Axillary Clearance Following Positive Sentinel Lymph Node Biopsy in Symptomatic Breast Cancer.

BACKGROUND/AIM: Symptomatic cancers display a different biological behaviour from screen-detected cancers, which may impact the management of axillary metastases. We aimed to determine the role of unselected axillary nodal clearance (ANC) in symptomatic patients with positive sentinel node biopsies (SNBs). PATIENTS AND METHODS: A case-note review was performed on 95 symptomatic breast cancer patients who underwent ANC following positive SNB. RESULTS: Thirty-eight (40%) patients were treated with a mastectomy and 57 (60%) with breast-conserving surgery. At ANC, 25 patients (26.3%) showed evidence of further lymph node metastases, with 15 (60%) having two or fewer macrometastases. The presence of more than 2 SNB macrometastases was associated with further ANC metastases (p<0.001). The presence of further metastases at ANC was not associated with either reduced overall survival or disease-free survival. CONCLUSION: A number of symptomatic breast cancer patients with positive SNBs may be overtreated. Ongoing trials examining the management of low volume SNB macrometastases need to consider the symptomatic subgroup in their conclusions.

Breast cancer stromal clotting activation (Tissue Factor and thrombin): A pre-invasive phenomena that is prognostic in invasion.

BACKGROUND: Tumor stroma, of which fibroblasts are the most abundant cell, resembles a non-healing wound, where a procoagulant environment creates a permissive milieu for cancer growth. We aimed to determine if tumor expression of coagulation factors (procoagulant phenotype), and systemic hypercoagulability, occur at the preinvasive (ductal carcinoma in situ; DCIS) stage and correlate with breast cancer subtype, disease-free survival (DFS), and overall survival (OS). METHODS: In a prospective cohort of early breast cancer (DCIS, n = 76; invasive, n = 248) tumor, normal breast and plasma were examined. Fibroblast and epithelial expression of Tissue Factor (TF), thrombin, PAR1, PAR2, and plasma thrombin-antithrombin (TAT) and D-dimer were correlated with clinicopathological data, and 5-year survival. RESULTS: Fibroblast expression of TF, thrombin, and PAR1 was increased in DCIS and invasive cancer compared to normal breast fibroblasts (P ≤ .003, all). Fibroblast TF, thrombin, PAR1, and PAR2 was increased in cancers with high Ki67, high grade, ER- (vs ER+), and HER2+ (vs HER2-) (all P < .05). On univariate analysis, fibroblast TF expression was inversely associated with DFS (P = .04) and OS (P = .02). D-dimer was higher in node positive (507 (CI: 411-625) ng/mL, n = 68) vs negative patients (428 (CI: 387-472) ng/mL, n = 171, P = .004) and inversely associated with OS (P = .047). On multivariate analysis, plasma TAT was associated with reduced OS (HR 3.26, CI 1.16-3.1, P = .02), with a high plasma TAT (≥3.2 ng/mL) associated with > 3-fold mortality risk compared to low TAT. CONCLUSION: This demonstrates procoagulant phenotypic changes occur in fibroblasts at the preinvasive stage. Fibroblast procoagulant phenotype is associated with aggressive breast cancer subtypes and reduced survival. Coagulation may be a therapeutic target in breast cancer.

Tissue Factor promotes breast cancer stem cell activity in vitro.

Cancer stem cells (CSCs) are a subpopulation of cells that can self-renew and initiate tumours. The clotting-initiating protein Tissue Factor (TF) promotes metastasis and may be overexpressed in cancer cells with increased CSC activity. We sought to determine whether TF promotes breast CSC activity in vitro using human breast cancer cell lines. TF expression was compared in anoikis-resistant (CSC-enriched) and unselected cells. In cells sorted into of TF-expressing and TF-negative (FACS), and in cells transfected to knockdown TF (siRNA) and overexpress TF (cDNA), CSC activity was compared by (i) mammosphere forming efficiency (MFE) (ii) holoclone colony formation (Hc) and (iii) ALDH1 activity. TF expression was increased in anoikis-resistant and high ALDH1-activity T47D cells compared to unselected cells. FACS sorted TF-expressing T47Ds and TF-overexpressing MCF7s had increased CSC activity compared to TF-low cells. TF siRNA cells (MDAMB231,T47D) had reduced CSC activity compared to control cells. FVIIa increased MFE and ALDH1 in a dose-dependent manner (MDAMB231, T47D). The effects of FVIIa on MFE were abrogated by TF siRNA (T47D). Breast CSCs (in vitro) demonstrate increased activity when selected for high TF expression, when induced to overexpress TF, and when stimulated (with FVIIa). Targeting the TF pathway in vivo may abrogate CSC activity.

Complete circumferential rectal ulceration and haemorrhage secondary to the use of a faecal management system.

This structured case report is a brief case report describing an episode of complete circumferential rectal ulceration and haemorrhage secondary to the use of a faecal management system. An elderly lady was admitted for elective cardiac surgery. Prior to admission, the patient was taking warfarin in view of her atrial fibrillation. Following surgery, the patient developed faecal incontinence, which was managed with a faecal management system. However, the patient subsequently developed massive rectal haemorrhage from an area of complete circumferential ulceration in the rectum. This ulceration resulted from pressure necrosis secondary to the faecal management system balloon placed in the patient's rectum. The implication for care is that faecal management systems are an important adjunct in the management of faecal incontinence, but caution must be exercised with prolonged use, particularly in anticoagulated patients.

The influence of the 'golden 24-h rule' on the prognosis of oesophageal perforation in the modern era.

OBJECTIVES: Rupture of the oesophagus is a surgical emergency with significant morbidity and mortality. We present our experience in managing such patients in a tertiary care cardiothoracic unit. METHODS: We conducted a retrospective clinical review of patients who were admitted following rupture of the oesophagus over a period of 6 years (2002-2008). RESULTS: In our unit, there were 27 admissions following isolated rupture of the oesophagus, of which 18 were males and nine were females. The median age was 65 years (range 22-87). Twenty-four (89%) presented with spontaneous perforations (Boerhaave's syndrome) and three (11%) were iatrogenic. Primary surgical repair was done in 21 (77%) patients, a two-stage repair in 8% and conservative management in 16.6%. Mean hospital stay was 31 days (range 13-80 days). Overall, in-hospital mortality was five out of 27 patients (18.5%). Time from onset of symptoms to diagnosis of oesophageal perforation was early (<24 h) in 17 (63%) patients and late (>24 h) in the remaining 10 (37%) patients. In four out of the five non-survivors, there was a >24-h delay in diagnosis. The mortality rate among patients with a delayed diagnosis was 40% compared to 6.2% among those who were diagnosed in <24 h (p=0.047). CONCLUSIONS: Our review confirms that an early diagnosis and management ('golden 24 h') are crucial for successful outcome in patients with rupture of the oesophagus. We reiterate the importance of critical care support, particularly in the early stages of management. For early detection, the primary and secondary care sectors need to be better educated.