As an adjuvant treatment for Dukes B2 and C colon cancer, adding oxaliplatin (L-OHP) to a regimen of fluorouracil and Leucovorin improved disease-free survival in Western countries. In Japan, however, adjuvant chemotherapy with L-OHP is not commonly used to treat Stage III colon cancer. We report the present condition of adjuvant treatment for colon cancer in our hospital. Between September 2009 and December 2011, 66 patients with Stage III colon cancer were enrolled after curative surgery. The details of adjuvant therapy with fluoropyrimidines with and without L-OHP were explained to the patients. After the explanation, 33.3% of the patients(IIIa: 18.9%, IIIb: 55.5%) selected L-OHP chemotherapy. Regardless of the side effects, adjuvant chemotherapy including L-OHP is expected to protect against cancer recurrence in patients with Stage IIIb colon cancer.
It is known that p16(INK4) tumor suppressor gene expression in colon cancer cells is repressed by methylation at the CpG island of promoter, but in vivo silencing of p16 gene is not fully understood. Some studies showed that primary colorectal cancer (CRC) tissues often overexpress the p16 protein, while others showed the high incidence of p16 methylation. The aim of this study was to clarify p16 gene regulation in vivo. We used real-time methylation-specific PCR (MSP) to examine density of p16 methylation, and immunohistochemistry, Western blot analysis to determine p16 protein expression. Methylation was detected in 5 CRC cell lines tested and 9 of 21 (42.9%) CRCs. Four of 5 CRC cell lines did not express p16 mRNA, but 6 of 9 CRCs did express p16 mRNA even with methylation. Real-time MSP showed that CRC tissues had a wide variety in methylation density (methylation index: 0.28-0.91) and that highly methylated CRC tissues displayed significantly lower p16 mRNA expression than those with no-methylation or low-methylation. Immunohistochemistry showed that the majority of CRCs (53 of 55: 96.4%) overexpressed the p16 protein. Low p16 expression was associated with lymph node metastasis (p=0.003) and large tumor size (p=0.048). Western blot in a subset of non-tumor and tumor samples showed a consistent overexpression of the p16 protein. These results showed that CRC tissues displayed variable methylation density, which may be characteristics of p16 gene methylation in vivo. Our data suggest that a low p16 expression due to methylation may contribute to tumor enlargement and expansion of CRC.
20070 Background: Although CEA is the most commonly used tumor marker for colorectal carcinoma (CRC) and it may correlate with poorer prognosis, data are insufficient to support its use to determine adjuvant therapy. Monitoring preoperative CEA might be useful if it would assist in staging and treatment planning. Methods: This study was a pooled data analysis of 1791 CRC patients (pts) collected prospectively from 25 hospitals participating in the MCSGO. The purpose of this study was to investigate the impact of preoperative CEA on the prediction of the number of LN metastasis (#LN). Data of 1328 pts were completed with preoperative CEA and clinicopathological (CP) data (number of dissected LN, #LN, tumor size, distant metastasis, macroscopic type, depth of invasion, histological type, and lymphatic and vessel invasion). Data of 582 pts with the number of dissected LN 12 were analyzed in this study. #LN was categorized in 5 levels (0, 1, 2, 3, and ≥4), and relationship between #LN and CEA was first investigated via a multivariate analysis based on adjusting for the other CP factors. Discrete logistic regression analysis was used, in which a random effect was incorporated to adjust some bias between hospitals. The linear effects for the factors were evaluated via the regression model. The multivariate adaptive regression spline (MARS), the most powerful tool in the statistical prediction, was employed for the prediction of #LN. Results: The effect of the CEA adjusted by the other CP factors had a positive trend with two-sided P-value of 0.0394 for #LN. The adjusted R-squared measure (R 2 *) by the MARS fitting, a prediction performance index of #LN, was 0.369, and that averaged based on Bootstrap sampling (Bagging method) was R 2 * = 0.405. The relative importance of each factor in the prediction of #LN estimated by the decrease rate of R 2 * on masking each factor is shown in the Table . The relative importance of CEA in the prediction of LN# was ranked second next to lymphatic invasion. Conclusions: Preoperative CEA has a significant impact on the prediction of #LN. [Table: see text] No significant financial relationships to disclose.
