Feasibility study of S-1 adjuvant chemotherapy in patients with colorectal cancer.

BACKGROUND: We evaluated the safety, efficacy, and compliance of 1-year treatment with S-1 in patients with stage II/III resectable colorectal cancer. METHODS: S-1 was administered orally in two divided doses daily. The dose was assigned according to body surface area (BSA) as follows: BSA <1.25 m(2), 80 mg/day; BSA ≥1.25 to <1.5 m(2), 100 mg/day; and BSA ≥1.5 m(2), 120 mg/day. S-1 was given for 28 consecutive days, followed by a 14-day rest. The study objects were the rate of completion of treatment as planned at 1 year, the ratio of the actually administered dose to the planned dose at 1 year, and the total number of days of treatment. RESULTS: At 1 year, the rate of completion of treatment as planned was 77.7 % (42/54 patients), and the ratio of the actually administered dose to the planned dose was 82.9 %. The mean and median total numbers of days of treatment were 209 and 252, respectively. Grade 3 or higher toxicity (watery eyes) occurred in only 1 patient. CONCLUSION: S-1 adjuvant chemotherapy had acceptable compliance, safety, and efficacy in patients with colorectal cancer. S-1 adjuvant chemotherapy is considered a possible standard treatment regimen for colorectal cancer.

[Multiple hepatic metastases of colon cancer responding to combined therapy with TS-1 and CPT-11--a case report].

We treated a patient with multiple liver metastases arising from colon cancer in whom the metastatic tumors were responsive to treatment with the combination of TS-1 and CPT-11. The patient was a 71-year-old woman with cancer of the ascending colon and metastatic hepatic tumors. She had undergone surgery on July 28, 2004, and abdominal contrast CT scans obtained after discharge from hospital revealed numerous LDA (low-density areas) in both lobes of the liver. The patient was given ambulatory chemotherapy with TS-1 (120 mg/day on days 1-14) and CPT-11 (100 mg/day on days 1 and 8). After completion of 2 courses of chemotherapy, abdominal contrast CT scans revealed that most of the LDAs in both lobes of the liver had disappeared, and the patient was judged to have achieved PR. No adverse reactions were observed except for a slight decrease of WBC, and her chemotherapy is being continued at present. This case suggests that the combination of TS-1 and CPT-11 may be an effective form of chemotherapy for the treatment of colon cancer with multiple hepatic metastases.

Thymidine phosphorylase mRNA expression may be a predictor of response to post-operative adjuvant chemotherapy with S-1 in patients with stage III colorectal cancer.

The aim of the present study was to investigate markers in surgically resected specimens of colorectal cancer that can be used to predict the response to chemotherapy. The mRNA expression levels of enzymes involved in 5-fluorouracil (5-FU) metabolism and folate metabolism were measured in formalin-fixed, paraffin-embedded tumor sections obtained from the primary tumors of 54 patients with resected stage II or III colorectal cancer who received S-1 for one year. The 5-FU metabolizing enzymes studied were thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase (TP). The folate metabolizing enzymes studied were folypolyglutamate synthetase, γ-glutamyl hydrolase and dihydrofolate reductase. The associations between the mRNA expression levels of these enzymes and clinical variables were investigated. Tumors were classified as exhibiting high or low expression as compared with the median mRNA expression level of each metabolizing enzyme defined as the cutoff value. The associations between the high and low expression levels of each enzyme and disease-free survival (DFS) were analyzed with the use of Kaplan-Meier curves and the log-rank test. DFS was not significantly associated with the relative mRNA expression level of any metabolizing enzyme in the study group as a whole, but there was a trend toward longer DFS in patients with high TP expression (P=0.066). In patients with stage III colorectal cancer, high TP expression was associated with significantly improved outcomes compared with low TP expression (P=0.039). These results indicate that the mRNA expression of TP, a metabolizing enzyme of 5-FU, is a significant predictor of response to post-operative chemotherapy with S-1 in patients with stage III colorectal cancer.

