Gastrointestinal Imaging • Original Research

Jia et al.
MRI of Rectal Cancer

Gastrointestinal Imaging
Original Research

MRI for Restaging Locally Advanced

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Rectal Cancer: Detailed Analysis of

Discrepancies With the Pathologic
Reference Standard
Xiaoxuan Jia1 OBJECTIVE. The purpose of this study was to analyze causes of discrepancies between
Yinli Zhang2 restaging MRI and pathologic findings in the assessment of morphologic indicators of tumor
Yi Wang1 response in patients with rectal cancer who have undergone neoadjuvant treatment.
Caizhen Feng1 MATERIALS AND METHODS. MRI and pathologic data from 57 consecutively reg-
Danhua Shen2 istered patients who underwent neoadjuvant treatment and total mesorectal excision between
August 2015 and July 2018 were retrospectively analyzed. The sensitivity and specificity of
Yingjiang Ye 3
restaging MRI in determining tumor regression grade, T category, N category, circumferen-
Nan Hong1 tial resection margin, and extramural vascular invasion were calculated with pathologic re-
Jia X, Zhang Y, Wang Y, et al. sults as the reference standard. One-by-one comparisons between MRI and pathologic find-
ings were conducted to identify causes of discrepancies.
RESULTS. The sensitivity of MRI in determining tumor regression grades 3–5 was 77.1%;
T3 and T4 category, 100.0%; node-positive disease, 75.0%; circumferential resection margin,
87.5%; and extramural vascular invasion, 91.7%. The specificity values were 72.7%, 62.5%,
70.7%, 85.7%, and 64.4%. Overstaging was mainly caused by misinterpretation of fibrotic
areas as residual tumor. Inflammatory cell infiltration could appear as high signal intensity
in fibrotic areas on DW images, an appearance similar to that of residual tumor. Edematous
mucosa and submucosa adjacent to the tumor and muscularis propria could also be mistaken
for residual tumor because of their intermediate signal intensity on T2-weighted MR images.
CONCLUSION. MRI was prone to overstaging of disease. Discrepancies between MRI
and pathologic findings were mainly caused by misinterpretation of fibrosis. Inflammatory
cell infiltration, pure mucin, edematous mucosa and submucosa adjacent to the tumor, and
muscularis propria could also be misinterpreted as residual tumor.

Keywords: diagnostic accuracy, MRI, neoadjuvant

or patients with locally advanced MRI is the imaging modality most wide-

chemoradiotherapy, pathology, rectal cancer
doi.org/10.2214/AJR.19.21383
X. Jia and Y. Zhang contributed equally to this study.
Received March 3, 2019; accepted after revision
May 27, 2019.
1
Department of Radiology, Peking University People’s
Hospital, 11 Xizhimen S St, Xicheng District Beijing
100044, China. Address correspondence to Y. Wang
(wangyi@pkuph.edu.cn).
2
Department of Pathology, Peking University People’s
Hospital, Beijing, China.
3
Department of Gastrointestinal Surgery, Peking
University People’s Hospital, Beijing, China.
AJR 2019; 213:1081–1090
0361–803X/19/2135–1081
© American Roentgen Ray Society
F
rectal cancer, advances in surgi-
cal technique and the introduc-
tion of neoadjuvant chemoradio-
therapy (CRT) have markedly improved
locoregional control [1, 2]. For instance, pa-
tients with disease staged pT0–2 or pT0–T3a
and pN0, free circumferential resection mar-
gin (CRM), and absence of lymphovascular
invasion after neoadjuvant CRT may have an
improved prognosis [3–5]. In addition, the
pathologic tumor regression grade (TRG) sys-
tem, which is based on the proportion of re-
sidual tumor and fibrosis present after neoad-
juvant CRT, has value in predicting long-term
survival [4]. If a good pathologic response
(e.g., pathologic complete response [pCR])
could be accurately predicted with this system
before surgery is performed, nonoperative
treatment strategies could instead be used, po-
tentially allowing organ preservation [6].
ly used for primary staging and restaging of
disease after neoadjuvant CRT in patients
with rectal cancer. Because of the high reso-
lution of MRI, this modality is highly accu-
rate in the identification of T category, N cat-
egory, and CRM before neoadjuvant CRT [7,
8]. However, it is challenging for radiologists
to identify the presence and infiltration depth
of residual tumor with restaging MRI. Previ-
ous studies have shown that restaging MRI
has unfavorable accuracy for the detection of
comprehensive indicators of tumor response,
especially MRI TRG (mrTRG), posttreat-
ment T category (ymrT), and posttreatment
N category (ymrN) [9–11].
Use of DWI technique improves the sen-
sitivity of MRI for the identification of re-
sidual tumor [12]. However, pitfalls contin-
ue to exist with this technique. For instance,
after neoadjuvant CRT, tumor cells may

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 Jia et al.

