2024-03-28T23:10:48Z
https://eprints.whiterose.ac.uk/cgi/oai2
oai:eprints.whiterose.ac.uk:407
2016-10-31T17:52:18Z
7374617475733D707562
74797065733D61727469636C65
756E69743D4C65656473:4C656564732E46412D4D444845:4C656564732E52432D4D4D4543:4C656564732E44492D50415448
696E737469747574696F6E3D4C65656473
7072696D6F3D6861735F7075626C6963
https://eprints.whiterose.ac.uk/407/
Association between family history and mismatch repair in colorectal cancer
Coggins, R.P.
Cawkwell, L.
Bell, S.M.
Crockford, G.P.
Quirke, P.
Finan, P.J.
Bishop, D.T.
BACKGROUND AND AIMS: Germline mutations in mismatch repair (MMR) genes cause a greatly increased
risk of cancer of the gastrointestinal and female reproductive tracts (hereditary non-polyposis colorectal
cancer (HNPCC)). Loss of MMR expression is common in colorectal cancer (CRC) overall. Such loss is
assumed to be acquired predominantly, although a population of CRC cases will include individuals with
unrecognised MMR mutations. This study examines the association between MMR gene expression and
family history of cancer among the CRC population.
METHODS: Individuals with CRC were identified from two well characterised populations: (1) consecutive
hospital patients (n = 644) and (2) a population based cases series (n = 249). CRC was examined for
expression of hMLH1 and hMSH2 using immunohistochemistry, and expression was related to family history using logistic regression.
RESULTS: hMLH1 and hMSH2 expression was assessed in 732 CRCs with 8% showing loss of expression.
No association was seen overall for hMLH1 or hMSH2 expression and family history of CRC. Loss of
hMSH2 was predicted by family history of extracolonic cancer (odds ratio (OR) 5.78 (95% confidence
interval (CI) 0.95–35.18)) and family history suggestive of HNPCC (OR 27.84 (95% CI 4.37–177.56)).
Loss of hMLH1 was not predicted by family history of extracolonic cancer or a family history suggestive of
HNPCC but was for a family history of at least two affected relatives (OR 4.88 (95% CI 1.25–19.03)).
CONCLUSIONS: Individuals with hMSH2 deficient CRC in the general population exhibit a family history and
other characteristics suggestive of HNPCC, and may carry germline MMR mutations. Loss of hMLH1 is only
associated with a strong family history of extracolonic cancer at older ages, suggesting a novel mechanism
of susceptibility.
2005
Article
PeerReviewed
text
en
attached
https://eprints.whiterose.ac.uk/407/1/quirkep3.pdf
Coggins, R.P., Cawkwell, L., Bell, S.M. et al. (4 more authors) (2005) Association between family history and mismatch repair in colorectal cancer. Gut, 54. pp. 636-642. ISSN 0017-5749
http://gut.bmjjournals.com/cgi/content/full/54/5/636
doi:10.1136/gut.2003.017517
oai:eprints.whiterose.ac.uk:558
2016-10-25T05:26:00Z
7374617475733D707562
74797065733D61727469636C65
756E69743D4C65656473:4C656564732E46412D4D444845:4C656564732E52432D4D4D4543:4C656564732E44492D50415448
696E737469747574696F6E3D4C65656473
7072696D6F3D6861735F7075626C6963
https://eprints.whiterose.ac.uk/558/
WISP genes are members of the connective tissue growth factor family that are up-regulated in Wnt-1-transformed cells and aberrantly expressed in human colon tumors
Pennica, D.
Swanson, T.A.
Welsh, J.W.
Roy, M.A.
Lawrence, D.A.
Lee, J.
Brush, J.
Taneyhill, L.A.
Deuel, B.
Lew, M.
Watanabe, C.
Cohen, R.L.
Melhem, M.F.
Finley, G.G.
Quirke, P.
Goddard, A.D.
Hillan, K.J.
Gurney, A.L.
Botstein, D.
Levine, A.J.
