[Colorectal cancer: current treatment options]. / Aktuelle Therapiemöglichkeiten des kolorektalen Karzinoms.

Colorectal Cancer is one of the leading causes for cancer related death in the industrialized world. The 5 year overall survival is only 50 - 60 %, although 70 - 80% of the patients are potentially cured by surgical resection. During the last 10 years intensive clinical studies helped to establish the value of adjuvant therapy for colorectal cancer. The introduction of new chemotherapeutic agents like Irinotecan and Oxaliplatin, has led to a significant increase in tumor response and median survival in patients with colorectal carcinoma receiving adjuvant or palliative chemotherapy. In the later situation the sequential application of new combination therapies enables an overall survival of exceeding more than 20 month. In addition the targeted manipulation of molecular tumor mechanisms with new substances like monoclonal antibodies against the epidermal growth factor receptor or the vascular endothelial growth factor shows promising effects. Besides the encouraging improvement of treatment results the introduction of the new drugs has also led to more complexity within choice, strategy and conduction of specific therapies. This manuscript introduces actual treatment concepts and their impact on colorectal cancer.

[Therapy of colorectal carcinoma in internal medicine]. / Internistische Therapie des kolorektalen Karzinoms.

A six month therapy with 5-fluorouracil/folinic has become the standard in adjuvant therapy for colon cancer. The impact of new substances like oxaliplatin, irinotecan or capecitabine on the results of adjuvant therapy is currently been tested in several multicenter studies. In the clinical setting of palliative therapy these substances have already extended our therapeutic options. A marked increase in remission rates for the first time also translates into a significant prolongation of survival. The coordinated sequence of therapies allows median survival times of 20 months. After years of stagnation we face a multitude of promising new approaches to improve the outcome of patients with advanced colorectal cancer.

Neoadjuvant, hyperfractionated irradiation induces apoptosis and decreases proliferation in squamous cell cancer of the oral cavity.

Twenty-eight patients with squamous cell carcinoma of the oral cavity were treated with a total dose of 20 Gy. Tissue samples for immunohistochemistry were taken at the time of diagnostic biopsy and at surgery after radiotherapy (RX). For detection of proliferating cells, the immunoperoxidase reaction with Ki67 was performed. Apoptotic cells were detected by the TdT-mediated biotin dUTP nick end labeling (TUNEL) method. RX reduced proliferation in 27 patients, only in one case did the proliferation index (PI) increase. Delta PI (PI before RX PI following RX) amounted to 4.11% (SD=3.2%; P<0.0001). The apoptotic index (AI) increased significantly subsequent to neoadjuvant RX. Delta AI (AI after RX--AI before RX) measured 1.82% (SD=0.9; P<0.001). These data indicate that RX of patients suffering from squamous cell carcinoma of the oral cavity with a dosis of 20 Gy induces apoptosis and inhibits proliferation of tumor cells.

Prolonged and enhanced secretion of glucagon-like peptide 1 (7-36 amide) after oral sucrose due to alpha-glucosidase inhibition (acarbose) in Type 2 diabetic patients.

GLP-1, an incretin hormone of the enteroinsular axis with insulinotropic and glucagonostatic activity, is secreted after nutrient ingestion. GLP-1 is mainly produced by intestinal L-cells in the lower gastrointestinal tract (GIT); simple carbohydrates are absorbed in the upper GIT and alpha-glucosidase inhibition leads to augmented and prolonged GLP-1 release in normal subjects. In a cross-over study, 100 mg acarbose or placebo was administered simultaneously with 100 g sucrose to 11 hyperglycaemic Type 2 diabetic patients poorly controlled with diet and sulphonylureas. Plasma levels of GLP-1, insulin, C-peptide, glugacon, GIP, glucose and H2-exhalation were measured over 6 h. Differences in the integrated responses over the observation period were evaluated by repeated measurement analysis of variance with fasting values used as covariates. With acarbose, sucrose reached the colon 60-90 min after ingestion as indicated by a significant increment in breath hydrogen exhalation (p = 0.005). After an early GLP-1 increment 15 min after sucrose under both conditions, GLP-1 release was prolonged in the acarbose group (p = 0.001; significant from 210 to 360 min.). Initially (0-150 min), glucose (p = 0.001), insulin (p = 0.001), and GIP (p < 0.001) were suppressed by acarbose, whereas later there were no significant differences. Glucagon levels were higher with acarbose in the last 3 h of the 6 h observation period (p = 0.02). We conclude that in hyperglycaemic Type 2 diabetic patients, ingestion of acarbose with a sucrose load leads to elevated and prolonged GLP-1 release.