P Quirke

Università degli Studi di Torino, Torino, Piedmont, Italy

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Publications (310)2288.16 Total impact

  • Diseases of the Colon & Rectum 06/2015; 58(6):613-6. DOI:10.1097/DCR.0000000000000356 · 3.20 Impact Factor
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    ABSTRACT: Excellent anatomical knowledge of the rectum and surrounding structures is essential for total mesorectal excision (TME). Denonviliers' fascia (DVF) has been frequently studied, though the optimal anterior plane in TME is still disputed. The relationship of the lateral edges of DVF to the autonomic nerves and mesorectal fascia is unclear. We studied whole mout microscopic sections of en-bloc cadaveric pelvic exenteration and describe implications for TME.
    European Journal of Surgical Oncology 04/2015; 41(6). DOI:10.1016/j.ejso.2015.03.224 · 2.89 Impact Factor
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    ABSTRACT: The prediction of lymph node metastasis by current histopathological methods is imprecise. The aim of this study was to evaluate currently used and possible new high-risk features associated with lymph node metastasis to identify the markers of lymph node metastasis. Two hundred seven pT1 cancers were identified through the Northern and Yorkshire Cancer Registry and Information Services database and digitally scanned. Phenotypic and quantitative features of the pT1 cancers were evaluated. Lymph node metastasis and high-risk feature status were obtained through pathology reports of resections, and high-risk phenotypic features were identified. Lymph node metastasis was noted in 19 patients (9.2%). pT1 cancers with lymph node metastasis had a significantly wider area of invasion (p = 0.001) and greater area of submucosal invasion (p < 0.001) compared with pT1 cancers without lymph node metastasis. Qualitative features such as grade of differentiation and vascular and lymphatic invasion were significant predictors of lymph node metastasis (p < 0.0001, p = 0.039, and p = 0.018). Modified receiver-operating characteristics curves generated cutoff values of 11.5 mm for the width of invasion and 35 mm for the area of submucosal invasion. When tested separately with other qualitative factors on multivariate analysis, both width greater than 11.5 mm (OR, 12.12; 95% CI, 2.19-67.23; p = 0.004) and area of submucosal invasion greater than 35 mm (OR, 22.44; 95% CI, 2.7-186.63; p = 0.004) was predictive of lymph node metastasis. This is a retrospective study and is limited by its small sample size. This study has shown that the width and area of submucosal invasion are potential predictors of lymph node metastasis and superior to the depth of invasion. Together with the other qualitative phenotypic features, these quantitative factors could be used to decide the most appropriate treatment for pT1 cancers.
    Diseases of the Colon & Rectum 04/2015; 58(4):393-400. DOI:10.1097/DCR.0000000000000315 · 3.20 Impact Factor
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    ABSTRACT: This study aimed to validate a magnetic resonance imaging (MRI) staging classification that preoperatively assessed the relationship between tumor and the low rectal cancer surgical resection plane (mrLRP). Low rectal cancer oncological outcomes remain a global challenge, evidenced by high pathological circumferential resection margin (pCRM) rates and unacceptable variations in permanent colostomies. Between 2008 and 2012, a prospective, observational, multicenter study (MERCURY II) recruited 279 patients with adenocarcinoma 6 cm or less from the anal verge. MRI assessed the following: mrLRP "safe or unsafe," venous invasion (mrEMVI), depth of spread, node status, tumor height, and tumor quadrant. MRI-based treatment recommendations were compared against final management and pCRM outcomes. Overall pCRM involvement was 9.0% [95% confidence interval (CI), 5.9-12.3], significantly lower than previously reported rates of 30%. Patients with no adverse MRI features and a "safe" mrLRP underwent sphincter-preserving surgery without preoperative radiotherapy, resulting in a 1.6% pCRM rate. The pCRM rate increased 5-fold for an "unsafe" compared with "safe" preoperative mrLRP [odds ratio (OR) = 5.5; 95% CI, 2.3-13.3)]. Posttreatment MRI reassessment indicated a "safe" ymrLRP in 33 of 113 (29.2%), none of whom had ypCRM involvement. In contrast, persistent "unsafe" ymrLRP posttherapy resulted in 17.5% ypCRM involvement. Further independent MRI assessed risk factors were EMVI (OR = 3.8; 95% CI, 1.5-9.6), tumors less than 4.0 cm from the anal verge (OR = 3.4; 95% CI, 1.3-8.8), and anterior tumors (OR = 2.8; 95% CI, 1.1-6.8). The study validated MRI low rectal plane assessment, reducing pCRM involvement and avoiding overtreatment through selective preoperative therapy and rationalized use of permanent colostomy. It also highlights the importance of posttreatment restaging.
