The article summarizes the expert discussion and recommendations on the use of molecular markers and of biological targeted therapies in metastatic colorectal cancer (mCRC), as well as a proposed ...treatment decision strategy for mCRC treatment. The meeting was conducted during the 11th ESMO/World Gastrointestinal Cancer Congress (WGICC) in Barcelona in June 2009. The manuscript describes the outcome of an expert discussion leading to an expert recommendation. The increasing knowledge on clinical and molecular markers and the availability of biological targeted therapies have major implications in the optimal management in mCRC.
The new German S3 guideline "Colorectal Carcinoma" was created as part of the German Guideline Program in Oncology of the Association of the Scientific Medical Societies in Germany, the German Cancer ...Society and the German Cancer Aid under the auspices of the German Society for Digestive and Metabolic Diseases and replaces the guideline from 2008. With its evidence-based treatment recommendations, the guideline contains numerous updates and detailed definitions regarding the diagnosis and treatment of colon and rectal cancer. In particular, consensus-based recommendations regarding early detection, preoperative diagnostic method selection, and the use of interventional radiological treatment methods are detailed. The guideline also includes quality indicators so that standardized quality assurance methods can be used to optimize patient-related processes.The present article discusses the significance of the current recommendations for radiological diagnosis and treatment and is intended to enhance the quality of patient information and care by increasing distribution.
Tumour angiogenesis via vascular endothelial growth factor (VEGF) is essential for promoting tumour progression and is overexpressed in colorectal cancer. The humanised monoclonal anti-VEGF antibody ...bevacizumab (Avastin®, Genentech Inc., South San Francisco, CA) has shown activity in metastatic colorectal cancer (mCRC) combined with conventional chemotherapy. The search for biomarkers to predict response to anti-angiogenic therapy in mCRC is of great interest. We investigated several potential predictive anti-angiogenic markers including circulating endothelial progenitor cells (EPC) in patients with mCRC receiving bevacizumab containing treatment within a randomised multicenter phase 2 study of the German AIO GI tumour study group.
We collected sequential blood samples and tumour tissues from patients participating in a clinical trial for patients with mCRC. We performed flow cytometry of mononuclear cells isolated from peripheral blood to assess CD 133 + or CD 34 + /KDR + EPC before the first bevacizumab containing chemotherapy and after 21 days. Circulating VEGF blood levels before a bevacizumab containing chemotherapy regimen and after 21 days and VEGF expression in tumour tissue were examined.
Patients with mCRC and a partial remission after six months of immuno-chemotherapy containing bevacizumab showed a reduction of CD 34 negative KDR positive cells as early as 3 weeks after start of therapy. In contrast, no remarkable change in the number of CD 34 /KDR positive or CD 34 /CD133 positive cells was seen. Furthermore, there was no correlation between treatment response and VEGF expression within the tumour tissue. The mAb bevacizumab reduced serum-VEGF levels in patients independent of their treatment response to bevacizumab.
We examined circulating endothelial progenitor cells (EPC), serum-VEGF levels and the tumour tissue VEGF expression of patients with mCRC under a bevacizumab containing chemotherapy. The patients with a partial remission after six months of immuno-chemotherapy showed a reduction of CD 34 negative KDR positive cells as early as 3 weeks after start of therapy. Neither serum nor tissue markers were of significant predictive value in our pilot study. Furthermore, we review the current data on biomarkers for anti-angiogenic therapy of mCRC.
Background and aims
Microsatellite instability (MSI) is a potential indicator of prognosis in patients with colorectal cancer (CRC). To date, there are a limited number of studies which investigated ...its role in advanced CRC. Our study investigated the value of high degree of MSI (MSI-H) in patients treated with 5-FU/oxaliplatin-based chemotherapy which has been done by only one further study recently.
Patients and methods
In this study, we investigated tumour tissues from 108 patients with metastatic CRC who were treated in a prospective, randomised trial comparing two oxaliplatin and 5-FU-based therapy regimens (FUFOX vs. CAPOX) involving a total of 474 patients. We determined the incidence and prognostic value of a high degree of microsatellite instability. The specimens were analysed by PCR corresponding to the National Institute of Health reference panel. In addition, immunostaining of the mismatch repair proteins MLH1, MSH2 and MSH6 was performed.
