CD44 variant 6 in endometrioid carcinoma of the uterus: its expression in the adenocarcinoma component is an independent prognostic marker

The expression of variant isoforms of CD44 (CD44v) correlates with the metastatic potential of various carcinomas. In endometrial cancer, however, the significance of CD44v-expression as a prognostic indicator has not been fully investigated, nor has it been compared with that of p53, estrogen receptor or Ki67. Surgical material consisted of 14 atypical endometrial hyperplasias (AEH) and 163 endometrial carcinomas (EC). Expression of CD44s, v3 and v6 in carcinoma tissue, and other prognostic markers were immunohistochemically evaluated. The expression in the squamous differentiation was strictly excluded for the evaluation of immunohistochemistry, because the significance was different from that in the adenocarcinoma component. CD44s was frequently expressed in AEH and EC. On the other hand, CD44v3- and v6-positivities were rare or nonexistent in AEH, but were observed in 8 and 35% of EC, respectively. CD44v3-expression correlated significantly with histologic grade and lymph node metastasis. However, there was no correlation between CD44v6 expression and any clinicopathologic factor, nor were other prognostic markers expressed. Univariate analysis revealed that each CD44 was a prognostic determinant in the patients with EC. However, employing multivariate analysis, there were only three independent factors: p53 overexpression, CD44v6 expression and myometrial invasion. CD44v6 expression in the adenocarcinoma component may directly affect the behavior of carcinoma and the prognosis of patients with EC.     

Risk factors for small intestinal adenocarcinomas that are common in the proximal small intestine

The frequency of primary small intestinal adenocarcinoma is increasing but is still low. Its frequency is approximately 3% of that of colorectal adenocarcinoma. Considering that the small intestine occupies 90% of the surface area of the gastrointestinal tract, small intestinal adenocarcinoma is very rare. The main site of small intestinal adenocarcinoma is the proximal small intestine. Based on this characteristic, dietary animal proteins/lipids and bile concentrations are implicated and reported to be involved in carcinogenesis. Since most nutrients are absorbed in the proximal small intestine, the effect of absorbable intestinal content is a suitable explanation for why small intestinal adenocarcinoma is more common in the proximal small intestine. The proportion of aerobic bacteria is high in the proximal small intestine, but the absolute number of bacteria is low. In addition, the length and density of villi are greater in the proximal small intestine. However, the involvement of villi is considered to be low because the number of small intestinal adenocarcinomas is much smaller than that of colorectal adenocarcinomas. On the other hand, the reason for the low incidence of small intestinal adenocarcinoma in the distal small intestine may be that immune organs reside there. Genetic and disease factors increase the likelihood of small intestinal adenocarcinoma. In carcinogenesis experiments in which the positions of the small and large intestines were exchanged, tumors still occurred in the large intestinal mucosa more often. In other words, the influence of the intestinal contents is small, and there is a large difference in epithelial properties between the small intestine and the large intestine. In conclusion, small intestinal adenocarcinoma is rare compared to large intestinal adenocarcinoma due to the nature of the epithelium. It is reasonable to assume that diet is a trigger for small intestinal adenocarcinoma.     

Comparison of K-ras point mutation distributions in intraductal papillary-mucinous tumors and ductal adenocarcinoma of the pancreas

Intraductal papillary-mucinous tumors (IPMT) consist of cells with varying histologic degrees of severity and exhibit multiple tumor loci; however, whether or not these lesions exhibit the same genetic changes has not been clarified. To investigate this point, we analyzed K-ras mutations in multiple IPMT lesions from each patient enrolled in our study and compared our findings to those for patients with ductal adenocarcinoma of the pancreas (DC). Twenty IPMT specimens and 7 DC specimens were resected, microdissected and analyzed for the presence of K-ras mutations. The mutated genes were then sequenced using a genetic analyzer. K-ras mutations were observed in 80% of IPMT and 100% of DC patients. More than 2 types of K-ras mutation were observed in the main tumors of 43.8% of IPMT and 0% of DC patients. K-ras mutations in peritumoral and separated lesions were observed in 66.7% and 62.5% of IPMT patients, respectively. At least one identical mutation between the main tumor and the peritumoral or separated lesions was recognized in all of the IPMT patients with those lesions. Different mutations from those in the main tumor were observed in 40% of IPMT patients with separated lesions. The survival curve of IPMT-carcinoma patients with more than 2 types of K-ras mutation in the main tumor was better than that with one type of K-ras mutation. IPMT patients exhibit a remarkably genetic heterogeneity in main tumor and have good prognosis.     