Received preoperative
treatment
(n = 85)

No restaging MRI scan

(n = 21)
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pTRG 1–2 ypEMVI—

(n = 16) Restaging MRI scan (n = 29)
ymrTRG1–2 (n = 64) ymrEMVI–
(n = 23) (n = 30)
pTRG 3–5 ypEMVI+
(n = 7) Excision not performed (n = 4) (n = 1)
Palliative resection (n = 3)
pTRG 1–2 ypEMVI+
(n = 28) Evaluable restaging MRI (n = 11)
ymrTRG3–5 and pathologic analysis ymrEMVI+
(n = 34) (n = 57) (n = 27)
pTRG 3–5 ypEMVI—
(n = 6) (n = 16)

ymrT0–T2 ymrT3–T4 ymrN0 ymrN+ ymrCRM– ymrCRM+

(n = 10) (n = 47) (n = 33) (n = 24) (n = 43 (n = 14)

ypT0–T2 ypT3–T4 ypN0 ypN+ ypCRM– ypCRM+

(n = 10) (n = 41) (n =29) (n = 12) (n = 42) (n = 7)

ypT3–T4 ypT0–T2 ypN+ ypN0 ypCRM+ ypCRM–

(n = 0) (n = 6) (n = 4) (n = 12) (n = 1) (n = 7)

Fig. 1—Flowchart shows patient selection. TRG = tumor regression grade, p = pathologic, y = classification after multimodality treatment, mr = MRI, EMVI– and EMVI+ =
extramural vascular invasion absent and present, N+ = node-positive disease, CRM– and CRM+ = circumferential resection margin uninvolved and involved.

be partially or totally replaced by fibrosis
and mucin, and this mixed response cor-
responds to different signal intensities on
T2-weighted images. As such, difficulties in
differentiating residual tumor from fibrosis
have been reported [13], and the presence
of pure mucin pools may also be misinter-
preted as viable tumor [14]. Mixed signal
intensity on T2-weighted images or high
signal intensity on DW images may be seen
in patients with pCR, leading to overestima-
tion of residual tumor and underestimation
of complete response [15]. Identification of
the imaging features that lead to these mis-
interpretations could improve the accuracy
of tumor response assessment. Few studies,
however, have thoroughly compared MRI
and pathologic findings in terms of the eval-
uation of posttreatment indicators, such as
TRG, T category, N category, CRM, and ex-
tramural vascular invasion (EMVI).
In this study, we sought to compare restag-
ing MRI and pathologic findings in patients
with rectal cancer who had undergone neo-
adjuvant treatment. In this comparison, we
investigated causes of discrepancies between
MRI and pathologic findings in the detection
of comprehensive morphologic indicators of
tumor response.
Materials and Methods
The institutional review board approved this
retrospective study with a waiver of the require-
ment for informed consent, and all patient data
were anonymized before the information was as-
sessed. For this study, we retrospectively assessed
data on consecutively registered patients with rec-
tal cancer who underwent neoadjuvant treatment
at our institution between August 2015 and July
2018 (n = 85). Eligible patients were required to
have undergone a restaging MRI examination af-
ter completion of neoadjuvant treatment. Eligi-
ble patients were also required to have undergone
total mesorectal excision. The exclusion criteria
were as follows: not undergoing restaging MRI
because of contraindications or because restag-
ing CT was used instead (n = 21); total mesorectal
excision not performed, the watch and wait ap-
proach instead being chosen for management (n =
4); and palliative surgery performed (n  = 3, in-
cluding two patients who underwent proximal co-
lostomy without excision of the primary tumor
and one patient who underwent local excision of
the tumor without removal of locoregional lymph
node). The final study cohort consisted of 57 pa-
tients (42 men, 15 women; median age, 62 years;
range, 33–88 years) (Fig. 1). The median age of
the men was 60 years (range, 37–88 years) and
of the women was 66 years (range, 33–80 years).
The patient MRI and pathologic data are summa-
rized in Table 1. All patients enrolled were found
to have mrT3 or node-positive disease at baseline
MRI examinations.
Neoadjuvant CRT was used to treat 43 of the 57
study patients (75.4%). Treatment of these patients
consisted of 50 Gy over 25 fractions (2.0 Gy/d)
for radiotherapy and concurrent chemotherapy
with capecitabine alone. Neoadjuvant radiothera-
py alone was administered to six patients (10.5%),
and neoadjuvant chemotherapy alone (consisting
of capecitabine and oxaliplatin) was administered
to eight patients (14.0%).
All patients underwent total mesorectal ex-
cision 6–8 weeks after completing neoadjuvant
treatment (median, 6.4 weeks; interquartile range,
5.6–7.2 weeks). These procedures were performed
by surgeons with more than 15 years’ experience
in rectal cancer surgery. The evaluation of tumor
response by means of restaging MRI was conduct-
ed prospectively before surgery. The median time
between restaging MRI and surgery was 7 days

