Microscopic spread of low rectal cancer in regions of mesorectum: pathologic assessment with whole-mount sections.
ABSTRACT To assess the microscopic spread of low rectal cancer in mesorectum regions to provide pathological evidence for the necessity of total mesorectal excision (TME).
A total of 62 patients with low rectal cancer underwent low anterior resection and TME, surgical specimens were sliced transversely on 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 metastatic foci were investigated microscopically on the sections for the metastatic mesorectal regions, frequency, types, involvement of lymphatic vessels and correlation with the original rectal cancer.
Microscopic spread of the tumor in mesorectum and ORM was observed in 38.7% (24/62) and 25.8% (16/62) of the patients, respectively. Circumferential resection margin (CRM) with involvement of 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. Most (20/24) of the patients with microscopic metastasis in mesorectum were in Dukes C stage.
Results of the present study support that complete excision of the mesorectum without destruction of the ORM is essential for surgical management of low rectal cancer, an optimal DMR clearance resection margin should be no less than 4 cm, further pathologic assessment of the regions in extramesorectum in the pelvis is needed.
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ABSTRACT: Although tumor deposits have been associated with poor prognosis in colorectal carcinoma, the prevalence and clinical significance of tumor deposits in rectal adenocarcinoma following neoadjuvant chemoradiation are relatively unexplored. The aims of this study are to assess the clinical significance of tumor deposits in rectal adenocarcinoma patients, including those receiving neoadjuvant therapy. Pathology slides and medical records from 205 consecutive patients who underwent resection for rectal adenocarcinoma between 1990 and 2010 at a single tertiary care center were reviewed. Patients with tumor deposits had higher tumor grade (P=0.006) and worse tumor stage (P<0.001) at presentation than patients without tumor deposits. Among 110 patients who underwent neoadjuvant chemoradiation, tumor deposits were associated with higher rates of lymph node involvement (P=0.035) and distant metastases (P=0.006), and decreased survival (P=0.027). These patients had a trend toward lower treatment response scores (P=0.285) and higher local recurrence (P=0.092). Of 52 patients with tumor deposits, those who underwent neoadjuvant chemoradiation had significantly worse pretreatment stage by endoscopic ultrasound (P<0.001) but interestingly had significantly lower rates of lymphovascular invasion on resection (P<0.001) compared with those who had not received neoadjuvant chemoradiation. Despite treatment with neoadjuvant chemoradiation, tumor deposits were present in over one-fifth of rectal adenocarcinoma patients. Overall, the outcome of patients with tumor deposits in treated and untreated patients were similar, however the association of tumor deposits with deeply invasive tumors and less tumor regression when comparing with treated patients without tumor deposits raises the possibility that these tumors could have a more aggressive biology, possibly explaining the association of tumor deposits with higher rates of recurrence and lower survival after neoadjuvant chemoradiation. Overall, tumor deposits appear to be a poor prognostic marker among rectal adenocarcinoma patients following neoadjuvant chemoradiation and may identify a subset of patients who require aggressive adjuvant therapy to prevent recurrence.Modern Pathology advance online publication, 17 January 2014; doi:10.1038/modpathol.2013.239.Modern Pathology 01/2014; · 5.25 Impact Factor
- Journal of The Korean Surgical Society - J KOREAN SURG SOC. 01/2010; 78(5).
Article: Pathology of Rectal Cancer[Show abstract] [Hide abstract]
ABSTRACT: Treatment of rectal cancer requires an interdisciplinary approach, with imaging techniques and morphological examination playing important roles. The pathologist is involved in several steps of diagnostics and treatment planning for patients with rectal tumors. Starting with the preoperative biopsy, the pathologist confirms the diagnosis of cancer and estimates the biological behavior of the tumor by classification and grading. Intraoperative diagnostics ensure the completeness of resection and postoperative examinations provide final histopathological and pTNM-classification. Additionally, information about the therapeutic response to neoadjuvant strategies is provided by the assessment of tumor regression. By including molecular pathological methods, the pathologist can evaluate predictive markers (e.g., KRAS mutation analysis for antibody therapy) and contribute to the diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) by analyzing microsatellite instability. This chapter describes the role of pathology in the management of rectal cancer.