Wnt family members are critical to many developmental processes, and components of the Wnt signaling pathway have been linked to tumorigenesis in familial and sporadic colon carcinomas. Here we report the identification of two genes, WISP-1 and WISP-2, that are up-regulated in the mouse mammary epithelial cell line C57MG transformed by Wnt-1, but not by Wnt-4. Together with a third related gene, WISP-3, these proteins define a subfamily of the connective tissue growth factor family. Two distinct systems demonstrated WISP induction to be associated with the expression of Wnt-1. These included (i) C57MG cells infected with a Wnt-1 retroviral vector or expressing Wnt-1 under the control of a tetracyline repressible promoter, and (ii) Wnt-1 transgenic mice. The WISP-1 gene was localized to human chromosome 8q24.1-8q24.3. WISP-1 genomic DNA was amplified in colon cancer cell lines and in human colon tumors and its RNA overexpressed (2- to >30-fold) in 84% of the tumors examined compared with patient-matched normal mucosa. WISP-3 mapped to chromosome 6q22-6q23 and also was overexpressed (4- to >40-fold) in 63% of the colon tumors analyzed. In contrast, WISP-2 mapped to human chromosome 20q12-20q13 and its DNA was amplified, but RNA expression was reduced (2- to >30-fold) in 79% of the tumors. These results suggest that the WISP genes may be downstream of Wnt-1 signaling and that aberrant levels of WISP expression in colon cancer may play a role in colon tumorigenesis.
1998-12-08
Article
PeerReviewed
text
en
attached
https://eprints.whiterose.ac.uk/558/1/quirkeep4.pdf
Pennica, D., Swanson, T.A., Welsh, J.W. et al. (17 more authors) (1998) WISP genes are members of the connective tissue growth factor family that are up-regulated in Wnt-1-transformed cells and aberrantly expressed in human colon tumors. Proceedings of the National Academy of Sciences, 95 (25). pp. 14717-14722. ISSN 0027-8424
http://www.pnas.org/cgi/content/full/95/25/14717
oai:eprints.whiterose.ac.uk:1925
2016-09-16T13:16:11Z
7374617475733D707562
74797065733D61727469636C65
756E69743D4C65656473:4C656564732E46412D4D444845:4C656564732E52432D4D4D4543:4C656564732E44492D50415448:4C656564732E53522D50414759
696E737469747574696F6E3D4C65656473
7072696D6F3D6861735F7075626C6963
https://eprints.whiterose.ac.uk/1925/
Basal-like grade III invasive ductal carcinoma of the breast: patterns of metastasis and long-term survival
Fulford, L.G.
Reis-Filho, J.S.
Ryder, K.
Jones, C.
Gillett, C.E.
Hanby, A.
Easton, D.
Lakhani, S.R.
INTRODUCTION
Cytokeratin (CK) 14, one of several markers expressed in normal myoepithelial/basal cells, is also expressed in a proportion of breast carcinomas. Previous studies have suggested that expression of such 'basal' markers predicts different biological behaviour, with more frequent lung and brain metastases and poorer prognosis than other carcinomas.
METHODS
We performed CK14 immunohistochemistry on 443 grade III invasive ductal carcinomas with extended clinical follow-up (mean 116 months), and we correlated CK14 immunopositivity (basal-like phenotype) with clinicopathological criteria.
RESULTS
Eighty-eight of 443 (20%) tumours showed CK14 expression. CK14-positive tumours were more likely to be oestrogen receptor-negative (p < 0.0001) and axillary node-negative (p = 0.001) than were CK14-negative cases. CK14-positive cases developed less bone and liver metastases (hazard ratio [HR] 0.49, p = 0.01, and HR 0.53, p = 0.035, respectively) but more frequent brain metastases (HR 1.92, p = 0.051). In patients without metastatic disease, disease-free survival in CK14-positive cases was significantly better than in CK14-negative cases (HR 0.65, p = 0.005). In patients with metastatic disease, however, CK14 positivity was associated with a poorer prognosis (HR 1.84, p = 0.001). The overall survival in CK14-positive and -negative patients was similar at 5 years (60% and 59%, respectively), but the long-term survival was better in CK14-positive patients (HR 0.69, p = 0.02).
CONCLUSION
These results demonstrate that basal-like tumours differ in their biological behaviour from other tumours, with a distinct pattern of metastatic spread. Compared to other grade III tumours, basal-like tumours appear to have a relatively good long-term survival but survival after metastases is poor.