S-1 plus cisplatin combination therapy for the patients with primary liver carcinomas

BACKGROUND/AIMS: 5-FU plus Cisplatin combination therapy had been employed against primary liver carcinomas for years. S-1 is a fourth-generation oral fluoropyrimidine and attracts considerable interest for the activity against gastric cancer. We herein examined the effect and adverse effects of S-1 plus Cisplatin combination therapy for primary liver carcinomas. METHODOLOGY: 4 patients with hepatocellular carcinoma (HCC) and 3 with cholangiocellular carcinoma (CCC) were employed for this study. They all had far-advanced diseases in and/or out of the liver at the time of the therapy initiation. They were 4 men and 3 women. Their ages were in the range of 42-73 (58 +/- 9.73, mean +/- SD) years old. The protocol of the therapy is a 3-week period of S-1 (70-80 mg/m2/day) oral administration combined with 2 intravenous administration of CDDP (20-35 mg/m2) during the period. With two weeks of intermission, the therapy was repeatedly performed 2-11 times for each patient. RESULTS: Three patients had PR and 2 had NC response with the therapy. Two patients with HCC and pre-treatment with 5-FU had PD response. Although the patients developed leukopenia and thrombocytopenia, the therapy was well tolerable also in the outpatient basis. CONCLUSIONS: S-1 plus Cisplatin combination therapy is a potential therapy for advanced primary liver carcinomas.     

Does repeated surgery improve the prognosis of colorectal liver metastases?

Hepatic resection for colorectal metastases was performed for 188 patients. Overall survival rates after the first hepatectomy are 41.4% and 32.7% for 5 and 10 years, respectively. The survival rate of 116 cases with unilobar hepatic metastases (H1) is significantly higher than those of 48 cases with two to four bilobar metastases (H2) and 24 cases with more than four (H3), respectively. However, the differences between the survival rates from H1 with multiple metastases, H2, and H3 are not significant, even though the H3 group has no 10-year survivors. The 5-year survival rates after the second hepatectomy (30 patients) and the resection of the lung (26 patients) are 30.3% and 35.2%, respectively, in this series. In those patients, the 5-year survival rates from the first metastasectomy are 43.4% and 50.3%, respectively. There are 14 5-year survivors with multiple metastases and 8 of those patients underwent multiple surgeries. There are 13 patients with three or more repeat resections of the liver and/or lung. The 5-year survival rates of the patients from the first and third metastasectomy are 53.9% and 22.5%, respectively. Repeat operations for the liver and the lung contribute to the improving prognosis. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18, 2005 (poster presentation).     

Complete response of lung metastasis to interferon-alpha therapy after radical nephrectomy for sarcomatoid renal cell carcinoma with Stauffer syndrome: a case report

A 75-year-old man was admitted to our hospital with liver dysfunction and elevated C-reactive protein level. He was diagnosed with renal tumor by ultrasonography. Computed tomography revealed a renal cell carcinoma (cT3aN0M0) with Stauffer syndrome. Laparoscopic radical nephrectomy was performed. Histological findings indicated clear cell carcinoma with a sarcomatoid component. After 1 month, lung metastasis was detected on an X-ray film. Interferon-α was administered, and complete response was achieved 2 months later. He has shown no evidence of recurrence in 27 months.