Total mesorectal excision is a standard technique for rectal cancer. The whole-mount section can encompass the entire specimen, so it is a more appropriate for measuring circumferential margin than conventional section. We analyzed the clinical characteristics and prognosis based on lateral margins (LMs) measured by whole-mount sections.
Medical records of patients who were operated on for T3 rectal cancer from 2005 to 2015 were reviewed retrospectively. A total of 154 patients were included. The slides of the whole-mount sections were re-reviewed by a single pathologist.
We divided the groups according to the length of the LM (1 mm, 1.5 mm, and 2 mm). There was significantly frequent lymphovascular invasion and N state was higher when LM was short in all groups. There were more micrometastasis in group LM ≤1 mm (53.3% ≤1 mm vs. 26.6% >1 mm, P=0.039), but not in other groups. When looking at local recurrence alone, there was no significant difference between groups, but the 5-year local recurrence-free survival was significantly worse when LM ≤2 mm (P=0.050). In each analysis based on 1 mm and 1.5 mm, overall survival was worse when LM was short. In all groups, disease-specific survival was worse when LM was short.
As previously known, securing a margin less than 1 mm negatively affects the prognosis. When LM was divided by 1.5 mm, there was a significant difference in overall survival. There was a significant difference in disease-specific survival when divided by 2 mm in T3 rectal cancer. However, further studies with more patients are necessary to secure the result.
Local recurrence after radical resection of rectal cancer has a significant effect on survival. Inadequate resection margin is one cause of local recurrence. Quirke et al. [
In the field of pathologic examination, several methods have been studied to measure accurate lateral margins (LMs) and discover micrometastases, which are the risk factors for rectal cancer recurrence. Quirke et al. [
Patients who had radical surgery for rectal cancer between January 2005 and December 2015 in the National Health Insurance Service Ilsan Hospital in Korea were included. Among these patients, 297 patients whose surgical specimen was diagnosed by a whole-mount section were included. Patients with synchronous or metachronous cancer were excluded, as were patients who underwent neoadjuvant chemoradiotherapy. We included patients with perirectal tissue invasion (T3), which is meaningful for measuring the LM in the mesorectum. Finally, 154 patients were included in this study. Their medical records were analyzed retrospectively. We collected their basic characteristics, including age and sex, laboratory results, and radiologic results.
Whole-mount sections were prepared using the following method. The postoperative specimen was delivered to the Department of Pathology without opening the rectum. This was fixed into 10% formalin for 24–48 hours. The specimen was cut in a direction perpendicular to the long axis at 5-mm intervals. After additional fixation with 10% formalin, the slide including the whole-mount section was prepared. For this study, we reinvestigated tumor differentiation, depth of invasion, lymphovascular invasion (LVI), perineural invasion (PNI), and micrometastasis, which is defined as a nodule composed only of tumor cells without normal vascular or lymphatic structure in the mesorectum. When there was micrometastasis in the mesorectum, the shortest length from the micrometastasis or main tumor was measured as the LM.
We performed statistical analysis using IBM SPSS Statistics ver. 23.0 (IBM Co., Armonk, NY, USA). Quantitative outcomes are presented as mean and standard deviation, and categorical results as frequencies and percentages. Chi-square and Fisher exact tests were used to compare categorical variables. Independent t-tests were used to compare continuous variables. To identify risk factors, we used simple and multiple regression analyses. Kaplan-Meier analysis was used to identify the survival rate. A value of P<0.05 was considered statistically significant. The study’s protocol was reviewed and approved by the Institutional Review Board of the National Health Insurance Service Hospital (IRB No. 2016-04-026) and informed consent was waived.
Overall, 154 patients were retrospectively enrolled in this study. Patient demographics and clinical features are presented in
We divided the groups according to the length of the LM. Starting from the previously known significant 1 mm LM, the groups were divided into groups up to 2 mm at intervals of 0.5 mm. There was no significant difference in clinical variables except for sex when the groups were divided into groups of LM by 1 mm. More male patients were included in the group with less than 1 mm of LM (P=0.013). Some of the pathologic variables showed significant differences. There was significantly frequent LVI in the LM group <1 mm (P=0.039). There was no significant difference in PNI. More micrometastatic nodules were identified in the LM <1 mm group (P=0.039). There was no significant difference in TNM stage between the 2 groups (P=0.167), but a significant difference in N stage was seen. More lymph-node metastases were identified in the LM <1 mm group (P=0.027). (
We compared the local recurrence according to LM length. There was no significant difference in local recurrence compared by LM of 1 mm, 1.5 mm, or 2 mm (
We analyzed overall survival (OS) and disease-specific survival (DSS) according to each group (
Many studies have shown that sufficient circumferential margin in rectal cancer is important for prognosis such as recurrence and distant metastasis [
The rate of patients with positive LMs is reported to be from 1% to 28% [
As in previous studies, we found that having a lateral resection margin of less than 1 mm was associated with a negative effect on patient survival rate. It is well known that an LM less than 1 mm adversely affects local recurrence, distant metastasis, and survival [
Many studies have mentioned the relationship between small LM and more local recurrence. We included only 154 patients in this study. There were only 9 patients (5.84%) with local recurrence after radical operation. Our local recurrence rates are not significantly different from those in other studies. However, the small number of local recurrent patients is a limitation of this study. For this reason, it was difficult to provide reliable results for LM and local recurrence. There are limitations with respect to accepting the results of this study in general, because the number of patients is not sufficient. Further studies with more patients may yield better results.