Biomed Central
2007-01
Article
PeerReviewed
text
en
attached
https://eprints.whiterose.ac.uk/1925/1/hanbya1pdf.pdf
Fulford, L.G., Reis-Filho, J.S., Ryder, K. et al. (5 more authors) (2007) Basal-like grade III invasive ductal carcinoma of the breast: patterns of metastasis and long-term survival. Breast Cancer Research, 9 (1).
http://dx.doi.org/10.1186/bcr1636
doi:10.1186/bcr1636
oai:eprints.whiterose.ac.uk:10787
2016-11-04T03:58:48Z
7374617475733D707562
74797065733D61727469636C65
756E69743D4C65656473:4C656564732E46412D4D444845:4C656564732E52432D4D4D4543:4C656564732E44492D50415448:4C656564732E53522D50414759
756E69743D4C65656473:4C656564732E46412D4D444845:4C656564732E52432D44454E54:4C656564732E53522D444F5241
696E737469747574696F6E3D4C65656473
7072696D6F3D6E6F5F646F63756D656E74735F617661696C61626C65
https://eprints.whiterose.ac.uk/10787/
Raman spectroscopy and advanced mathematical modelling in the discrimination of human thyroid cell lines
Harris, A.T.
Garg, M.
Yang, X.B.
Fisher, S.E.
Kirkham, J.
Smith, A.
Martin-Hirsch, D.P.
High, A.S.
Raman spectroscopy could offer non-invasive, rapid and an objective nature to cancer diagnostics. However, much work in this field has focused on resolving differences between cancerous and non-cancerous tissues, and lacks the reproducibility and interpretation to be put into clinical practice. Much work is needed on basic cellular differences between malignancy and normal. This would allow the establishment of a clinically relevant cellular based model to translate to tissue classification. Raman spectroscopy provides a very detailed biochemical analysis of the target material and to 'unlock' this potential requires sophisticated mathematical modelling such as neural networks as an adjunct to data interpretation. Commercially obtained cancerous and non-cancerous cells, cultured in the laboratory were used in Raman spectral measurements. Data trends were visualised through PCA and then subjected to neural network analysis based on self-organising maps; consisting of m maps, where m is the number of classes to be recognised. Each map approximates the statistical distribution of a given class. The neural network analysis provided a 95% accuracy for identification of the cancerous cell line and 92% accuracy for normal cell line. In this preliminay study we have demonstrated th ability to distinguish between "normal" and cancerous commercial cell lines. This encourages future work to establish the reasons underpinning these spectral differences and to move forward to more complex systems involving tissues. We have also shown that the use of sophisticated mathematical modelling allows a high degree of discrimination of 'raw' spectral data.
Biomed Central
2009-10
Article
NonPeerReviewed
Harris, A.T., Garg, M., Yang, X.B. et al. (5 more authors) (2009) Raman spectroscopy and advanced mathematical modelling in the discrimination of human thyroid cell lines. Head & Neck Oncology , 1. ISSN 1472-6963
http://dx.doi.org/10.1186/1758-3284-1-38
doi:10.1186/1758-3284-1-38
oai:eprints.whiterose.ac.uk:75791
2018-03-29T17:13:36Z
7374617475733D707562
74797065733D61727469636C65
756E69743D4C65656473:4C656564732E46412D46455053:4C656564732E52432D434F4D50:4C656564732E53522D41494253
756E69743D4C65656473:4C656564732E46412D4D444845:4C656564732E52432D4D4D4543:4C656564732E44492D50415448
696E737469747574696F6E3D4C65656473
7072696D6F3D6E6F5F646F63756D656E74735F617661696C61626C65
https://eprints.whiterose.ac.uk/75791/
Towards Routine Use of 3D Histopathology As a Research Tool
Roberts, N
Magee, D
Song, Y
Brabazon, K
Shires, M
Crellin, D
Orsi, N
Quirke, R
Quirke, P
Treanor, D
Three-dimensional (3D) reconstruction and examination of tissue at microscopic resolution have significant potential to enhance the study of both normal and disease processes, particularly those involving structural changes or those in which the spatial relationship of disease features is important. Although other methods exist for studying tissue in 3D, using conventional histopathological features has significant advantages because it allows for conventional histopathological staining and interpretation techniques. ntil now, its use has not been routine in esearch because of the technical difficulty in constructing D tissue models. We describe a novel system or 3D histological reconstruction, integrating hole-slide imaging (virtual slides), image serving, registration, and visualization into one user-friendly package. It produces high-resolution 3D reconstructions with minimal user interaction and can be used in a histopathological laboratory without input from computing specialists. It uses a novel method for slice-to-slice image registration using automatic registration algorithms custom designed for both virtual slides and histopathological images. This system has been applied to >300 separate 3D volumes from eight different tissue types, using a total of 5500 virtual slides comprising 1.45 TB of primary image data. Qualitative and quantitative metrics for the accuracy of 3D reconstruction are provided, with measured registration accuracy approaching 120 m for a 1-cm piece of tissue. Both 3D tissue volumes and generated 3D models are presented for four demonstrator cases.