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 MRI of Rectal Cancer

TABLE 1: Summary of MRI and Pathologic Data covery fast spin-echo imaging (TR/TE, 3200/85;
FOV, 270 × 270 mm; slice thickness, 3 mm; gap,
Characteristic Baseline MRI Restaging MRI Pathologic Analysis
0.5 mm; matrix, 256 × 256); high-resolution oblique
Tumor location axial and coronal T2-weighted imaging perpendicu-
Low rectum 13 (22.8) 8 (14.0) lar and parallel to the long axis of the primary tumor
(TR/TE, 3200/85; FOV, 160 × 160 mm; slice thick-
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Middle to high rectum 36 (63.2) 49 (86.0)

ness, 3 mm; gap, 0.5 mm; matrix, 512 × 512); and
Data missing 8 (14.0) 0 (0.0) axial DWI (TR/TE, 3000/60; b values, 0 and 1000
T category s/mm2; slice thickness, 6 mm; gap, 0.5 mm; matrix,
T0 0 (0.0) 1 (1.8) 4 (7.0) 160 × 160).
T1 0 (0.0) 0 (0.0) 2 (3.5)
MRI Interpretation
T2 0 (0.0) 9 (15.7) 10 (17.5) Two board-certified gastrointestinal radiolo-
T3a 3 (5.3) 8 (14.0) 8 (14.0) gists with 6 and 5 years’ experience in the inter-
T3b 9 (15.8) 15 (26.3) 15 (26.3) pretation of rectal MRI reviewed all of the MR
images independently at a PACS workstation. A
T3c 20 (35.1) 12 (21.1) 9 (15.8)
third assessment was performed to reach consen-
T3d 5 (8.8) 1 (1.8) 1 (1.8) sus when the readers disagreed. The readers were
T4a 5 (8.8) 6 (10.5) 5 (8.8) blinded to patient information and histopathologic
T4b 7 (12.2) 5 (8.8) 3 (5.3) findings (except for the fact that all patients under-
went neoadjuvant treatment).
Data missing 8 (14.0) 0 (0.0) 0 (0.0)
Clinical mrT and mrN categories, EMVI, and
N category CRM were assessed on pretreatment and post-
N0 11 (19.3) 33 (57.9) 41 (71.9) treatment MR images, and mrTRG was assessed
N1a 4 (7.0) 8 (14.0) 8 (14.0) on posttreatment MR images.
We used the mrTRG scoring system described
N1b 2 (3.5) 11 (19.3) 4 (7.0)
by Patel et al. [5], which was derived from the
N1c 0 (0.0) 1 (1.8) 1 (1.8) pTRG system and resembles the Mandard TRG
N2a 8 (14.0) 4 (7.0) 3 (5.3) system [16] (Table 2). In cases of adenocarcinoma,
N2b 24 (42.1) 0 (0.0) 0 (0.0) the primary tumor manifested as intermediate
signal intensity on baseline MR images. In cases
Data missing 8 (14.0) 0 (0.0) 0 (0.0)
of mucinous adenocarcinoma, mucin appeared as
Circumferential resection margin high signal intensity mixed with areas composed
Involved 24 (42.1) 14 (24.6) 8 (14.0) of tumor cells appearing as intermediate signal in-
Uninvolved 25 (43.9) 43 (75.4) 49 (86.0) tensity on baseline MR images. After treatment,
tumor cells could be replaced by fibrotic areas of
Data missing 8 (14.0) 0 (0.0) 0 (0.0)
low signal intensity or by pure mucin with fluid-
Extramural vascular invasion like high signal intensity. The presence of pure
Present 35 (61.4) 27 (47.4) 12 (21.1) mucin after treatment was considered evidence
Absent 14 (24.6) 30 (52.6) 45 (78.9) of tumor response and was therefore considered
equivalent to fibrosis during grading [14].
Data missing 8 (14.0) 0 (0.0) 0 (0.0)
DWI was used to identify the presence and
Tumor regression grade infiltration depth of residual tumor in fibrotic or
1 1 (1.8) 4 (7.0) mucinous areas detected on T2-weighted images
2 22 (38.6) 18 (31.6) after treatment. At restaging DWI, high signal in-
tensity in fibrotic or mucinous areas, correspond-
3 24 (42.1) 27 (47.4)
ing to the primary tumor at baseline MRI, was
4 10 (17.5) 8 (14.0) considered evidence of residual tumor. The ab-
5 0 (0.0) 0 (0.0) sence of intermediate signal intensity in fibrotic
Note—Data are numbers of patients with percentages in parentheses. or mucinous areas on T2-weighted images and the
absence of high signal intensity in the correspond-
(interquartile range, 5.0–11.5 days). A detailed the same 3-T MRI system, which was equipped with ing area at restaging DWI were considered evi-
comparison between MRI and pathologic findings an eight-channel torso-array coil. Patients were in- dence of a complete response.
was performed retrospectively. structed to empty their intestines before the MRI ex- The mrT and mrN categories were based on the
amination. Bowel cleansing and spasmolytic agents American Joint Commission on Cancer, 8th edi-
MRI Technique were not used. A conventional rectal MRI protocol tion, staging system. The mrT3 category was sub-
MRI examinations performed for primary stag- was used for all patients. This protocol included the divided on the basis of extramural depth (EMD)
ing and preoperative restaging were completed with following sequences: sagittal T2-weighted fast-re- of tumor invasion as follows: T3a (EMD < 1 mm),

