G Brown

Publications (42)147.84 Total impact

• Article: A meta-analysis comparing simultaneous versus delayed resections in patients with synchronous colorectal liver metastases.

  A A P Slesser, C Simillis, R Goldin, G Brown, S Mudan, P P Tekkis
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  ABSTRACT: INTRODUCTION: The traditional surgical management for patients presenting with synchronous colorectal liver metastases (SCLM) has been a delayed resection. However, in some centres, there has been a shift in favour of 'simultaneous' resections. The aim of this study was to use a meta-analytical model to compare the short-term and long-term outcomes in patients with synchronous colorectal liver metastases (SCLM) undergoing simultaneous resections versus delayed resections. METHOD: Comparative studies published between 1991 and 2010 were included. Evaluated endpoints were intra-operative parameters, post-operative parameters, post-operative adverse events and survival. A random-effects meta-analytical model was used and sensitivity analysis performed to account for bias in patient selection. RESULTS: Twenty-four non-randomized studies were included, reporting on 3159 patients of which 1381 (43.7%) had simultaneous resections and 1778 (56.3%) had delayed resections. The bilobar distribution (P = 0.01), size of liver metastases (P < 0.001) and the proportion of major liver resections (P < 0.001) was found to be higher in the delayed resection group compared to the simultaneous resection group. There was no significant difference in operative blood loss (95% CI, -279.28, 22.53; P = 0.1) or duration of surgery (WMD -23.83, 95% CI, -85.04, 37.38; P = 0.45). Duration of hospital stay was significantly reduced in simultaneous resections by 5.6 days (95% CI: 2.4-8.9 days, P = 0.007) No significant differences in post-operative complications (36% vs 37%, P = 0.27), overall survival (HR 1.00, 95% CI 0.86-1.15, P = 0.96) or disease free survival (HR 0.85, 95% CI 0.71-1.02, P = 0.08) were found. Sensitivity analysis revealed that these findings were consistent for the duration of hospital stay, post-operative complications, overall survival and disease free survival. CONCLUSION: This study demonstrates that the selection criteria for patients undergoing simultaneous or delayed resections differs resulting in a discrepancy in the metastatic disease severity being compared between the two groups. The comparable intra-operative parameters, post-operative complications and survival found between the two groups suggest that delayed resections may result in better outcomes. Similarly, the reduced length of hospital stay in simultaneous resections may only be as a result of the reduced disease severity in this group. Simultaneous resections can only be recommended in patients with limited hepatic disease until prospective studies comparing similar disease burdens between the two resection groups are available.
  Surgical Oncology 12/2012; · 2.44 Impact Factor
• Article: The tumour biology of synchronous and metachronous colorectal liver metastases: a systematic review.

  A A P Slesser, P Georgiou, G Brown, S Mudan, R Goldin, P Tekkis
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  ABSTRACT: Forty to fifty percent of colorectal cancer (CRC) patients develop colorectal liver metastases (CLM) that are either synchronous or metachronous in presentation. Clarifying whether there is a biological difference between the two groups of liver metastases or their primaries could have important clinical implications. A systematic review was performed using the following resources: MEDLINE from PubMed (1950 to present), Embase, Cochrane and the Web of Knowledge. Thirty-one articles met the inclusion criteria. The review demonstrated that the majority of studies found differences in molecular marker expression between colorectal liver metastases and their respective primaries in both the synchronous and metachronous groups. Studies investigating genetic aberrations demonstrated that the majority of changes in the primary tumour were 'maintained' in the colorectal liver metastases. A limited number of studies compared the primary tumours of the synchronous and metachronous groups and generally demonstrated no differences in marker expression. Although there were conflicting results, the colorectal liver metastases in the synchronous and metachronous groups demonstrated some differences in keeping with a more aggressive tumour subtype in the synchronous group. This review suggests that biological differences may exist between the liver metastases of the synchronous and metachronous groups. Whether there are biological differences between the primaries of the synchronous and metachronous groups remains undetermined due to the limited number of studies available. Future research is required to determine whether differences exist between the two groups and should include comparisons of the primary tumours.
  Clinical and Experimental Metastasis 11/2012; · 3.52 Impact Factor
• Article: Outcome of abdominosacral resection for locally advanced primary and recurrent rectal cancer.