Elsevier
2012-05
Article
PeerReviewed
Roberts, N, Magee, D, Song, Y et al. (7 more authors) (2012) Towards Routine Use of 3D Histopathology As a Research Tool. American Journal of Pathology, 180 (5). 1835 - 1842. ISSN 0002-9440
http://dx.doi.org/10.1016/j.ajpath.2012.01.033
10.1016/j.ajpath.2012.01.033
oai:eprints.whiterose.ac.uk:75822
2014-09-15T03:21:17Z
7374617475733D707562
74797065733D61727469636C65
756E69743D4C65656473:4C656564732E46412D46455053:4C656564732E52432D434F4D50:4C656564732E53522D41494253
756E69743D4C65656473:4C656564732E46412D4D444845:4C656564732E52432D4D4D4543:4C656564732E44492D50415448
696E737469747574696F6E3D4C65656473
7072696D6F3D6861735F7075626C6963
https://eprints.whiterose.ac.uk/75822/
Tracking with virtual slides: a tool to study diagnostic error in histopathology
Treanor, D
Lim, C
Magee, D
Bulpitt, AJ
Quirke, P
Aims: To determine the reasons for diagnostic error by virtual slides which allow unsupervised study of diagnosis and error. Methods and results: Software was developed to produce visualizations of the diagnostic track followed by pathologists as they viewed virtual slides. These showed the diagnostic path in four dimensions (x, y, time and zoom), areas studied for >1000 ms, and included pathologists’ comments about the areas viewed. The system was used to study two trainee and two expert pathologists diagnosing 60 Barrett’s oesophageal biopsy specimens. Comparisons of the diagnostic tracks showed the reason for errors. Forty-six cases had an expert consensus diagnosis. The trainees made errors in 21 and 15 cases, respectively, of which 11 and nine were clinically significant. Errors were made across the whole spectrum of diagnoses from negative to intramucosal carcinoma. Detailed examination of the tracks showed that in all errors there was incorrect interpretation of information; in three errors there was an additional failure to identify diagnostic features. Conclusions: Tracking with virtual slides is a useful tool in studying diagnosis and error, which has the potential for use in training and assessment
Wiley Blackwell
2009-07
Article
NonPeerReviewed
text
en
https://eprints.whiterose.ac.uk/75822/15/mageed5.pdf
Treanor, D, Lim, C, Magee, D et al. (2 more authors) (2009) Tracking with virtual slides: a tool to study diagnostic error in histopathology. Histopathology, 55 (1). 37 - 45. ISSN 0309-0167
http://dx.doi.org/10.1111/j.1365-2559.2009.03325.x
10.1111/j.1365-2559.2009.03325.x
oai:eprints.whiterose.ac.uk:76823
2018-01-18T19:32:20Z
7374617475733D707562
74797065733D61727469636C65
756E69743D4C65656473:4C656564732E46412D4D444845:4C656564732E52432D4D4D4543:4C656564732E44492D4E594354
756E69743D4C65656473:4C656564732E46412D4D444845:4C656564732E52432D4D4D4543:4C656564732E44492D4F4E434F
756E69743D4C65656473:4C656564732E46412D4D444845:4C656564732E52432D4D4D4543:4C656564732E44492D4F504E45
756E69743D4C65656473:4C656564732E46412D4D444845:4C656564732E52432D4D4D4543:4C656564732E44492D50415448
696E737469747574696F6E3D4C65656473
7072696D6F3D6861735F7075626C6963
https://eprints.whiterose.ac.uk/76823/
NuMA overexpression in epithelial ovarian cancer.
