Shingo Ishiguro

Randomized trial of dietary fiber and Lactobacillus casei administration for prevention of colorectal tumors

The epidemiologic evidence that dietary fiber protects against colorectal cancer is equivocal. No large‐scale clinical study of the administration of Lactobacillus casei has been reported. We examined whether dietary fiber and L. casei prevented the occurrence of colorectal tumors. Subjects were 398 men and women presently free from tumor who had had at least 2 colorectal tumors removed. Subjects were randomly assigned to 4 groups administered wheat bran, L. casei, both or neither. The primary end point was the presence or absence of new colorectal tumor(s) diagnosed by colonoscopy after 2 and 4 years. Among 380 subjects who completed the study, 95, 96, 96 and 93 were assigned to the wheat bran, L. casei, both and no treatment groups, respectively. Multivariate adjusted ORs for occurrence of tumors were 1.31 (95% CI 0.87–1.98) in the wheat bran group and 0.76 (0.50–1.15) in the L. casei group compared to the control group. There was a significantly higher number of large tumors after 4 years in the wheat bran group. The occurrence rate of tumors with a grade of moderate atypia or higher was significantly lower in the group administered L. casei. No significant difference in the development of new colorectal tumors was observed with administration of either wheat bran or L. casei. However, our results suggest that L. casei prevented atypia of colorectal tumors.

Perioperative changes in plasma brain natriuretic peptide concentrations in patients undergoing cardiac surgery

The plasma concentrations of brain natriuretic peptide (BNP), a cardiac hormone, were measured in 30 consecutive adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) during the perioperative period. BNP concentrations remained unchanged until 6 h after the cessation of bypass, and were elevated 12, 24, and 48 h post-bypass (P<0.0001 versus baseline). They had returned to the baseline values when measured 3 weeks postoperatively. The preoperative plasma BNP concentration correlated significantly with the left ventricular ejection fraction (r=-0.895). The peak plasma BNP concentration 24 h after bypass correlated with the cardiac index (r=-0.64), stroke volume index (r=-0.62), injection rate of dopamine hydrochloride (r=0.65), and aortic crossclamp time (r=0.57). There was also a significant correlation between the preoperative BNP concentration and the plasma BNP concentration 24 h post-CPB. These findings led us to conclude that the plasma concentrations of BNP become markedly and acutely elevated after cardiac surgery with CPB, and reflect the state of left ventricular function. Moreover, the severity of acute heart failure after cardiac surgery can be predicted by the preoperative plasma BNP concentration.

Optimal calcium concentration in the initial reperfusate for post-ischemic myocardial performance (calcium concentration during reperfusion)

The dose-response curves of calcium concentration in the initial reperfusate to mechanical recovery of ischemic myocardium was investigated with an isolated working rat heart preparation. After 20 mins of normothermic ischemic arrest, the recovery of aortic flow by reperfusion with Krebs-Henseleit buffer was 54.0 +/- 2.4% (mean +/- S.E.M.). Reduction of calcium concentration during 10 mins of initial reperfusion after 20 mins of normothermic ischemic arrest increased or decreased the recovery of aortic flow with a bell-shaped dose-response curves obtained. The maximal percent recovery of aortic flow was 75.2 +/- 1.7 at 0.5 mM calcium with normal potassium-normal magnesium solution, 74.9 +/- 3.1 at 0.1 mM with high potassium (20 mM)-normal magnesium solution, 65.4 +/- 1.5 at 1.2 mM with high potassium-high magnesium (20 mM K, 16 mM Mg) solution, and 73.4 +/- 2.7 at 1.3 mM with normal potassium-high magnesium (16 mM) solution. All of them were significantly better than that of the control group (P less than 0.01). A high concentration of potassium and magnesium affected the dose-response of calcium in the initial reperfusate. These results suggest that the control of calcium concentration in the reperfusate is important during the early stages of reperfusion, and reperfusion injury may be considerably reduced.

