Metabolic syndrome, central obesity and insulin resistance are associated with adverse pathological features in postmenopausal breast cancer.

Aims: Obesity is associated with both an increased risk of postmenopausal breast cancer and increased mortality rates. The mechanism is unclear, and central (visceral) obesity, insulin resistance, altered sex steroids and altered adipokines are mooted as possible factors. These features may cluster in the so-called metabolic syndrome.

Management of gastro-bronchial fistula complicating a subtotal esophagectomy: a case report.

Background: The development of a fistula between the tracheobronchial tree and the gastric conduit post esophagectomy is a rare and often fatal complication.

Case Presentation: A 68 year old man underwent radical esophagectomy for esophageal adenocarcinoma. On postoperative day 14 the nasogastric drainage bag dramatically filled with air, without deterioration in respiratory function or progressive sepsis.

The excessive cost of baseline diagnostic imaging in early breast cancer.

Many patients with newly diagnosed breast cancer undergo multiple staging investigations. We aimed to assess the use and yield of baseline diagnostic imaging in early-stage breast cancer. A review of all patients diagnosed with breast cancer over five years at a single institution was carried out.

Differential molecular changes in patients with asymptomatic long-segment Barrett's esophagus treated by antireflux surgery or medical therapy.

Background: The Barrett's to adenocarcinoma sequence is characterized by molecular changes including activation of nuclear factor-kappaB (NF-kappaB) and related cytokines. In this observational nonrandomized study this molecular environment was compared in matched asymptomatic cohorts who had undergone either fundoplication or therapy with proton pump inhibitors (PPIs).

Methods: Asymptomatic patients with long-segment Barrett's esophagus had endoscopic biopsy specimens taken from 2 cm below the squamocolumnar junction for measurement of activated NF-kappaB and a panel of cytokines and growth factors.

Peptide length significantly influences in vitro affinity for MHC class II molecules.

Background: Class II Major Histocompatibility Complex (MHC) molecules have an open-ended binding groove which can accommodate peptides of varying lengths. Several studies have demonstrated that peptide flanking residues (PFRs) which lie outside the core binding groove can influence peptide binding and T cell recognition. By using data from the AntiJen database we were able to characterise systematically the influence of PFRs on peptide affinity for MHC class II molecules.

Tumor necrosis factor blockers influence macrophage responses to Mycobacterium tuberculosis.

Tumor necrosis factor (TNF)-alpha is a proinflammatory cytokine that mediates inflammation in response to various pathogens, including Mycobacterium tuberculosis, but is also a key factor in the pathogenesis of rheumatoid arthritis and other autoimmune diseases. Three TNF-alpha-suppressing drugs have been approved to treat selected autoimmune diseases; 2 are monoclonal antibodies against TNF-alpha (adalimumab and infliximab), and the other is a soluble TNF receptor/Fc fusion protein (etanercept). TNF blockers have been shown to increase the risk of reactivation of latent tuberculosis, and this risk is higher in patients treated with the monoclonal antibodies.

The tissue plasminogen activator gene promoter: a novel tool for radiogenic gene therapy of the prostate?

Background: Radiation therapy is a treatment modality routinely used in cancer management so it is not unexpected that radiation-inducible promoters have emerged as an attractive tool for controlled gene therapy. The human tissue plasminogen activator gene promoter (t-PA) has been proposed as a candidate for radiogenic gene therapy, but has not been exploited to date. The purpose of this study was to evaluate the potential of this promoter to drive the expression of a reporter gene, the green fluorescent protein (GFP), in response to radiation exposure.

Tuberculosis reactivation during immunosuppressive therapy in rheumatic diseases: diagnostic and therapeutic strategies.

Purpose Of Review: Biological agents used to treat rheumatologic conditions have made a significant impact on these difficult to treat autoimmune diseases. The tradeoff has been an increase in infections, and particularly tuberculosis with tumor necrosis factor blocker use. Because reactivation of latent tuberculosis infection is preventable, new data have demonstrated that these agents can be made safer when the clinician addresses latent tuberculosis infection.

Breast cancer outcomes following a national initiative in Ireland to restructure delivery of services for symptomatic disease.

Background: A national initiative in Ireland in 2000 defined 13 designated Units to provide care for symptomatic breast cancer, and resources, including an ability to develop audit programmes, were provided. In the absence of a national audit of breast cancer outcomes, the aim of this study is to provide a detailed report of one Unit's subsequent experience, in particular comparing process and outcome data with international norms and benchmarks, and to infer on the likely impact of the national initiative.

Methods: A 5-year prospective audit of patients presenting to the Symptomatic Breast Clinic from 2001 to 2005 was conducted.

Hypoxia in prostate cancer: a powerful shield against tumour destruction?

Tumour hypoxia is progressively emerging as a common feature of prostate tumours associated with poor prognosis. While the molecular basis of disease progression is increasingly well documented, the potential role of hypoxia in these processes remains poorly evaluated. By dissecting the impact of hypoxia-inducible factor 1 alpha on molecular responses, this review provides evidence for a powerful protecting role of oxygen deprivation against oxidative stress injury, androgen deprivation, chemotherapeutic and radiation cytotoxicity.

Primary care prescribing patterns in Ireland after the publication of large hypertension trials.

Aims: This study assessed prescribing patterns of antihypertensive therapies (AHT) before and after the publication of the LIFE, ALLHAT and VALUE trials between 2000 and 2005.

Methods: The Irish HSE-PCRS prescribing database was used to identify those initiated any AHT. Any change 12 months before and after the trial publications was examined using a segmented regression analysis.

The absence of a mucosal lesion on standard histological examination does not exclude diagnosis of celiac disease.