  A Bhangu, G Brown, M Akmal, P Tekkis
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  ABSTRACT: The aim was to assess the indications for and outcomes of abdominosacral resection for patients with locally advanced primary and recurrent rectal cancer. Consecutive patients undergoing abdominosacral resection between January 2006 and December 2011 were identified from a prospectively maintained database. The main endpoints were 3-year local recurrence-free (LRFS) and disease-free (DFS) survival. Thirty patients underwent abdominosacral resection, 22 for recurrent rectal cancer and eight for locally advanced primary cancer. Sacrectomy was performed at S1/2 in five, S3 in 11 and S4/5 in 14 patients. R0 resection was achieved in 23 patients; all seven positive margins (R1) were in patients with recurrent disease. There were no deaths in hospital or within 30 days. S1/2 sacrectomy was associated with the highest rate of major complications (60 per cent versus 27 and 29 per cent for S3 and S4/5 respectively) and long-term complications (60, 36 and 14 per cent). Overall 3-year LRFS was 66 per cent and 3-year DFS was 55 per cent. Both were significantly better in patients with negative compared with positive margins (LRFS: 87 versus 0 per cent, P < 0·001; DFS: 71 versus 0 per cent, P = 0·033). Abdominosacral resection was associated with long-term survival in carefully selected patients with advanced rectal cancer. Postoperative complications were common and often multiple. Sacrectomy for locally advanced primary rectal cancer was associated with a low margin-positive rate and should be considered as an acceptable treatment. Margin-positive resection was associated with poor survival outcomes and should be avoided. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
  British Journal of Surgery 10/2012; 99(10):1453-61. · 4.61 Impact Factor
• Article: Perfusion CT to assess angiogenesis in colon cancer: technical limitations and practical challenges.

  S Dighe, E Castellano, H Blake, N Jeyadevan, M U Koh, M Orten, I Swift, G Brown
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  ABSTRACT: Objective Perfusion CT may have the potential to quantify the degree of angiogenesis of solid tumours in vivo. This study aims to identify the practical and technical challenges inherent to the technique, and evaluate its feasibility in colorectal tumours. Methods 51 patients from 2 institutions prospectively underwent a single perfusion CT on 2 different multidetector scanners. The patients were advised to breath-hold as long as possible, followed by shallow breathing, and were given intravenous buscopan to reduce movement. Numerous steps were explored to identify the challenges. Results 43 patients successfully completed the perfusion CT as per protocol. Inability to detect the tumour (n=3), misplacement of dynamic sequence co-ordinates (n=2), failure of contrast injection (n=2) and displacement of tumour (n=1) were the reasons for failure. In 14 cases excessive respiratory motion displaced the tumour out of the scanning field along the temporal sequence, leading to erroneous data capture. In nine patients, minor displacements of the tumour were corrected by repositioning the region of interest (ROI) to its original position after reviewing each dynamic sequence slice. In 20 patients the tumour was stable, and data captured from the ROI were representative, and could have been analysed by commercially available Body Tumor Perfusion 3.0® software (GE Healthcare, Waukesha, WI). Hence all data were manually analysed by MATLAB® processing software (MathWorks, Cambridge, UK). Conclusion Perfusion CT in tumours susceptible to motion during acquisition makes accurate data capture challenging and requires meticulous attention to detail. Motion correction software is essential if perfusion CT is to be used routinely in colorectal cancer.
  The British journal of radiology 04/2012; 85(1018):e814-25. · 2.11 Impact Factor
• Article: Relevance of magnetic resonance imaging-detected pelvic sidewall lymph node involvement in rectal cancer.

  O C Shihab, F Taylor, N Bees, H Blake, N Jeyadevan, R Bleehen, L Blomqvist, M Creagh, C George, A Guthrie, H Massouh, D Peppercorn, B J Moran, R J Heald, P Quirke, P Tekkis, G Brown
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  ABSTRACT: The significance of magnetic resonance imaging (MRI)-suspected pelvic sidewall (PSW) lymph node involvement in rectal cancer is uncertain. Magnetic resonance images were reviewed retrospectively by specialist gastrointestinal radiologists for the presence of suspicious PSW nodes. Scans and outcome data were from patients with biopsy-proven rectal cancer and a minimum of 5 years' follow-up in the Magnetic Resonance Imaging and Rectal Cancer European Equivalence Study. Overall disease-free survival (DFS) was analysed using the Kaplan-Meier product-limit method and stratified according to preoperative therapy. Binary logistic regression was used to match patients for propensity of clinical and staging characteristics, and further survival analysis was carried out to determine associations between suspicious PSW nodes on MRI and survival outcomes. Of 325 patients, 38 (11·7 per cent) had MRI-identified suspicious PSW nodes on baseline scans. Such nodes were associated with poor outcomes. Five-year DFS was 42 and 70·7 per cent respectively for patients with, and without suspicious PSW nodes (P < 0·001). Among patients undergoing primary surgery, MRI-suspected PSW node involvement was associated with worse 5-year DFS (31 versus 76·3 per cent; P = 0·001), but the presence of suspicious nodes had no impact on survival among patients who received preoperative therapy. After propensity matching for clinical and tumour characteristics, the presence of suspicious PSW nodes on MRI was not an independent prognostic variable. Patients with suspicious PSW nodes on MRI had significantly worse DFS that appeared improved with the use of preoperative therapy. These nodes were associated with adverse features of the primary tumour and were not an independent prognostic factor.
  British Journal of Surgery 12/2011; 98(12):1798-804. · 4.61 Impact Factor
• Article: A dose escalation study of gemcitabine plus oxaliplatin in combination with imatinib for gemcitabine-refractory advanced pancreatic adenocarcinoma.

