P. Demetter et al.
Criteria required for histopathological assessment of TME
Appendix A The PROCARE steering group consists of delegates from all Belgian scientific organizations involved in the treatment of rectal cancer:, i.e. the Belgian Section of Colorectal Surgery, a section of the Royal Belgian Society of Surgery (C. Bertrand, D. De Coninck, M. Duinslaeger, A. Kartheuser, F. Penninckx, J. Van de Stadt, W. Vaneerdeweg), the Belgian Society of Surgical Oncology (D. Claeys), the Belgian Group for Endoscopic Surgery (D. Burnon), the Belgian Society of Radiotherapy – Oncology (K. Haustermans, P. Scalliet, Ph. Spaas), the Belgian Society of Pathology and the Digestive Pathology Club (P. Demetter, A. Jouret-Mourin, C. Sempoux), the Belgian Society of Medical Oncology (W. Demey, Y. Hum-
blet, E. Van Cutsem), the Belgian Group for Digestive Oncology (S. Laurent, E. Van Cutsem, J. L. Van Laethem), the Royal Belgian Society of Radiology (E. Danse, B. Op de Beeck, P. Smeets), the Societe Royale Belge de Gastro-enterologie (M. Melange, J. Rahier), the Vlaamse Vereniging voor Gastro-enterologie Flemish Society for Gastroenterology (M. Cabooter, P. Pattyn, M. Peeters) and the Belgian Society of Gastro-intestinal Endoscopy (M. Buset). Also represented are the Belgian Professional Surgical Association (L. Haeck, B. Mansvelt, K. Vindevoghel), the Foundation Belgian Cancer Registry (E. Van Eycken) and the RIZIV/INAMI (J. P. Dercq, A. Thijs). F. Penninckx chairs the PROCARE Steering Group.
Commentary on Demetter et al. The level of interest in as well as the quality of colorectal cancer pathology has changed markedly over the last 30 years, but the data from Demetter et al. [1] issue a timely challenge to pathologists and also indirectly to the rest of the multidisciplinary team (MDT). Whilst this is a relatively small study of 444 selected cases from a total of 2460 cases registered in the Belgium PROCARE study and is limited in its scope by omitting the reporting of some of the key prognostic factors, e.g. extramural vascular invasion, peritoneal involvement, tumour perforation and distance of extramural spread, it does make points of major importance for pathologists and the MDT. Due to the selection process it is possible that this study shows the pathology reporting in PROCARE in a better light than might be seen were all the cases to have been available for review. Only 743, with submitted pictures and slides, out of the total of 2460 cases were reviewed centrally and of these 444 were felt to be of a standard where the quality of surgery could be assessed by the review panel. What was the data completeness in the non-submitted cases or the cases with poor photographic evidence? It is unlikely to be better than the pathologists work now reported, who had made the effort to take good quality photographs. In the cases that reached the review stage, one in 10 had no record of the circumferential resection margin status with a similar number not recording the grade of the plane of surgery. Furthermore one in five had no record of regression grading after preoperative therapy. Pleasingly the number of lymph nodes identified was recorded in 97% of specimens, but the majority failed to dissect at least 12 lymph nodes, again an area of
1358
doi:10.1111/codi.12433
concern. Whilst preoperative therapy does reduce nodal yield we should expect better performance from the reporting pathologists. The failure to capture the key data systematically in all patients is unforgivable and is still all too frequent worldwide. There is extensive evidence that proforma reporting improves data capture [2 6], yet proformas were used here, showing that they are not the total solution. Is it time to apply a degree of supervision of pathology reporting? This could be immediate, with modern IT systems prompting pathologists when they have omitted data. Local named pathologists could be responsible for cancer data completeness with a further tier of independent regional or national audit of cancer pathology data as the final layer. By failing to bring pathologists to task by formal supervision or by MDT acceptance of incomplete data, patients may suffer suboptimal management from a poorly informed MDT. Indeed, should we go further and demand that full data collection occurs from the entire MDT. Pathologists have been at the forefront of standardization of practice, guidelines, data collection and audit whereas other clinicians still fail to capture any data routinely apart from the bare minimum. Radiologists and others have much to learn from the process of change that pathologists have been through even though we have not yet reached our required destination. The second point that emerges from this paper is the continuing tolerance by pathologists of systems of grading of differentiation (kappa = 0.67) and tumour regression (kappa = 0.50) with relatively poor interobserver agreement. We need to strive for better, more consistent and preferably quantitative criteria, to grade tumours
Colorectal Disease ª 2013 The Association of Coloproctology of Great Britain and Ireland. 15, 1351–1360