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A B C
Fig. 2—37-year-old man with rectal adenocarcinoma with extramural vascular invasion.
A, Oblique axial high-resolution T2-weighted baseline MR image shows extramural vessels expanded and filled with intermediate signal intensity (arrow).
B, Oblique axial high-resolution T2-weighted restaging MR image shows persistent expansion of extramural vessel filled with soft-tissue component manifesting as
intermediate signal intensity (arrow).
C, Photomicrograph of whole-mount histologic section (H and E, ×2) shows tumor cells within vascular structure outside muscularis propria (arrow).

T3b (EMD ≥ 1–5 mm), T3c (EMD > 5–15 mm), or
T3d (EMD > 15 mm) [13]. A case of primary tu-
mor penetrating the visceral peritoneum was de-
fined as T4a, and a case of tumor invading or ad-
hering to other organs was defined as T4b.
A suspicious positive node was identified when
heterogeneous signal intensity or an irregular bor-
der was detected on T2-weighted images, irre-
spective of size [17].
CRM involvement was defined as the presence
of any tumor, including primary tumor, positive
lymph nodes, tumor deposits, and EMVI, within
1 mm of the mesorectal fascia (MRF) [13]. The
presence of fibrosis or pure mucin next to the MRF
was not considered evidence of CRM involvement
on restaging MRI. Similarly, the presence of fibro-
sis or mucin outside the muscularis propria was
not included in the calculation of EMD for assess-
ment of ymrT category.
On MR images, EMVI was considered pres-
ent when tumorlike signal intensity was observed
within vessels outside the muscularis propria,
with or without expansion of the vessel lumen
(Fig. 2). The five-level EMVI grading system pro-
posed by Smith et al. [18] was used to evaluate the
presence of EMVI. A score of 0–2 corresponded
to the absence of EMVI, and a score of 3 or 4 cor-
responded to the presence of EMVI. The diameter
of the largest invaded vessel was measured, and
these vessels were divided into two groups with 3
mm as the cutoff point.
Histopathologic Evaluation
The circumferential resection planes of each
specimen were painted with ink before dissection
to determine CRM status. After being fixed in for-
malin for 48 hours, the samples were stained with
H and E. Tumors were then cross-sectioned at 3-
to 4-mm intervals and processed into whole-mount
sections and conventional sections according to the
method reported by Quirke et al. [19]. When the
macroscopic area of residual tumor or fibrotic scar
was small and could be processed with conven-
tional embedding boxes, only conventional slic-
es were processed to ensure immediate reporting.
The slices were numbered from the most proximal
and optimal slices to correlate the results with MRI
findings. The shapes of the tumor area, muscula-
ris propria, and adjacent vessels and lymph nodes
were compared between MR images and corre-
sponding pathologic slices to ensure consistency.
Histopathologic evaluation was performed
by one pathologist with 7 years’ experience in
colorectal pathology. The pathologist was blinded
to patient information and the results of restaging
MRI. The pT and pN categories were based on the
American Joint Commission on Cancer, 8th edi-
tion, staging system, and the maximum EMD was
measured to determine T3 subtypes. The shortest
distance between any tumor-containing tissue and
the CRM was recorded. The presence of tumor
cells within 1 mm from the inked MRF was de-
fined as pCRM involvement. The pEMVI status
was based on whether tumor cells could be seen
within the vascular structure outside the muscu-
laris propria (Fig. 2). The diameter of the largest
invaded vessel was measured and grouped accord-
ing to the criteria used for MRI analysis. We as-
sessed pTRG using the Mandard TRG system [16]
(Table 2), and the presence of an acellular mu-
cin pool was considered equivalent to fibrosis for
grading purposes.

