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Expression profile of malignant and non-malignant diseases of the thyroid gland reveals altered expression of a common set of genes in goiter and papillary carcinomas.

Using cDNA microarrays with 3800 cDNA fragments, we determined the expression profile of normal thyroid tissue, goiter, adenoma and papillary carcinoma (10 samples from each class). After background correction and statistical analysis, we identified a set of 160 genes as being differentially expressed in all pair-wise comparisons. Here we demonstrate that, at least on the basis of these differentially expressed genes, a positive correlation between goiter and papillary carcinomas could be observed. We identified a common set of genes whose expression is diminished in both goiter and papillary carcinomas as compared to normal thyroid tissue. Moreover, no genes with inverse correlation in samples from goiter and papillary carcinomas could be detected. Using Real-Time PCR and/or tissue microarrays, we confirmed the altered expression of some of the identified genes. Of notice, we demonstrate that the reduced mRNA levels of p27(kip1) observed in papillary carcinomas as compared to either goiter or normal thyroid tissues (P<0.001) is accompanied by an altered protein distribution within the cell. In papillary carcinomas, P27(KIP1) is preferentially cytoplasmic as opposed to goiter or normal thyroid tissue, where P27(KIP1) is preferentially located in the nucleus. The exploitation of the data presented here could contribute to the understanding of the molecular events related to thyroid diseases and gives support to the notion that common molecular events might be related to the frequent observation of areas of papillary carcinomas in the gland of patients with goiter.

Carcinoma, Papillary↗

Palliation of malignant oesophageal perforation and proximal oesophageal malignant dysphagia with covered metal stents.

Twelve patients underwent placement of nine polyethylene-covered self-expanding metal stents (Cook), and three polyurethane-covered Wallstents (Schneider). All obstructing lesions were crossed fluoroscopically and stents placed under fluoroscopic control. Eleven of the 12 patients had recently undergone failed endoscopic stent insertion, which had resulted in oesophageal perforation. Technical success was achieved in 100% of patients, with no immediate complications. The stents were well tolerated and allowed the patients to eat within 12 h of their insertion. Covered stents are technically safe to insert, are best inserted fluoroscopically, and are particularly cost-effective in proximal oesophageal lesions and perforations, where Atkinson tubes are often not tolerated.

Adult↗

Allogeneic sibling umbilical-cord-blood transplantation in children with malignant and non-malignant disease.

Allogeneic bone marrow transplantation is limited by the availability of suitable marrow donors and risk of graft-versus-host disease (GVHD) and opportunistic infection. In an attempt to ameliorate these limitations, umbilical cord blood has been postulated as an alternative source of allogeneic haemopoietic stem cells for transplantation. From September, 1994, umbilical cord blood from sibling donors has been used to reconstitute haemapoiesis in 44 children with acquired or congenital lympho-haemapoietic disorders, neuroblastoma, or metabolic diseases. Patients who had HLA-identical and HLA-1 antigen disparate grafts, had a probability of engraftment at 50 days after transplantation of 85%. No patient had late graft failure. The probability of grade II-IV GVHD at 100 days was 3% and the probability of chronic GVHD at one year was 6%. With a median follow-up of 1.6 years, the probability of survival for recipients of HLA-identical or HLA-1 antigen disparate grafts is 72%. We conclude that umbilical cord blood is a sufficient source of transplantable haemopoietic stem cells for children with HLA-identical or HLA-1 antigen disparate sibling donors with very low risk of acute or extensive chronic GVHD. The feasibility of umbilical-cord-blood transplantation with HLA-2 and HLA-3 antigen disparate sibling donors remains to be determined.

Acute Disease↗