Oesophageal cancer treatment: studies, strategies and facts.

Esophageal cancer is among the ten most frequent cancers in the world. Once diagnosis is established prognosis is poor with five-year survival rates below 10%. Over the last few years, the evidence--base for treatment of oesophageal cancer has changed with the publication of several important articles in this field. This article reviews these and other relevant publications with focus on current evidence which holds potential for an improvement in survival in oesophageal cancer patients. Prevention and early detection represent the mainstay in the ongoing struggle to improve prognosis, which is most stringently linked to tumor stage. Other efforts have been dedicated to optimise surgical treatment, radiotherapy and chemotherapy and to discover the most efficient combinations of these treatment modalities. Strong but not unanimous evidence in favour of a multimodality approach with chemoradiotherapy followed by surgery has accumulated in recent years, and confirmatory trials are presently ongoing. A pathological complete response to chemoradiotherapy has been identified to significantly enhance survival. Among the strategies to achieve higher response rates, variations in the administration of the most commonly used drugs rather than higher drug and radiation dosages seem promising. Occult lymphatic spread has been recognized as a major source of recurrence and has been successfully targeted by three field surgical dissection and extended field radiotherapy. In search of the optimal treatment for patients with oesophageal cancer, a variety of different tracks are being pursued. This review outlines and analyses current treatment approaches and investigates how recent advances may impact on patient management.

Cell cycle-regulated expression of mammalian CDC6 is dependent on E2F.

The E2F transcription factors are essential regulators of cell growth in multicellular organisms, controlling the expression of a number of genes whose products are involved in DNA replication and cell proliferation. In Saccharomyces cerevisiae, the MBF and SBF transcription complexes have functions similar to those of E2F proteins in higher eukaryotes, by regulating the timed expression of genes implicated in cell cycle progression and DNA synthesis. The CDC6 gene is a target for MBF and SBF-regulated transcription. S. cerevisiae Cdc6p induces the formation of the prereplication complex and is essential for initiation of DNA replication. Interestingly, the Cdc6p homolog in Schizosaccharomyces pombe, Cdc18p, is regulated by DSC1, the S. pombe homolog of MBF. By cloning the promoter for the human homolog of Cdc6p and Cdc18p, we demonstrate here that the cell cycle-regulated transcription of this gene is dependent on E2F. In vivo footprinting data demonstrate that the identified E2F sites are occupied in resting cells and in exponentially growing cells, suggesting that E2F is responsible for downregulating the promoter in early phases of the cell cycle and the subsequent upregulation when cells enter S phase. Our data also demonstrate that the human CDC6 protein (hCDC6) is essential and limiting for DNA synthesis, since microinjection of an anti-CDC6 rabbit antiserum blocks DNA synthesis and CDC6 cooperates with cyclin E to induce entry into S phase in cotransfection experiments. Furthermore, E2F is sufficient to induce expression of the endogenous CDC6 gene even in the absence of de novo protein synthesis. In conclusion, our results provide a direct link between regulated progression through G1 controlled by the pRB pathway and the expression of proteins essential for the initiation of DNA replication.

Peri-operative complications following surgical closure of atrial septal defect type II in 232 patients--a baseline study.

This study intends to provide a detailed overview of the types and rates of peri-operative complications after surgical correction of an isolated ASD II. The transvenous approach to the occlusion of atrial septal defects has yielded promising results during its first 5 years of clinical trials, but before it can be established as a routine measure, definite proof is needed to demonstrate that its rate of serious complications does at least not exceed that of the surgical closure. Between 1985 and 1992, 232 consecutive patients underwent surgical closure of a secundum atrial septal defect. Among the patients 118 were children (< 18 years; 79 girls and 39 boys) with a mean age of 8.9 +/- 5.2 years (4 months-17 years) and 114 adults (74 women and 40 men) with a mean age of 28.5 +/- 10.8 years (18-69 years). Pre-operatively eight children (6.8%) and eight adults (7%) were treated for right heart failure. Mean pulmonary artery pressure was 20.4 +/- 10.4 mmHg for the children and 19.3 +/- 7 mmHg for the adults. The average pulmonary artery to systemic flow ratios were 2.9:1 and 3:1 for children and adults, respectively. Thirty children (25.4%) and 15 adults (13.2%) underwent patch closure while direct suture was the method used for the remaining patients. Average cardiopulmonary bypass time was 35.7 +/- 17.9 min for the children and 41.5 +/- 19.9 min for the adults. The length of the procedure (skin to skin) was a mean of 116 min in the young group, and 141 min in the adult group.(ABSTRACT TRUNCATED AT 250 WORDS)