  N Starling, E A Hawkes, I Chau, D Watkins, J Thomas, J Webb, G Brown, K Thomas, Y Barbachano, J Oates, D Cunningham
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  ABSTRACT: Targeting platelet-derived growth factor receptor-β (PDGFR-β) is a potential strategy to reduce tumour-related interstitial fluid pressure, enhance cytotoxic drug uptake and reduce chemoresistance. This study aimed to define safe doses of gemcitabine plus oxaliplatin when combined with imatinib (potent PDGFR-β inhibitor) in patients with advanced gemcitabine-refractory pancreatic cancer (PC). Using a 3 + 3 dose escalation design, patients of performance status zero or one were entered into five sequential dose levels (DLs) of gemcitabine [day 1, from 400 (DL1) to 1000 mg/m(2) (DL4)] and oxaliplatin [day 2, 85 (DL1-4) and 100 mg/m(2) (DL5)] two weekly. Imatinib 400 mg od was given for 7 days (day minus 2-5) each cycle. Twenty-seven patients received 168 cycles in total. Median age was 61 years (44-74 years). Dose-limiting toxicities occurred in two of two patients at DL5 (G4 thrombocytopenia, G3 lethargy), defined as the maximum tolerated dose and one of six patients at DL4 (G3 lethargy). DL4 was expanded. There were 2 of 27 partial responses and 14 of 27 stable disease [disease control 52%, 95% confidence interval (CI) 32% to 71%]. Median progression-free survival and overall survival were 4.6 (95% CI 2.1-7.0) and 5.6 months (95% CI 2.5-8.7), respectively. In gemcitabine-refractory PC, gemcitabine (1000 mg/m(2)) and oxaliplatin (85 mg/m(2)) can be safely combined with imatinib given on a 7 days on and 7 days off intermittent schedule.
  Annals of Oncology 07/2011; 23(4):942-7. · 6.43 Impact Factor
• Article: One millimetre is the safe cut-off for magnetic resonance imaging prediction of surgical margin status in rectal cancer.

  F G M Taylor, P Quirke, R J Heald, B Moran, L Blomqvist, I Swift, S St Rose, D J Sebag-Montefiore, P Tekkis, G Brown
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  ABSTRACT: A pathologically involved margin in rectal cancer is defined as tumour within 1 mm of the surgical resection margin. There is no standard definition of a predicted safe margin on magnetic resonance imaging (MRI). The aim of this study was to assess which cut-off (1, 2 or 5 mm) was the best predictor of local recurrence based on preoperative MRI assessment of the circumferential resection margin (CRM). Data were collected prospectively on the distance between the tumour and mesorectal fascia for patients with documented radiological margin status in the MERCURY study. Positive margin and local recurrence rates were compared for MRI distances from the tumour to the mesorectal fascia of 1 mm or less, more than 1 mm up to 2 mm, more than 2 mm up to 5 mm, and more than 5 mm. The Cox proportional hazard regression method was used to determine the effect of level of margin involvement on time to local recurrence. Univariable analysis showed that, relative to a distance measured by MRI of more than 5 mm, the hazard ratio (HR) for local recurrence was 3·90 (95 per cent confidence interval 1·99 to 7·63; P < 0·001) for a margin of 1 mm or less, 0·81 (0·36 to 1·85; P = 0·620) for a margin of more than 1 mm up to 2 mm, and 0·33 (0·10 to 1·08; P = 0·067) for a margin greater than 2 mm up to 5 mm. Multivariable analysis of the effect of MRI distance to the mesorectal fascia and preoperative treatment on local recurrence showed that a margin of 1 mm or less remained significant regardless of preoperative treatment (HR 3·72, 1·43 to 9·71; P = 0·007). For preoperative staging of rectal cancer, the best cut-off distance for predicting CRM involvement using MRI is 1 mm. Using a cut-off greater than this does not appear to identify patients at higher risk of local recurrence.
  British Journal of Surgery 06/2011; 98(6):872-9. · 4.61 Impact Factor
• Article: A multicentre study of capecitabine, oxaliplatin plus bevacizumab as perioperative treatment of patients with poor-risk colorectal liver-only metastases not selected for upfront resection.