Hepatic resection has gained acceptance as the most effective therapy for liver metastases from colorectal cancer. Microwave coagulation therapy (MCT) and radiofrequency ablation as well as resection are also reported as effective therapies. We analyzed the prognosis of 52 patients with liver metastases from colorectal cancer treated with MCT as the first radical therapy. A total of 4 percutaneous MCT's (3 cases with interruption of hepatic blood flow), 23 MCT's with laparotomy, and 25 with hepatic resection + MCT with laparotomy were performed. Thirty-three MCT's performed as a second therapy for recurrence in the liver were also analyzed. Clinical risk scoring as reported by Fong, et al was used in our cases. The indication for percutaneous MCT with interruption of hepatic blood flow is solitary tumor less than 20 mm in diameter. The 5-year survival rate for the 4 percutaneous MCT's, 23 MCT's with laparotomy, and 25 hepatic resection + MCT's with laparotomy and 68 hepatic resections were 20, 24 and 24%, respectively. No significant difference was found among them. The 5-year survival rate for the 17 MCT's and 12 hepatic resections with recurrence in the liver were 20% and 24%, respectively. There was no significant difference found between them. The 5-year survival rate for the 28 CRS3 was 17%, almost equal to the rate, 20%, reported by Fong, et al for hepatic resections only. MCT is effective therapy for liver metastases from colorectal cancer, recurrence in the liver, and hepatic resections.
Appendiceal mucinous neoplasms are rare, and thus the literature is sparse with regard to histological types, staging, and prognosis. In particular, it is unclear how long-term outcome may differ between mucinous adenocarcinomas and other adenocarcinomas. In the present study, we aimed to investigate the histological types and stages of appendiceal neoplasms, and to evaluate the prognostic impacts of these factors in patients with mucinous adenocarcinomas and non-mucinous adenocarcinomas.Patients with appendiceal tumors diagnosed between 2007 and 2016 were retrospectively identified from the databases of 19 institutions in the Clinical Study Group of Osaka University, Colorectal Group.A total of 266 patients with appendiceal tumors were identified, of whom 130 had pathologically diagnosed adenocarcinomas, including 57 with mucinous adenocarcinomas and 73 with non-mucinous adenocarcinomas. Five-year overall survival (OS) rates were 64.5% for mucinous adenocarcinomas, and 49.0% for non-mucinous adenocarcinomas. OS was significantly shorter among patients with non-mucinous adenocarcinomas compared to mucinous adenocarcinomas. Among patients with mucinous adenocarcinomas, 5-year OS rates were 53.6% for stage 0/I, 82.6% for II/III, and 48.4% for IV. Among patients with non-mucinous adenocarcinomas, 5-year OS rates were 90.9% for stage 0/I, 68.8% for II/III, and 7.1% for IV. Analysis of patients with stage IV disease revealed significantly shorter OS among patients with non-mucinous adenocarcinomas compared to mucinous adenocarcinomas.Our present findings showed a better prognosis in patients with mucinous adenocarcinomas compared to non-mucinous adenocarcinomas. In this setting, Union for International Cancer Control staging was associated with prognosis for non-mucinous adenocarcinomas, but not for mucinous adenocarcinomas.
A 70-year-old male patient underwent right nephrectomy for renal clear cell carcinoma. After 8 years an X-ray showed a nodule on the left lung, and CT scan detected it to be a 15 × 12 mm mass in S1+2 segment of the left lung. CT also detected another 15 × 7 mm mass in the right S3 segment. These lesions had a high FDG accumulation. Pre-operative diagnosis is bilateral pulmonary metastases from renal cell carcinoma, and bilateral lung segmentectomy was performed. Left S1+2 resected tumor was histologically clear cell carcinoma by intra-operative examination, then right S3 segmentectomy was done. And that time, small tumor was found in the middle lung lobe, and a wedge resection was performed. These specimens revealed a primary lung carcinoma of right S3, and tumourlet of middle lobe. It is very rare that three different histlogical types of lung tumor were found.