Brüning-Richardson, A
Bond, J
Alsiary, R
Richardson, J
Cairns, DA
McCormac, L
Hutson, R
Burns, PA
Wilkinson, N
Hall, GD
Morrison, EE
Bell, SM
Highly aneuploid tumours are common in epithelial ovarian cancers (EOC). We investigated whether NuMA expression was associated with this phenomenon.NuMA protein levels in normal and tumour tissues, ovarian cell lines and primary cultures of malignant cells derived from ovarian ascitic fluids were analysed by Affymetrix microarray analysis, immunoblotting, immunohistochemistry (IHC) and immunofluorescence (IF), with results correlated to associated clinical data. Aneuploidy status in primary cultures was determined by FACS analysis.Affymetrix microarray data indicated that NuMA was overexpressed in tumour tissue, primary cultures and cell lines compared to normal ovarian tissue. IHC revealed low to weak NuMA expression in normal tissues. Expression was upregulated in tumours, with a significant association with disease stage in mucinous EOC subtypes (p = 0.009), lymph node involvement (p = 0.03) and patient age (p = 0.04). Additional discontinuous data analysis revealed that high NuMA levels in tumours decreased with grade (p = 0.02) but increased with disease stage (p = 0.04) in serous EOC. NuMA expression decreased in late disease stage 4 endometrioid EOCs. High NuMA levels decreased with increased tumour invasion in all subtypes (p = 0.03). IF of primary cultures revealed that high NuMA levels at mitotic spindle poles were significantly associated with a decreased proportion of cells in cytokinesis (p = 0.05), increased binucleation (p = 0.021) and multinucleation (p = 0.007), and aneuploidy (p = 0.008).NuMA is highly expressed in EOC tumours and high NuMA levels correlate with increases in mitotic defects and aneuploidy in primary cultures.
Public Library of Science
2012-06
Article
PeerReviewed
text
en
https://eprints.whiterose.ac.uk/76823/1/Bruning-Richardson%20A.pdf
Brüning-Richardson, A, Bond, J, Alsiary, R et al. (9 more authors) (2012) NuMA overexpression in epithelial ovarian cancer. PLoS One, 7 (6). ARTN e38945. e38945 - ?. ISSN 1932-6203
http://dx.doi.org/10.1371/journal.pone.0038945
10.1371/journal.pone.0038945
oai:eprints.whiterose.ac.uk:95007
2016-11-16T16:48:37Z
7374617475733D707562
74797065733D61727469636C65
756E69743D4C65656473:4C656564732E46412D4D444845:4C656564732E52432D4D4D4543:4C656564732E44492D50415448:4C656564732E53522D50414759
696E737469747574696F6E3D4C65656473
7072696D6F3D6861735F7075626C6963
https://eprints.whiterose.ac.uk/95007/
Teenagers and young adults with cancer in Europe: From national programmes to a European integrated coordinated project
Stark, D
Bielack, S
Brugieres, L
Dirksen, U
Duarte, X
Dunn, S
Erdelyi, DJ
Grew, T
Hjorth, L
Jazbec, J
Kabickova, E
Konsoulova, A
Kowalczyk, JR
Lassaletta, A
Laurence, V
Lewis, I
Monrabal, A
Morgan, S
Mountzios, G
Olsen, PR
Renard, M
Saeter, G
van der Graaf, WT
Ferrari, A
Over 14 000 patients aged 15-24 are estimated to be diagnosed with cancer in the European Union (EU) each year. Teenagers and young adults (TYA) often fall down gaps between children's and adults cancer services. The specific challenges of providing optimal care to them are described, but we present a summary of recent progress. Progress to overcome these challenges is happening at different rates across Europe. We summarise the European national projects in this field but more recently we have seen the beginnings of European coordination. Within the EU 7th Funding Programme (FP7) European Network for Cancer Research in Children and Adolescents programme (ENCCA), a specific European Network for Teenagers and Young Adults with Cancer has held a series of scientific meetings, including professionals, patients and caregivers. This group has proposed unanswered research questions and agreed key features of a high-quality service that can improve outcomes for TYA with cancer, including the primacy of collaboration between adult and paediatric services to eliminate the gap in the management of TYA with cancer.