PO Box 2345, Beijing 100023, China World J Gastroenterol 2004;10(20):2949-2953
Fax: +86-10-85381893 World Journal of Gastroenterology
E-mail: email@example.com www.wjgnet.com Copyright © 2004 by The WJG Press ISSN 1007-9327
• COLORECTAL CANCER •
Microscopic spread of low rectal cancer in regions of mesorectum:
Pathologic assessment with whole-mount sections
Zhao Wang, Zong-Guang Zhou, Cun Wang, Gao-Ping Zhao, You-Dai Chen, Hong-Kai Gao, Xue-Lian Zheng, Rong Wang,
Dai-Yun Chen, Wei-Ping Liu
Zhao Wang, Zong-Guang Zhou, Cun Wang, Gao-Ping Zhao, You-
Dai Chen, Hong-Kai Gao, Xue-Lian Zheng, Rong Wang,
Department of Gastroenterology Surgery and Institution of Digestive
Surgery, West China Hospital, Sichuan University, Chengdu 610041,
Sichuan Province, China
Dai-Yun Chen, Wei-Ping Liu, Department of Pathology, West China
Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Supported by the Key Project of National Outstanding Youth
Foundation of China, No. 39925032 and National Natural Science
Foundation of China, No. 30271283
Correspondence to: Dr. Zong-Guang Zhou, Department of
Gastroenterology Surgery and Institute of Digestive Surgery, West
China Hospital, Sichuan University, Chengdu 610041, Sichuan
Province, China. firstname.lastname@example.org
Telephone: +86-28-85422525 Fax: +86-28-85422484
Received: 2004-02-02 Accepted: 2004-02-18
AIM: To assess the microscopic spread of low rectal cancer
in mesorectum regions to provide pathological evidence
for the necessity of total mesorectal excision (TME).
METHODS: A total of 62 patients with low rectal cancer
underwent low anterior resection and TME, surgical specimens
were sliced transversely on 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 metastatic foci were investigated
microscopically on the sections for the metastatic mesorectal
regions, frequency, types, involvement of lymphatic vessels
and correlation with the original rectal cancer.
RESULTS: Microscopic spread of the tumor in mesorectum
and ORM was observed in 38.7% (24/62) and 25.8% (16/62)
of the patients, respectively. Circumferential resection
margin (CRM) with involvement of 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.
Most (20/24) of the patients with microscopic metastasis
in mesorectum were in Dukes C stage.
CONCLUSION: Results of the present study support that
complete excision of the mesorectum without destruction
of the ORM is essential for surgical management of low
rectal cancer, an optimal DMR clearance resection margin
should be no less than 4 cm, further pathologic assessment
of the regions in extramesorectum in the pelvis is needed.
Wang Z, Zhou ZG, Wang C, Zhao GP, Chen YD, Gao HK,
Zheng XL, Wang R, Chen DY, Liu WP. Microscopic spread of
low rectal cancer in regions of mesorectum: Pathologic
assessment with whole-mount sections. World J Gastroenterol
2004; 10(20): 2949-2953
Local tumor recurrence after surgical resection of rectal cancer
remains a major problem. Since Heald et al. first reported
evidence of isolated tumor deposits in the mesorectum, more
authors have demonstrated that residual foci of the tumor within
pelvis resulting from inadequate excision of the mesorectum
were the cause of such recurrence[2,3]. Further studies revealed
that remnant of microscopic tumor nodules in the mesorectum,
which cannot easily be detected by imaging preoperatively or
by palpation intraoperatively, other than large nodules,
contributes to most of local failures[4,5].
Comparison of clinical outcomes between conventional
surgery[6,7] and total mesorectal excision (TME)[1,8] 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, investigations on discrete
tumor nodules spread in this region are rare. A comprehensive
assessment of ORM in patients with low rectal cancer may
provide further pathological evidence for supporting the TME
Although TME has been extensively employed as a standard
procedure for surgical treatment of patients with low rectal
cancer in western countries, conventional resection has been
dominated in China due to little pathological information
standing for TME. The present study investigated the regional
spread of microscopic tumor nodules in mesorectum using
MATERIALS AND METHODS
Sixty-two consecutive patients with biopsy-proven adenocarcinoma
of the rectum underwent TME at the Division of Gastroenterology
Surgery of Affiliated West China Hospital of Sichuan University
between November 2001 and June 2002, and specimens were
examined prospectively by the same pathologist (Chen DY).