P. Demetter et al.
and the degree of residual tumour after therapy. Mesker et al. [7, 8] have shown that the amount of stroma is a simple reproducible predictor of prognosis and we have confirmed this in the Quasar randomized trial (unpublished data) as well as using the tumour cell density which is an alternative approach [9]. Others have suggested tumour budding but there is little agreement on the methodology, currently precluding its routine adoption [10]. Should we be quantitating the number of residual tumour cells after therapy [11] rather than just estimating the effects of the therapy by the proportion of stroma? If we fail to improve the histopathology methods then clinicians will be driven to adopt molecular prognosticators of dubious efficacy and with significant cost. Unfortunately we cannot comment on the rate of agreement between the local pathologist and the central review for the circumferential resection margin as these data were not reported. A major theme of this paper is the assessment of the quality of surgery. Of the 2460 cases we are not told how many of the total were actually graded locally. Of the 444 cases, with photographs deemed acceptable to review, only 89% reported the plane. In the Medical Research Council (MRC) CR07/NCIC-CTG CO16 trial [12] the local plane of surgery grade was available in an equivalent number of cases [1156/1350 (86%)] but this covered all cases entered into the trial. Demetter et al. [1] have a locally reported rate of 12% of intramuscular plane resections compared with a locally reported rate of 13% showing the muscularis propria plane (as used in the trial and Royal College of Pathologists national guidelines [13]) in MRC CR07. The central review by a group of pathologists with a special interest increased the rate of this group to 25% in the PROCARE study. Thus after training and local reporting, both in this study and in MRC CR07, one in eight cases had suboptimal planes rising to one in four when there was a central review. This indicates that even after training surgery could be optimized further in both cohorts. Demetter et al. [1] report a kappa of 0.41 for such grading between the local pathologist and the review group, which can be judged as fair to moderate interobserver agreement. They did not report the level of intraobserver agreement that was obtainable between the experts. We realize this classification is subjective. Clearly improving it would be helpful and this may be possible by splitting the assessment of the mesorectal portion and the abdominoperineal area below the mesorectum as we have undertaken in the UK LOREC programme [14]. The development of a more quantitative measurement would be better but this appears very difficult given currently available tools. It would be possible to investigate whether we can improve the
Criteria required for histopathological assessment of TME
agreement on grading the plane by giving feedback from a central review committee to the local pathologists so that they may benefit from their expertise. The purpose of reporting the plane of surgery to surgeons is mainly aimed at providing immediate feedback so that they can consider how they might have undertaken the dissection more effectively so as to improve their surgery in the future; however, it is also relevant to an individual patient as it appears to predict an increased risk of local recurrence and in some studies survival [12,15 19]. There is now substantial evidence of improving survival related to total mesorectal excision, and improvements in low rectal cancer survival are expected as the planes of surgery are improved in abdominoperineal excision. The mandating of photographs and judgement of the planes of surgery in this study are welcome but clearly there is a long way to go in implementing this approach since this was only possible in 444/2460 cases in this study. We would commend the routine implementation of such policies as well as the audit measures above and their funding through local, regional and national audit programmes as surgical excellence is key to improving the outcome in rectal and possibly, in the future, colon cancer as more evidence accumulates of the importance of the quality of surgery undertaken. This paper shows that there is still a long way to go with rectal cancer care. The surgery is still not optimal, pathologists continue to fail to report key diagnostic features and we have significant interobserver variation. Despite this we see increasing rectal cancer survival rates and improving total mesorectal excision and low rectal cancer surgery. We need to reduce our tolerance of suboptimal care and ensure a focus on the plane of surgery achieved, the completeness of all MDT data and continued use of such data to improve outcome. Time and funding spent on audit will be repaid more effectively than money currently spent on expensive new drugs and new molecular prognosticators of marginal effectiveness.
