The diagnosis and management of malignant phaeochromocytoma and paraganglioma

Malignant phaeochromocytomas are rare tumours accounting for ~10% of all phaeochromocytomas; the prevalence of malignancy among paragangliomas is higher, especially those associated with succinate dehydrogenase subunit B gene mutations. Although a subset of these tumours has metastatic disease at initial presentation, a significant number develops metastases during follow-up after excision of an apparently benign tumour. Clinical, biochemical and histological features cannot reliably distinguish malignant from benign tumours. Although a number of recently introduced molecular markers have been explored, their clinical significance remains to be elucidated from further studies. Several imaging modalities have been utilised for the diagnosis and staging of these tumours. Functional imaging using radiolabelled metaiodobenzylguanidine (MIBG) and more recently, (18)F-fluorodopamine and (18)F-fluorodopa positron emission tomography offer substantial sensitivity and specificity to correctly detect metastatic phaeochromocytoma and paraganglioma and helps identify patients suitable for treatment with radiopharmaceuticals. The 5-year mortality rate of patients with malignant phaeochromocytomas and paragangliomas greater than 50% indicates that there is considerable room for the improvement of currently available therapies. The main therapeutic target is tumour reduction and control of symptoms of excessive catecholamine secretion. Currently, the best adjunctive therapy to surgery is treatment with radiopharmaceuticals using (131)I-MIBG; however, this is very rarely curative. Chemotherapy has been used for metastatic disease with only a partial and mainly palliative effect. The role of other forms of radionuclide treatment either alone or in combination with chemotherapy is currently evolving. Ongoing microarray studies may provide novel intracellular pathways of importance for proliferation/cell cycle control, and lead to the development of novel pharmacological agents.     

Endocrine pancreatic insufficiency in chronic pancreatitis.

Chronic pancreatitis (CP) is considered to be a rare cause of diabetes mellitus. However, in both the developed and developing world, there is an increasing number of patients suffering from pancreatitis probably due to lifestyle changes, which is partially associated with both social factors and the poor health status of immigrants. Owing to these circumstances, CP has evolved with one of the possible causes of diabetes in a selected group of patients and should be included in the differential diagnosis of diabetes. Several studies have shown that the long-term rate of diabetic complications in patients with CP and insulin-dependent diabetes is similar to that in patients with type 1 diabetes of equal duration. The hypothesis that early diagnosis of CP should result in better prognosis is not validated and may complicate the issue, since the risk of diabetes has been shown to increase significantly only once pancreatic calcification has developed. Accumulative evidence suggests that the risk of diabetes is not influenced by elective pancreatic surgical procedures other than distal pancreatectomy. The lack of contemporary data points to the urgent need for large prospective studies in order to accurately evaluate the special characteristics of disorders in glucose homeostasis in patients with CP.     

Cancer: A reproductive strategy of "ultra-selfish" genes?

A hypothesis is presented in which the process of "malignant transformation" which ultimately results in the rapidly dividing tumor(s)(cells) causing "cancer", is regarded as an evolved reproductive strategy of "ultra-selfish" (proto-)(onco-)genes, already present in the genome, or introduced by a virus.     

Endocrine manifestations in Langerhans cell histiocytosis.

Langerhans cell histiocytosis is a rare, multisystem disease that shows a particular predilection for hypothalamo-pituitary axis involvement. Diabetes insipidus is the most frequent permanent consequence of Langerhans cell histiocytosis, developing in around a quarter of patients. Although the exact prevalence of anterior pituitary hormone deficiencies is not known, it is probably high and is almost always associated with diabetes insipidus. Established pituitary hormone deficiencies are mostly permanent and require prompt diagnosis and treatment, whereas continuous follow-up is needed to detect deficiencies that might evolve later during the course of the disease. Involvement of endocrine tissues other than the pituitary has also been described but is relatively rare. Further studies are needed to evaluate the effect that endocrine deficiencies exert on the overall prognosis of patients with Langerhans cell histiocytosis.     

酶联免疫吸附试验中HBsAg室内质控参考品的制备和应用

目的建立室内质控参考品以鉴别诊断试剂的质量和控制操作误差,提高乙型肝炎病毒表面抗原的检测准确度。方法以国家标准品为标准制备灵敏度系列参考品、特异性参考品及精密性参考品。检测其稳定性,并进行同厂家、不同批号试剂的比较及不同厂家、三批试剂的比较。结果制备的室内质控参考品在-20℃与4℃保存3～4周检测结果无统计学差异。采用同一厂家、不同批号的HBsAg诊断试剂检测室内质控参考品,结果无统计学差异。采用不同厂家、同一批号的HBsAg诊断试剂检测结果有统计学差异。结论我们建立的室内质控参考品适宜作HBsAg室内质控,提醒我们在更换试剂厂家时应特别注意室内质控参考品的变化。     

HLA DQA1*0501 and DRB1*0301 antigens do not independently convey susceptibility to Graves' disease

Genes of, or closely associated to, the HLA complex are assumed to contribute to the genetic predisposition of Graves' disease. The aim of this study was to investigate the presence of the HLA DQA1*0501 and DRB1*0301 antigens in Greek patients with Graves' disease. In addition, we tried to establish if there is any association between these antigens and any of the clinical manifestations of the disease. We examined 117 patients with Graves' disease and 104 healthy controls. DNA was extracted from peripheral lymphocytes and the HLA DQA1*0501 and DRB1*0301 genomic regions were amplified by PCR and characterized by hybridization with sequence specific oligonucleotides (SSO). Two of the patients had a positive family history for Graves' disease and 46 had clinical thyroid eye disease (TED). The frequencies of both DQA1*0501 and DRB1*0301 antigens were significantly increased in patients compared to controls (relative risk [RR] 4.2 and 4.5 for each antigen respectively). Neither of these two antigens was an independent risk factor for Graves' disease. However, the combination of both these HLA antigens resulted in a striking increase in the RR for development of Graves' disease especially in females (RR/F=27, RR/M=8.4). No association was found between these antigens and positive family history or the presence of TED. These data suggest that HLA DQA1*0501 and DRB1*0301 antigens are not independent risk factors for the development of Graves' disease. On the contrary, the presence of both these alleles results in a significant increase in the RR for the development of Graves' disease in the Greek population, particularly in females.