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Buenos Aires, Argentina

Ahmed J.,Queen Alexandra Hospital NHS Trust | Nasir M.,Queen Alexandra Hospital NHS Trust | Flashman K.,Queen Alexandra Hospital NHS Trust | Khan J.,Queen Alexandra Hospital NHS Trust | And 2 more authors.
International Journal of Colorectal Disease | Year: 2016

Introduction: Robotic surgery provides an alternative option for a minimal access approach. It provides a stable platform with high definition three-dimensional views and improved access, which enhances the capabilities for precise dissection in a narrow surgical field. These distinctive features have made it an attractive option for colorectal surgeons. Aim: The aim of this study was to present a standardised technique for single-docking robotic rectal resection and to analyse clinical outcomes of the first 100 robotic rectal procedures performed in a single centre between May 2013 and April 2015. Method: Prospectively collected data related to 100 consecutive patients who underwent single-docking robotic rectal surgery was analysed for surgical and oncological outcomes. Results: Sixty-six patients were male, the median age was 67 years (range-24–92). Eighteen patients had neo-adjuvant chemoradiotherapy whilst 23 patients had BMI >30. Procedures performed included anterior resection (n = 74), abdominoperineal resection (n = 10), completion proctectomy (n = 9), restorative proctectomy with ileal pouch–anal anastomosis (IPAA) (n = 5) and Hartmann’s procedure (n = 2). The median operating time was 240 min (range-135–456), and median blood loss was 10 ml (range 0–200). There was no conversion or intra-operative complication. Median length of stay was 7 days (range, 3–48) and readmission rate was 12 %. Thirty-day mortality was zero. Postoperatively, two patients had an anastomotic leak whilst two had small bowel obstruction. The median lymph node harvest was 18 (range, 6–43). Conclusion: The single-docking robotic technique should be considered as an alternative option for rectal surgery. This approach is safe and feasible and in our study it has demonstrated favourable clinical outcomes. © 2016, Springer-Verlag Berlin Heidelberg. Source

Salama P.,University of Western Australia | Stewart C.,King Edward Memorial Hospital | Forrest C.,Fremantle Hospital | Platell C.,University of Western Australia | And 2 more authors.
Cancer Immunology, Immunotherapy | Year: 2012

There are few clearly established prognostic factors available to guide the use of adjuvant chemotherapy in early stage colon cancer patients. Some of the most promising candidates include the invasion of extramural blood vessels by tumour cells and the densities of FOXP3+ T regulatory cells (Tregs) in tumour and adjacent normal colonic mucosal tissue. The aim of our study was to evaluate the prognostic signiWcance of these markers in AJCC stage II colon cancer, with particular reference to lymphoid follicles in the mucosa. Histopathological review for the presence of vascular and serosal invasion was conducted on a series of 165 stage II colon cancers treated by surgery alone. Immunohistochemical staining for FOXP3 was performed on tumour tissue and histologically normal colonic mucosa from the surgical margin. Image analysis software was used to evaluate the density of FOXP3+ cells in the tumour core, invading margin and lymphoid follicles from the colonic mucosa. For survival analysis, cases were classiWed into high- or lowdensity of FOXP3+ cells according to the median value. The mean density of FOXP3+ Tregs in lymphoid follicles was twofold and Wvefold higher than in the invading margin and tumour core, respectively. Multivariate analysis identiWed extramural vascular invasion (HR, 2.47; 95% CI: 1.00-6.07; P = 0.05) and high FOXP3+ cell density in lymphoid follicles (HR, 4.22; 95% CI: 1.49-11.91; P = 0.007) as independent factors for worse survival, whereas a high frequency of lymphoid follicles in histologically normal colonic mucosa was associated with better survival (HR, 0.31; 95% CI: 0.12- 0.79; P = 0.014). Our data suggest that host factors related to the immune system have major prognostic signiWcance in early stage colon cancer. The density of FOXP3+ cells within lymphoid follicles and the frequency of these structures in normal colonic mucosa represent novel and independent prognostic factors. © Springer-Verlag 2012. Source

Salama P.,University of Western Australia | Phillips M.,Western Research Institute | Platell C.,University of Western Australia | Platell C.,Colorectal Cancer Unit | Iacopetta B.,University of Western Australia
Histopathology | Year: 2011