  R Wong, D Cunningham, Y Barbachano, C Saffery, J Valle, T Hickish, S Mudan, G Brown, A Khan, A Wotherspoon, A S Strimpakos, J Thomas, S Compton, Y J Chua, I Chau
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  ABSTRACT: Perioperative chemotherapy improves outcome in resectable colorectal liver-only metastasis (CLM). This study aimed to evaluate perioperative CAPOX (capecitabine-oxaliplatin) plus bevacizumab in patients with poor-risk CLM not selected for upfront resection. Poor-risk CLM was defined as follows: more than four metastases, diameter >5 cm, R0 resection unlikely, inadequate viable liver function if undergoing upfront resection, inability to retain liver vascular supply, or synchronous colorectal primary presentation. Patients underwent baseline computed tomography, magnetic resonance imaging, and/or positron emission tomography (PET) for staging and received neoadjuvant CAPOX plus bevacizumab, with resectability assessed every four cycles. Primary end point was radiological objective response rate (ORR). Forty-six patients were recruited, of which 91% underwent PET to ensure metastases confined to liver. Following neoadjuvant CAPOX plus bevacizumab, the ORR was 78% (95% confidence interval 63% to 89%). This allowed 12 of 30 (40%) patients with initial nonsynchronous unresectable CLM to be converted to resectability. In addition, 10 of 15 (67%) patients with synchronous resectable CLM underwent liver resection, with four additional patients being observed alone due to excellent response to neoadjuvant therapy. No grade 3-4 perioperative complications were seen. Neoadjuvant CAPOX plus bevacizumab resulted in a high response rate for patients with CLMs with poor-risk features not selected for upfront resection and converted 40% of patients to resectability.
  Annals of Oncology 02/2011; 22(9):2042-8. · 6.43 Impact Factor
• Source

  Available from: birjournals.org

  Article: Segmental liver hyperintensity in malignant biliary obstruction on diffusion weighted MRI: associated MRI findings and relationship with serum alanine aminotransferase levels.

  H H Tam, D J Collins, T Wallace, G Brown, A Riddell, D-M Koh
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  ABSTRACT: Segmental liver hyperintensity can be observed in malignant biliary obstruction on diffusion weighted MRI (DW-MRI). We describe MRI findings associated with this sign and evaluate whether DW-MRI segmental hyperintensity has any relationship with serum alanine aminotransferase (ALT) levels. The DW-MRI T(1) weighted, T(2) weighted and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced T(1) weighted images obtained in 21 patients with hepatic malignancy, who demonstrated biliary obstruction and segmental hyperintensity on DW-MRI (b=0-750 s mm(-2)), were retrospectively reviewed by 2 readers blinded to clinical results. DW-MRI hyperintense liver segments were recorded as hypointense, isointense or hyperintense relative to normal liver on T(1)/T(2) weighted imaging. It was also noted whether contrast enhancement was similar to that observed in normal liver or diminished in the hepatocellular phase. The mean apparent diffusion coefficient (ADC) value (×10(-3) s mm(-2)) of DW-MRI hyperintense segments, normal liver and tumour were compared using Student's t-test. The frequency of MRI findings was corroborated with serum ALT levels, which reflect hepatocyte injury. DW-MRI hyperintense segments frequently showed T(1) hyperintensity (10/21), T(2) hyperintensity (19/21) and/or diminished contrast enhancement (15/21). Tumours showed significantly lower mean ADC values than liver (1.23 ± 0.08 vs 1.43 ± 0.05; p=0.013). Segments showing concomitant T(1) hyperintensity had lower mean ADC values than liver (1.30 ± 0.05 vs 1.43 ± 0.05; p=0.023). The patients (8/10) with concomitant T(1) and DW-MRI segmental hyperintensity showed elevated ALT levels (p=0.030, Fisher's exact test). Concomitantly high T(1) weighted and DW-MRI signal in liver segments was associated with lower ADC values and abnormal liver function tests, which could reflect underlying cellular swelling and damage.
  The British journal of radiology 01/2011; 85(1009):22-8. · 2.11 Impact Factor
• Article: Diagnostic precision of CT in local staging of colon cancers: a meta-analysis.

