Adjuvant therapy for adenocarcinoma of the rectum

Surgical resection continues to be the primary curative modality for patients with adenocarcinoma of the rectum. However, local tumor recurrence in the pelvis and/or distant metastasis may occur in spite of complete excision of grossly visible malignant disease. Surgical and pathologic staging can identify a subset of surgically treated rectal cancer patients at high risk for tumor relapse and death. Irradiation and chemotherapy have been used as adjuvant therapy in conjunction with surgery as single modalities and in combination for patients with high risk rectal cancer. Evidence from controlled clinical trials indicates a significant decrease in local tumor recurrence, and a significant improvement in disease-free and overall survival with the use of combined postoperative irradiation and chemotherapy in this setting. A current national clinical trial in the United States of America is studying whether irradiation can be combined with new chemotherapy regimens which have shown significant therapeutic benefit as surgical adjuvant therapy for patients with high risk colon cancer (5FU + levamisole) and for patients with metastatic colorectal cancer (5FU + leucovorin) to further improve the efficacy of surgical adjuvant therapy for adenocarcinoma of the rectum.

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Resumen La resección quirúrgica continúa siendo la modalidad curativa primaria en pacientes con adenocarcinoma del recto. Sin embargo, la recurrencia local del tumor en la pelvis y/o las metástasis distantes puede ocurrir a pesar de la resección completa de la enfermedad maligna macroscópicamente visible. La estadificación operatoria y patológica puede indentificar un subgrupo de pacientes tratados quirúrgicamente con alto riesgo de relapso tumoral y meserte. La irradiación y la quimioterapia han sido utlizados como terapia adyuvante en unión con la cirugía como modalidades únicas y en combinación para pacientes con cáncer rectal de alto riesgo. La evidencia surgida de ensayos clínicos controlados señala una disminución significativa en las tasas de recurrencia tumoral local, y una superación significativa en las tasas globales de sobrevida y de sobrevida libre de enfermedad con el uso de la combinación postoperatoria de irradiación y quimioterapia. Un ensayo clínico nacional que se ejecute en el momento actual en los Estados Unidos investiga si la irradiación puede ser combinada con los nuevos regímenes quimioterapéuticos que han demostrado beneficio significantivo como terapia quirúrgica adyuvante en pacientes con cáncer de colon de alto riesgo (5 FU + levamisol) y en pacientes con cáncer colorrectal metastásico (5 FU + leucovorin) con el propósito de mejorar aún más la eficicacia de la terapia quirúrgica adyuvante en el adenocarcinoma del recto.

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Résumé La chirurgie est le principal moyen thérapeutique de l'adénocarcinome du rectum. La récidive tumorale pelvienne et/ou à distance peut cependant se produire malgré une résection apparemment complète. Un bilan d'extension chirurgical et anatomopathologique peut identifier un sous-groupe de patients susceptible de présenter une récidive ou d'en mourir. La radio-et chimiothérapie ont été préconisées comme traitement adjuvant après l'exérèse chirurgicale, soit seule, soit combinée, chez cez patients à risque. Les résultats de plusieurs essais thérapeutiques semblent indiquer que la radio-et la chimiothérapie combinée à la chirurgie diminuent significativement le taux de récidives locales et améliorent significativement la survie globale et la survie sans maladie. Un essai actuellement en cours aux Etats-Unis étudie si la radiothérapie peut être utilement combinée avec les nouveaux régimes chimiothérapeutiques ayant fait preuve de leur efficacité chez les patients à risque (5FU + lévamisole) ou chez les patients ayant des métastases (5FU + leucovin).

     

A novel 37-Kd adhesive membrane protein from cloned murine bone marrow stromal cells and cloned murine hematopoietic progenitor cells

The adhesion of hematopoietic progenitor cells to bone marrow stromal cells is critical to hematopoiesis and involves multiple effector molecules. Stromal cell molecules that participate in this interaction were sought by analyzing the detergent-soluble membrane proteins of GBI/6 stromal cells that could be adsorbed by intact FDCP-1 progenitor cells. A single-chain protein from GBI/6 cells having an apparent molecular weight of 37 Kd was selectively adsorbed by FDCP-1 cells. This protein, designated p37, could be surface-radiolabeled and thus appeared to be exposed on the cell membrane. An apparently identical 37- Kd protein was expressed by three stromal cell lines, by Swiss 3T3 fibroblastic cells, and by FDCP-1 and FDCP-2 progenitor cells. p37 was selectively adsorbed from membrane lysates by a variety of murine hematopoietic cells, including erythrocytes, but not by human erythrocytes. Binding of p37 to cells was calcium-dependent, and was not affected by inhibitors of the hematopoietic homing receptor or the cell-binding or heparin-binding functions of fibronectin. It is proposed that p37 may be a novel adhesive molecule expressed on the surface of a variety of hematopoietic cells that could participate in both homotypic and heterotypic interactions of stromal and progenitor cells.     

The effects of co-culture with human fibroblasts on human embryo development in vitro and implantation

In a human in-vitro fertilization (IVF) programme, the effect of co- culture of embryos with human fibroblasts was evaluated with respect to pregnancy rate and embryo development. Patients were included in the study after giving informed written consent. The IVF treatments were randomly assigned by stratification of both age (<36 versus > or =36 years) and previous IVF attempts (yes versus no). After fertilization was established, the zygotes were transferred to a 4-well dish with or without fibroblasts and cultured for 2 days. On the third day after ovum pick-up (OPU), cell number and quality [5 (good) to 1 (poor)] of the embryos were scored and a maximum of three embryos was transferred. Supernumerary embryos of good quality were cryopreserved. The design of this study was a group sequential trial with the objective of detecting differences between pregnancy rates following IVF with conventional incubation or incubation in co-culture with fibroblasts. This design included one evaluation at half-way data collection. In the study, 148 patients had an OPU, of whom 77 were allocated to the co-culture group. There was no statistically significant difference in pregnancy rate, cell number and embryo quality between the two groups. The ongoing pregnancy rate per embryo transfer was 27% in co-culture and 30% in the conventional culture group. The implantation rates per transferred embryo were 17 and 18% respectively. Using a multivariate logistic regression model for the probability of ongoing pregnancies, the odds ratio of co-culture, adjusted for age and previous IVF attempts, was not statistically significant. In conclusion, co-culture with human fibroblasts does not contribute to an improvement of embryo quality nor to a higher pregnancy rate after IVF in an unselected group of patients.