Clinical characteristics of lower bowel perforation with chronic renal failure.

BACKGROUND/AIMS: This study was conducted to evaluate the clinical characteristics of lower bowel perforation (LBP) with chronic renal failure (CRF). METHODOLOGY: In 58 patients with LBP, clinical variables, such as findings of clinical examinations, operative findings, and results of laboratory blood tests were examined as possible prognostic factors for in-hospital death, and compared between CRF and non-CRF groups. RESULTS: Of the 58 patients, 21 died during hospitalization (mortality rate, 36.2%). The mortality rate of patients with CRF was 54.2%. In the patients with LBP, the following variables were significantly correlated with in-hospital death (p<0.05): hypotension, CRF, fecal peritonitis, and low white blood cell (WBC) count, and low albumin and base excess (BE) levels. The odds ratios of in-hospital death were highest for a WBC count of 9000/mm3 and a BE of -3mEqL. Between the CRF and non-CRF groups, significant differences in the rates of age < 70 years, fecal peritonitis, in-hospital death, and low WBC count and BE were found (p<0.05). CONCLUSIONS: We identified prognostic factors of LBP and demonstrated the clinical characteristics of LBP with CRF. These results indicate that patients who have LBP with CRF tend to have immediate sepsis and a poor prognosis.

Clinical characteristics of gastric cancer with metastasis to the lymph node along the superior mesenteric vein (14v).

AIM: We investigated the clinical significance of metastasis to the lymph node (LN) along the superior mesenteric vein (14v) in gastric cancer. METHODS: A retrospective study of 2,513 gastrectomy patients with a 14v dissection was done using the Ganken Igan Database. RESULTS: The incidence of 14v metastasis correlated with tumor location, depth of tumor invasion, regional LN metastases, peritoneal metastasis, peritoneal cytology-positive, hepatic metastasis and postoperative recurrence (p < 0.01). Metastases to the infra-pyloric LN (6), supra-pyloric LN (5) and left para-cardial LN (2) were independent variables affecting 14v metastasis (p < 0.05), and the 6 status was a useful predictive factor for a 14v-negative status with a low false-negative rate (1.9%). The patients with 14v metastasis after curative surgery demonstrated a significantly lower survival rate than those without (5-year overall survival rate; 11.3 vs. 60.2%, p < 0.0001). In them, LN around the abdominal aorta (16)-positive group showed a significantly lower survival rate than the negative group (p < 0.05). CONCLUSIONS: Advanced gastric cancer with invasion to the lower stomach often metastasizes to 14v, and the 6 status can predict 14v negative. Most patients with 14v metastasis have a poor prognosis, similar to those with systemic metastasis, although some such patients may benefit from a curative dissection.

Significance of skp2 expression in primary breast cancer.

PURPOSE: We previously reported the p27 expression level to be an independent prognostic factor, and a high S-phase kinase-associated protein 2 (Skp2) expression level was significantly correlated with a poor prognosis in patients with gastric cancer. We herein examined the Skp2 expression in breast cancer and attempted to identify any associations between the Skp2 expression status and either the clinicopathologic variables or the patient's prognosis. EXPERIMENTAL DESIGN: We established four Skp2-transfected breast cancer cell lines and assessed the correlations between the Skp2 and p27 expressions using real-time reverse transcription-PCR and a Western blot analysis. We then analyzed the clinicopathologic significance of Skp2 mRNA expression in 169 Japanese patients with breast cancer. An immunohistochemical analysis was also done. RESULTS: The p27 protein expression markedly decreased after Skp2 transfection, whereas no alteration in the p27 mRNA expression was observed. The Skp2 protein expression level as determined by immunohistochemical staining thus showed a significant correlation with the Skp2 mRNA expression (P = 0.001) and a significant inverse correlation with the p27 protein expression (P = 0.042). The patients with a high Skp2 gene expression were significantly younger than those with a low expression (P = 0.002). The prognosis of patients with a high Skp2 expression was significantly (P = 0.022) poorer than for those with a low expression. Moreover, a high expression of Skp2 was an independent variable that correlated with a shorter disease-free survival (relative risk, 3.33; 95% confidence interval, 1.296-8.578; P = 0.013). CONCLUSIONS: The present results suggest that Skp2 may play an important role particularly in young breast cancer, and it is also considered to have strong independent prognostic potential and thus may prove to be a useful target for the treatment of breast cancer.

Detection of occult cancer cells in peripheral blood and bone marrow by quantitative RT-PCR assay for cytokeratin-7 in breast cancer patients.