    Annals of surgery 03/2015; DOI:10.1097/SLA.0000000000001193 · 7.19 Impact Factor
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    ABSTRACT: Total mesorectal excision (TME) is the current optimal surgical treatment for patients with rectal carcinoma. A complete TME is related to lower local recurrence rates and increased patient survival. Many confounding factors in the patient's anatomy and prior therapy can make it difficult to obtain a perfect plane, and thus a complete TME. The resection specimen can be thoroughly evaluated, grossly and microscopically, to identify substandard surgical outcomes and increased risk of local recurrence. Complete and accurate data reporting is critical for patient care and helps surgeons improve their technique.
    Clinics in Colon and Rectal Surgery 03/2015; 28(1):43-52. DOI:10.1055/s-0035-1545069
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    ABSTRACT: There is variability in clinical outcome for patients with apparently the same stage colorectal cancer (CRC). Single nucleotide polymorphisms (SNPs) mapping to chromosomes 1q41, 3q26.2, 6p21, 8q23.3, 8q24.21, 10p14, 11q13, 11q23.1, 12q13.13, 14q22, 14q22.2, 15q13.3, 16q22.1, 18q21.1, 19q13.11, 20p12, 20p12.3, 20q13.33 and Xp22 have robustly been shown to be associated with the risk of developing CRC. Since germline variation can also influence patient outcome the relationship between these SNPs and patient survivorship from CRC was examined. All enrolled into the National Study of Colorectal Cancer Genetics (NSCCG) were genotyped for 1q41, 3q26.2, 6p21, 8q23.3, 8q24.21, 10p14, 11q13, 11q23.1, 12q13.13, 14q22, 14q22.2, 15q13.3, 16q22.1, 18q21.1, 19q13.11, 20p12, 20p12.3, 20q13.33 and xp22 SNPs. Linking this information to the National Cancer Data Repository allowed patient genotype to be related to survival. The linked dataset consisted of 4,327 individuals. 14q22.22 genotype defined by the SNP rs4444235 showed a significant association with overall survival. Specifically, the C allele was associated with poorer observed survival (per allele hazard ratio 1.13, 95% confidence interval 1.05-1.22, P = 0.0015). The CRC susceptibility SNP rs4444235 also appears to exert an influence in modulating patient survival and warrants further evaluation as a potential prognostic marker.