TABLE 2: Tumor Regression Grade Scoring Systems

Score MRI Pathologic
1 Absence of any tumor signal intensity Complete regression; absence of residual tumor; fibrosis extending
through the different layers of the wall
2 Small amounts of residual tumor visible but with predominantly Presence of rare residual tumor cells scattered throughout the fibrosis
fibrotic low signal intensity
3 Mixed areas of fibrotic low signal intensity and intermediate signal Increased number of residual tumor cells but fibrosis still predominant
intensity but without predominance of tumor
4 Predominant tumor signal intensity with minimal fibrotic low signal Residual tumor outgrowing fibrosis
intensity
5 No fibrosis, only tumor signal visible Absence of regressive changes

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 MRI of Rectal Cancer

TABLE 3: Accuracy of MRI Evaluation After Neoadjuvant Treatment

Variable Sensitivity Specificity Positive Predictive Value Negative Predictive Value
Tumor regression grade
1 25.0 (0.6–80.6) 100.0 (93.3–100) 100.0 (2.5–100) 94.6 (85.1–98.9)
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1–2 72.7 (49.8–89.3) 77.1 (59.9–89.6) 66.7 (44.7–84.4) 81.8 (64.2–93.2)

3–5 77.1 (59.9–89.6) 72.7 (49.8–89.3) 81.8 (64.2–93.2) 66.7 (44.7–84.4)
T category
T0 25.0 (0.6–80.6) 100.0 (93.3–100) 100.0 (2.5–100) 94.6 (85.1–98.9)
T0–T2 62.5 (35.4–84.8) 100.0 (91.4–100) 100.0 (69.2–100) 87.2 (74.3–95.2)
T0–T3a 66.7 (44.7–84.4) 93.9 (79.8–99.3) 88.9 (64.4–98.7) 79.5 (63.5–90.7)
T3–T4 100.0 (91.4–100) 62.5 (35.4–84.8) 87.2 (74.3–95.2) 100.0 (69.2–100)
T3b–T4 93.9 (79.8–99.3) 66.7 (44.7–84.4) 79.5 (63.5–90.7) 88.9 (64.4–98.7)
N category
Node-negative disease 70.7 (54.5–83.9) 75.0 (47.6–92.7) 87.9 (71.8–96.6) 50.0 (29.1–70.9)
Node-positive disease 75.0 (47.6–92.7) 70.7 (54.5–83.9) 50.0 (29.1–70.9) 87.9 (71.8–96.6)
N1 61.5 (31.6–86.1) 72.7 (57.2–85.0) 40.0 (19.1–63.9) 86.5 (71.2–95.5)
N2 66.7 (9.4–99.2) 96.3 (87.3–99.5) 50.0 (6.8–93.2) 98.1 (89.9–100)
CRM
CRM uninvolved 85.7 (72.8–94.1) 87.5 (47.3–99.7) 97.7 (87.7–99.9) 50.0 (23.0–77.0)
CRM involved 87.5 (47.3–99.7) 85.7 (72.8–94.1) 50.0 (23.0–77.0) 97.7 (87.7–99.9)
EMVI
EMVI absent 64.4 (48.8–78.1) 91.7 (61.5–99.8) 96.7 (82.8–99.9) 40.7 (22.4–61.2)
EMVI present 91.7 (61.5–99.8) 64.4 (48.8–78.1) 40.7 (22.4–61.2) 96.7 (82.8–99.9)
Note—Data are percentages. Values in parentheses are 95% CIs. CRM = circumferential resection margin, EMVI = extramural vascular invasion.