Results and findings
The incidence of MSI-H was 4%. MSI-H was correlated with a lower rate of disease control compared to non-MSI-H patients (
p
= 0.02). However, there was no correlation between MSI-H and progression-free survival or overall survival.
Interpretation and conclusion
MSI-H incidence in metastatic CRC was low. Our data suggest that MSI-H may be correlated with a poorer response to a 5-FU/oxaliplatin treatment. This finding needs confirmation in a larger cohort.
An 83 year-old man presented with watery diarrhea and a rash. He was hypotensive, febrile and dehydrated. The rash was maculopapular and most pronounced on the dorsal trunk.
The lab tests showed an ...acute renal failure with hypokalemia and hyponatremia. Salmonella typhimurium was isolated from the aerobic blood culture, stool cultures were negative. The rash was consistent with an infection-associated Sweet's syndrome. THERAPY AND COURSE OF DISEASE: The patient was admitted and received iv fluids and potassium. An empiric antibiotic treatment with i. v. ciprofloxacin was started and changed to p. o. after 8 days. Antibiotic therapy was given 11 days total. After the administration of steroids the skin rash resolved.
It is important to draw blood cultures in patients presenting with diarrhea if fever is present. Complications associated with non-typhoidal salmonella bacteremia occur most frequently in elderly patients and include pneumonia, infected aneurysms and bone/soft part infections. In rare cases patients can also present with a skin rash.
Over the past decade various clinical trials have used monoclonal antibodies as therapeutic agents against solid tumours. No consistent pattern of response or improved survival has yet emerged ...although antigenic heterogeneity and insufficient accessibility of cells in advanced tumours have been offered as explanations for these failures. We designed a study in which a monoclonal antibody was used to target minimal residual disease in an early stage of tumour cell dissemination in patients with colorectal cancer. Only patients in Dukes' stage C who had undergone curative surgery and were free of manifest residual tumour were admitted. 189 patients with colorectal cancer of stage Dukes' C were randomly assigned to an observation regimen or to postoperative treatment with 500 mg of 17-1A antibody, followed by four 100 mg infusions each month. A balance of risk factors in the two groups was achieved by dynamic randomisation procedure. After a median follow-up of 5 years, antibody treatment reduced the overall death rate by 30% (Cox's proportional hazard, p=0·04, log-rank p=0·05) and decreased the recurrence rate by 27% (p=0·03, p=0·05). The effect of antibody was most pronounced in patients who had distant metastasis as first sign of a relapse (p=0·0014, p=0·002), an effect that was not seen for local relapses (p=0·74, p=0·67). Toxic effects of 17-1A antibody were infrequent, consisting mainly of mild constitutional and gastrointestinal symptoms. During 371 infusions four anaphylactic reactions were seen, all controllable by intravenous steroids and none necessitated admission to hospital. Adjuvant therapy with 17-1A antibody extends life and prolongs remission in patients with colorectal cancer of Dukes' stage C.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBJE, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Aim was to investigate possible underlying causes of presumed cryptogenic liver disease.
A cohort of 126 consecutive patients with presumed cryptogenic hepatitis referred to a university hospital ...were reanalysed with respect to their clinical, laboratory and histological data.
In 19 patients there was evidence for an exogenous-toxic liver damage. Diagnosis of non-alcoholic steatohepatitis could be established in 22 patients. Viral origin was excluded in all patients by serological and PCR-based assays for the known hepatitis viruses and the viruses GBV-C and SENV. Furthermore, transmission studies in non-human primates using acute phase plasma of patients with severe cryptogenic hepatitis revealed no episode of transmissible hepatitis, that could give a hint to so far unknown viruses as etiological agent. In all patients negative autoantibodies were recorded. Nevertheless, in 43 patients the diagnosis of definite or probable seronegative autoimmune hepatitis (AIH) could be assumed by the application of the International Autoimmune Hepatitis (IAH)-Score. Only 42 patients still remained with cryptogenic liver disease (CLD). Compared to patients with seronegative AIH patients with CLD were significantly older, had a longer duration of their disease, lower values of transaminases, more frequently a cholestatic liver enzyme pattern, a lower grade of inflammation in the liver and no response to immunosuppressive therapy.
Only one third of patients with initially presumed cryptogenic liver disease remained cryptogenic, while another third of patients could be identified as seronegative autoimmune hepatitis by the IAH-Score with obvious benefit from immunosuppressive therapy.
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