P. Quirke, G. G. A. Hutchins and N. P. West Department of Pathology, Anatomy and Tumour Biology, Leeds Institute of Cancer and Pathology, School of Medicine, University of Leeds, Leeds, UK E-mail: [email protected]
References 1 Demetter P, Vandendael T, Sempoux C et al. Need for objective and reproducible criteria in histopathological assessment of total mesorectal excision specimens: lessons from a national improvement project. Colorectal Dis 2013; 15: 1351–8.
Colorectal Disease ª 2013 The Association of Coloproctology of Great Britain and Ireland. 15, 1351–1360
1359
P. Demetter et al.
Criteria required for histopathological assessment of TME
2 Bull AD, Biffin AH, Mella J et al. Colorectal cancer pathology reporting: a regional audit. J Clin Pathol 1997; 50: 138–42. 3 Cross SS, Feeley KM, Angel CA. The effect of four interventions on the informational content of histopathology reports of resected colorectal carcinomas. J Clin Pathol 1998; 51: 481–2. 4 Rigby K, Brown SR, Lakin G, Balsitis M, Hosie KB. The use of a proforma improves colorectal cancer pathology reporting. Ann R Coll Surg Engl 1999; 81: 401–3. 5 Siriwardana PN, Pathmeswaran A, Hewavisenthi J, Deen KI. Histopathology reporting in colorectal cancer: a proforma improves quality. Colorectal Dis 2009; 11: 849–53. 6 Beattie GC, McAdam TK, Elliott S, Sloan JM, Irwin ST. Improvement in quality of colorectal cancer pathology reporting with a standardized proforma a comparative study. Colorectal Dis 2003; 5: 558–62. 7 Mesker WE, Junggeburt JM, Szuhai K et al. The carcinoma stromal ratio of colon carcinoma is an independent factor for survival compared to lymph node status and tumor stage. Cell Oncol 2007; 29: 387–98. 8 Huijbers A, Tollenaar RA, v Pelt GW et al. The proportion of tumor-stroma as a strong prognosticator for stage II and III colon cancer patients: validation in the VICTOR trial. Ann Oncol 2013; 24: 179–85. 9 West NP, Dattani M, McShane P et al. The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients. Br J Cancer 2010; 102: 1519– 23. 10 Vieth M, Quirke P, Lambert R, von Karsa L, Risio M. European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition Annotations of colorectal lesions. Endoscopy 2012; 44(Suppl 3): SE131–9. 11 West NP, Grabsch H, Treanor D et al. Quantitative assessment of tumor cell density in rectal cancer following three
1360
12
13
14 15
16
17
18
19
different preoperative therapies compared to surgery alone. J Clin Oncol 2010; 28 (Suppl ASCO Meeting Abstracts Part 1): 3651. Quirke P, Steele R, Monson J et al. Effect of the plane of surgery achieved on local recurrence in patients with operable rectal cancer: a prospective study using data from the MRC CR07 and NCIC-CTG CO16 randomised clinical trial. Lancet 2009; 373: 821–8. http://www.rcpath.org/Resources/RCPath/Migrated Resources/Documents/G/G049-ColorectalDataset-Sep07. pdf. http://www.lorec.nhs.uk/resources/Prof_Phil_Quirke_ Background_to_abdominoperineal_excision.pdf. Nagtegaal ID, van de Velde CJ, van der Worp E, Kapiteijn E, Quirke P, van Krieken JH. Macroscopic evaluation of rectal cancer resection specimen: clinical significance of the pathologist in quality control. J Clin Oncol 2002; 20: 1729–34. Maslekar S, Sharma A, MacDonald A et al. Mesorectal grade predicts recurrences after curative resection for rectal cancer. Dis Colon Rectum 2007; 50: 168–75. Garcıa-Granero E, Faiz O, Mu~ noz E. Macroscopic assessment of mesorectal excision in rectal cancer: a useful tool for improving quality control in a multidisciplinary team. Cancer 2009; 115: 3400–11. Leite JS, Martins SC, Oliveira J, Cunha MF, Castro-Sousa F. Clinical significance of macroscopic completeness of mesorectal resection in rectal cancer. Colorectal Dis 2011; 13: 381–6. Bosch SL, Nagtegaal ID. The importance of the pathologist’s role in assessment of the quality of the mesorectum. Curr Colorectal Cancer Rep 2012; 8: 90–8.