Statistical Analysis shown in Table 3. With dichotomous classifi- Three of four patients with pTRG1 disease
All statistical analyses were performed with cation, the interobserver agreement for evalu- had their disease identified as mrTRG2 on
SPSS (version 21.0, IBM) and MedCalc (version ation of mrTRG was fair (κ = 0.370), and mod- the basis of the presence of high signal inten-
11.4, MedCalc Software) software. Demographic erate agreement was found in evaluations of sity in the fibrotic area on DW images. These
characteristics, MRI data, and pathologic data were ymrEMVI (κ = 0.509), ymrCRM (κ = 0.572), patients had evidence of massive inflamma-
described with summary statistics. Sensitivity, ymrT (κ = 0.558), and ymrN (κ = 0.535). tory cell infiltration in the fibrotic area at
specificity, positive predictive value, and negative pathologic analysis (Fig. 3).
predictive value of mrTRG, ymrEMVI, ymrCRM, Tumor Regression Grade With dichotomous classification, over-
ymrT, and ymrN were calculated. The kappa values In the five-tier regression system, TRG staging of TRG occurred in 6 of 57 patients
of these various indicators were determined to as- was correctly predicted with MRI in 59.6% (10.5%). Three of the six patients had severe
sess interobserver agreement. In addition, dichoto- (34/57) of patients (Table 4). With dichoto- edema of the mucosa and submucosa adja-
mous classification was performed to calculate in- mous classification, the probability increased cent to the tumor, which was misinterpreted
terobserver agreement for mrTRG (i.e., mrTRG3–5 to 77.2% (44/57). as residual tumor. Overstaging occurred in
vs mrTRG1–2), ymrT (i.e., ymrT0–T2 vs ymrT3–
T4) and ymrN (i.e., ymrN0 vs ymr node positive). TABLE 4: Comparison Between MRI and Pathologic Tumor Regression Grade
Kappa values were assessed as follows:  >  0.8–
1.0, excellent agreement;  > 0.6–0.8, good agree- Pathologic
ment;  >  0.4–0.6, moderate agreement;  >  0.2–0.4, MRI 1 2 3 4 5 Total
fair agreement; 0.0–0.2, poor agreement. A five-ti-
1 1 0 0 0 0 1
er regression system was used to compare mrTRG
with pTRG. One-by-one comparisons between re- 2 3 12 7 0 0 22
staging MRI and pathologic results were conducted 3 0 5 16 3 0 24
to determine causes of discrepancy. 4 0 1 4 5 0 10
5 0 0 0 0 0 0
Results
The overall accuracy of restaging MRI with Total 4 18 27 8 0 57
pathologic results as the reference standard is Note—Data are number of patients.

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A B

C D E
Fig. 3—66-year-old woman with rectal adenocarcinoma.
A, Baseline axial T2-weighted oblique MR image shows primary tumor as area of intermediate signal intensity (arrow).
B, Baseline axial DW image shows primary tumor as area of high signal intensity (arrow).
C, Oblique axial T2-weighted MR image obtained after neoadjuvant chemoradiotherapy (CRT) shows primary tumor has been replaced by area of low signal intensity
(arrow).
D, DW image obtained after neoadjuvant CRT shows primary tumor as area of high signal intensity (arrow). Disease was classified MRI tumor regression grade (TRG) 2.
E, Photomicrograph (H and E, ×100) of histologic slice shows fibrosis and massive inflammatory cells. Absence of residual tumor cells shows that disease in this patient is
pathologic TRG1.

two patients because the muscularis propria
abutting the fibrotic area appeared as inter-
mediate signal intensity on T2-weighted im-
ages and was misinterpreted as residual tu-
mor. The sixth patient received a diagnosis
of mucinous adenocarcinoma, which pre-
sented predominantly as tumor signal inten-
sity with minimal fluidlike mucinous signal
intensity at MRI. Pathologic analysis, how-
ever, showed a mucin pool scattered in mas-
sive fibrosis with only a few tumor cells re-
maining (Fig. 4). Understaging of TRG
occurred in 7 of 57 patients (12.3%), all of
whom had pTRG3 disease that was identi-
fied as mrTRG2 because of obvious fibrosis
in the tumor area.
T and N Categories
The accuracy of ymrT categorization
reached 80.7% (46/57) when T3 disease was
not subdivided. When T3 was subdivided on
the basis of EMD, the posttreatment T cate-
gory was correctly predicted on the basis of
MRI findings in only 59.6% (34/57) of pa-
tients. Overstaging occurred in 35.1% (20/57)
of patients and understaging in 5.3% (3/57).
In 9 of the 16 patients (56.25%) with pT0–
T2 disease, disease was overstaged with MRI.
This included three patients with pT0 and six
patients with pT1–T2 disease. Overstaging
was mainly attributable to the presence of fi-
brosis outside the rectal wall, which manifest-
ed as irregular spiculation into the perirectal
fat and was mistaken for residual tumor.
Among the 33 patients with pT3 disease,
11 (35.0%) patients had disease that was
overstaged. Nine of these patients had dis-
ease identified as mrT3 with overestimated
EMD. Disease in the other two patients was
identified as mrT4b. In these patients, base-
line MRI showed the primary tumor invad-
ing the small bowel or levator ani. Restaging
MRI seemed to show massive fibrosis mixed
with tumor signal intensity abutting the adja-
cent structures. However, tumor cells within
the area of fibrosis were not found to reach
the adjacent structures at pathologic analy-
sis (Fig. 5). In three patients with pT3 dis-
ease, the disease was understaged with MRI:
disease in two patients with pathologically
determined EMD of 2 or 3 mm was classi-
fied as mrT3a, and disease in one patient with
pT3c disease (EMD, 7 mm) was identified as
ymrT3b (EMD, 4 mm). In all patients with
pT4a (5/57 [8.8%]) or pT4b (3/57 [5.3%]) dis-
ease, MRI was accurate in staging.
The accuracy of ymrN categorization was
71.9% (41/57). In 12 of the 57 patients (21.1%),
pN0 disease was overstaged as ymrN-posi-
tive because of the presence of lymph nodes
with mixed signal intensity or irregular bor-
der on MR images. In 4 of 57 patients (7.0%),
pN1a disease was missed with MRI. In three
of these patients, MRI showed lymph nodes
with a regular border and homogeneous
signal intensity and with a diameter smaller
than 3 mm. In the fourth patient, no lymph
nodes were seen on T2-weighted images.
Circumferential Resection Margin
CRM status was correctly predicted with
MRI in 86.0% (49/57) of patients. Overstag-
ing of CRM occurred in 7 of 57 patients
(12.3%), three of whom had massive fibro-
sis mixed with tumor signal intensity abut-
ting the MRF. In these patients, the patho-
logic results showed no tumor cells abutting
the MRF. In two patients with low rectal can-