    PLoS ONE 02/2015; 10(2):e0117816. DOI:10.1371/journal.pone.0117816 · 3.53 Impact Factor
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    ABSTRACT: Background The last 30 years have witnessed a signifi-cant increase in the diagnosis of early-stage rectal cancer and the development of new strategies to reduce the treatment-related morbidity. Currently, there is no con-sensus on the definition of early rectal cancer (ERC), and the best management of ERC has not been yet defined. The European Association for Endoscopic Surgery in collabo-ration with the European Society of Coloproctology developed this consensus conference to provide recom-mendations on ERC diagnosis, staging and treatment based on the available evidence. Methods A multidisciplinary group of experts selected on their clinical and scientific expertise was invited to critically review the literature and to formulate evidence-based recommendations by the Delphi method. Recommendations were discussed at the plenary session of the 14th World Congress of Endoscopic Surgery, Paris, 26 June 2014, and then posted on the EAES website for open discussion. Results Tumour biopsy has a low accuracy. Digital rectal examination plays a key role in the pre-operative work-up. Magnification chromoendoscopy, endoscopic ultrasound and magnetic resonance imaging are complementary staging modalities. Endoscopic submucosal dissection and transanal endoscopic microsurgery are the two established approaches for local excision (LE) of selected ERC. The role of all organ-sparing approaches including neoadjuvant therapies followed by LE should be formally assessed by randomized controlled trials. Rectal resection and total mesorectal excision is indicated in the presence of unfa-vourable features at the pathological evaluation of the LE
    Surgical Endoscopy 01/2015; 29(4). DOI:10.1007/s00464-015-4067-3 · 3.31 Impact Factor
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    ABSTRACT: Aim Over recent years there has been a new focus on the quality of colon cancer surgery following the description and introduction of complete mesocolic excision (CME). In the same period, laparoscopic surgery has been widely applied to the treatment of colon cancer. We aimed to evaluate the introduction of both CME and laparoscopic-assisted surgery at Aarhus University Hospital, Denmark between 2008 and 2011. Secondly we aimed to evaluate the impact on the quality of surgery of post-operative team meetings where pathologists demonstrated the plane of surgery on the specimens. Method A series of 209 consecutive and prospectively collected colon cancer specimens were evaluated by assessing the plane of surgery and measuring the amount of tissue resected. Multivariate analyses were used to control for influencing factors. Results The proportion of specimens resected in the mesocolic plane was high and increased significantly following the introduction of post-operative team meetings (52 % to 76 %, p = 0.02). Laparoscopic surgery enhanced the distance between the tumour and the arterial tie by a mean of 27 mm (p < 0.0001) and the distance between the nearest bowel wall and the arterial tie by 26 mm (p < 0.0001) when compared to an open approach. Factors such as body mass index and age influenced the outcome for surgical quality. Conclusion Implementation of CME and laparoscopic-assisted surgery for colon cancer is a challenge and requires continuous training and feedback. Post-operative multidisciplinary team meetings may be a key element in this process.
    European Journal of Surgical Oncology 11/2014; DOI:10.1016/j.ejso.2014.04.004 · 2.89 Impact Factor
  • Journal of Clinical Oncology 10/2014; 32(35). DOI:10.1200/JCO.2014.58.3161 · 17.88 Impact Factor
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    ABSTRACT: Purpose: To determine the prevalence and prognostic value of mismatch repair (MMR) status and its relation to BRAF mutation (BRAF(MT)) status in metastatic colorectal cancer (mCRC). Experimental Design: A pooled analysis of four phase III studies in first-line treatment of mCRC (CAIRO, CAIRO2, COIN and FOCUS) was performed. Primary outcome parameter was the hazard ratio (HR) for median progression-free survival (PFS) and overall survival (OS) in relation to MMR and BRAF. For the pooled analysis, Cox regression analysis was performed on individual patient data. Results: The primary tumors of 3063 patients were analyzed, of which 153 (5.0%) exhibited deficient MMR (dMMR) and 250 (8.2%) a BRAF(MT). BRAF(MT) was observed in 53 (34.6%) of patients with dMMR tumors compared to 197 (6.8%) of patients with proficient MMR (pMMR) tumors (p<0.001). In the pooled data set, median PFS and OS were significantly worse for patients with dMMR compared to pMMR tumors (HR 1.33, 95% CI 1.12-1.57 and HR 1.35, 95% CI 1.13-1.61, respectively), and for patients with BRAF(MT) compared to BRAF wild-type (BRAF(WT)) tumors (HR 1.34, 95% CI 1.17-1.54 and HR 1.91, 95% CI 1.66-2.19, respectively). PFS and OS were significantly decreased for patients with BRAF(MT) within the group of patients with pMMR, but not for BRAF status within dMMR, or MMR status within BRAF(WT) or BRAF(MT). Conclusions: Prevalence of dMMR and BRAF(MT) in mCRC patients is low and both biomarkers confer an inferior prognosis. Our data suggest that the poor prognosis of dMMR is driven by BRAF(MT) status.