The clinical significance of occult micrometastasis (O.M) remains unknown. We investigated it in peripheral blood (P.B.) and bone marrow (B.M.) in breast cancer patients with surgery. First, we investigated the expression levels of 7 representative molecular markers for detecting O.M (CEA, CK-7, CK-18, CK-19, CK-20, MAM and MUC-1) in 27 cancer and 8 non-epithelial cell lines using quantitative RT-PCR (QRT-PCR), and showed that the expression level of CK-7 was higher in every cancer cell line than in the non-epithelial cell lines. Next, we studied the clinical significance of O.M in P.B. and B.M. by QRT-PCR for CK-7 in breast cancer patients with surgery. Based on comparison with 17 non-cancer controls, 37 (18.0%) and 100 (48.5%) of the 206 patients were positive for CK-7 in P.B. and B.M., respectively. In 98 cases observed over 24 months after surgery, the CK-7-positive group in P.B. had poorer disease-free survival (DFS) than the negative group (p<0.01). The CK-7-positive group in P.B. showed poorer DFS than the negative group in 132 lymph node-negative cases (p=0.01), and moreover, in 61 lymph node-negative cases observed over 24 months after surgery, the CK-7-positive group in P.B. showed poorer DFS than the negative group (p<0.0001). In B.M., no significant difference in DFS was found between the CK-7-positive and CK-7-negative groups. QRT-PCR for CK-7 could be a useful and universal method for detecting O.M, and the quantitative detection of CK-7 in P.B. would have a prognostic value as a marker of early recurrence in breast cancer patients with surgery.

Cyclin-dependent kinase 1 gene expression is associated with poor prognosis in gastric carcinoma.

PURPOSE: A low expression level of cyclin-dependent kinase (Cdk) inhibitor p27 is associated with high aggressiveness and poor prognosis of various carcinomas. Human Cdk subunit 1 (Cks1), as well as S-phase kinase-associated protein 2 (Skp2), is an essential and specific factor in the p27 proteolysis by SCF(Skp2) ubiquitin ligase. The purpose of this study is to clarify the clinical significance of Cks1 expression and the relationship between Cks1 and p27 expression in gastric carcinomas. EXPERIMENTAL DESIGN: We measured Cks1 expression using quantitative reverse transcription-PCR in 76 human gastric carcinomas and p27 expression using immunohistochemistry in 28 cases. Moreover, we established Cks1- and/or Skp2-transfected gastric carcinoma cell lines and assessed the relationship between Cks1, Skp2, and p27 expression using quantitative reverse transcription-PCR and Western blot analysis. RESULTS: Cks1 high expression was correlated with poor prognosis (P < 0.05) and Cks1 expression was inversely correlated with the expression level of p27 protein in gastric carcinomas (P < 0.05). Using combined Skp2 data [T-a. Masuda, Cancer Res., 62: 3819-3825, 2002], 88.9% of the Cks1/Skp2 double-high cases expressed a low level of p27 protein and showed the poorest prognosis (P < 0.05). Western blot analysis showed that Cks1/Skp2-cotransfected cells expressed a much lower level of p27 protein than the controls. CONCLUSIONS: These findings indicate that Cks1, as well as Skp2, regulates the expression level of p27 protein in gastric carcinomas. Cks1 could play an important role in gastric carcinoma progression and would be a novel target for the treatment of gastric carcinomas as well as a strong prognostic marker.

Clinical and biological significance of S-phase kinase-associated protein 2 (Skp2) gene expression in gastric carcinoma: modulation of malignant phenotype by Skp2 overexpression, possibly via p27 proteolysis.

Reduced expression level of p27, a cyclin-dependent kinase inhibitor, is associated with high aggressiveness and poor prognosis of various malignant tumors, including gastric carcinoma. S-phase kinase-associated protein 2 (Skp2), a member of the F-box family of substrate-recognition subunits of Skp1-Cullin-F-box ubiquitin-protein ligase complexes, is necessary for p27 ubiquitination and degradation. In the present study, we examined the clinical and biological significance of Skp2 expression in human gastric carcinoma and the relationship between the expression of Skp2 and p27. Northern blot analysis showed that Skp2 mRNA was overexpressed in carcinoma tissues (P < 0.05), and the high Skp2 expression group showed significantly poorer prognosis in 98 patients with gastric carcinoma (P < 0.05). Immunohistochemical analysis showed that Skp2 protein was expressed predominantly in carcinoma cells. We also found an inverse correlation between the expression of Skp2 mRNA and p27 protein in vivo (P < 0.01). To analyze the biological behavior of Skp2, we established stably Skp2-transfected gastric carcinoma cell lines. Western blot analysis showed that Skp2-transfected cells expressed lower levels of p27 protein than the control cells. Skp2-transfected cells showed significantly higher levels of growth rate (P < 0.05), percentage of bromodeoxyuridine-positive cells after serum starvation (P < 0.01), resistance to apoptosis induction by actinomycin D treatment (P < 0.05), and invasion potential (P < 0.01) than the control cells. These findings indicate that Skp2 expression can modulate the malignant phenotype of gastric carcinoma, possibly via p27 proteolysis. Skp2 can play an important role in gastric carcinoma progression and would be a novel target for the treatment of gastric carcinoma as well as a strong prognostic marker.