Colorectal Disease ª 2013 The Association of Coloproctology of Great Britain and Ireland. 15, 1351–1360
Copyright of Colorectal Disease is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Criteria required for histopathological assessment of TME
Appendix A The PROCARE steering group consists of delegates from all Belgian scientific organizations involved in the treatment of rectal cancer:, i.e. the Belgian Section of Colorectal Surgery, a section of the Royal Belgian Society of Surgery (C. Bertrand, D. De Coninck, M. Duinslaeger, A. Kartheuser, F. Penninckx, J. Van de Stadt, W. Vaneerdeweg), the Belgian Society of Surgical Oncology (D. Claeys), the Belgian Group for Endoscopic Surgery (D. Burnon), the Belgian Society of Radiotherapy – Oncology (K. Haustermans, P. Scalliet, Ph. Spaas), the Belgian Society of Pathology and the Digestive Pathology Club (P. Demetter, A. Jouret-Mourin, C. Sempoux), the Belgian Society of Medical Oncology (W. Demey, Y. Hum-
blet, E. Van Cutsem), the Belgian Group for Digestive Oncology (S. Laurent, E. Van Cutsem, J. L. Van Laethem), the Royal Belgian Society of Radiology (E. Danse, B. Op de Beeck, P. Smeets), the Societe Royale Belge de Gastro-enterologie (M. Melange, J. Rahier), the Vlaamse Vereniging voor Gastro-enterologie Flemish Society for Gastroenterology (M. Cabooter, P. Pattyn, M. Peeters) and the Belgian Society of Gastro-intestinal Endoscopy (M. Buset). Also represented are the Belgian Professional Surgical Association (L. Haeck, B. Mansvelt, K. Vindevoghel), the Foundation Belgian Cancer Registry (E. Van Eycken) and the RIZIV/INAMI (J. P. Dercq, A. Thijs). F. Penninckx chairs the PROCARE Steering Group.
Commentary on Demetter et al. The level of interest in as well as the quality of colorectal cancer pathology has changed markedly over the last 30 years, but the data from Demetter et al. [1] issue a timely challenge to pathologists and also indirectly to the rest of the multidisciplinary team (MDT). Whilst this is a relatively small study of 444 selected cases from a total of 2460 cases registered in the Belgium PROCARE study and is limited in its scope by omitting the reporting of some of the key prognostic factors, e.g. extramural vascular invasion, peritoneal involvement, tumour perforation and distance of extramural spread, it does make points of major importance for pathologists and the MDT. Due to the selection process it is possible that this study shows the pathology reporting in PROCARE in a better light than might be seen were all the cases to have been available for review. Only 743, with submitted pictures and slides, out of the total of 2460 cases were reviewed centrally and of these 444 were felt to be of a standard where the quality of surgery could be assessed by the review panel. What was the data completeness in the non-submitted cases or the cases with poor photographic evidence? It is unlikely to be better than the pathologists work now reported, who had made the effort to take good quality photographs. In the cases that reached the review stage, one in 10 had no record of the circumferential resection margin status with a similar number not recording the grade of the plane of surgery. Furthermore one in five had no record of regression grading after preoperative therapy. Pleasingly the number of lymph nodes identified was recorded in 97% of specimens, but the majority failed to dissect at least 12 lymph nodes, again an area of
1358
doi:10.1111/codi.12433
concern. Whilst preoperative therapy does reduce nodal yield we should expect better performance from the reporting pathologists. The failure to capture the key data systematically in all patients is unforgivable and is still all too frequent worldwide. There is extensive evidence that proforma reporting improves data capture [2 6], yet proformas were used here, showing that they are not the total solution. Is it time to apply a degree of supervision of pathology reporting? This could be immediate, with modern IT systems prompting pathologists when they have omitted data. Local named pathologists could be responsible for cancer data completeness with a further tier of independent regional or national audit of cancer pathology data as the final layer. By failing to bring pathologists to task by formal supervision or by MDT acceptance of incomplete data, patients may suffer suboptimal management from a poorly informed MDT. Indeed, should we go further and demand that full data collection occurs from the entire MDT. Pathologists have been at the forefront of standardization of practice, guidelines, data collection and audit whereas other clinicians still fail to capture any data routinely apart from the bare minimum. Radiologists and others have much to learn from the process of change that pathologists have been through even though we have not yet reached our required destination. The second point that emerges from this paper is the continuing tolerance by pathologists of systems of grading of differentiation (kappa = 0.67) and tumour regression (kappa = 0.50) with relatively poor interobserver agreement. We need to strive for better, more consistent and preferably quantitative criteria, to grade tumours
Colorectal Disease ª 2013 The Association of Coloproctology of Great Britain and Ireland. 15, 1351–1360