Patients (30 males) had a mean age of 58 years (range, 21-78).
Lesions were classified as upper or low rectal cancers based on
the location of peritoneal reflection, and all diseases from our
series were categorized as low rectal cancers with sigmoidoscopy
preoperatively. Thirty-two patients had the lower board of
primary tumors within 5 cm of anal verge, and another 30 patients
had the lower board located not farther than 10 cm from anal
verge and above the level of 5 cm from anal verge. None of the
patients received any preoperative adjuvant therapy.
All patients were operated on by the same chief surgeon (Professor.
Zhou ZG) and two assistants according to TME principles.
The rectum and mesorectum were mobilized as a package
enveloped within the fascia properia with the preservation of
autonomic nerves. Under direct vision, electrocautery was used
to divide the rectosacral ligament posterior, the peritoneum
posterior to the seminal vesicle in the males and the peritoneal
reflection in Douglas’ pouch in the females anteriorly, lateral
ligaments medial to the pelvic plexus laterally. Sharp dissection
was continued down to the pelvic floor in front of Denonvilliers’
fascia anteriorly and along the fascia properia posteriorly.
Eventually, over 2 cm of distal clearance margin of rectal wall
and over 4 cm of mesorectum were attained by transecting the
rectum without stretching the bowel wall.
Each specimen was straightened without stretching and pinned
to a cork board, different from Quirke’s method. The specimens
were not opened longitudinally along the antimesenteric border,
and fixed in 40 g/L buffered formaldehyde for 48 h. Serial
longitudinal tissue blocks were cut at 5 mm intervals from the
distal portion. Each block, consisting of the full thickness of
the rectal wall with the mesorectum, was fixed in 40 g/L buffered
formaldehyde for another 48 h, and then embedded in paraffin.
Whole-mount sections of the bowel wall and mesorectum were
sliced transversely on the embedded tissue blocks in 4 µm at
2.5 mm intervals, stained with hematoxylin and eosin (HE), and
examined for discrete tumor nodules microscopically (Figure 1).
Circumferential resection margin (CRM) involvement was
assessed in the conventional manner.
The following pathological parameters were used for analysis,
namely Dukes stage, differentiation grade, presence of microscopic
tumor nodules, local metastasis of lymph nodes, outer region
of mesorectum (ORM), distal mesorectum (DMR), CRM
1 mm, or clear >1 mm), and distant metastases.
Microscopic metastatic nodules of rectal cancer were defined
as tumor nodules
1 mm in diameter, which could not be detected
either preoperatively or intraoperatively. Large metastatic
nodules of rectal cancer were defined as tumor nodules >5 mm
in diameter, most of which could be easily detected by palpation
during operation. The mesorectum on the transverse whole-
mount section was divided into three regions (Figure 2).
Discrete tumor nodule spread in the mesorectum 1 mm or
less away from the outermost board of CRM was recorded as
involvement of CRM, and discrete tumor nodule spread in the
mesorectum blow the lowest board of primary tumor was defined
as involvement of DMR.
Figure 1 Illustration for regions of mesorectum.
Figure 2 Transverse whole-mount sections of the specimen,
HE staining, macroscopic view.
The clinicopathologic characteristics of the patients are summarized
in Table 1. All the 62 patients underwent low anterior resection.
In 52 patients (83.9%) the operation was potentially curative,
while residual tumors in 2 patients (3.3%) were noticed to remain
in pelvis on operation and distant metastases were observed in
8 patients (12.9%).
