Study Of Mesorectal Spread And Micrometastasis For Patients With Rectal Cancer

[Background and Objective]Radical surgery remains the first choice of treatment in rectal cancer. As diagnostic assessment is performed more and more precisely and surgical techniques have been clearly improved within the last decade, the rate of curative resection and sphincter-saving procedure for rectal cancer has been significantly increased and mortality rate decreased. Following the studies of Heald, Quirke and colleagues, local recurrence is conceived to result from microscopically incomplete distal and radial resection. These microscopic tumor remnants, unlike large tumor nodules, could not easily be detected by preoperative image and intraoperative palpation. Moreover, the adoption of total mesorectum excision remarkably reduced local recurrence rate from 30-40% to 5-15%. This decrease is partly attributed to excision of the outer part of the mesorectum that was formerly left in the pelvis of patient by a conventional surgery. Yet most of the previous studies emphasized the overall spread of tumors in the whole mesorectum but different regions of mesorectum were not evaluated respectively. In this study, we first investigated the distribution of neoplastic foci within the mesorectum on large tissue slices. Secondly, examination of lymph node involvement andpossible micrometastasis was processed combining a tissue microarray technique. Therefore, the purpose is to provide colorectal surgeons with a regular pattern of tumor spread and metastasis in the mesorectum for a more radical local clearance of cancer. [Materials and Methods]Specimens from 62 consecutive patients with biopsy-proven adenocarcinoma of the rectum who underwent Total Mesorectal Excision (TME), from October 2001 to January 2002, were investigated. Efforts were made to make sure that the mesorectum was conformed to biological dimensions during fixation in buffered formalin. Serial transverse tissue blocks were cut at 5mm interval, consisting full thickness of the rectum with surrounding mesorectum. Thin sections of 4um thickness were mounted on large glass slides (15 6cm) and stained with hematoxylin-eosin. Histological examination included direct tumor infiltration, lymph node involvement, deposit of carcinoma in the mesorectum, as well as distal clearance margin and circumferential margin. We divided the mesorectum into 3 regions (i.e. left, right and rear regions) according to its observed shape on large slice. In each divided regions, we went further to separate them into 3 layers (i.e. outer, middle and inner layers) on the basis of their distance from the out limit of serosa. Therefore, we got nine areas and could locate each focus to one or more of them. Next, all the negative lymph nodes were noted and corresponding core biopsies were transferred to a recipient block utilizing tissue microarray technique. The ensuing paraffin array blocks were sliced and further analyzed by immunohistochemistry. [Results]Three hundred and forty-nine mesorectal neoplastic foci were examined from 37 specimens. Our data showed that 63 (18.1%), 171 (49%), 115 (33%) of the neoplastic foci were located in the inner, middle and outer layers ofmesorectum respectively. Concerning regions, the rate was 20.6% (72), 48.7% (170) and 30.7% (107) for left, rear and right regions respectively. Concerning position of primary tumor, ipsolateral neoplastic foci (38.5%) were significantly more than contralateral neoplstic foci (11.9%). Extramural distal spread was found in 8 of the 62 patients with the distance ranged from lcm to 3.5cm. Significant different occurrence rate of distal spread was observed in tumors of different TNM stages. Twenty-three specimens had circumferential margin involved. In them, 8 were observed to have real positive margin. Significant difference in CMI rate was obtained among malignancies of distinct differentiation (p<0.05), but not for location.Nine hundred and seventy-two lymph nodes were examined from specimens of 31 patients. In them, 128 were involved by tumor while the other 844 were diagnosed as negative ones. The average number of examined lymph node per specimen was 31.4. The metastasis rate of lymph nodes was related to the depth of tumor infiltration (r=0.558, p=0.001) and tumor differentiation (r=-0.426, p=0.017), but not to primary tumor location. No certain relationship between the occurrence of CMI and T stage, tumor location and differentiation was affirmed processed by logistic regression analysis. Altogether 9 of 31 patients (29.0 percent) from TNM I -IV stage were revealed to have occult tumor cells in the lymph node specimens. The difference was not significant concerning T stage, N status and differentiation. [Conclusion]?Large slice technique provides a holistic view of rectum with its surrounding mesentery, giving information about the pathologic characteristics of tumor as well as the distribution of neoplastic foci. ?More accurate and comprehensive study of regional lymphatic spread of rectal cancer was promoted by the combination of large tissue slice andnewly-developed tissue microarray technique. (3)TME procedure should be strictly followed because of outer scattering and lateral discrepancy for neoplastic foci distribution within the mesorectum. (4)A distal clearance margin of mesorectum of 4cm would be sufficient. ?Circumferential margin involvement and micrometastasis observed suggests the significance of preoperative and/or postoperative radiochemotherapy.