The whole-mount section has the advantage that the whole rectal cancer specimen can be observed without distortion of its structure. Therefore, this method can provide a more extensive and precise pathologic result. However, because of the difficulties associated with this method, such as the time, cost, and special equipment required to produce whole-mount slides, it is not widely used in clinical practice. In this study, we analyzed clinicopathologic features compared among groups with LMs measured by whole-mount sections. Only T3 patients were included to focus more on the meaning of the whole-mount section in advanced rectal cancer. Previously, LM was discussed with only “1 mm.” However, in this study, to extend the range to 1.5 mm and 2 mm was meaningful. The “2 mm” LM also showed significant differences in prognosis. Therefore, it will be necessary to secure as much of the LM as possible in rectal cancer pathological specimens.
No potential conflict of interest to this article is reported.
Overall survival (OS) and disease-specific survival (DSS) by groups followed by length of lateral margin (LM).
Patient clinicopathologic characteristics
Features | Value |
---|---|
Age (yr) | 63.40 ± 11.98 |
Sex | |
Male | 99 (64.3) |
Female | 55 (35.7) |
CEA (ng/mL) (n = 144) | 12.13 ± 34.53 |
Operation method | |
LAR | 116 (75.3) |
LAR with intersphincteric resection | 26 (16.9) |
Abdominoperineal resection | 11 (7.1) |
Differentiation | |
Well differentiated | 34 (22.1) |
Moderately differentiated | 114 (74.0) |
Poorly differentiated | 4 (2.6) |
Mucinous | 2 (1.3) |
Tumor size (cm) | 5.72 ± 1.54 |
Lateral margin (mm) | 8.41 ± 6.56 |
Lymphovascular invasion (n = 153) | 106 (68.8) |
Perineural invasion (n = 152) | 73 (47.4) |
Values are presented as mean±standard deviation or number (%).
CEA, carcinoembryonic antigen; LAR, low anterior resection.
Comparison of clinicopathologic features followed by length of lateral margin by 1 mm, 1.5 mm, and 2 mm
Variable | Lateral margin |
|||||||||
---|---|---|---|---|---|---|---|---|---|---|
≤1 mm (n=15) | >1 mm (n=139) | P-value | ≤1.5 mm (n=16) | >1.5 mm (n=138) | P-value | ≤2 mm (n=25) | >2 mm (n=129) | P-value | ||
Age (yr) | ||||||||||
Male sex | 14 (93.3) | 85 (61.2) | 0.013 | 14 (87.5) | 85 (61.6) | 0.041 | 19 (76.0) | 80 (62.0) | 0.182 | |
CEA (ng/mL) (n = 144) | 21.55 ± 36.58 | 11.20 ± 34.33 | 0.304 | 20.54 ± 35.35 | 11.23 ± 34.46 | 0.340 | 14.90 ± 28.38 | 11.61 ± 35.66 | 0.676 | |
Preoperative clinical stage (TNM) | 0.182 | 0.186 | 0.205 | |||||||
I | 0 (0) | 4 (2.9) | 0 (0) | 4 (2.9) | 0 (0) | 4 (3.1) | ||||
II | 1 (6.7) | 22 (15.8) | 1 (6.3) | 22 (15.9) | 3 (12.0) | 20 (15.5) | ||||
III | 11 (73.3) | 96 (69.1) | 12 (75.0) | 95 (68.8) | 17 (68.0) | 90 (69.8) | ||||