P. Demetter et al.
and the degree of residual tumour after therapy. Mesker et al. [7, 8] have shown that the amount of stroma is a simple reproducible predictor of prognosis and we have confirmed this in the Quasar randomized trial (unpublished data) as well as using the tumour cell density which is an alternative approach [9]. Others have suggested tumour budding but there is little agreement on the methodology, currently precluding its routine adoption [10]. Should we be quantitating the number of residual tumour cells after therapy [11] rather than just estimating the effects of the therapy by the proportion of stroma? If we fail to improve the histopathology methods then clinicians will be driven to adopt molecular prognosticators of dubious efficacy and with significant cost. Unfortunately we cannot comment on the rate of agreement between the local pathologist and the central review for the circumferential resection margin as these data were not reported. A major theme of this paper is the assessment of the quality of surgery. Of the 2460 cases we are not told how many of the total were actually graded locally. Of the 444 cases, with photographs deemed acceptable to review, only 89% reported the plane. In the Medical Research Council (MRC) CR07/NCIC-CTG CO16 trial [12] the local plane of surgery grade was available in an equivalent number of cases [1156/1350 (86%)] but this covered all cases entered into the trial. Demetter et al. [1] have a locally reported rate of 12% of intramuscular plane resections compared with a locally reported rate of 13% showing the muscularis propria plane (as used in the trial and Royal College of Pathologists national guidelines [13]) in MRC CR07. The central review by a group of pathologists with a special interest increased the rate of this group to 25% in the PROCARE study. Thus after training and local reporting, both in this study and in MRC CR07, one in eight cases had suboptimal planes rising to one in four when there was a central review. This indicates that even after training surgery could be optimized further in both cohorts. Demetter et al. [1] report a kappa of 0.41 for such grading between the local pathologist and the review group, which can be judged as fair to moderate interobserver agreement. They did not report the level of intraobserver agreement that was obtainable between the experts. We realize this classification is subjective. Clearly improving it would be helpful and this may be possible by splitting the assessment of the mesorectal portion and the abdominoperineal area below the mesorectum as we have undertaken in the UK LOREC programme [14]. The development of a more quantitative measurement would be better but this appears very difficult given currently available tools. It would be possible to investigate whether we can improve the
Criteria required for histopathological assessment of TME
agreement on grading the plane by giving feedback from a central review committee to the local pathologists so that they may benefit from their expertise. The purpose of reporting the plane of surgery to surgeons is mainly aimed at providing immediate feedback so that they can consider how they might have undertaken the dissection more effectively so as to improve their surgery in the future; however, it is also relevant to an individual patient as it appears to predict an increased risk of local recurrence and in some studies survival [12,15 19]. There is now substantial evidence of improving survival related to total mesorectal excision, and improvements in low rectal cancer survival are expected as the planes of surgery are improved in abdominoperineal excision. The mandating of photographs and judgement of the planes of surgery in this study are welcome but clearly there is a long way to go in implementing this approach since this was only possible in 444/2460 cases in this study. We would commend the routine implementation of such policies as well as the audit measures above and their funding through local, regional and national audit programmes as surgical excellence is key to improving the outcome in rectal and possibly, in the future, colon cancer as more evidence accumulates of the importance of the quality of surgery undertaken. This paper shows that there is still a long way to go with rectal cancer care. The surgery is still not optimal, pathologists continue to fail to report key diagnostic features and we have significant interobserver variation. Despite this we see increasing rectal cancer survival rates and improving total mesorectal excision and low rectal cancer surgery. We need to reduce our tolerance of suboptimal care and ensure a focus on the plane of surgery achieved, the completeness of all MDT data and continued use of such data to improve outcome. Time and funding spent on audit will be repaid more effectively than money currently spent on expensive new drugs and new molecular prognosticators of marginal effectiveness.