  S Dighe, S Purkayastha, I Swift, P P Tekkis, A Darzi, R A'Hern, G Brown
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  ABSTRACT: To determine the accuracy of computed tomography (CT) in detecting disease with invasion beyond the muscularis propria (MP) and malignant lymph nodes. A literature search of Ovid, Embase, the Cochrane database, and Medline using Pubmed, Google Scholar and Vivisimo search engines was performed to identify studies reporting on the accuracy of CT to predict the staging of colonic tumours. Publication bias was demonstrated by Funnel plots. The sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated using a bivariate random effects model and hierarchical summary operating curves (HSROC) were generated. Nineteen studies fulfilled all the necessary inclusion criteria. The pooled sensitivity, specificity, DOR for detection of tumour invasion were 86% (95% CI: 78-92%); 78% (95% CI: 71-84%); 22.4 (95% CI: 11.9-42.4). Similarly, the values for nodal detection were 70% (95% CI: 63-73%); 78% (95% CI: 73-82%); 8.1(95% CI: 4.7-14.1). In the subgroup analysis, the best results were obtained in studies utilizing multidetector CT (MDCT). Preoperative staging CT accurately distinguishes between tumours confined to the bowel wall and those invading beyond the MP; however, it is significantly poorer at identifying nodal status. MDCT provides the best results.
  Clinical radiology 09/2010; 65(9):708-19. · 1.65 Impact Factor
• Article: Magnetic resonance imaging-detected lymph nodes close to the mesorectal fascia are rarely a cause of margin involvement after total mesorectal excision.

  O C Shihab, P Quirke, R J Heald, B J Moran, G Brown
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  ABSTRACT: In rectal cancer the management of suspicious magnetic resonance imaging (MRI)-detected lymph nodes lying close to the mesorectal fascia poses an ongoing dilemma. Key decisions in treatment planning are commonly based on the prediction of margin status. However, it is unclear whether a lymph node that appears to contain tumour close to the mesorectal fascia will result in a positive margin. Some 396 patients with rectal cancer were included. MRI assessment of mesorectal nodes, the pathologically involved circumferential resection margin (CRM) rate and causes of margin involvement were analysed to establish the clinical significance of MRI-detected suspicious lymph nodes at the resection margin. Fifty (12.6 per cent) of 396 patients had a positive CRM on histopathological analysis, five (10 per cent) solely due to an involved lymph node. Four of the five malignant nodes were not predicted on MRI. Thirty-one of the 396 MRI studies had suspicious nodes 1 mm or less from the CRM. None of these patients had a positive CRM owing to nodal involvement. Involvement of the CRM by lymph node metastases alone is uncommon.
  British Journal of Surgery 09/2010; 97(9):1431-6. · 4.61 Impact Factor
• Article: Accuracy of multidetector computed tomography in identifying poor prognostic factors in colonic cancer.

  S Dighe, H Blake, M-D Koh, I Swift, A Arnaout, L Temple, Y Barbachano, G Brown
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  ABSTRACT: Recent neoadjuvant strategies for high-risk colonic tumours have renewed interest in accurate preoperative staging. The aim of this study was to validate prospectively the accuracy of multidetector computed tomography (MDCT) in stratifying patients into good and poor prognostic groups in a multicentre setting. Staging MDCT scans of 84 patients with colonic cancer were reviewed by two independent radiologists and stratified into low-risk (T1/T2 and T3 with extramural tumour depth (EMD) of less than 5 mm) and high-risk (T3 with EMD of at least 5 mm and T4) tumours. Nodal status and extramural venous invasion (EMVI) were also assessed. The accuracy, sensitivity, specificity and positive predictive value of stratification by CT compared with histological examination was 74 (95 per cent confidence interval 64 to 82), 78 (65 to 87), 67 (49 to 81) and 81 (68 to 89) per cent respectively. Accuracy for detecting malignant lymph nodes and EMVI was 58 and 70 per cent respectively. The agreement for predicting prognostic stratification was moderate (kappa = 0.54). As the ability of CT to identify node status is poor, the depth of tumour invasion beyond the muscularis propria is the most accurate way to identify patients with a poor prognosis who may be suitable for neoadjuvant treatment.
  British Journal of Surgery 09/2010; 97(9):1407-15. · 4.61 Impact Factor
• Source

  Available from: David Watkins

  Article: Defining patient outcomes in stage IV colorectal cancer: a prospective study with baseline stratification according to disease resectability status.