IV | 3 (20) | 17 (12.2) | 3 (18.8) | 17 (12.3) | 5 (20) | 15 (11.6) | ||||
Operation method | 0.524 | 0.379 | 0.325 | |||||||
LAR | 10 (71.4) | 106 (76.3) | 10 (66.7) | 106 (76.8) | 16 (66.7) | 100 (77.5) | ||||
LAR with intersphincteric resection | 2 (14.3) | 24 (17.3) | 3 (20) | 23 (16.7) | 5 (20.8) | 21 (16.3) | ||||
Abdominoperineal resection | 2 (14.3) | 9 (6.5) | 2 (13.3) | 9 (6.5) | 2 (12.5) | 8 (6.2) | ||||
Differentiation | 0.505 | 0.531 | 0.809 | |||||||
Well differentiated | 4 (26.7) | 30 (21.6) | 4 (25.0) | 30 (21.7) | 6 (24.0) | 28 (21.7) | ||||
Moderately differentiated | 10 (66.7) | 104 (74.8) | 11 (68.8) | 103 (74.6) | 18 (72.0) | 96 (74.4) | ||||
Poorly differentiated | 1 (6.7) | 3 (2.2) | 1 (6.3) | 3 (2.2) | 1 (4.0) | 3 (2.3) | ||||
Mucinous | 0 (0) | 2 (1.4) | 0 (0) | 2 (1.4) | 0 (0) | 2 (1.6) | ||||
Tumor size (cm) | 6.15 ± 1.76 | 5.67 ± 1.51 | 0.259 | 6.15 ± 1.70 | 5.67 ± 1.52 | 0.238 | 5.89 ± 1.69 | 5.69 ± 1.51 | 0.551 | |
Lymphovascular invasion (n = 153) | 14 (93.3) | 82 (66.7) | 0.039 | 15 (93.8) | 91 (66.4) | 0.024 | 22 (88.0) | 84 (65.6) | 0.027 | |
Perineural invasion (n = 152) | 9 (60) | 64 (46.7) | 0.328 | 9 (56.3) | 64 (47.1) | 0.486 | 17 (68.0) | 56 (44.1) | 0.029 | |
Micrometastasis (+) | 8 (53.3) | 37 (26.6) | 0.039 | 8 (50) | 37 (26.8) | 0.079 | 10 (40) | 35 (27.1) | 0.195 | |
N stage | 0.027 | 0.010 | 0.047 | |||||||
N0 | 2 (13.3) | 62 (44.6) | 2 (12.5) | 62 (44.9) | 6 (24.0) | 58 (45.0) | ||||
N1 | 4 (26.7) | 37 (26.6) | 4 (25.0) | 37 (26.8) | 6 (24.0) | 35 (27.1) | ||||
N2 | 9 (60) | 40 (28.8) | 10 (62.5) | 39 (28.3) | 13 (26.5) | 36 (27.9) | ||||
TNM stage | 0.167 | 0.100 | 0.054 | |||||||
I | 0 (0) | 1 (0.7) | 0 (0) | 1 (0.7) | 0 (0) | 1 (0.8) | ||||
II | 2 (13.3) | 56 (40.3) | 2 (12.5) | 56 (40.6) | 4 (16.0) | 54 (41.9) | ||||
III | 10 (66.7) | 64 (46.0) | 11 (68.8) | 63 (45.7) | 16 (64.0) | 58 (45.0) | ||||
IV | 3 (20) | 18 (12.9) | 3 (18.8) | 18 (13.0) | 5 (20) | 16 (12.4) | ||||
Adjuvant therapy, yes | 13 (86.7) | 104 (74.8) | 0.524 | 14 (87.5) | 103 (74.6) | 0.360 | 22 (88.0) | 95 (73.6) | 0.199 |
Values are presented as mean±standard deviation or number (%).
CEA, carcinoembryonic antigen; LAR, low anterior resection.
Comparison of local recurrence according to lateral margin
Lateral margin |
|||||||||
---|---|---|---|---|---|---|---|---|---|
≤ 1 mm (n = 15) | > 1 mm (n = 139) | P-value | ≤ 1.5 mm (n=16) | > 1.5 mm (n = 138) | P-value | ≤ 2 mm (n = 25) | > 2 mm (n=129) | P-value | |
No recurrence | 14 (93.3) | 131 (94.2) | 1.000 | 15 (93.8) | 130 (94.2) | 1.000 | 22 (88.0) | 123 (95.3) | 0.163 |
Local recurrence | 1 (6.7) | 8 (5.8) | - | 1 (6.3) | 8 (5.8) | - | 3 (12.0) | 6 (4.7) | - |
5-Year local recurrence-free survival | 83.3 | 92.9 | 0.533 | 85.7 | 92.8 | 0.676 | 82.5 | 93.6 | 0.050 |
Values are presented as number (%).