    Clinical Cancer Research 08/2014; 20(20). DOI:10.1158/1078-0432.CCR-14-0332 · 8.19 Impact Factor
  • Zeitschrift für Gastroenterologie 08/2014; 52(08). DOI:10.1055/s-0034-1386011 · 1.67 Impact Factor
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    ABSTRACT: Background Complete mesocolic excision with central vascular ligation (CME) produces an optimal colonic cancer specimen. The ability of expert laparoscopic surgeons to produce equivalent specimens is unknown.Methods Fresh specimen photographs and clinicopathological data from patients undergoing laparoscopically assisted CME at St Mark's Hospital, Harrow, were submitted for independent pathological review. Surgery was performed by a mixture of consultant specialists and trainees under consultant specialist supervision, between February 2010 and July 2011. The planes of surgery were graded and tissue morphometry was performed using standard methods. The results were compared with published data from open CME and non-CME surgery.ResultsIn total, 69 patients were identified, and in 96 per cent resection was performed completely or partially by surgical trainees. Laparoscopic CME produced a similar specimen to open CME. The laparoscopic mesocolic plane resection rate was similar to that for open surgery (90 versus 88 per cent). The distance between the bowel wall and site of vascular division was similar for laparoscopic and open right-sided CME (92 versus 95 mm respectively). The corresponding values for left-sided CME were also similar (103 versus 107 mm). Compared with values from two non-CME series, laparoscopic CME had a higher mesocolic plane rate (90 versus 40 and 48 per cent), and resected more tissue between the bowel wall and the vascular division (right-sided: 92 versus 72 and 76 mm; left-sided: 103 versus 85 and 70 mm). The lymph node yield remained low following laparoscopic CME compared with open CME (median 18 versus 32; P < 0·001) and identical to that of non-CME surgery (median 18).Conclusion Laparoscopic CME can be performed to the same standard as open surgery by supervised trainees. However, this did not increase the lymph node yield.
    British Journal of Surgery 08/2014; 101(11). DOI:10.1002/bjs.9602 · 5.21 Impact Factor
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    ABSTRACT: Most cancers arise and evolve as a consequence of somatic mutations. These mutations influence tumor behavior and clinical outcome. Consequently, there is considerable interest in identifying somatic variants within specific genes (such as BRAF, KRAS and EGFR) so that chemotherapy can be tailored to the patient's tumor genotype rather than using a generic treatment based on histological diagnosis alone. Owing to the heterogeneous nature of tumors, a somatic mutation may be present in only a subset of cells, necessitating the use of quantitative techniques to detect rare variants. The highly quantitative nature of next-generation sequencing (NGS), together with the ability to multiplex numerous samples, makes NGS an attractive choice with which to screen for somatic variants. However, the large volumes of sequence data present significant difficulties when applying NGS for the detection of somatic mutations. To alleviate this, we have developed methodologies including a set of data analysis programs, which allow the rapid screening of multiple formalin-fixed, paraffin-embedded samples for the presence of specified somatic variants using unaligned Illumina NGS data.Laboratory Investigation advance online publication, 28 July 2014; doi:10.1038/labinvest.2014.96.
    Laboratory Investigation 07/2014; 94(10). DOI:10.1038/labinvest.2014.96 · 3.83 Impact Factor
  • Journal of Clinical Oncology 06/2014; 32(17):1804-1811. DOI:10.1200/JCO.2013.54.3694 · 17.88 Impact Factor
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    ABSTRACT: Colorectal adenomas measuring ten millimetres or more are at increased neoplastic risk and therefore undergo more rigorous follow up. Currently there is no standardised method of assessing polyp size. We aimed to determine the correlation between endoscopic and histopathological measurements to determine the most appropriate method for clinical use.