KAI1/CD82 expression in nonsmall cell lung carcinoma is a novel, favorable prognostic factor

The KAI1/CD82 gene, the product of which is a member of the transmembrane‐4 superfamily, is a suppressor of metastasis; as a result, it is inversely associated with tumor progression and is a favorable prognostic factor in some tumors. This study was performed to determine the prognostic value of KAI1/CD82 protein levels in nonsmall cell lung carcinoma (NSCLC). In addition, levels of KAI1/CD82 expression in metastatic lesions were determined and compared with those in primary NSCLC lesions.

Myoepithelioma of the lung: Report of two cases and review of the literature

Myoepithelial tumors occur mainly in the salivary glands, the sweat glands or the breast, but uncommonly in the lung. Herein, we describe two cases of myoepithelioma of the lung. Both patients were 58-year-old men, in whom the tumors were located in the right-upper bronchus and in the left-upper bronchus, respectively, with endobronchial growth pattern. Surgery was performed, but metastasis occurred into the forearm and hip muscles in the former case, and into the liver in the latter. Histologically, the tumor in the former was a spindle-plasmacytoid type, and that in the latter was a plasmacytoid type in part with squamous differentiation. Based on histochemical, immunohistochemical and ultrastructural analyses, both were compatible with myoepithelioma. The clinicopathological uniqueness of this neoplasm is discussed, together with a review of reports of this disease in the literature.

New indication for endoscopic treatment of colorectal carcinoma with submucosal invasion

Background and Aims:  Although an increasing number of early colorectal cancers (CRC) have been curatively treated by endoscopy, there have been no definitive criteria to decide the effectiveness of such therapy. We retrospectively analyzed clinicopathological factors to establish criteria for curative endoscopic treatment of early CRC.

Intraoperative Cytodiagnosis for Detecting a Minute Invasion of the Portal Vein during Pancreatoduodenectomy for Adenocarcinoma of the Pancreatic Head

During pancreatoduodenectomy for adenocarcinoma of the pancreatic head, we frequently encountered cases in which the superior mesenteric-portal venous confluence (SMPVC) was involved with cancer. With regard to the indication of the concomitant SMPVC resection, as suggested by recent papers, a better long-term outcome would be expected if the cancer invasions were limited to the tunica adventitia or media of the SMPVC wall. Since this raised fears whether such a small SMPVC invasion was always detectable by macroscopic inspection alone, we have performed an intraoperative cytology on the touch smear of the exposed SMPVC wall for 23 patients with pancreatic head cancer. All of their SMPVCs were separated from the pancreatic head and appeared to be intact at a macroscopic level. As a result of the cytologic examination, however, 7 patients (30%) were newly diagnosed as having cancer cells on the SMPVC wall, and they received an additional resection of the SMPVC. Postoperative histology indicated that cancer invasion into the SMPVC wall was present in 6 of the 7 patients, and that the cancer invasions were limited in the tunica adventitia in 5 patients and to the tunica media in 1 patient. Thus, in order not to miss the chance of cure by SMPVC resection, our intraoperative cytology on the touch smear of the SMPVC is worth performing more actively on the macroscopically intact-looking SMPVC during resection of pancreatic cancer.

K‐ras point mutation is associated with enhancement by deoxycholic acid of colon carcinogenesis induced by azoxymethane, but not with its attenuation by all‐trans‐retinoic acid

The effects of deoxycholic acid (DCA) with and without all‐trans‐retinoic acid (ATRA) on the incidence of colon tumors induced by azoxymethane, the incidence of K‐ras point mutation in colon tumors and the labeling index of colon mucosa were investigated in male Wistar rats. Rats received 5 weekly injections of 7.4 mg/kg body weight of azoxymethane. From the start of the experiment, all rats in 3 groups also received chow pellets containing 0.3% DCA with and without s.c. injections of 0.75 or 1.5 mg/kg body weight of ATRA every other day until the end of week 45. Oral administration of DCA significantly increased the incidence of colon tumors in week 45. Concomitant use of DCA and ATRA at either dose significantly attenuated the enhancement by DCA of colon tumorigenesis. Administration of DCA significantly increased the incidence of K‐ras point mutation in colon tumors and the labeling index in the colon mucosa. Combined administration of DCA and ATRA significantly reduced the labeling index of colon mucosa, which was increased by DCA, but did not affect the incidence of K‐ras point mutation in colon tumors. These findings suggest that DCA enhances development of colon tumors and that this enhancement is attenuated by ATRA. A possible mechanism of this enhancement is induction of K‐ras point mutation. However, decreased cell proliferation in the colon mucosa may be closely related to the attenuation of DCA‐enhanced colon tumorigenesis, but not suppression of K‐ras point mutation. Int. J. Cancer 88:157–161, 2000.