Wiley
2016-05
Article
NonPeerReviewed
text
en
https://eprints.whiterose.ac.uk/95007/9/EJCC_TYA%20in%20Europe%20revised%20Feb%202015.pdf
Stark, D, Bielack, S, Brugieres, L et al. (21 more authors) (2016) Teenagers and young adults with cancer in Europe: From national programmes to a European integrated coordinated project. European Journal of Cancer Care, 25 (3). pp. 419-427. ISSN 0961-5423
http://dx.doi.org/10.1111/ecc.12365
10.1111/ecc.12365
oai:eprints.whiterose.ac.uk:97363
2016-11-04T00:52:00Z
7374617475733D707562
74797065733D636F6E666572656E63655F6974656D
756E69743D4C65656473:4C656564732E46412D4D444845:4C656564732E52432D4D4D4543:4C656564732E44492D50415448:4C656564732E53522D50414759
696E737469747574696F6E3D4C65656473
7072696D6F3D6E6F5F646F63756D656E74735F617661696C61626C65
https://eprints.whiterose.ac.uk/97363/
Pre-Treatment and Post-Treatment Epidermal Growth Factor Receptor Pathway Mutations in a Prospective Phase II Trial (NWCOG EXCITE) of Cetuximab-Containing Chemoradiation in Locally Advanced Rectal Cancer
West, NP
Kodavatiganti, R
Hemmings, G
Tinkler-Hundal, E
Chambers, P
Taylor, M
Bottomley, D
Quirke, P
Gollins, S
Pre-operative chemoradiotherapy (CRT) with anti-EGFR antibodies may change the status of EGFR pathway mutations. We assessed the mutational status of a number of EGFR pathway genes before and after CRT in the NWCOG EXCITE trial. Patients with MRI-threatened surgical margins were given pelvic radiotherapy (45Gy) with capecitabine, irinotecan and cetuximab followed by surgery after 8 weeks. DNA was retrospectively extracted from the pre-treatment biopsy and resection specimen by macrodissecting areas of greatest residual tumour. The mutational status of KRAS (codons 12/13/61/146), NRAS (12/13/61), PIK3CA (542/545/546/1047) and BRAF (V600E hotspot) were determined by pyrosequencing. The work is presented on behalf of the NWCOG EXCITE trial investigators and was part-funded by a PathSoc fellowship. 80 patients commenced treatment and 76 underwent surgery with pathological complete response in 14 (18%) and near-complete in 6 (8%). Pre-treatment testing (n=78) detected mutations in KRAS (n=34), BRAF (n=3), NRAS (n=3) and PIK3CA (n=10). Any EGFR pathway mutation was detected in 58%. Following CRT, cases with residual tumour able to be tested (n=54) showed mutations in 32 patients (59%). There was a discrepancy compared to pre-treatment biopsy in 18 cases (33%): from wild-type (wt) to mutant (mut) in 9, from mut to dierent mut in 1 and from mut to wt in 7. One patient changed in 3 codons (mut to wt in KRAS 146/PIK3CA 545 and wt to mut in KRAS 12). In 12 patients (22%) this changed their overall EGFR pathway status (6x wt to mut and 6x mut to wt). Intratumour heterogeneity may explain some of the dierences in EGFR pathway mutations reported between biopsies and resections presenting a challenge to personalised medicine. However, cetuximab may also drive the growth of undetectable mutant clones to detectable levels on pyrosequencing. Further assessment using more sensitive sequencing technologies is currently being employed to investigate these differences.
Wiley
2015-09
Conference or Workshop Item
NonPeerReviewed
West, NP, Kodavatiganti, R, Hemmings, G et al. (6 more authors) (2015) Pre-Treatment and Post-Treatment Epidermal Growth Factor Receptor Pathway Mutations in a Prospective Phase II Trial (NWCOG EXCITE) of Cetuximab-Containing Chemoradiation in Locally Advanced Rectal Cancer. In: Dublin Pathology 2015: 8th Joint Meeting of the British Division of the International Academy of Pathologyand the Pathological Society of Great Britain & Ireland, 23-25 Jun 2015, Dublin.
http://dx.doi.org/10.1002/path.4631
10.1002/path.4631
oai:eprints.whiterose.ac.uk:97365
2022-12-19T13:33:40Z
7374617475733D707562
74797065733D7075626C69736865645F636F6E666572656E63655F70726F63656564696E6773
756E69743D4C65656473:4C656564732E46412D4D444845:4C656564732E52432D4D4D4543:4C656564732E44492D50415448:4C656564732E53522D50414759
696E737469747574696F6E3D4C65656473
7072696D6F3D6E6F5F646F63756D656E74735F617661696C61626C65
https://eprints.whiterose.ac.uk/97365/
Defining the Rectum and Sigmoid Colon: Should We Abolish the Term 'Rectosigmoid' to Improve Outcomes in Colorectal Cancer?