P. Quirke, G. G. A. Hutchins and N. P. West Department of Pathology, Anatomy and Tumour Biology, Leeds Institute of Cancer and Pathology, School of Medicine, University of Leeds, Leeds, UK E-mail: [email protected]
References 1 Demetter P, Vandendael T, Sempoux C et al. Need for objective and reproducible criteria in histopathological assessment of total mesorectal excision specimens: lessons from a national improvement project. Colorectal Dis 2013; 15: 1351–8.
Colorectal Disease ª 2013 The Association of Coloproctology of Great Britain and Ireland. 15, 1351–1360
1359
P. Demetter et al.
Criteria required for histopathological assessment of TME
2 Bull AD, Biffin AH, Mella J et al. Colorectal cancer pathology reporting: a regional audit. J Clin Pathol 1997; 50: 138–42. 3 Cross SS, Feeley KM, Angel CA. The effect of four interventions on the informational content of histopathology reports of resected colorectal carcinomas. J Clin Pathol 1998; 51: 481–2. 4 Rigby K, Brown SR, Lakin G, Balsitis M, Hosie KB. The use of a proforma improves colorectal cancer pathology reporting. Ann R Coll Surg Engl 1999; 81: 401–3. 5 Siriwardana PN, Pathmeswaran A, Hewavisenthi J, Deen KI. Histopathology reporting in colorectal cancer: a proforma improves quality. Colorectal Dis 2009; 11: 849–53. 6 Beattie GC, McAdam TK, Elliott S, Sloan JM, Irwin ST. Improvement in quality of colorectal cancer pathology reporting with a standardized proforma a comparative study. Colorectal Dis 2003; 5: 558–62. 7 Mesker WE, Junggeburt JM, Szuhai K et al. The carcinoma stromal ratio of colon carcinoma is an independent factor for survival compared to lymph node status and tumor stage. Cell Oncol 2007; 29: 387–98. 8 Huijbers A, Tollenaar RA, v Pelt GW et al. The proportion of tumor-stroma as a strong prognosticator for stage II and III colon cancer patients: validation in the VICTOR trial. Ann Oncol 2013; 24: 179–85. 9 West NP, Dattani M, McShane P et al. The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients. Br J Cancer 2010; 102: 1519– 23. 10 Vieth M, Quirke P, Lambert R, von Karsa L, Risio M. European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition Annotations of colorectal lesions. Endoscopy 2012; 44(Suppl 3): SE131–9. 11 West NP, Grabsch H, Treanor D et al. Quantitative assessment of tumor cell density in rectal cancer following three
1360
12
13
14 15
16
17
18
19
different preoperative therapies compared to surgery alone. J Clin Oncol 2010; 28 (Suppl ASCO Meeting Abstracts Part 1): 3651. Quirke P, Steele R, Monson J et al. Effect of the plane of surgery achieved on local recurrence in patients with operable rectal cancer: a prospective study using data from the MRC CR07 and NCIC-CTG CO16 randomised clinical trial. Lancet 2009; 373: 821–8. http://www.rcpath.org/Resources/RCPath/Migrated Resources/Documents/G/G049-ColorectalDataset-Sep07. pdf. http://www.lorec.nhs.uk/resources/Prof_Phil_Quirke_ Background_to_abdominoperineal_excision.pdf. Nagtegaal ID, van de Velde CJ, van der Worp E, Kapiteijn E, Quirke P, van Krieken JH. Macroscopic evaluation of rectal cancer resection specimen: clinical significance of the pathologist in quality control. J Clin Oncol 2002; 20: 1729–34. Maslekar S, Sharma A, MacDonald A et al. Mesorectal grade predicts recurrences after curative resection for rectal cancer. Dis Colon Rectum 2007; 50: 168–75. Garcıa-Granero E, Faiz O, Mu~ noz E. Macroscopic assessment of mesorectal excision in rectal cancer: a useful tool for improving quality control in a multidisciplinary team. Cancer 2009; 115: 3400–11. Leite JS, Martins SC, Oliveira J, Cunha MF, Castro-Sousa F. Clinical significance of macroscopic completeness of mesorectal resection in rectal cancer. Colorectal Dis 2011; 13: 381–6. Bosch SL, Nagtegaal ID. The importance of the pathologist’s role in assessment of the quality of the mesorectum. Curr Colorectal Cancer Rep 2012; 8: 90–8.
Colorectal Disease ª 2013 The Association of Coloproctology of Great Britain and Ireland. 15, 1351–1360
Copyright of Colorectal Disease is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