    Histopathology 06/2014; 66(4). DOI:10.1111/his.12472 · 3.30 Impact Factor
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    ABSTRACT: Histopathologic grading using poorly-differentiated clusters predicts outcome in colorectal carcinoma. Hector Li-Chang,1 Bojana Mitrovic2, Kelly Handley3, Richard Gray3, Naziheh Assarzadegan2, Gordon Hutchins4, Philip Quirke4, Robert Riddell2, Richard Kirsch2 1 Department of Molecular Oncology, BC Cancer Agency, Vancouver, Canada 2 Clinical Trial Service Unit, University of Oxford, Oxford, United Kingdom 3 Department of Pathology, Mount Sinai Hospital, Toronto, Canada 4 Department of Pathology and Tumour Biology, Leeds Institute of Cancer & Pathology Background: Tumour grade is an independent prognostic factor in colorectal cancer (CRC), and is considered when deciding on the administration of adjuvant treatment. However, current grading schemes may overlook the significance of small but clinically significant high-grade components. The grading of CRC through the quantification of poorly-differentiated clusters (PDCs) has been proposed as being superior to conventional grading schemes in terms of both reproducibility and prognostic power. However, its impact on response to chemotherapy has not been studied. Methods: A pathologist, blinded to outcome and case information, used PDC quantification to grade whole-slide digital hematoxylin and eosin images of 770 CRC cases from the QUick And Simple And Reliable (QUASAR) trial. The latter is the largest reported randomized study of observation versus adjuvant chemotherapy in patients with resected stage II colon cancer, and demonstrated that adjuvant 5-FU/leucovorin treatment benefits a small but significant population of stage II patients. PDCs were defined as groups of 5 or more tumour cells that lacked gland formation. Tumors were graded as follows: Grade 1: <5 PDCs; Grade 2: 5-9 PDCs and Grade 3: >9 PDCs in any high-power (400x) microscopic field at the leading edge of the tumor. Grading based on PDCs was compared to other clinicopathologic features, including outcome. Results: PDC grades among the 770 CRC cases were follows:, Grade 1 (n=399), Grade 2(n=149) and grade 3 (n=102). No differences in T-stage amongst the 3 PDC grades were noted. A trend towards more frequent lymph node metastases was present amongst those subjects with PDC grade 3 tumors. PDC grade 3 tumors were significantly associated with proximal location (p = 0.03), vascular invasion (p = 0.01), microsatellite instability (p = 0.001), and wild-type KRAS status (p = 0.02). PDC grades of 2 and 3 were significantly associated with the presence of high-grade tumor budding (p < 0.0001). Log-rank tests showed that PDC grade showed prognostic significance for both the risk of recurrence (p = 0.01) and mortality (p = 0.03) following study follow-up periods of 10 years. Subgroup analysis showed no differences in 2-year recurrence rates within individual PDC grades between those receiving and not receiving chemotherapy. Conclusions: Grading through the quantification of PDCs is prognostically valid in CRC patients, but does not predict response to adjuvant 5-FU with leucovorin. The use of this grading method may improve the prognostic power of histopathologic examination, and warrants further study.
    DDW, Chicago, IL; 05/2014
  • Article: Response.