Hughes, J
Palmer, TJ
Young, C
Quirke, P
West, NP
The risk of circumferential resection margin (CRM) involvement is conned to tumours of the rectum with the risk of peritoneal involvement increasing the further a tumour is located above the peritoneal reection. There is no internationally accepted denition of the upper limit of the rectum, and the term ‘rectosigmoid’ is frequently applied to tumours in this area leading to confusion around the risks and whether radiotherapy can be given. The photographs from 331 abdominoperineal excision specimens were available for quantitation using Aperio ImageScope. Both fresh and xed specimen images were included where available. The position of the anal verge, top of the sphincters, anterior peritoneal reection, mesorectal apex (dening the limit of the mesorectum) and high vascular tie were identied and the distances between each point measured. The work was supported by a PathSoc bursary. There was wide variation in the length of the mesorectum in both fresh (median 172 mm, IQR 146 to 199 mm) and xed (166 mm, 140 to 196 mm) specimens. The length of the anal canal also showed variation (fresh 66 mm, 49 to 78 mm; xed 66 mm, 53 to 75 mm). The height of the anterior peritoneal reection was lower in females compared to males (fresh 125 vs. 132 mm, p=0.288; xed 111 vs. 126 mm, p=0.034). There is marked variability in the anatomy of the rectum between individuals and genders. This potentially aects the risk of either CRM or peritoneal involvement and whether radiotherapy could be oered. A xed denition of the upper limit of the rectum for all patients is not helpful. This should be determined for individual patients on the basis of the MRI ndings. The term ‘rectosigmoid’ should be abolished and more accurate denitions based on the position of the mesorectal apex and commencement of the sigmoid mesentery should be used to dene the boundaries of the rectum and sigmoid colon and determine subsequent risks to the patient.
Wiley
2015-09
Proceedings Paper
NonPeerReviewed
Hughes, J, Palmer, TJ, Young, C et al. (2 more authors) (2015) Defining the Rectum and Sigmoid Colon: Should We Abolish the Term 'Rectosigmoid' to Improve Outcomes in Colorectal Cancer? In: Journal of Pathology. 8th Joint Meeting of the British Division of the International Academy of Pathologyand the Pathological Society of Great Britain & Ireland, 23-25 Jun 2015, Dublin, Ireland. Wiley , S38-S38.
http://dx.doi.org/10.1002/path.4631
10.1002/path.4631
oai:eprints.whiterose.ac.uk:97386
2016-11-04T00:52:03Z
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https://eprints.whiterose.ac.uk/97386/
A Research Career in Pathology
West, NP
The number of pathologists actively engaging in research has risen again over recent years following the introduction of a defined academic training pathway and the support of bodies like the Pathological Society. A research career is exceptionally rewarding and offers the chance to undertake potentially ground breaking research alongside clinical practice. An interest in pathology research can begin as an undergraduate and a number of opportunities now exist to allow students to explore a research career and embed themselves within academic pathology groups at an early stage. Most medical schools offer special study modules where students can apply to do a piece of research in an area of interest. Several students also opt to undertake research placements during the summer holidays. This can be taken further with a full year out from a medical degree to intercalate a BSc/MRes, or even undertake a three year Doctoral degree. Following university, academic foundation placements allow for a four month period of research and lead into specialist training pathways where further experience can be gained as an academic clinical fellow (ACF) with up to 25% of time spent in research. This is usually followed by three years out of clinical training to complete a higher degree and leads into a clinical lectureship (CL) where 50% of time is spent undertaking research at an increasingly independent level. ACF and CL opportunities are advertised across the UK in centres of academic excellence. On completion of clinical training, a senior lectureship allows continuation of academic activities at a senior level alongside working as a consultant. A research career is stimulating and varied and offers the chance to undertake research in a world class environment. You get the opportunity to travel widely and experience pathology practice across the world as well as present your work to the scientific community. It is a career path highly recommended by the speaker!
Wiley
2015-09
Proceedings Paper
NonPeerReviewed
West, NP (2015) A Research Career in Pathology. In: Journal of Pathology. Dublin Pathology 2015. 8th Joint Meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain & Ireland, 23-25 Jun 2015, Dublin. Wiley , S10-S10.