  D J Watkins, I Chau, D Cunningham, S S Mudan, N Karanjia, G Brown, S Ashley, A R Norman, A Gillbanks
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  ABSTRACT: Stage IV colorectal cancer encompasses a broad patient population in which both curative and palliative management strategies may be used. In a phase II study primarily designed to assess the efficacy of capecitabine and oxaliplatin, we were able to prospectively examine the outcomes of patients with stage IV colorectal cancer according to the baseline resectability status. At enrolment, patients were stratified into three subgroups according to the resectability of liver disease and treatment intent: palliative chemotherapy (subgroup A), conversion therapy (subgroup B) or neoadjuvant therapy (subgroup C). All patients received chemotherapy with capecitabine 2000 mg m(-2) on days 1-14 and oxaliplatin 130 mg m(-2) on day 1 repeated every 3 weeks. Imaging was repeated every four cycles where feasible liver resection was undertaken after four or eight cycles of chemotherapy. Of 128 enrolled patients, 74, 22 and 32 were stratified into subgroups A, B and C, respectively. Attempt at curative liver resection was undertaken in 10 (45%) patients in subgroup B and 19 (59%) in subgroup C. The median overall survival was 14.6, 24.5 and 52.9 months in subgroups A, B and C, respectively. For patients in subgroups B and C who underwent an attempt at curative resection, 3-year progression-free survival was 10% in subgroup B and 37% for subgroup C. This prospective study shows the wide variation in outcome according to baseline resectability status and highlights the potential clinical value of a modified staging system to distinguish between these patient subgroups.
  British Journal of Cancer 01/2010; 102(2):255-61. · 5.04 Impact Factor
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  Available from: PubMed Central

  Article: A phase II trial of preoperative chemotherapy with epirubicin, cisplatin and capecitabine for patients with localised gastro-oesophageal junctional adenocarcinoma.

  N Starling, A Okines, D Cunningham, W Allum, A Wotherspoon, M Benson, J Thompson, J Thomas, G Brown, A Riddell, F Stavridi, S Ashley, J Oates, I Chau
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  ABSTRACT: Preoperative cisplatin/fluorouracil is used for the treatment of localised oesophageal carcinoma. This phase II study aimed to assess the efficacy and safety of administering preoperative epirubicin/cisplatin/capecitabine (ECX). Patients with stage II or III oesophageal/gastro-oesophageal junctional adenocarcinoma from one institution received 4 cycles of ECX (epirubicin 50 mg m(-2) day 1, cisplatin 60 mg m(-2) day 1, capecitabine 625 mg m(-2) b.i.d. daily) followed by surgery. The primary end point was the pathological complete response (pCR) rate based on a Simon two-stage design. Secondary end points included overall and progression-free survival (OS/PFS). Thirty-four patients were recruited: median age 60 years (range 41-81), 91% male, 97% PS 0/1, 80% T3, 68% N1. Thirty-one patients completed four ECX cycles. Grade 3/4 toxicities >or=5% included neutropenia (62%), hand-foot syndrome (15%) and nausea/vomiting (9%). Thirteen out of 28 (46%) evaluable patients responded to chemotherapy by EUS (>or=30% reduction in maximal tumour thickness). Twenty-six out of 34 (76%) patients underwent resection (R0=73%, R1=27%). Post-operatively, two patients died within 60 days of surgery. The pCR rate was 5.9% (95% CI 0-14%) in the intent-to-treat population. According to the statistical design, this prompted early study termination. However, with a median follow-up of 34 months the median OS and 1- and 2-year survival rates were 17 months, 67 and 39% respectively. Median PFS was 13 months. Of the 14 relapsed patients, 10 presented with distant metastases. Preoperative ECX is feasible and well tolerated. Although associated with a low pCR rate, survival with ECX was comparable with published studies suggesting that pCR may not correlate with satisfactory outcome from preoperative chemotherapy for localised oesophageal adenocarcinoma.
  British Journal of Cancer 05/2009; 100(11):1725-30. · 5.04 Impact Factor
• Article: CT staging of colon cancer.