    CancerSpectrum Knowledge Environment 04/2014; DOI:10.1093/jnci/dju087 · 15.16 Impact Factor
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    ABSTRACT: Background: Molecular characteristics of cancer vary between individuals. In future, most trials will require assessment of biomarkers to allocate patients into enriched populations in which targeted therapies are more likely to be effective. The MRC FOCUS3 trial is a feasibility study to assess key elements in the planning of such studies. Patients and Methods: Patients with advanced colorectal cancer were registered from 24 centres between February 2010 and April 2011. With their consent, patients' tumour samples were analysed for KRAS/BRAF oncogene mutation status and topoisomerase 1 (topo-1) immunohistochemistry. Patients were then classified into one of four molecular strata; within each strata patients were randomised to one of two hypothesis-driven experimental therapies or a common control arm (FOLFIRI chemotherapy). A 4-stage suite of patient information sheets (PISs) was developed to avoid patient overload. Results: A total of 332 patients were registered, 244 randomised. Among randomised patients, biomarker results were provided within 10 working days (w.d.) in 71%, 15 w.d. in 91% and 20 w.d. in 99%. DNA mutation analysis was 100% concordant between two laboratories. Over 90% of participants reported excellent understanding of all aspects of the trial. In this randomised phase II setting, omission of irinotecan in the low topo-1 group was associated with increased response rate and addition of cetuximab in the KRAS, BRAF wild-type cohort was associated with longer progression-free survival. Conclusions: Patient samples can be collected and analysed within workable time frames and with reproducible mutation results. Complex multi-arm designs are acceptable to patients with good PIS. Randomisation within each cohort provides outcome data that can inform clinical practice.
    British Journal of Cancer 04/2014; 110(9). DOI:10.1038/bjc.2014.182 · 4.82 Impact Factor

Publication Stats

15k Citations
2,288.16 Total Impact Points

Institutions

  • 2015
    • Università degli Studi di Torino
      Torino, Piedmont, Italy
  • 1984–2015
    • University of Leeds
      • • School of Medicine
      • • Astbury Centre for Structural Molecular Biology (ACSMB)
      • • Section of Pathology and Tumour Biology
      • • Leeds Institute of Molecular Medicine (LIMM)
      • • Division of Clinical Trials Research
      • • Division of Reproduction and Early Development
      • • Section of Epidemiology and Biostatistics
      Leeds, England, United Kingdom
  • 1987–2014
    • St. James University
      Сент-Джеймс, New York, United States
  • 2013
    • Cardiff University
      • Institute of Cancer & Genetics
      Cardiff, Wales, United Kingdom
  • 2010–2013
    • Institute of Genetics and Molecular Medicine
      Edinburgh, Scotland, United Kingdom
    • The Institute of Structural and Molecular Biology
      Londinium, England, United Kingdom
  • 1992–2013
    • Leeds Teaching Hospitals NHS Trust
      Leeds, England, United Kingdom
    • University of Wales
      • College of Medicine
      Cardiff, Wales, United Kingdom
  • 2012
    • Vítkovice Hospital
      Ostrava, Moravskoslezský, Czech Republic
  • 2011
    • The Institute for Molecular Medicine
      Huntington Beach, California, United States
  • 2009
    • Newcastle University
      Newcastle-on-Tyne, England, United Kingdom
    • Universitätsklinikum Erlangen
      • Department of Surgery
      Erlangen, Bavaria, Germany
  • 2006
    • Leiden University
      Leyden, South Holland, Netherlands
    • Saint James School Of Medicine
      Park Ridge, Illinois, United States
  • 1996
    • Centre for Digestive Diseases
      Newtown, New South Wales, Australia
    • Sapienza University of Rome
      • Laboratory of Experimental Medicine and Pathology Environmental
      Roma, Latium, Italy
  • 1995
    • Royal Liverpool and Broadgreen University Hospitals NHS Trust
      Liverpool, England, United Kingdom
  • 1993
    • Bradford College
      Bradford, England, United Kingdom
  • 1991
    • IRCCS Ospedale Casa Sollievo della Sofferenza
      • Department of Anatomical pathology
      Giovanni Rotondo, Apulia, Italy
  • 1988–1989
    • The University of Edinburgh
      • Division of Pathology
      Edinburgh, Scotland, United Kingdom
    • University of Leicester
      Leiscester, England, United Kingdom