Table 1 Clinicopathologic characteristics of the 62 patients
Age (yr, range, mean)
Sex (No. of patients)
Dukes stage (No. of patients)
Differentiation grade (No. of patients)
Distance of the primary tumor from anal verge
(No. of patients)
Diameter of the primary tumor (No. of patients)
M icroscopic spread types and involvement of mesorectum
Four types of microscopic spread of the tumor were observed
in mesorectum: discrete microscopic tumor nodules, blood
vessel invasion, lymphatic vessel invasion and perineural
invasion (Figure 3). Microscopic spread in mesorectum was
observed in 38.7% (24 of 62) of the patients (Table 2).
Table 2 Mesorectal regions with involvement of discrete tumor nodules (%)
Involved mesorectal regions
MR ORM MRM IRM DMR CRM
Tumor nodules58.1 (36/ 62) 45.2 (28/ 62)35.5 (22/ 62) 41.9 (26/ 62)6.5 (4/ 62) 6.5 (4/ 62)
Microscopic tumor nodules38.7 (24/ 62) 25.8 (16/ 62)25.8 (16/ 62) 29.0 (18/ 62)6.5 (4/ 62) 6.5 (4/ 62)
MR: mesorectum; ORM: outer region of mesorectum; MRM: middle region of mesorectum; IRM: inner region of mesorectum;
DMR: distal mesorectum; CRM: circumferential resection margin.
0 1 cm 2 3 4 5 6
Outer region of
Middle region of
Inner region of
2950 ISSN 1007-9327 CN 14-1219/ R World J Gastroenterol October 15, 2004 Volume 10 Number 20
M icroscopic spread of the tumor in outer region of mesorectum
Microscopic spread in ORM (Figure 4) occurred in 25.8% (16 of
62) of the patients (Table 2).
M icroscopic spread of the tum or in circum ferential resection m argin
Four of 36 patients with tumor involvement of mesorectum and
2 of the 52 patients having potentially curative resections had
microscopic spread in CRM.
Table 3 Mesorectal regional discrete microscopic tumor nod-
ules involving lymph nodes or lymphatic vessels
Involvement of MR Involvement of ORM
L type (No. of patients)
NL type (No. of patients)
MR: mesorectum; ORM: outer region of mesorectum; L type:
involving lymph nodes or lymphatic vessel; NL type: with-
out involving lymph nodes or lymphatic vessels.
Microscopic spread of the tumor in distal mesorectum
DMR with involvement of microscopic tumor nodules was
observed in 4 patients. The utmost spread was 3.0 cm or less
from the low edge of primary carcinoma. The most extensive
distal infiltration was seen in two cases of Dukes stage C.
Table 4 Correlation between mesorectal microscopic spread
and primary tumors
Primary tumor Spread in MR Spread in ORM
(No. of patients) (No. of patients)
high/ medium/ low
A / B/ C/ D
From anal verge:
5 cm/ >5 cm
10/ 14 8/ 8
0/ 10/ 14 0/ 8/ 8
0/ 2/ 20/ 2 0/ 2/ 12/ 2
12/ 12 8/ 8
MR: mesorectum; ORM: outer region of mesorectum.
M icroscopic spread of the tumor in mesorectal lymph nodes or
Microscopic spread nodules without involvement of lymph nodes
or lymphatic vessels in mesorectum were observed in 18 patients,
and such a spread in ORM was found in 13 patients (Table 3).
Correlation between regional mesorectal microscopic spread
and primary tumors
Most patients (20 of 24) with mesorectal microscopic spread in
Wang Z et al. Microscopic spread in regions of mesorectum 2951
Figure 3 Spread types of microscopic tumor nodules (
B: Blood vessel invasion; C: Lymphatic vessel invasion; D: Perineural invasion.
) in the mesorectum, HE, ×100. A: Discrete microscopic tumor nodules;
Figure 4 Microscopic tumor nodule spread (
) in outer region of the mesorectum (ORM) (4a), CRM (4b) and DMR(4c) , HE, ×100.
MR and 12 of 16 microscopic spreads in ORM were Dukes C
stage (Table 4).
Correlation between microscopic tumor nodules and large tumor
Microscopic tumor nodules coexisting with large tumor nodules
were observed in 14 of 24 (58.3%) patients with microscopic
spread in mesorectum.