Aims: Tumour-infiltrating forkhead box P3 (FoxP3 +) regulatory T cells (T regs) have stronger prognostic significance than cytotoxic CD8 + T cells in colorectal cancer (CRC). Because there is evidence that some tumour-infiltrating CD8 + T cells may be inactive, the present study aimed to investigate the prognostic significance of Granzyme B, one of the major effector molecules of T cells. Methods and results: A tissue microarray containing 963 CRCs was stained immunohistochemically for Granzyme B and the level of expression quantified by digital image analysis. Granzyme B expression was higher in tumours with microsatellite instability (P<0.0001), a dense lymphocytic infiltrate (P<0.0001) and location in the proximal colon (P=0.009), but lower in tumours with vascular invasion (P=0.007), perineural invasion (P=0.041) and positive nodal status (P<0.001). Elevated expression of Granzyme B was associated with improved survival on univariate analysis (hazard ratio=0.65; 95% confidence interval 0.51-0.84; P=0.001), but not in a multivariate model that included stage, vascular invasion and FoxP3 + T reg cell density. Conclusions: Low expression of Granzyme B was associated with early signs of metastasis in CRC. The stronger prognostic significance of FoxP3 + T regs is in keeping with animal models that suggest these cells act as gatekeepers for the release of Granzyme B from CD8 + T cells. © 2011 Blackwell Publishing Limited. Source

Platell C.,Colorectal Cancer Unit | Platell C.,University of Western Australia | Spilsbury K.,Curtin University Australia
ANZ Journal of Surgery | Year: 2014

Background: Recent trials on rectal cancer have demonstrated significant improvements in local recurrence without improvements in overall survival. The aim of this paper was to define the influence of local recurrence on survival in a prospective series of patients who underwent R0 or R1 resections for rectal cancer. Methods: Patients presenting with rectal cancer from 1996 to 2012 were prospectively audited. The study included patients who underwent an R0 or R1 resection. Local recurrence was defined as cancer regrowth detected in the pelvis regardless of whether or not new metastases were found elsewhere. Kaplan-Meier curves, smoothed hazard functions and Cox models using both time since diagnosis and age as the time scale were used to define the influence of local recurrence on overall survival. Results: The study involved 483 patients, of mean age 66 years (standard deviation = 13) and a median follow-up of 5.2 years. The results at 5 years were overall survival 71% (95% confidence interval (CI) 66-75), local recurrence 7% (95% CI 5-10) and distant recurrence 18% (95% CI 14-22). Patients diagnosed with local recurrence died faster than patients diagnosed with either distant recurrence or no recurrence, and this was particularly obvious for younger patients (local hazard ratio (HR) 54, 95% CI 12-253 and distant HR19, 95% CI 4-80). Local recurrence that developed early following surgery also had worse survival outcomes. Conclusions: Within this cohort of rectal cancer patients, the early development of local recurrence was the single most important indicator of a reduced survival, and carried a worse prognosis than the development of distant metastases alone. © 2013 Royal Australasian College of Surgeons. Source

Houlston R.S.,Institute of Cancer Research | Cheadle J.,University of Cardiff | Dobbins S.E.,Institute of Cancer Research | Tenesa A.,University of Edinburgh | And 43 more authors.
Nature Genetics | Year: 2010

Genome-wide association studies (GWAS) have identified ten loci harboring common variants that influence risk of developing colorectal cancer (CRC). To enhance the power to identify additional CRC risk loci, we conducted a meta-analysis of three GWAS from the UK which included a total of 3,334 affected individuals (cases) and 4,628 controls followed by multiple validation analyses including a total of 18,095 cases and 20,197 controls. We identified associations at four new CRC risk loci: 1q41 (rs6691170, odds ratio (OR) = 1.06, P = 9.55-10-10 and rs6687758, OR = 1.09, P = 2.27-10-9), 3q26.2 (rs10936599, OR = 0.93, P = 3.39-10-8), 12q13.13 (rs11169552, OR = 0.92, P = 1.89-10-10 and rs7136702, OR = 1.06, P = 4.02-10 -8) and 20q13.33 (rs4925386, OR = 0.93, P = 1.89-10-10). In addition to identifying new CRC risk loci, this analysis provides evidence that additional CRC-associated variants of similar effect size remain to be discovered. © 2010 Nature America, Inc. All rights reserved. Source

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