Pathological and epidemiological factors associated with advanced stage at diagnosis of breast cancer.

BACKGROUND: Breast cancer is a highly heterogeneous disease, but the stage at presentation significantly influences outcome. It is important to dissect the pathobiological and epidemiological factors that influence the stage at presentation in order to develop effective strategies to improve clinical outcome. SOURCES OF DATA: PubMed references relating to breast cancer subtypes, molecular classification of breast cancer, genetic susceptibility, young women and breast cancer. AREAS OF AGREEMENT: HER-2 positive, basal-like tumours and inflammatory breast cancers (IBC) more frequently present as late stage disease. Socioeconomic, cultural and ethnic background also influence stage at presentation. AREAS OF CONTROVERSY: The biology of IBC is poorly understood. Relative contribution of social and genetic factors in certain ethnic groups. GROWING POINTS Molecular determinants of breast cancer behaviour. Genetic and biological factors influencing disease phenotype in different ethnic groups. AREAS TIMELY FOR DEVELOPING RESEARCH: Biology of basal-like tumours and IBC. Role of predisposition of genetic variants in determining breast cancer phenotypes. Biological differences in breast cancer from different ethnic groups.

A UK-Wide Survey of Life-Threatening Thyroidectomy Complications.

Background and Aims. Complications following thyroidectomy can prolong hospital stay and cause significant morbidity particularly for patients treated for benign thyroid conditions. Our aim was to administer a UK-wide survey of thyroid surgery units on frequency and timing of the onset of life-threatening airway complications & correlate to factors that might be associated with them. Methods. A questionnaire including the number of and timing of the onset of life-threatening airway complications, number of thyroidectomy procedures performed per year, surgeon years of experience, the use of difficult airway management protocol, post-operative patient destination, and patient deaths, was sent to 80 UK surgical units. Results. 23/41 hospitals responded reported no postthyroidectomy airway complications. Life-threatening airways complications all occurred within the first 12 hours postoperatively, with 9 cases occurring in the recovery room and in less than 2 hours, 3 cases occurring 2-6 hours, and 3 cases occurring 6 to 12 hours after surgery. Conclusion. The results may support recent publications that advocate thyroidectomy as a less-than-24-hour surgery procedure in selected patients. Further a larger study and standardised protocol are required to establish patients' selection criteria to determine who are likely to develop serious postoperative complication and may require HDU bed.

A review of the S100 proteins in cancer.

AIM: In the quest to reduce mortality and morbidity from cancer, there is continued effort to identify novel biomarkers to aid in the early detection and the accurate prediction of tumour behaviour. One group of proteins that is emerging as a potentially important group of markers in multiple tumour types is the S100 family. This review summarises the biological and clinical relevance of these proteins in relation to different tumour types. METHODS: A literature search was performed using the PubMed database and the reference lists of relevant articles. Single case studies were excluded and only reports with a clinical relevance from 1961 to 2007 were included. RESULTS: The search yielded over 1000 published articles and reports. Important reports and studies were reviewed, screened and tracked for further relevant publications. Only the most relevant publications are discussed with relation to individual members of the S100 family. CONCLUSION: There is increasing evidence that altered expression of S100 family members is seen in many cancers including breast, lung, bladder, kidney, thyroid, gastric, prostate and oral cancers. S100 proteins are commonly up-regulated in tumours and this is often associated with tumour progression. In contrast S100A2, S100A11 and S100A9 have been documented as tumour suppressors in some cancers but as tumour promoters in others. This demonstrates the complexity of the family and variability of their functions. Although the precise roles of these proteins in cancer is still to be discovered many of the family are associated with promoting metastases through interactions with matrix metalloproteinases or by acting as chemoattractants. There is also evidence that some members can regulate transcription factors such as p53. S100B already has a role in a clinical setting in the diagnosis and therapeutic monitoring of malignant melanoma. As our understanding of this family develops it is likely that many more members will aid the diagnosis, monitoring and potential treatment of cancers in the future.

Hepatic and splanchnic nitric oxide activity in patients with cirrhosis.

BACKGROUND: In animal models of cirrhosis, altered activity of nitric oxide (NO) has been implicated in the pathogenesis of increased intrahepatic portal vascular resistance and abnormal mesenteric vasodilatation. AIMS: To investigate NO activity in the liver and splanchnic vascular bed of patients with cirrhosis. METHODS: Activity of the calcium dependent constitutive and calcium independent inducible isoforms of NO synthase (cNOS and iNOS, respectively) was assayed biochemically in biopsy specimens of liver and a vascular portion of the greater omentum (representative of mesenteric vasculature) obtained from patients with cirrhosis undergoing liver transplantation (n=14) and non-cirrhotic control patients undergoing liver resection for metastases (n=9). The concentration of NO metabolites (NO2 + NO3) in portal and peripheral venous plasma was measured. RESULTS: The activity of cNOS was lower in cirrhotic compared with non-cirrhotic subjects for both liver and omentum. Hepatic and omental iNOS activities did not differ significantly between the two groups. Portal (NO2 + NO3) was threefold higher in cirrhotic than non-cirrhotic patients, but no differences were observed in systemic venous samples from the two groups. CONCLUSIONS: The activity of cNOS is diminished in the cirrhotic human liver. The resultant decrease in constitutive NO release may promote an increase in the intrahepatic portal vascular resistance. Elevated portal venous (NO2 + NO3) indicates enhanced splanchnic vascular release of NO in cirrhotic patients, but the absence of increased NOS activity in the mesenteric vasculature suggests differential regulation of NO synthesis within the splanchnic vascular bed.