Some patients with undiagnosed celiac disease have minor mucosal lesions that may not be apparent during routine histological analysis. Twenty-five such patients of our institution were discharged to their primary-care physicians despite having positive endomysial antibody serology. To re-evaluate diagnosis for these patients, immunohistological staining with antibodies to CD2, CD3, CD7, CD8, CD69, and Ki67 was conducted on original biopsies from twenty patients.

In silico mining identifies IGFBP3 as a novel target of methylation in prostate cancer.

Promoter hypermethylation is central in deregulating gene expression in cancer. Identification of novel methylation targets in specific cancers provides a basis for their use as biomarkers of disease occurrence and progression. We developed an in silico strategy to globally identify potential targets of promoter hypermethylation in prostate cancer by screening for 5' CpG islands in 631 genes that were reported as downregulated in prostate cancer.

Management of spontaneous rupture of the oesophagus (Boerhaave's syndrome): single centre experience of 18 cases.

Background: Spontaneous oesophageal rupture (Boerhaave's syndrome) is rare, and carries a high attendant risk of mortality.

Methods: A retrospective eight-year review from a tertiary unit.

Results: Eighteen patients were managed, with a mean age of 57 (39 - 88 years).

FDG-PET scanning in the management of cancer of the oesophagus and oesophagogastric junction: early experience with 100 consecutive cases.

Background: The aim was to evaluate the impact of FDG-PET scan on tumour staging and management decisions in oesophageal cancer.

Methods: One-hundred consecutive patients referred for consideration of surgery underwent a whole body FDG-PET scan in addition to CT imaging.

Results: Based on CT scan, a curative approach could be considered in 62 patients.

Combination of SELDI-TOF-MS and data mining provides early-stage response prediction for rectal tumors undergoing multimodal neoadjuvant therapy.

Objective: We investigated whether proteomic analysis of the low molecular weight region of the serum proteome could predict histologic response of locally advanced rectal cancer to neoadjuvant radiochemotherapy (RCT).

Summary Background Data: Proteomic analysis of serum is emerging as a powerful new modality in cancer, in terms of both screening and monitoring response to treatment. No study has yet assessed its ability to predict and monitor the response of rectal cancer to RCT.

Clinicopathologic factors predicting complete pathological response to neoadjuvant chemoradiotherapy in esophageal cancer.

Multimodal therapy comprising neoadjuvant chemotherapy and radiation therapy prior to radical resection is increasingly utilized in gastroesophageal cancer. The achievement of a complete pathological response (pCR) or a major response is associated with an improved survival. However, up to 70% of patients show an incomplete or no response to the neoadjuvant regimen, and the identification of factors which predict a response would be of considerable clinical benefit.

Prospective evaluation of quality of life in patients with localized oesophageal cancer treated by multimodality therapy or surgery alone.

Background: Health-related quality of life (HRQL) outcomes are important in assessing new approaches to the treatment of cancer. Neoadjuvant therapy is being used increasingly before surgery in patients with localized oesophageal cancer. This prospective non-randomized study evaluated HRQL in patients treated by preoperative chemotherapy and radiation therapy followed by surgery (multimodal therapy) or by surgery alone.

Mycobacterium tuberculosis at autopsy--exposure and protection: an old adversary revisited.

Background: The risk of encountering tuberculosis (TB) has reduced with the decreased incidence of the disease; however, it still can be found at autopsy.

Aim: To assess the magnitude of exposure to Mycobacterium tuberculosis at autopsy in a large general hospital setting, in a country with low incidence.

Methods: Retrospective search of the autopsy records from 1991 to 2004.

Major upper gastrointestinal surgery is associated with an antigen-dependent proinflammatory T cell response.

Background: T cells play a central role in the immune response to injury. Oesophageal and pancreatic resections are associated with significant risk of systemic inflammatory response syndrome and sepsis. This study involved a detailed analysis of T cell function in a consecutive cohort of patients undergoing such surgery.

TNF-blocking agents and tuberculosis: new drugs illuminate an old topic.

Newer TNF blockers (etanercept, infliximab and adalimumab) have contributed greatly to the control of chronic inflammatory disease. Many of the damaging inflammatory mechanisms that they inhibit are, however, important in maintaining tuberculosis in the latent phase (latent tuberculosis infection or LTBI). There is considerable evidence that links reactivation of LTBI to the use of anti-TNF monoclonal antibody (mAb) treatments, which appear to result in disruption of the granuloma that normally compartmentalizes but does not kill Mycobacterium tuberculosis during LTBI.

NF-kappaB activation in esophageal adenocarcinoma: relationship to Barrett's metaplasia, survival, and response to neoadjuvant chemoradiotherapy.

Objective: To examine the expression of the transcription factor nuclear factor kappa B (NF-kappaB) in Barrett's epithelium and adenocarcinoma and the impact of NF-kappaB expression on tumor stage and response to neoadjuvant chemotherapy and radiation therapy.

Summary Background Data: Progression of Barrett's esophagus to adenocarcinoma is associated with a wide range of cellular and molecular abnormalities. Nuclear factor-kappa B (NF-kappaB) regulates several genes involved in inflammatory, immune and apoptotic responses, but its role in esophageal inflammation and tumorigenesis has not been reported.

Gastrointestinal stromal tumours.

Background: Gastrointestinal stromal tumours (GISTs), previously classified as benign or malignant smooth muscle tumours, are the most common mesenchymal tumours of the gastrointestinal tract. GISTs express a growth factor receptor with tyrosine kinase activity, termed KIT. Mutations of KIT are common in malignant GISTs and lead to constitutional activation of tyrosine kinase function, which causes cellular proliferation and resistance to apoptosis.