The Glasgow prognostic score is valuable for colorectal cancer with both synchronous and metachronous unresectable liver metastases.

Systemic inflammation as evidenced by the Glasgow prognostic score (GPS) predicts cancer-specific survival in various types of cancer. The aim of this study was to evaluate the significance of GPS in patients with both synchronous and metachronous unresectable colorectal cancer liver metastases (CRLM). The subjects were 40 patients who were diagnosed as having unresectable CRLM between March 2000 and August 2010 at Jikei University Hospital. For the assessment of systemic inflammatory response using the GPS, the patients were classified into three groups: patients with normal albumin (≥3.5 g/dl) and normal CRP (≤1.0 mg/dl) as GPS 0 (n=27), those with low albumin (<3.5 g/dl) or elevated CRP (>1.0 mg/dl) as GPS 1 (n=6), and both low albumin (<3.5 g/dl) and elevated CRP (>1.0 mg/dl) as GPS 2 (n=7). We retrospectively investigated the relationship between patient characteristics including GPS and survival using univariate and multivariate analyses. Results of the univariate analysis revealed that absence of primary tumor resection (p=0.0161), absence of systemic chemotherapy (p=0.0119), serum carcinoembroynic antigen (CEA) of ≥100 ng/ml (p=0.0148), serum carbohydrate antigen (CA)19-9 of ≥100 U/ml (p<0.0001) and GPS 2 (p=0.0362) were significant predictors of poor survival. Results of the multivariate analysis revealed that serum CEA of ≥100 ng/ml (p=0.0015), CA19-9 of ≥100 U/ml (p<0.0001) and GPS 2 (p=0.0042) were independent predictors. In conclusion, GPS at diagnosis of unresectable CRLM is an independent prognostic predictor of overall survival.

Carcinoembryonic antigen and carbohydrate antigen 19-9 are prognostic predictors of colorectal cancer with unresectable liver metastasis.

No evidence currently exists to demonstrate the prognostic value of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in patients with unresectable colorectal cancer liver metastases (CRLM). Therefore, we retrospectively investigated the correlation between serum CEA and CA19-9 levels and overall survival in patients with unresectable CRLM. The study involved 40 patients who were diagnosed with unresectable CRLM between March 2000 and August 2010 at Jikei University Hospital, Japan. We retrospectively investigated the correlation between patient characteristics, including serum CEA and CA19-9 levels, and overall survival using univariate and multivariate analyses. In the univariate analysis, the absence of primary tumor resection (p=0.0161), the absence of systemic chemotherapy (p=0.0119), serum CEA ≥100 ng/ml (p=0.0148) and CA19-9 ≥100 U/ml (p<0.0001) were significant predictors of poor survival. In the multivariate analysis, the absence of systemic chemotherapy (p=0.0356), serum CEA ≥100 ng/ml (p=0.0079) and CA19-9 ≥100 U/ml (p=0.0002) were independent predictors. Serum CEA and CA19-9 levels are therefore independent prognostic predictors of survival in patients with unresectable CRLM.

Preoperative Diagnosis of Adult Intussusception Caused by Small Bowel Lipoma.

Adult intussusception is rare, accounting for only 5% of all intussusceptions, for which preoperative diagnosis is difficult. We herein report a preoperatively diagnosed case of adult intussusception caused by a small bowel lipoma. A 33-year-old man was admitted to our hospital with three weeks history of colicky epigastric pain. Computed tomography revealed thickening of the ileal wall suggestive of intussusception. Colonoscopy revealed an ileocolic intussusception. Barium enema for reduction of ileocolic intussusception demonstrated a small bowel tumor in the ileum 15 cm proximal to the ileocecal valve. The intussusception was reduced, and the patient underwent partial resection of the ileum encompassing the small bowel tumor. Histological findings confirmed the diagnosis of lipoma of the small bowel. The patient made a satisfactory recovery and remains well.