http://dx.doi.org/10.1002/path.4631
10.1002/path.4631
oai:eprints.whiterose.ac.uk:97388
2016-11-08T18:44:33Z
7374617475733D707562
74797065733D7075626C69736865645F636F6E666572656E63655F70726F63656564696E6773
756E69743D4C65656473:4C656564732E46412D4D444845:4C656564732E52432D4D4D4543:4C656564732E44492D50415448:4C656564732E53522D50414759
696E737469747574696F6E3D4C65656473
7072696D6F3D6E6F5F646F63756D656E74735F617661696C61626C65
https://eprints.whiterose.ac.uk/97388/
Residual Tumour Cell Density and the Relationship to Survival Following Pre-Operative Chemoradiation in Locally Advanced Rectal Cancer: Results of the NWCOG RICE Trial
West, NP
Kodavatiganti, R
Hundal, ET
Quirke, P
Gollins, S
Pre-operative chemoradiotherapy (CRT) is commonly used to downstage locally advanced rectal cancer (LARC). The degree of response is assessed using a number of subjective tumour regression grading systems. Tumour cell density (TCD) has been developed as an objective linear measure of response and may be more sensitive and reproducible.Patients with MRI-dened LARC received pre-operative CRT using a novel irinotecan-containing regimen, with surgery 9 weeks later. TCD analysis was performed on digitally scanned glass slides. TCD was measured in the pre-treatment biopsy (PTBTCD) and a representative slide from the resection specimen including a 9mm2 area of greatest TCD (GTCD) and the whole tumour area and/or scar TCD (WTTCD). A systematic sample of 300 random points were inserted into each area using virtual graticule software and manually assessed, TCD was expressed as the percentage of informative points falling on tumour cells. The work is presented on behalf of the NWCOG RICE trial investigators and was part-funded by a PathSoc fellowship. 142 patients commenced CRT and 135 underwent surgery. Median TCD for PTBTCD, GTCD and WTTCD was 38.7%, 7.8% and 1.7% respectively. The number (%) of patients with a TCD of 0% was 0 (0%), 30 (23.6%) and 36 (28.3%) respectively. Distribution of TCD was normal in PTBTCD but highly positively skewed post-resection. Low PTBTCD (split by the median) predicted better 3-year disease free survival (DFS; 76% vs. 60%, p=0.05) although not overall survival (OS; p=0.47). Low WTTCD predicted better DFS and OS (DFS 71% vs. 58%, p=0.05; OS 90% vs. 77%, p=0.02) although no dierence was seen for GTCD (p=0.26; p=0.26). Pre-operative CRT markedly reduces TCD in LARC, and provides a continuous measure to compare dierent regimens. In the pre-treatment biopsy, lower TCD may predict improved DFS. Following resection, TCD across the whole tumour and scar more accurately predicts DFS and OS than using a selected area of greatest TCD.
Wiley
2015-09
Proceedings Paper
NonPeerReviewed
West, NP, Kodavatiganti, R, Hundal, ET et al. (2 more authors) (2015) Residual Tumour Cell Density and the Relationship to Survival Following Pre-Operative Chemoradiation in Locally Advanced Rectal Cancer: Results of the NWCOG RICE Trial. In: Journal of Pathology. Dublin Pathology 2015. 8th Joint Meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain & Ireland, 23-25 Jun 2015, Dublin, Ireland. Wiley , S22-S22.
http://dx.doi.org/10.1002/path.4631
10.1002/path.4631
oai:eprints.whiterose.ac.uk:97495
2018-01-19T16:12:08Z
7374617475733D707562
74797065733D7075626C69736865645F636F6E666572656E63655F70726F63656564696E6773
756E69743D4C65656473:4C656564732E46412D4D444845:4C656564732E52432D4D4D4543:4C656564732E44492D50415448:4C656564732E53522D50414759
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7072696D6F3D6861735F7075626C6963
https://eprints.whiterose.ac.uk/97495/
Rectal cancer resection specimen quality and pathological response at 6 vs. 12 weeks after long-course chemoradiotherapy: data from a pilot randomised controlled trial
Foster, J
Cooper, E
West, N
Francis, N
Investigators, STARRCATT
BMJ Publishing Group
2015-06
Proceedings Paper
NonPeerReviewed
text
en
https://eprints.whiterose.ac.uk/97495/1/2015-02%20Starrcat%20DDF15-1954-preview-3.pdf
Foster, J, Cooper, E, West, N et al. (2 more authors) (2015) Rectal cancer resection specimen quality and pathological response at 6 vs. 12 weeks after long-course chemoradiotherapy: data from a pilot randomised controlled trial. In: GUT - June 2015, Volume 64, Suppl 1 - Abstracts. 2nd Digestive Disorders Federation Conference 22–25 June 2015, 22-25 Jun 2015, London, UK. BMJ Publishing Group , A356-A357.
https://dx.doi.org/10.1136/gutjnl-2015-309861.779
10.1136/gutjnl-2015-309861.779