1086 AJR:213, November 2019

 MRI of Rectal Cancer
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A B C
Fig. 4—65-year-old man with mucinous adenocarcinoma.
A, Baseline oblique axial T2-weighted MR image shows primary tumor as area of intermediate signal intensity (arrow), suggestive of mucin and solid cellular
components.
B, Restaging oblique axial T2-weighted MR image shows small area of high signal intensity (black arrow) within intermediate signal intensity of primary tumor (white
arrow). This finding is interpreted as acellular mucin. Disease was classified MRI tumor regression grade (TRG) 4.
C, Photomicrograph (H and E, ×15) of histologic slice shows only small number of tumor cells (black arrowheads) scattered in massive fibrosis (white arrowheads) and
acellular mucin (arrow). Disease was classified pathologic TRG2.

cer, tumor appeared to abut the levator mus-
cle, and in another two patients, tumor ap-
peared to abut the anterior MRF, where the
mesorectal fat was thin. In one patient with
mucinous adenocarcinoma, a mucinous pool
appeared to abut the levator ani, but no tu-
mor cells were found in this pool at patholog-
ic analysis. Understaging occurred in only
one patient (1.7%). In this patient, restaging
MRI showed an area of low signal intensity
around the invaded vessel abutting the MRF.
The pathologic results, however, showed tu-
mor cells mixed in the fibrotic area adjacent
to the MRF.
Extramural Vascular Invasion
EMVI status was correctly predicted with
MRI in 70.2% (40/57) of patients. The pres-
ence of ymrEMVI was detected in 27 of 57
patients (47.4%). In 15 of these 27 patients
(55.6%), the diameter of the largest invaded
vessel was greater than 3 mm, whereas in 12
patients (44.4%), the diameter was less than
3 mm. However, pathologic EMVI was de-
tected in only 12 of 57 patients (21.1%). Eight
of these 12 patients (66.7%) had invasion of
vessels with a diameter greater than 3 mm,
and four (33.3%) had invasion of vessels with
a diameter less than 3 mm.
In 17 patients, MRI evidence of EMVI was
not consistent with the pathologic results. In
the 16 cases of MRI overstaging of EMVI,
nine patients had invasion of vessels with a di-
ameter less than 3 mm, and one had invasion
of a vessel with a diameter greater than 3 mm
on MR images. At pathologic analysis, all of
these findings appeared as fibrosis around the
tumor. In the other six patients, invasion of
vessels with a diameter greater than 3 mm
identified at MRI was not seen at pathologic
analysis. In one of these six patients, tumor-
like intermediate signal intensity was seen in
a branch of the superior rectal vein, a finding

A B C
Fig. 5—52-year-old man with locally advanced rectal cancer.
A, Baseline oblique axial T2-weighted MR image shows primary tumor growing out of mesorectal fascia (white arrow) and invading bladder wall (black arrow). Disease
was classified T4b with circumferential resection margin involvement.
B, Restaging oblique axial T2-weighted MR image shows primary tumor has shrunk but involvement of bladder wall (black arrow) and mesorectal fascia (white arrow)
persist.
C, Photomicrograph (H and E, ×5) of histologic slice shows thickening of bladder wall caused by infiltration of massive fibrosis and inflammatory cells (black arrow)
without presence of residual tumor cells. Bladder wall is adjacent to strands of fibrosis (white arrows), not tumor cells.