  S Dighe, I Swift, G Brown
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  ABSTRACT: Computer tomography (CT) has been the principal investigation in the staging of colon cancers. The information obtained with routine CT has been limited to identifying the site of the tumour, size of the tumour, infiltration into surrounding structures and metastatic spread. The Foxtrot trial National Cancer Research Institute (NCRI) has been specifically designed to evaluate the efficacy of neoadjuvant treatment in colon cancers by using preoperative chemotherapy with or without an anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody to improve outcome in high-risk operable colon cancer. Patients are selected based on their staging CT examination. The criteria for poor prognosis are T4 and T3 tumours with more than 5mm extramural depth. Thus the success of the trial would depend upon the confidence of the radiologist to identify the patients that would receive the neoadjuvant treatment. The aim of this review is to explain the process of identifying high-risk features seen on the staging CT images. This will help to identify a cohort of patients that could truly benefit from neoadjuvant strategies.
  Clinical radiology 01/2009; 63(12):1372-9. · 1.65 Impact Factor
• Article: A phase II trial evaluating capecitabine and irinotecan as second line treatment in patients with oesophago-gastric cancer who have progressed on, or within 3 months of platinum-based chemotherapy.

  Alexandra Leary, L Assersohn, D Cunningham, A R Norman, G Chong, G Brown, P J Ross, C Costello, L Higgins, J Oates
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  ABSTRACT: There is no standard second line therapy for relapsed oesophago-gastric (O-G) cancer. We recruited 29 eligible patients with relapsed O-G cancer who had progressed during or within 3 months of prior chemotherapy to assess the efficacy and toxicity of capecitabine [2,000 mg/(m(2) day) on days 1-14] and irinotecan (250 mg/m(2)) given every 3 weeks. Five patients (17%) demonstrated objective response, while a further seven patients (24%) achieved disease stabilisation. Median progression-free survival and overall survival were 3.1 months (95% CI = 2.2-4.1 months) and 6.5 months (95%CI = 6-7.1 months), respectively. Among symptomatic patients, palliation of tumour-related symptoms included resolution of reflux (5/12 pts), dysphagia (3/9 pts) and weight loss (4/9 pts), improvements in anorexia (4/10 pts), nausea (3/4 pts), vomiting (4/6 pts) and pain (4/16 pts). Grade 3-4 toxicities were diarrhoea (15%), nausea and vomiting (7%), lethargy (31%), neutropenia (31%), anemia (14%) and thrombocytopenia (7%). Capecitabine and irinotecan has anti-tumour activity as second line treatment for relapsed O-G cancer, and provides an important improvement in disease related symptoms.
  Cancer Chemotherapy and Pharmacology 01/2009; 64(3):455-62. · 2.83 Impact Factor
• Article: Sites of surgical wasting in the abdominoperineal specimen.

  G Salerno, I Chandler, A Wotherspoon, K Thomas, B Moran, G Brown
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  ABSTRACT: In the abdominoperineal excision (APE) specimen 'surgical wasting' has been described, where the least amount of tissue covers the rectum. This is associated with high positive margin rates. The aim of this study was to locate the site of surgical wasting, namely the least amount of tissue excised at APE. Distances from the anal verge to the distal and proximal edges of the sphincter, puborectalis and levator muscles were measured in 12 patients using morphological features on magnetic resonance images. Distances from the mucularis propria to the outer surface of the pelvic muscles and the outer edge of the specimen were measured on axial images. The height from the anal verge at which axial measurements of tissue were minimal was determined. The presence of a surgical waist between 35 and 42 mm above the anal verge, corresponding to the puborectalis, was confirmed. A smaller amount of perirectal tissue was resected at this level than at other heights (P < 0.001). Because less tissue is excised at the puborectalis, careful dissection along the levator plane is necessary, especially if tumour is present. More radical excision of the levators and puborectalis may be of benefit in such patients.
  British Journal of Surgery 09/2008; 95(9):1147-54. · 4.61 Impact Factor
• Source

  Available from: european-radiology.org

  Article: Detection of colorectal hepatic metastases using MnDPDP MR imaging and diffusion-weighted imaging (DWI) alone and in combination.

