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Due to advanced disease at the time of diagnosis the prognosis of oesophageal cancer is generally poor. As mass screening for oesophageal cancer is neither feasible nor reasonable, high-risk groups should be identified and surveilled. The aim of this study was to define the risk of oesophageal cancer in patients with (previous) head and neck cancer. A total of 148 patients with (previous) head and neck cancer were prospectively screened for oesophageal cancer by video-oesophagoscopy and random oesophageal biopsies. Even in a macroscopically normal looking oesophagus, four biopsy specimens were taken every 3 cm throughout the entire length of the squamous oesophagus. Low- or high-grade squamous cell dysplasia was detected histologically in 10 of the 148 patients (6.8%). All but one dysplasias were diagnosed synchronously with the head and neck cancers. In addition, oesophageal squamous cell carcinoma was diagnosed in 11 of the 148 patients (7.4%). Most invasive cancers (63.6%) occurred metachronously. The risk of squamous cell neoplasia of the oesophagus is high in patients with (previous) head and neck cancer. Surveillance is recommended in this high-risk group. [ABSTRACT FROM AUTHOR]

Extracellular nucleotides induce apoptosis and inhibit growth of colorectal cancer cells. To understand the underlying signaling pathways, we investigated the role of nucleotide-sensitive P2 receptors and focused on the receptor-mediated signaling of intracellular Ca2+ and cyclic adenosine monophosphate (cAMP) in two colorectal carcinoma cell lines (HT29, Colo320 DM). Expression and functionality of P2 receptor subtypes evaluated by RT-PCR and [Ca2+]i imaging revealed that solely metabotropic P2 receptors of the subtype P2Y2 were expressed on a functional level in both cell lines. Short-term stimulation of P2Y2 receptors caused Ca2+ mobilization from intracellular stores and a subsequent transmembrane Ca2+ influx. The receptor-induced [Ca2+]i elevation was shown to increase basal-stimulated [cAMP]i moderately and to potentiate forskolin-stimulated [cAMP]i vigorously, since the effects were dose-dependently inhibited by preloading the cells with the [Ca2+]i chelator BAPTA. In contrast, activation of protein kinase C (PKC) did not contribute to a receptor-mediated rise in [cAMP]i, since the PKC inhibitor staurosporine completely failed to reduce P2Y2 receptor-induced increases in [cAMP]i. Prolonged application of P2Y2 receptor agonists induced a time-dependent increase in apoptosis (up to 50% above control values) in both cell lines and caused dose-dependent inhibition of cell proliferation of up to 85% (Colo320 DM) or 64% (HT29). Chelating [Ca2+]i with BAPTA almost completely abolished P2Y2 receptor-induced cell death. Rises in [cAMP]i elicited by either forskolin or cAMP derivatives inhibited growth in both cell lines, too. In line with the potentiating effect of P2Y2 receptors on forskolin-stimulated [cAMP]i increases, costimulation with forskolin and P2Y2 receptor agonists led to synergistic antiproliferative effects. Moreover, a synergistic growth inhibition was observed when coincubating the cells with the P2Y2 receptor agonist ATP and the cytostatic drug 5-fluorouracil, which forms the basis for most currently applied chemotherapeutic regimes in colorectal cancer treatment. Our results demonstrate the growth inhibitory potency of P2Y2 receptors in colorectal carcinoma cells. Receptor-induced [Ca2+]i signaling appears to play a major role in the observed antiproliferative and apoptosis-inducing effects. [ABSTRACT FROM AUTHOR]

Background/aims: About half of all Crohn's disease (CD) patients undergo surgery at some point, many because of strictures. An alternative possibility is to dilate strictures endoscopically. However, little is known about prognostic factors., Patients and Methods: Thirty-two patients with primary CD (n=2), radiogenic strictures (n=1), or postoperative strictures (27 because of CD; 2 after resection because of cancer), were planned to undergo colonoscopic dilatation of which 25 patients were dilated (10 men; 15 women; median age 48). Length of stenosis, diameter of stricture, balloon size, smoking status, ulcer in the stricture, passage postdilatation, hemoglobin level, complications, redilatation, and subsequent surgery were recorded. Only patients with at least 6 months follow up were included., Results: Five out of 32 patients had no stenosis, marked inflammation, or fistulas adjacent to the stricture. One patient each had a long stricture (8 cm) or a filiform stenosis ruling out dilatation [technical success, 25/27 (92.6%)]. Among these 25 patients, 39 colonoscopies with 51 dilatations were performed. After a single dilatation, 52% were asymptomatic while 48% needed another intervention, half of them surgery. Bleeding without need for transfusion occurred in 3 out of 39 colonoscopies and one perforation required surgery. Significant prognostic factors were smoking and ulcers in the stricture (P<0.05 each). Some ulcers led to intussusception requiring surgery in spite of good dilatation results., Conclusion: Through the endoscope balloon stricture dilatation is a relatively safe and often effective treatment modality in ileocolonic strictures. The presence of ulcers in the stricture have a worse outcome as do smokers.

Background/aims: Following malignant transformation, epithelial cells of colorectal carcinomas, unlike normal colonic epithelial cells, no longer express the alpha 5 beta 1 fibronectin receptor. We hypothesized that the loss of alpha 5 beta 1 expression might facilitate the tumorigenicity of transformed colonic cells., Methods: To examine this hypothesis, we established subclones of the human colon adenocarcinoma cell line HT 29, which differ in their fibronectin receptor expression and tested their tumorigenicity in nude mice., Results: Our data indicate that the capacity to form tumors in nude mice after subcutaneous injection was significantly lower for alpha 5-positive than for alpha 5-negative cell clones. In addition, tumors from clones expressing no detectable levels of alpha 5 beta 1 grew rapidly, whereas tumors expressing elevated levels of fibronectin receptor grew slowly. Despite similar rates of adhesion to fibronectin for alpha 5-positive and alpha 5-negative cell clones in vitro, deposition of fibronectin in tumor-surrounding stroma was increased in tumors derived from alpha 5-positive cells., Conclusions: Our results indicate that an increase of the alpha 5 beta 1-mediated interaction of malignant cells with the extracellular matrix may be responsible for decreased tumorigenicity of malignant transformed cells in colorectal carcinomas.

Following malignant transformation, epithelial cells of colorectal carcinomas unlike normal colonic epithelial cells do not any longer express the classical alpha 5 beta 1 fibronectin receptor. We speculated that the loss of alpha 5 beta 1 expression may facilitate the tumorigenicity of transformed colonic cells. To examine this hypothesis, we established subclones of the human colon adenocarcinoma cell line HT29 which differ in their fibronectin receptor expression and tested their tumorigenicity in nude mice. Our data indicate that the capacity to form tumors in nude mice after subcutaneous injection was significantly lower for alpha 5 beta 1-positive than for alpha 5 beta 1-negative cell clones. In addition, tumors from clones expressing to detectable levels of alpha 5 beta 1 grew rapidly, while tumors expressing elevated levels of fibronectin receptor grew slowly. Deposition of fibronectin in tumor-surrounding stroma was increased in tumors derived from alpha 5 beta 1-positive cells compared to tumors derived from alpha 5 beta 1-negative cells. Our results indicate that a reduction of the alpha 5 beta 1-mediated interaction of epithelial cells with the extracellular matrix may be responsible for increased tumorigenicity of malignant transformed cells in colorectal carcinomas.