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Alexandra Chrisoulidou, Stylianos Mandanas, Efterpi Margaritidou, Lemonia Mathiopoulou, Maria Boudina, Konstantinos Georgopoulos, Kalliopi Pazaitou-PanayiotouDepartment of Endocrinology, Theagenio Cancer Hospital, Thessaloniki, GreeceObjective: The aim of the present study was to assess patient compliance with tyrosine kinase inhibitor (TKI) treatment used for refractory and progressive thyroid cancer, in addition to the efficacy and serious adverse events associated with these agents.Methods: We retrospectively analyzed data from adult patients with metastatic differentiated or medullary thyroid cancer unresponsive to conventional treatment and treated with TKIs. Patients received treatment until disease progression or onset of serious adverse events, or until they expressed an intention to stop treatment.Results: Twenty-four patients received TKIs. The median duration of treatment was four (range: 1–19) cycles. The most frequent adverse events were fatigue, nausea, diarrhea, hypertension, and stomatitis, and the most severe were nasal bleeding, diarrhea, heart failure, rhabdomyolysis, renal failure, QT prolongation, neutropenia, and severe fatigue. Dose reduction was required in eight patients, while five decided to terminate TKI therapy because adverse events impaired their everyday activities. During therapy, two patients showed a partial response and three showed stable disease. The lungs were the metastatic sites favoring a response to treatment.Conclusion: Patient selection and meticulous pretreatment education are necessary in order to ensure adherence with TKI therapy. If adverse events appear, dose reduction or temporary treatment interruption may be offered because some adverse events resolve with continuation of treatment. In the event of serious adverse events, treatment discontinuation is necessary. Keywords: medullary thyroid carcinoma, differentiated thyroid cancer, TKIs, sorafenib, sunitinib, vandetanib

Background and Study Aims: Self-expanding metal stents have long been used in the management of patients with malignant eosphageal and malignant biliary obstruction, The aim of the present study was to report on the palliation of malignant gastric outlet obstruction using self-expanding endoprostheses. Patients and Methods: Between March 1993 and December 1994, 12 patients (eight women, four men, mean age 64 years) suffering from malignant gastric outlet obstruction due to recurrent gastric carcinoma (seven patients) and pancreatic head carcinoma (five patients) presented with an inability to eat and intractable vomiting, The patients were managed with peroral insertion of self-expanding metal stents. Results: Peroral introduction of the stent with the aid of a stabilizing overtube was successful in all patients, with the stent being supported as it was being advanced through the stenosis, Proper release of the stent into the stenotic area was achieved in all cases, relieving the intractable vomiting, The procedure was accomplished without any complications. All patients were able to eat semisolid food four days after the stent insertion, Apart from an asymptomatic partial stent occlusion in one patient, no other complications were seen during the shortterm follow-up one, two, and three months after discharge, Conclusions: These preliminary results suggest that self-expanding stents can effectively relieve malignant gastric outlet obstruction.

When large-bowel obstruction supervenes in patients ,vith rectal tumor recurrence and extensive nonresectable disease, a proximal diverting colostomy may be indicated. In this study, nonsurgical palliation of the obstruction was attempted by inserting self-expandable endoprostheses to bridge the stenotic lesion. The endoprostheses were positioned in two patients with large-bowel obstruction due to recurrent stenotic tumor, and extensive disease excluding palliative resection. Self-expandable endoprostheses with inner diameters of 18 mm and 22 mm were successfully inserted under endoscopic and radiographic control. Proper expansion of the endoprostheses was achieved in both patients, resulting in immediate decompression of the bowel and lasting relief of the obstruction.

The existence of cross-reactivity between Klebsiella antigens and cells from donors who are HLA-B27 positive and exhibit ankylosing spondylitis (AS) has been reinvestigated. Cells and antisera from different laboratories have been tested together using simultaneously microcytoxicity, chromium release and enzyme linked immunosorbent assays (ELISA). No reproducible interaction has been found. Mitogenic stimulation did not induce cross-reactivity and 'transformation' of B27+AS- cells by Klebsiella culture supernatants failed. Two transformed cell lines from B27+ AS+ donors exhibited specific cross reaction with two anti-Klebsiella antisera but only by chromium release. Immunoprecipitation with these cells and antisera showed the absence of any AS+ -specific antigen. It is concluded that the involvement of Klebsiella in ankylosing spondylitis through simple immunological cross-reactivity or through interaction with HLA-B27 is unlikely.

The molecular and cellular requirements for the development of different populations of human dendritic cells (DC) were studied. Conditions were defined that support DC production from lymphoid progenitors but that fail to induce DC formation from peripheral monocytes. The production of these lymphoid-related DC was severely blocked when hematopoietic progenitors overexpressed Ik7, a mutant dominant-negative Ikaros protein. In contrast, Ik7 did not block the formation of DC in conditions supporting the development of monocyte-derived DC. Furthermore, Ik7 did not block the formation of monocyte/macrophages and enhanced granulopoiesis. One of the molecular mechanisms mediated by Ik7 appears to be down-regulation of the flt3-receptor mRNA. Thus, distinct signals control the formation of DC demonstrating that some aspects of DC diversity are determined in part by distinct molecular cues at the hematopoietic level. (Blood. 2000;95:128-137)

The Ikaros gene is an essential regulator in the development and homeostasis of the mouse lymphopoietic system. To study the role of the Ikaros gene in the human lymphopoietic system, we cloned and characterized human Ikaros cDNAs. In the human, as in the mouse, differential splicing of Ikaros primary transcripts generates a family of lymphoid-restricted zinc finger DNA binding proteins, highly conserved in sequence composition and relative expression to the mouse homologues. Expression of Ikaros isoforms is highly restricted to the lymphopoietic system and is particularly enriched in maturing thymocytes. The Ikaros gene maps at a syntenic locus located on the short arm of human chromosome 7 and on mouse chromosome 11 next to the epidermal growth factor receptor (Egfr). The high degree of conservation of the Ikaros gene at the genetic and expression levels strongly suggests that it plays a fundamental role in the ontogeny of the lymphopoietic system across species.