  D M Koh, G Brown, A M Riddell, E Scurr, D J Collins, S D Allen, I Chau, D Cunningham, N M deSouza, M O Leach, J E Husband
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  ABSTRACT: To compare the diagnostic accuracy of MnDPDP MR imaging and diffusion-weighted imaging (DWI), alone and in combination, for detecting colorectal liver metastases in patients with suspected metastatic disease. Thirty-three consecutive patients with suspected colorectal liver metastases underwent MR imaging. Three image sets (MnDPDP, DWI and combined MnDPDP and DWI) were reviewed independently by two observers. Lesions were scored on a five-point scale for malignancy and the areas (Az) under the receiver operating characteristic curves were calculated for each observer and image set. The sensitivity and specificity for lesion detection were calculated for each image set and compared. There were 83 metastases, 49 cysts and 1 haemangioma. Using the combined set resulted in the highest diagnostic accuracy for both observers (Az=0.94 and 0.96), with improved averaged sensitivity of lesion detection compared with the DWI set (p=0.01), and a trend towards improved sensitivity compared with the MnDPDP set (p=0.06). There was no difference in the averaged specificity using any of the three image sets (p>0.5). Combination of MnDPDP MR imaging and DWI resulted in the highest diagnostic accuracy and can increase sensitivity without loss in specificity.
  European Radiology 05/2008; 18(5):903-10. · 3.22 Impact Factor
• Article: Pelvic phased-array MR imaging of anal carcinoma before and after chemoradiation.

  D M Koh, A Dzik-Jurasz, B O'Neill, D Tait, J E Husband, G Brown
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  ABSTRACT: The aim of this study was to evaluate the MR findings of anal carcinoma using an external pelvic phased-array coil before and after chemoradiation treatment. 15 patients with carcinoma of the anal canal underwent T(2) weighted and short-tau inversion recovery (STIR) imaging before and after chemoradiation. Images were reviewed in consensus by two radiologists. At pre-treatment imaging, the tumour size and stage, signal intensity and infiltration of adjacent structures were recorded. MR imaging was repeated immediately after chemoradiation, every 6 months for the first year and then yearly. Tumour response was assessed by recording change in tumour size and signal intensity. Prior to treatment, the mean tumour size was 3.9 cm (range, 1.8-6.4 cm). Tumours appeared mildly hyperintense at T(2) weighted and STIR imaging. There was good agreement in T staging between clinical examination and MR imaging (kappa = 0.68). In 12 responders with long disease remission, a greater percentage reduction in the size of MR signal abnormality in the tumour area was observed at 6 months (mean 54.7%; 46-62%) than immediately after treatment (mean 38.6%; 30-46%) (p = 0.002, t-test). 7/12 showed stabilization of T(2) signal reduction in the tumour area after 1 year, and 5/12 showed complete resolution of signal alterations at 2 years. Pelvic phased-array MR imaging is useful for local staging of anal carcinoma and assessing treatment response. After treatment, a decrease in tumour size accompanied by reduction and stability of the MR T(2) signal characteristics at 1 year after chemoradiation treatment was associated with favourable outcome.
  The British journal of radiology 03/2008; 81(962):91-8. · 2.11 Impact Factor
• Article: Accuracy of CT prediction of poor prognostic features in colonic cancer.

  S Burton, G Brown, N Bees, A Norman, O Biedrzycki, A Arnaout, A M Abulafi, R I Swift
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  ABSTRACT: Whilst imaging of poor prognostic features in rectal cancers has assisted pre-operative treatment stratification, such features have yet to be evaluated in colonic cancers. This study aims to develop criteria for identifying poor prognostic features in colonic tumours and assess the accuracy of CT prediction against histopathology. Criteria were developed for predicting T-stage and N-stage, the presence of extramural vascular invasion and involvement of the retroperitoneal surgical margin (RSM). These criteria were tested on 33 patients with colonic cancer who underwent pre-operative high-resolution CT of their tumour. Two radiologists (Obs 1 and Obs 2) identified independently these poor prognostic features and the results were compared with the final histopathological results. Histological agreement and interobserver variation were calculated using the kappa test. Accuracy of CT prediction of tumour extension beyond muscularis propria was 82% (Obs 1) and 70% (Obs 2). Correct prediction of RSM involvement was 76% (95% confidence interval (CI): 57.8-88.9%) and 79% (95%CI: 61.1-91%) for Obs1 and Obs 2, respectively, with significant agreement between observers (kappa = 0.455, p = 0.050). Prognosis was correctly predicted using CT in 82% (95%CI: 61.5-81.2%) (Obs1) and 85% (95%CI: 68.1-94.9%) (Obs2) with moderate agreement (kappa = 0.459, kappa = 0.527, respectively) with histology. In conclusion, CT has potential as the imaging modality of choice in the pre-operative prediction of poor prognostic features in colonic cancers and could play a role in future treatment stratification.
  The British journal of radiology 02/2008; 81(961):10-9. · 2.11 Impact Factor