It may be acceptable to use an expectant management towards benign and borderline tumours that are excised without adequate surgical margins. However, surgery for locally recurrent tumours, as well as malignant tumours, should aim to achieve adequate surgical margins to reduce the risk of local recurrence, particularly that of a malignant recurrence.
Recent work using expression profiling to computationally predict the estrogen receptor (ER) status of breast tumors has revealed that certain tumors are characterized by a high prediction uncertainty ('low-confidence'). We analyzed these 'low-confidence' tumors and determined that their 'uncertain' prediction status arises as a result of widespread perturbations in multiple genes whose expression is important for ER subtype discrimination. Patients with 'low-confidence' ER+ tumors exhibited a significantly worse overall survival (P=0.03) and shorter time to distant metastasis (P=0.004) compared with their 'high-confidence' ER+ counterparts, indicating that the 'high-' and 'low-confidence' binary distinction is clinically meaningful. We then discovered that elevated expression of the ERBB2 receptor is significantly correlated with a breast tumor exhibiting a 'low-confidence' prediction, and this association was subsequently validated across multiple independently derived breast cancer expression datasets employing a variety of different array technologies and patient populations. Although ERBB2 signaling has been proposed to inhibit the transcriptional activity of ER, a large proportion of the perturbed genes in the 'low-confidence'/ERBB2+ samples are not known to be estrogen responsive, and a recently described bioinformatic algorithm (DEREF) was used to demonstrate the absence of potential estrogen-response elements (EREs) in their promoters. We propose that a significant portion of ERBB2's effects on ER+ breast tumors may involve ER-independent mechanisms of gene activation, which may contribute to the clinically aggressive behavior of the 'low-confidence' breast tumor subtype.
This study evaluates the oncological outcomes of RARP in a multiracial Asian population from a single institution. All suitable patients from 1st January 2003-30th June 2013 were identified from a prospectively maintained cancer registry. Peri-operative and oncological outcomes were analysed. Significance was defined as p < 0.05. There were n = 725 patients identified with a mean follow-up duration 28 months. The mean operative time, EBL and LOS were 186 min, 215 ml and 3 days, respectively. The pathological stage was pT2 in 68.6% (n = 497/725), pT3 in 31.3% (n = 227/725) and n = 1 patient with pT4 disease. The pathological Gleason scores (GS) were 6 in 27.9% (n = 202/725), GS 7 in 63.6% (n = 461/725) and GS ≥ 8 in 8.0 % (n = 58/725). The node positivity rate was 5.8% (n = 21/360). The positive margin rates were 31.0% (n = 154/497) and 70.9% (n = 161/227) for pT2 and pT3, respectively, and decreasing PSM rates are observed with surgical maturity. The biochemical recurrence rates were 9.7% (n = 48/497) and 34.2% (n = 78/228) for pT2 and pT3/T4, respectively. On multivariate analysis, independent predictors of BCR were pathological T stage and pathological Gleason score. Post-operatively, 78.5% (n = 569/725) of patients had no complications and 17.7% (n = 128/725) had minor (Clavien grade I-II) complications. This series, representing the largest from Southeast Asia, suggests that RARP can be a safe and oncologically feasible treatment for localised prostate cancer in an institution with moderate workload.
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