biliary endoprosthesis.

A case of multiple cavernous hemangioma of the small intestine and clinical review of the Japanese literature.

We report a case of multiple cavernous hemangioma of the small intestine which was diagnosed definitively before operation. A 33-yr-old male was found to have multiple polypoid lesions in the small intestine during examination for recurrent iron deficiency anemia. Plain X-ray film of the abdomen revealed multiple calcifications in the middle to lower region, suggestive of cavernous hemangioma, which was further confirmed by angiography and scintigraphy with Tc 99m-labeled red blood cells. Endoscopy during surgery was used to determine the extent of surgical resection. Seventy-three cases of hemangioma of the small intestine were reported in Japan between 1953 and 1988 and their clinical features were reviewed.