Whole-mount sections were used to facilitate the precise and
effective assessment of rectal cancer, especially in mesorectal
regional spread of discontinuous microscopic tumor nodules.
All whole-mount sections showed that whole morphological
features of the surgical specimen enclosing the primary tumor,
bowel wall and the mesorectum, could be directly observed
with naked eyes and by microscopy, which enabled the
investigators to obtain valuable pathological outcomes on rectal
The present study showed the incidence of discrete
microscopic tumor nodules was 38.7% (24 of 62) of patients in
mesorectum and 25.8% (16 of 62) of patients in ORM. The high
frequency of microscopic tumor nodules in mesorectum
(especial ORM) highlighted the importance of complete excision
of mesorectum with fascia propria circumferentially intact for
low rectal cancer. Disturbance of ORM during operation would
predispose local recurrence because the undetected microscopic
foci in the mesorectum, especially in ORM were easily left behind
in pelvis[4,12,13]. Frequency of CRM involvement after conventional
resection was reported up to 27%[2,11,14,15], compared with 6.5%
after TME[16,17], which is consistent with our findings. The
decrease of CRM involvement rates after TME justified the
theory: the frequency of microscopic spread in ORM could be
very high, and destruction of ORM which often occurred in
conventional resection, could easily lead to positive CRM.
Distal mesorectal spread can be evaluated pathologically
after TME, after standard resection of the rectal cancer, the
DMR remained inside pelvis. Frequency of discrete tumor
cancer spread 3 cm or more from the primary lesions in DMR
varied from 0 to 10% of the cases[4,17,19-22], and discontinuous
spread in DMR could be found even up to 5 cm beyond the
lower margin of the primary tumor[1,6], some patients with DMR
spread had poor prognosis[21-23]. The present study showed
that four cases with tumor involvement of DMR had the spread
within 3 cm of primary mural tumors, with a maximum of 3.0 cm.
Therefore, we support a safe DMR resection margin of no less
than 4 cm for lower rectal cancer, and consider that failure to
adequate excision of the involved DRM would risk in leaving
behind residual microscopic cancer foci in a significant
percentage of patients. The most common pattern of pelvic
recurrence is extramural diseases emanating from the sacral
hollow or pelvic floor, which is entirely compatible with this
hypothesis. But others argued that pathological evidence
of DMR spread in itself did not necessarily justify total removal
of DMR in all cases because the local recurrence rate and survival
rate were not improved significantly even after TME[4,17].
Cawthorn reported that mesorectal involvement of large
tumor nodules (greater than 4 mm) was associated with
significant poorer prognosis than that of small ones (less than
4 mm). However, the author cautioned that the poor prognosis
might result from residual microscopic tumor nodules, which
coexist with large nodules and can easily be overlooked and
left behind during operation. Ueno et al. demonstrated that
large tumor nodules and microscopic tumor nodules correlated
closely, and that large tumor nodules had a predicting value for
existence of microscopic tumor nodules. The present study
showed that 58.3% (14/24) patients with microscopic tumor
foci involvement of the mesorectum had large tumor nodules
(greater than 5 mm) in the mesorectum, which was lower than
that reported by Ueno et al.
Kapiteijn et al. recently reported that standardized TME in
combination with preoperative radiotherapy could significantly
decrease the local recurrence rate in patients with rectal cancer,
though its benefits in survival were not demonstrated because
of a relatively short time of follow-up. Other authors also
concluded that preoperative radiotherapy could improve the
prognosis of patients with rectal cancer. In our series, no
patients were treated with adjuvant therapy due to the high
frequency of postoperative complications and its controversial
impact on prognosis.
Extended lateral dissection beyond the extent of TME has
been widely accepted in Japan as the improvement in survival
rates was reported[28,29], but some argued that it had a limited
advantage in prognosis and the functional problems were
considerable[30,31]. Microscopic tumor nodule involvement of
CRM after TME in our series suggested that a proportion of
the patients had microscopic tumor spread in the extramesorectal
regions in the pelvis. Further comprehensive pathological
assessment of the extramesorectum is required to evaluate the
curative value of TME in rectal cancer.
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Wang Z et al. Microscopic spread in regions of mesorectum 2953