No abstract

The Bethesda guidelines are useful for selecting patients for microsatellite instability testing. MLH1 and MSH2 testing should be recommended in all patients with colorectal cancer and microsatellite instability who fulfill at least one Bethesda criterion. MLH1 promoter methylation may accompany rather than initiate carcinogenesis in patients with colorectal cancer who have mismatch repair gene defects.

No abstract

In numerous tumors, metastasis can be limited to the liver. In non-resectable patients, regional treatment modalities, especially arterial cytostatic infusion, are favored in contrast to systemic chemotherapy, whereas intraportal or intraperitoneal application is not successful. Improved results with high response rates have been reported after development of intra-arterial (i.a.) long-term regimens with FUdR in patients with colorectal liver metastases using implantable pumps and ports. However, a survival benefit could only be demonstrated in comparison with a control group only treated symptomatically. Because of several reports on major local toxicity of i.a. FUdR treatment (i.e. chemical hepatitis and biliary sclerosis) several other effective i.a. 5-FU regimens have been developed. A randomized study has demonstrated superiority of i.a. 5-FU versus i.a. FUdR. In comparison with systemic treatment, superiority has only been demonstrated in patients with an intrahepatic tumor burden of < 25%. Publications about regional treatment of patients with breast, gastric cancer or carcinoid liver metastases are rare. Despite the high response rates reported, the benefit of arterial chemotherapy remains questionable. Overall, local long-term chemotherapy cannot be recommended outside of studies as a primary treatment. However, extensive experience and new drugs support the idea of conducting further regional studies.

No abstract

The use of neoadjuvant chemotherapy in resectable liver metastases induced significant remissions without increasing morbidity. The rate of severe complications and cases of no R0-resection in this study was 31 % and was with that significantly lower than 50 % (95 % CI 17.6 %-47.1 %). The risk to the patient is therefore acceptable when undergoing neoadjuvant treatment in a prospective intergroup trial.

No abstract

Background: Effective second-line treatments of inoperable metastatic colorectal cancer are rare. Therefore, the efficacy and toxicity of weekly intravenous high-dose infusions of 5-fluoro-uracil (5-FU) and folinic acid (FA) in pretreated patients with metastatic colorectal cancer were evaluated. Patients and Methods: In 32 patients, 580 applications of an intravenous high-dose infusion of 5-FU/FA were administered. All patients had been pretreated. Thirty patients had received hepatic arterial (n = 8) or intravenous infusions (n = 22) of 5-FU/FA and 2 patients, hepatic arterial infusions of 5-fluorodeoxyuridine (FUdR). The high-dose chemotherapy regimen consisted of a weekly intravenous infusion of FA (500 mg/m²) over 1 h, immediately followed by a continuous intravenous infusion of 5-FU over 24 h. The starting dose of 5-FU was 2,400 mg/m². One course consisted of 12 weekly applications, interrupted by 1 week after 6 applications and by 4 weeks after 12 applications. Results: Diarrhea, nausea, and vomiting were the most frequent manifestations of toxicity. Two patients experienced WHO grade IV diarrhea, 15 patients experienced one episode of WHO grade III diarrhea. Hematological toxicity was never observed. Partial remission was observed in 11/32 patients (34%) and disease stabilization in 9/32 patients (28%), while the disease progressed in 12/32 patients (38%) under intravenous high-dose 5-FU with FA. The median overall survival was 22 months after start of first-line treatment and 12 months after initiation of 24-hour high-dose treatment. Conclusion: 5-FU given as an intravenous 24-hour high-dose infusion with FA is well tolerated and produced a further response in progressive patients who were refractory to regional or conventional intravenous 5-FU/FA treatment. Therefore, we recommend that this treatment should be further studied in patients with metastatic colorectal cancer whose disease progressed under conventional pretreatment.