Microscopic Spread Of Rectal Cancer In Regions Of Mesorectum And Its Curative Surgical Management

Background and Objective: Local tumor recurrence after surgical resection of rectal cancer remains a major problem. Many authors reported that residual foci of the tumor within pelvis resulting from inadequate excision of the mesorectum were the cause of such recurrence. Further studies revealed that remnant of microscopic tumor nodules in the mesorectum contributes to the most of local failures. Comparison of clinical outcomes between conventional surgery and total mesorectal excision (TME) showed that a proportion of microscopic tumor nodules of rectal cancer causing local pelvic collapse might settle in the outer region of mesorectum (ORM). Unfortunately, the investigation on discrete tumor nodules spread in such region is rare. Furthermore, though TME has been extensively employed as standard procedure for surgical treatment of patients with low rectal cancer in western countries, conventional resection has been dominatedin China due to little pathological information standing for TME. The present study investigated regional spread of the microscopic tumor nodules in mesorectum using whole-mount sections and tissue microarray to provide further pathological evidence for supporting the TME procedure.Methods: In 62 patients with low rectal cancer undergoing low anterior resection and total mesorectal excision, whole-mount sections of the entire operative specimen were prepared by transversely slicing the serial embedded blocks at 2.5 mm interval, and stained with hematoxylin and eosin (HE). The mesorectum on whole-mount sections was divided into three regions: outer region of mesorectum (ORM), middle region of mesorectum (MRM) and inner region of mesorectum (IRM). Microscopic tumor nodules were investigated microscopically on the sections for mesorectal regional spread, frequency, types, involvement of lymphatic system and correlation with the main tumor. The nodules considered disease free by HE stain were studied for the nature using a high-density tissue microarray by in situ hybridization (ISH) through detecting mRNAs of CEA and CK20 with non-radioactive biotin-tagged oligonucleotide probes. The analysis with tissue microarray also was combined with immunohistochemistry stain which was performed using an avidin-biotin complex method and monoclonal antibodies against CEA and CK20.Results: On whole-mount sections stained with HE, microscopic spread of the tumor in mesorectum and ORM were observed in 38.7 % (24 / 62) of the patients and in 25.8 % (16 / 62), respectively. Circumferential resection margin (CRM) involved by microscopic metastatic foci occurred in 6.5 % (4 /62) of the patients, and distal mesorectum (DMR) involved was 6.5 % (4 / 62) with the spread extent within 3 cm of low board of the main lesions. On tissue microarray sections analyzed with IHC and ISH, microscopic spread of the tumor in mesorectum and ORM were observed in 7 new patients and in 8, respectively. Circumferential resection margin (CRM) involved by microscopic tumor nodules occurred in 1 new patient, and there was no new patient with distal mesorectum (DMR) involved by microscopic tumor nodules.Consequently, utilizing whole-mount section technique in conjunction with tissue microarray analysis, the number of patients with microscopic spread of tumor in mesorectum and in ORM increased up to 31 (50.0%) and 24 (38.7%), respectively; CRM involvement increased up to 5 (8.1%); DMR involvement was still 4 (6.5%). Most (26 of 31) of the patients with microscopic spread in mesorectum were in Dukes C stage.Conclusions: Completely excising the mesorectum without violation of ORM is essential for surgical management of low rectal cancer due to high rate of microscopic spread in this region; present study support an optimal DMR resection margin of not less than 4 cm based on the pathological evidence of that DMR involvement by discontinuous spread can be found up to 3 cm beyond the lower margin of primary tumor; further detail pathologic assessment of the regions of extramesorectum in the pelvic cavity is needed because of a proportion of tumor positive CRM of TME specimen observed.