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© 2002 American Society for Clinical Oncology
Pathologic Evaluation of Total Mesorectal Excision: Big Brother Is WatchingThe University of Texas, M.D. Anderson Cancer Center, Houston, TX LOCAL RECURRENCE after curative surgery for rectal adenocarcinoma remains a clinical problem. Prognosis in rectal adenocarcinoma can be related to tumor or surgical factors, with pathologic stage of the tumor as the most important tumor-related factor.1 Margins of excision, including circumferential margin, en bloc resection of adherent tumors, avoidance of inadvertent perforation, and experience of the surgeon are surgery-related factors.1,2 In this issue of the Journal of Clinical Oncology, Nagtegaal et al3 report that not only is the role of the pathologist limited to the microscopic evaluation of the specimen after curative rectal cancer but that macroscopic evaluation of the specimen will provide feedback to the surgeon with regard to the quality of the operation performed, which may indeed have prognostic significance. The cohort in this report is part of the prospective randomized trial organized by the Dutch Colorectal Cancer Group to investigate the efficacy of preoperative radiotherapy in combination with standardized total mesorectal excision (TME) in patients with rectal cancer.4 Nagtegaal et al3 hypothesized that, in addition to an assessment of the circumferential margins of resection, routine determination and reporting of the quality of the mesorectum might improve the prognostic value of the pathologic work-up and eventually improve the quality of the surgical technique. The technique of TME is not new. Advocated by Heald et al,5 it involves sharp dissection under direct visualization of the plane between the endopelvic fascia and the mesorectum, removal of the mesorectum with its intact fascia propria, and preservation of the pelvic fascia and the autonomic nerve plexuses. With this technique, local recurrence rates after surgery alone for rectal adenocarcinoma have been reported to be less than 8%.4,6-8 The concept of macroscopic evaluation of the completeness of mesorectal excision proposed by Nagtegaal et al3 will provide the surgeon who works closely with a pathologist objective evidence of the quality of the surgical procedure. However, it must be accepted with caution because there are several unaddressed issues. First, why were there only 180 patients with a detailed description of the specimen when 1,530 Dutch patients were randomized in this two-arm study? Does this reveal lack of interest from participating pathologists who were specifically trained by studying videos and newsletters and attending workshops, or does this indicate that the protocol described is cumbersome and takes too long? Second, the authors define a macroscopic classification and state that since there was no difference in prognosis between complete and nearly complete mesorectal excision, the groups were combined for further analyses. There may not have been a difference in prognosis, but the "nearly complete" classification allows for "moderate coning of the specimen," which is considered a poor surgical technique because it potentially allows for an increase in circumferential margin of involvement. Third, even though stage of disease is the most important prognostic factor after curative surgery in rectal adenocarcinoma, from the data presented, it is not possible to determine the relationship between stage of the disease and recurrence.
Despite surgery being performed by surgeons trained specifically in TME, in 23.9% of the patients the mesorectum was macroscopically incompletely removed. Distance from the anal verge was related to the completeness of mesorectal excision. Thirty-nine percent of the patients whose tumors were located What does this all mean? Do patients with an incomplete TME have a worse prognosis? At 2-year follow-up, the overall recurrence in patients with complete or nearly complete TME was 21.5% versus 35.6% for those patients with an incomplete TME. Despite the statistically significant difference in overall recurrence, there was no statistically significant difference in local recurrence (15% v 8.7%) or survival (86% v 76%). There needs to be longer follow-up in these patients. Does an incomplete TME influence prognosis in patients with circumferential margin of involvement? Approximately 25% of patients whose rectal cancer surgery has been considered curative will have an involved circumferential margin.9 In the present study, 23% of the patients had a positive circumferential margin. At 2-year follow-up, the presence of an involved circumferential margin of excision did not influence the prognosis in patients with an incomplete TME. However, in patients with a negative circumferential margin, the overall recurrence and survival were statistically significantly worse in patients with an incomplete TME compared with those with a complete or nearly complete TME (28.6% v 14.9% and 90.5% v 76.9%, respectively). Thus, the completeness of mesorectal excision may serve as a prognostic factor in patients with negative circumferential margins of excision. In patients with node-negative rectal cancer, time to recurrence and survival have been correlated with the number of lymph nodes examined in the specimen.10 It has been suggested that approximately 14 lymph nodes need to be examined in node-negative rectal cancer specimens.10 In the present study, there is no mention of the number of lymph nodes examined after TME. Even though the study by Nagtegaal et al3 is not perfect, it is an important study with a clear message. Patients who undergo potentially curative rectal cancer surgery and have an incomplete TME seem to do worse than those patients with a complete or nearly complete TME. The study should provide stimulus to both surgeons and pathologists to standardize their procedures. The College of American Pathologists has already published a protocol for examining colorectal cancer specimen.11 Clearly, there needs to be increased communication between surgeons and pathologists. By examining the gross macroscopic appearance of the mesorectum, the pathologist will provide feedback to the surgeon regarding the surgical procedure, thus allowing the surgeon to reevaluate the surgical technique and modify it as deemed appropriate for the benefit of the patient. The surgeon in turn can help the pathologist with orientation of the specimen and clarification of any doubts the pathologist has. REFERENCES
1.
Nelson H, Petrelli N, Carlin A, et al: Guidelines 2000 for colon and rectal surgery. J Natl Cancer Inst 93: 583-596, 2001 2. Porter GA, Soskolne CL, Yakimets WW, et al: Surgeon-related factors and outcome in rectal cancer. Ann Surg 227: 157-167, 1998[CrossRef][Medline]
3.
Nagtegaal ID, van de Velde CJH, van der Worp E, et al: Macroscopic evaluation of rectal cancer resection specimen: Clinical significance of the pathologist in quality control. J Clin Oncol 20: 1729-1734, 2002
4.
Kapiteijn E, Marijnen CAM, Nagtegaal ID, et al: Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 345: 638-646, 2001 5. Heald RJ, Husband EM, Ryall RDH: The mesorectum in rectal cancer the clue to pelvic recurrence? Br J Surg 69: 613-616, 1982[Medline] 6. MacFarlane JK, Ryall RD, Heald RJ: Mesorectal excision for rectal cancer. Lancet 341: 457-460, 1993[CrossRef][Medline] 7. Enker WE, Thaler HT, Cranor ML, et al: Total mesorectal excision in the operative treatment of carcinoma of the rectum. J Am Coll Surg 181: 335-346, 1995[Medline] 8. Aitken RJ: Mesorectal excision for rectal cancer. Br J Surg 83: 214-216, 1996[CrossRef][Medline] 9. Quirke P, Durdey P, Dixon MF, et al: Local recurrence of rectal adenocarcinoma due to inadequate surgical resection: Histopathological study of lateral tumour spread and surgical excision. Lancet 2: 996-999, 1986[CrossRef][Medline]
10.
Tepper JE, O’Connell MJ, Niedzwiecki D, et al: Impact of number of lymph nodes retrieved on outcome in patients with rectal cancer. J Clin Oncol 19: 157-163, 2001 11. Comptom CC: Updated protocol for the examination of specimens from patients with carcinomas of the colon and rectum, excluding carcinoid tumors, lymphomas, sarcomas, and tumors of the vermiform appendix. Arch Pathol Lab Med 124: 1016-1025, 2000[Medline]
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Copyright © 2002 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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5 cm from the anal verge had complete mesorectal excision, whereas 67% of patients with tumors at a distance greater had 10 cm from the anal verge had complete mesorectal excision. More disturbing is the fact that in only 34% of the patients who underwent an abdominoperineal resection, in which a complete TME is expected, was there a complete mesorectal excision. 
