Sadaaki Inutsuka

Overexpression of cyclin B1 in gastric cancer and its clinicopathological significance: an immunohistological study.

Abstract Purpose. Cyclin B1 is a key regulator of progression through the G2/M transition during the cell cycle. Although cyclin B1 proteins are overexpressed in various types of human cancers, the relationship between cyclin B1 status in gastric cancer and its clinical significance remains unknown. Methods. We examined cyclin B1 expression by immunohistological means in 61 patients with gastric cancer in terms of histological type, tumor invasion, and metastatic behavior. Specimens were considered positive when the cytoplasm of over 10% of the cancer cell population was stained. Results. Cyclin B1 was overexpressed in 32 (53%) of 61 patients with gastric cancer. Tumors that expressed cyclin B1 were predominant in older patients, in well- and moderately differentiated adenocarcinomas and in expanding-growth type tumors. Conversely, expression of cyclin B1 was lower in poorly differentiated adenocarcinomas, and in those of the infiltrative growth type. Moreover, the disease was more advanced (stages III and IV) and widespread nodal involvement was more frequent when cyclin B1 expression was low. Logistic regression analyses showed that histological type is a significant factor related to cyclin B1 protein expression. Conclusions. These findings suggested that cyclin B1 protein overexpression is closely associated with less aggressive tumor behavior. Therefore, G2/M cyclin alternatives and the possible role of cyclins in cancer development warrants further attention.

Fas ligand expression is correlated with metastasis in colorectal carcinoma

The Fas/Fas ligand (FasL) system is one apoptotic pathway through which malignant tumors can evade immune surveillance. While FasL is expressed in malignant tumors, Fas is conversely downregulated to escape host immune attack, resulting in tumor invasion. The aim of the current study was to find out further clinicopathological significance of FasL expression in carcinoma of the colon and rectum. FasL expression was investigated using immunohistochemical staining in 143 consecutive patients with primary colorectal carcinomas. Seventy-nine carcinomas (55.2%) expressed FasL. The incidence of lymph node and distant metastases in carcinomas expressing FasL was significantly higher than in carcinomas that did not express FasL (p = 0.031 and p = 0.0003, respectively). Although univariate analysis showed that survival in patients with carcinomas expressing FasL was significantly poorer than that in patients with carcinomas without FasL expression (p = 0.001), only Dukes’ stage was an independent prognosticator by multivariate analysis. FasL expression was found to be correlated with lymph node involvement and distant metastases in colorectal carcinoma.

Prognostic significance of serum superoxide dismutase activity in patients with gastric cancer.

Abstract.Background: Although superoxide dismutase (SOD) may play an important role in helping to protect against carcinogenesis or tumor progression, little information is available regarding the clinical evaluation of antioxidant defense in patients with gastric cancer. Methods: Serum SOD activity in 34 patients with gastric cancer was estimated and the data compared with clinicopathological parameters. Results: The mean serum SOD activity in the patients was 15.9% ± 2.6%, which was higher than the value obtained in healthy donors. The serum SOD activity in patients over 70 years of age was 14.5% ± 3.0%, which was significantly lower than the value of 16.6% ± 7.3% in those under 70 years of age (P < 0.01). According to the stage of disease, the reduction in SOD activity in the patients aged over 70 years was significant in those with far advanced tumor, classified as stage IV (P < 0.01), but not in those with stage I–III disease. When the cutoff value for high- and low-SOD groups was determined as 18.0%, based on the median value for serum SOD activity in 15 patients with stage IV gastric cancer, the survival rate of patients with stage IV tumor was significantly higher in the high-SOD group than in the low-SOD group (P < 0.05). Conclusion: These findings suggested that the reduction in serum SOD activity in elderly patients may be due to weakness of the antioxidant defense of the host, thus resulting in a poor prognosis in those with far-advanced (stage IV) gastric cancer.

Increased intestinal permeability correlates with gastrointestinal toxicity among formulations of the fluorouracil analogue tegafur in rats.

