Shuichi Akao

Plasma D-Dimer Level in Patients with Colorectal Cancer : Its Role as a Tumor Marker

The purpose of this study was to explore the relationship between the preoperative plasma D-dimer (DD) levels and the tumor pathology of colorectal cancer. The plasma DD levels were measured preoperatively in 108 patients with colorectal cancer, and then were correlated with the tumor pathology and stage. The diagnostic value of the DD levels for the tumor stage was then compared with that of the preoperative carcinoembryonic antigen (CEA) levels. The preoperative DD levels were higher in patients with either a large-sized tumor or a tumor showing deep wall penetration. Lymph-node metastasis, lymphatic invasion, hepatic metastasis, and peritoneal dissemination were all associated with higher DD levels. A stepwise increase in the median DD level was found with the tumor stage. The preoperative DD levels also significantly correlated with CEA levels. When a cutoff value of 0.6μ/ml was used in the DD assay, the sensitivity and specificity for Dukes C or D cancer were 67.2% and 64.0%, and those for Dukes D cancer were 91.3% and 57.6%, respectively. Although the DD assay was less specific, its diagnostic value in the preoperative staging of colorectal cancer was comparable to that of the CEA assay. The measurement of the preoperative DD level is thus considered to be useful for the preoperative staging of colorectal cancer.

Distribution of a synthetic protease inhibitor in rat pancreatic acini after supramaximal secretagogue stimulation

Protease inhibitors may have a beneficial effect in acute pancreatitis. The effects of E3123, a new low molecular weight protease inhibitor, on the ultrastructure of isolated pancreatic acini were examined using transmission electron microscopy. Acini supramaximally stimulated with cerulein (10−8 M) formed large cytoplasmic vacuoles similar to those generated in the cerulein-induced in vivo model of pancreatitis. Pretreatment of isolated acini with E3123 significantly reduced the size and number of vacuoles associated with cerulein treatment. The distribution of 3H-E3123 in acinar cells was examined using a pulse-chase protocol and electron microscopic autoradiography. Cellular levels of 3H-E3123 increased about 30-fold in acinar cells treated with cerulein (10−8 M) compared to unstimulated controls. In cerulein-treated acini examined after a 5-min chase, 47.4% of the autoradiographic grains were associated with the rough endoplasmic reticulum and 13.2% were associated with zymogen granules. After 30 min of incubation, the grains associated with the endoplasmic reticulum decreased to 18.5% but increased to 26.3% over zymogen granules. Thus, E3123 is taken up by the acinar cell and follows a cellular itinerary similar to that of newly synthesized secretory proteins. One potential conclusion from these studies is that the ability of E3123 to reduce the formation of vacuoles in supramaximally stimulated acini may be due to its inhibition of proteases within the secretory pathway.

The tight junction of pancreatic exocrine cells is a morphometrically dynamic structure altered by intraductal hypertension.

Abstract: The tight junction of pancreatic exocrine cells is thought to regulate paracellular permeability, and is a possible reflux route of pancreatic juice into the blood flow. Morphological changes in the tight junction of canine pancreatic acinar cells following intraductal hypertension and secretin stimulation were morphometrically analyzed to obtain evidence of the control of the paracellular reflux. Pancreatic tissues obtained from 25 dogs after intraductal hypertension, 3 dogs after secretin stimulation, and 5 control dogs were studied. Intraductal pressure was either 20 cmH2O, 30 cmH2O, or 40 cmH2O. Freeze fracture replicas of these pancreatic tissues were observed by electron microscopy. Tight junctions were classified into six morphometric types. Reticular type, parallel type, and mixed type comprised the common types predominantly found in all groups, and three special types were found, infrequently, only after intraductal hypertension. The percentages of the common types were significantly different between the groups. The areas of the tight junctions, and other morphometric parameters, were significantly less after 20 cmH2O intraductal hypertension and secretin stimulation than in the controls. However, these findings after 30 cmH2O or 40 cmH2O intraductal hypertension did not differ from those in the controls. The areas of the three special types of tight junctions were larger than those of the common types. These results suggest that the tight junction of pancreatic exocrine cells is a morphologically dynamic structure that is altered by the extent of intraductal hypertension, and support the hypothesis that paracellular permeability is the mechanism of the reflux of pancreatic juice.

The tight junction of main pancreatic duct epithelial cells is a morphometrically dynamic structure altered by intraductal hypertension

 Intercellular tight junctions play a role in the reflux of the exocrine pancreatic juice. Tight junctions of the main pancreatic duct were electron-microscopically compared between dogs with intraductal hypertension and controls, using a freeze–fracture technique and morphometrical analysis. Intraductal hypertension was created in seven dogs. Intraductal pressure was 20 cm H2O in two dogs, 30 cm H2O in two dogs, and 40 cm H2O in three dogs. Two dogs were killed as a control without any procedures. Freeze–fracture replicas were observed with an electron microscope. Tight junctions found in the replicas were morphometrically analyzed regarding the complexity, depth of strands, number of strands, and number of anastomoses. Parallel type and reticular type were recognized as two types of tight-junction complexity. The number of strands, the maximum and minimum depths, and the number of anastomoses were significantly higher in the reticular type than in the parallel type. The parallel type was predominant in the intraductal hypertension group and controls, and the parallel type was increased in the dogs with 20 cm H2O intraductal pressure. Morphometrical comparison between the intraductal hypertension groups and controls showed that the number of strands, the number of anastomoses, and the minimum and maximum depths of strands were significantly decreased only in the dogs with 20 cm H2O intraductal pressure. Intraductal hypertension may affect paracellular permeability through alterations in the number of strands and complexity in tight junctions of the main pancreatic duct epithelial cells.

5′-deoxy-5-fluorouridine, medroxyprogestrone acetate and mitoxantrone hydrochloride for advanced or recurrent Breast Cancer

BackgroundIn trecurrent breast cancer, anthracycline-containing chemotherapy is usd to maintain quality of life. However, there are several drawbacks including theraardiotoxicity. We evaluated the efficacy and toxicity of combination chemotherapy-5-fluorouridine (5′-DFUR), medroxyprogestrone acetate (MPA) and mitoxantrone hydrochloride (MIT)MethodsSixteanced or recurrent breast cancer were enrolled. Chemotherapy was gle, starting with MIT 10 mg/m2 intravenously on day 1, then oral 5′-DFUR 800 mg anTwo or more cycles were givenResultsFifteessable for response and toxicity. Thirteen patients had been treated previcycline containing regimen and 2 with CMF. There were 2 partial response patiemplete response patient (6.7%). There were 11 patients showing no change (NC) was a minor responder and 7 with a long period of NC. There was only one wase patient. The overall response rate was 20.0%. Adverse events occurred in 5 patsuppression was the most common with 5 patients becoming leukopenic (33.3was the second most common side effect, affecting 2 patients (13.3%)ConclusionGivennd preservation of QOL, the combination of MIT, 5-DFUR and MPA cine therapy for advanced or recurrent breast cancer, especially for anthra-cycline-resistant cases.