The E-cadherin-catenin complex is important for cell-cell adhesion of epithelial cells. Impairment of one or more components of this complex is associated with poor differentiation and increased invasiveness of carcinomas. Oesophageal adenocarcinomas causes early metastases, progress rapidly, and consequently have a poor prognosis. By means of immunohistochemistry, the expression of E-cadherin and alpha- and beta-catenin was studied in 65 oesophageal adenocarcinomas and 15 lymph node metastases. Expression of these proteins was evaluated with respect to clinico-pathological parameters and patient survival. Expression of the proteins was strongly correlated. In carcinomas, reduced expression of E-cadherin, alpha-catenin, and beta-catenin was found in 74, 60, and 72 per cent, respectively. Expression of E-cadherin and alpha-catenin correlated significantly with stage and grade of the carcinomas, whereas expression of beta-catenin correlated only with grade. Reduced expression of all three proteins correlated with shorter patient survival. In contrast to grade, E-cadherin and beta-catenin were significant prognosticators for survival, independent of disease stage. We conclude that in oesophageal adenocarcinomas, decreased expression of E-cadherin, alpha-catenin and beta-catenin are related events. Furthermore, expression of at least E-cadherin and beta-catenin is significantly correlated with poor prognosis.
Pouchitis is the major long-term complication after ileal pouch-anal anastomosis for ulcerative colitis. Metronidazole and ciprofloxacin are commonly used for treatment; however, nothing is known about the effects on the pouch flora during and after pouchitis episodes. This study was designed to evaluate the effect of both antibiotics on eradication of pathogens and the restoration of normal pouch flora.The fecal flora obtained from 13 patients with ulcerative colitis was examined at the beginning of a pouchitis episode before treatment, during treatment with metronidazole or ciprofloxacin, and during pouchitis-free periods. Some patients experienced more than one pouchitis episode. Therefore, a total of 104 samples was obtained. Each sample was cultured under aerobic and anaerobic conditions and the isolated bacteria were identified. Furthermore, the clinical response to both antibiotics was compared using the Pouchitis Disease Activity Index score.During pouchitis-free periods, the patients had a flora characterized by high numbers of anaerobes and no or low numbers of pathogens. This flora resembles normal colon flora. During pouchitis episodes, we found a significant decrease of anaerobes ( P = 0.01), a significant increase of aerobic bacteria ( P = 0.01), and significantly more numbers of pathogens, such as Clostridium perfringens (in 95 percent of the samples; P < 0.01) and hemolytic strains of Escherichia coli (in 57 percent of the samples; P = 0.05). Treatment with metronidazole resulted in a complete eradication of the anaerobic flora, including C. perfringens. However, no changes in the numbers of E. coli were found. In contrast, when the patient was treated with ciprofloxacin, not only C. perfringens, but also all coliforms including hemolytic strains of E. coli disappeared. The larger part of the anaerobic flora was left undisturbed during the administration of ciprofloxacin. Patients treated with ciprofloxacin experienced significant larger reductions in Pouchitis Disease Activity Index score compared with patients treated with metronidazole ( P = 0.04).This study strongly suggests a role of pathogenic bacteria ( C. perfringens and/or hemolytic strains of E. coli) in pouchitis. From a microbiologic and a clinical point of view, ciprofloxacin is preferable to metronidazole, because treatment with ciprofloxacin eradicates both pathogens and results in an optimal restoration of normal pouch flora.
textabstractPatients suffering from a certain disease generally differ greatly regarding the course
of their disease. The identification of factors from which much of this variability
between patients can be explained may be of great importance. The study of such prognostic
factors in clinical medicine is usually done for a variety of reasons which to
some extent may overlap each other. One of the reasons may be to better understand
how the disease is likely to behave. It is hardly ever possible nowadays to study the
pure natural history of a disease because usually some form of treatment will have
been undertaken. The treatment often will be curative in intent, but may also be
directed towards the relief of symptoms or avoiding or delaying these in case no
curative treatment is available. It is known from their natural history that certain
illnesses do not require treatment at all because they are self-limited processes.
Knowledge about prognostic factors in such cases will make it possible to provide
information to the patient about the probable duration and course of the disease.
Knowledge of factors which are related to the outcome of disease may be helpful to
physicians in understanding the mechanism of the disease. Such better understanding
may assist in modifying treatment protocols, searching for new treatments or fonnulating
strategies for the optimal use of expensive medical tests. Sometimes knowledge
of prognostic factors may be of use to alter the course of disease by remedial action.
This will particularly be so if these factors are elements of lifestyle such as diet,
exercise or habits. For instance, patients with alcoholic liver cirrhosis who stop taking
alcohol appear to have a better prognosis regarding survival as compared to those
who continue drinking alcohol [Borowsky et ai, 1981]. Such scientifically based facts
may be helpful in encouraging patients to change their drinking habits.
Knowledge of prognostic factors often will be of importance in planning therapeutic
trials. It may be desirable to evaluate certain therapies only in patients who belong to
certain prognostic categories. Also the number of patients required in a randomized
clinical trial depends on the distribution of prognostic factors among patients to be
included in the study.