Background: S-1 is a new antitumor agent which was developed based on biochemical modulation of fluorouracil. S-1 consists of tegafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1. S-1 has been reported to enhance therapeutic effects and to reduce the gastrointestinal toxicity as compared with 5-fluorouracil. In this study performed in rats, S-1 was used to assess the relationship between gastrointestinal mucosal toxicity and changes in intestinal barrier function. Methods: Fifteen rats were equally divided into three groups: group A (untreated controls), group B (FT and CDHP mixture), and group C (FT and CDHP in combination with Oxo). The animals in groups B and C received equitoxic doses of the drugs in their food for 14 consecutive days. The intestinal permeability was determined on the basis of the urinary recovery of orally administered lactulose and mannitol (L/M). Injury to the small intestines was evaluated by light microscopy. The cell surface expression of CD44 was evaluated immunohistochemically. Results: Recovery of L/M in urine (expressed as a fraction of the dose administered) was 0.15 ± (SE) 0.08, 0.23 ± 0.13, and 0.09 ± 0.04 in groups A, B, and C, respectively. The intestinal permeability in group B was significantly higher than that in group C (p < 0.05). Treatment with FT and CDHP (groups B and C) induced injury to the small intestine and decreased expression of CD44 within the intestinal mucosa, but the extent of damage was reduced by coadministration of Oxo (group C). Conclusion: This experimental study suggested that the gastrointestinal toxicity resulting from administration of anticancer drugs is accompanied by an impaired gut barrier function measurable as an increase in intestinal permeability to L/M.

p34cdc2 expression is an independent indicator for lymph node metastasis in colorectal carcinoma.

PurposeThe significance of p34cdc2 expression in human tumors has not been fully explained. The aim of the current study was to elucidate the clinicopathologic significance of immunohistochemical p34cdc2 expression in carcinoma of the colon and rectum.MethodsThe immunohistochemical expression of p34cdc2 was examined in 90 consecutive colorectal tumor cases, and p34cdc2 expression and the clinicopathologic features of the patients and their tumors were compared.ResultsLymph node metastasis was significantly more frequent in tumors expressing p34cdc2 (47.8%, 11 of 23 tumors) than in tumors not expressing p34cdc2 (22.4%, 15 of 67 tumors; P=0.020). Multivariate analysis demonstrated that tumor depth (P=0.008) and p34cdc2 expression (P=0.022) were independently associated with lymph node metastases of colorectal carcinomas.ConclusionsThe immunohistochemical expression of p34cdc2 is independently associated with lymph node metastasis in colorectal carcinoma.

Assessment of the Intestinal Permeability following Postoperative Chemotherapy for Human Malignant Disease

Purpose: Administration of anticancer drugs may damage gastrointestinal epithelium, thereby increasing the permeability of the gastrointestinal mucosa. We estimated the usefulness of oral lactulose and mannitol (L/M) test for assessment the extent of mucosal damage following postoperative chemotherapy for human malignant disease. Methods: The permeability index (PI): the urinary recovery ratio of excreted L to M was measured before and after chemotherapy in 31 patients with gastrointestinal cancers who underwent surgical resection. These findings were compared with data on 12 patients with breast cancer. The effect of chemotherapy was evaluated by the ratio of increase in PI, which was designed as post-chemotherapy value on day 7 divided by pre-chemotherapy value. Results: The mean PIs before chemotherapy in patients who underwent gastrectomy or colectomy were significantly higher than the value in those treated with mastectomy (p < 0.05). In the gastrointestinal cancer patients, the mean PIs significantly increased after chemotherapy compared with the pre-chemotherapeutic value (p < 0.01), however no significant difference was seen in breast cancer patients. When the ratios of increase in PI were calculated among gastric cancer patients, the total gastrectomy group showed a significantly higher increase in PI compared with the partial gastrectomy group (p < 0.05). Conclusions: Since the oral L/M absorption test is useful for assessing the degree of mucosal damage and measurement of intestinal permeability, this analysis should be recommended to determine the optimum timing and the adequate dosage of the anticancer drug administration.

Laparoscopic cholecystectomy for cholecystolithiasis in a case with situs inversus totalis

We report a case of cholecystolithiasis associated with situs inversus totalis (SIT) that had been successfully treated with a laparoscopic cholecystectomy. Although cholecystolithiasis associated with SIT is rare, trained surgeons who perform unusual surgical procedures, even if they have not experienced such a case, would perform laparoscopic cholecystectomy for cholecystolithiasis associated with SIT easily and safely.