Usefulness of Diagnostic Criteria for Aspiration Cytology of Hepatocellular Carcinoma

OBJECTIVE To establish new criteria for cytodiagnosis of hepatocellular carcinoma by comparing cytologic findings of hepatocellular carcinoma with those of liver cirrhosis. STUDY DESIGN Review of cytologic findings of hepatocellular carcinoma on preoperative aspiration biopsy of 31 lesions from 27 patients who underwent surgical resection and comparison of these findings with those of liver cirrhosis in 17 patients. RESULTS In the 11 lesions of moderately and poorly differentiated hepatocellular carcinoma, significant cytologic findings included monotonous and abundant cytoplasm, thick cytoplasm, increased nuclear/cytoplasmic ratio, irregular nuclear contours, increased chromatin density, intranuclear vacuoles and naked nuclei. In the 20 lesions demonstrating well-differentiated hepatocellular carcinoma, significant cytologic findings included monotonous and scant cytoplasm, well-defined cytoplasmic borders, thick cytoplasm, eccentric nuclei, increased nuclear/cytoplasmic ratio, thick nuclear membranes and increased chromatin density. We established the criteria for moderately and poorly differentiated hepatocellular carcinoma as including three cytologic parameters: increased nuclear/cytoplasmic ratio, irregular nuclear contours and increased chromatin density. We also established the criteria for well-differentiated hepatocellular carcinoma as including six cytologic parameters: monotonous cytoplasm, scant cytoplasm, well-defined cytoplasmic borders, thick cytoplasm, eccentric nuclei and increased nuclear/cytoplasmic ratio. For all 31 hepatocellular carcinoma lesions, including 27 lesions that were < or = 2 cm in diameter, both sensitivity and specificity were 100% by concurrently employing both criteria. CONCLUSION The new criteria for cytodiagnosis we established were useful for differentiating hepatocellular carcinoma from liver cirrhosis. In particular, our criteria ensured appropriate diagnostic accuracy for well-differentiated hepatocellular carcinoma.

Expression and clinical significance of the G1-S modulators in intrahepatic cholangiocellular carcinoma

Objective: To elucidate the clinical roles of G1-S modulators in cholangiocellular carcinoma (CCC). Methods: We performed immunohistochemistry using antibodies against the retinoblastoma gene product (pRb), p16, p21, p27, p53 and cyclin D1 for 41 cases of CCC as well as normal bile ducts. Results: The p27 labeling index (LI) was significantly higher in cases without lymph node metastasis than in normal bile ducts, but it decreased greatly in cases with lymph node metastasis. It was inversely related to the Ki-67 LI. The p16 LI also showed a relationship with lymph node metastasis, but not with the Ki-67 LI. The p21 LI was even higher in poorly differentiated cases and showed a direct relationship with the Ki-67 LI, although it is a negative regulator of the cell cycle. pRb expression did not correlate with any clinicopathological features. Cyclin D1 overexpression was more frequently observed in cases with poor or moderate differentiation and with lymph node metastasis. Cyclin D1 overexpression and aberrant p53 expression showed direct relationships with the Ki-67 LI. Conclusions: These results suggest that in CCC: (1) p27 expression reflects the biological character of the carcinoma and may regulate its progression; (2) cyclin D1 plays a crucial role in cell cycle progression, and (3) aberrant p53 expression has some effect on CCC cell proliferating activity.