AJR:213, November 2019 1087

 Jia et al.

TABLE 5: Most Common Pitfalls Leading to Overstaging and Understaging for Each Indicator Evaluated With MRI
Indicator Overstaging Understaging
Tumor regression grade Severe edema of the mucosa and submucosa adjacent to Underestimated residual tumor in area of fibrosis
tumor misinterpreted as residual tumor
T category Fibrosis outside the rectal wall misinterpreted as residual Underestimated extramural depth of tumor invasion
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N category
Circumferential resection margin
Extramural vascular invasion
tumor
Benign lymph nodes appearing as mixed signal intensity
or irregular border mistaken as malignant nodes
Tumor signal intensity scattered in massive fibrosis
abutting the mesorectal fascia misinterpreted at MRI
Obvious fibrosis around tumor misinterpreted as invaded
vessels
Small lymph nodes with regular border and homogeneous
signal intensity found to be malignant nodes at pathologic
analysis
Omission of tumor cells mixed in the fibrotic area abutting
the mesorectal fascia
Invaded vessel filled with mucin misinterpreted as primary
tumor

that pathologic analysis showed to be tumor
cells surrounding the vascular wall without
invasion within the lumen.
In one patient with mucinous adeno-
carcinoma, a large vessel abutting the rectum
and filled with a mucin pool was detected at
pathologic analysis. This finding was identi-
fied as the mucinous change of primary tu-
mor on MRI.
Discussion
In this study, we found that restaging MRI
was prone to overstaging of disease after
neoadjuvant treatment of patients with rec-
tal cancer. Discrepancies between MRI and
pathologic findings were mainly caused by
misinterpretation of fibrotic areas as residu-
al tumor. In addition, on DW images inflam-
matory cell infiltration could appear as high
signal intensity in fibrotic areas, an appear-
ance similar to that of residual tumor. Edem-
atous mucosa and submucosa adjacent to the
tumor and muscularis propria could also be
mistaken for residual tumor owing to their in-
termediate signal intensity on T2-weighted
images. Table 5 summarizes the most com-
mon pitfalls causing overstaging and under-
staging for each indicator evaluated with MRI.
In the patient population studied, we found
that the presence of fibrotic areas can result in
disease overstaging with MRI in several con-
texts. First, we found that irregular spicula-
tion into perirectal fat could be caused by ei-
ther fibrosis or residual tumor, and this could
lead to overstaging of pT2 disease. Second,
the EMD of residual tumor in fibrotic areas
could not be accurately identified; therefore,
accurate T3 categorization could not be per-
formed. Third, the massive fibrotic area abut-
ting the MRF or adjacent organs mixed with
tumorlike signal intensity was often inter-
preted as persistent CRM involvement or T4b
disease, findings that were unsupported by
pathologic results in some patients. Fourth, fi-
brosis could manifest as a shape and signal
intensity similar to the shape and signal in-
tensity of invaded vessels that shrank after
treatment, resulting in overstaging of EMVI
(especially in vessels with a diameter small-
er than 3 mm). Finally, irregular border and
signal intensity inhomogeneity were some-
times seen in benign lymph nodes after neo-
adjuvant treatment, causing overestimation
of N status. The findings of irregular border
and signal intensity inhomogeneity in these
cases may have been caused by the pres-
ence of fibrosis and mucinous deposits within
the lymph nodes after neoadjuvant CRT [13,
20]. However, this inference could not be as-
sessed, because a node-by-node comparison
of MRI and pathologic results was not per-
formed in this retrospective study.
DWI of some patients with pCR showed
high signal intensity in fibrotic areas, which
was misidentified as residual tumor. Al-
though previous studies have shown that fi-
brotic areas manifest as low signal intensity
on high-b-value DW images [21, 22], we be-
lieve that inflammatory cell infiltration in the
fibrotic areas, which can be difficult to dif-
ferentiate from residual tumor on DW imag-
es, may have caused the high signal intensity.
Previous studies have shown that quantified
DWI, namely apparent diffusion coefficient
(ADC) mapping, could be used as an im-
aging biomarker to predict pCR, accuracy
reaching as high as 86% [23]. However, there
is no widely accepted cutoff value for post-
treatment ADC, and changes in ADC after
neoadjuvant CRT have not been addressed.
Moreover, ADC varies across ROIs, and re-
peatability with this technique is poor. Re-
cent studies [24, 25] in which T2-weighted
MRI–based radiomics were used to evaluate
pCR showed better diagnostic performance
than with visual assessment on T2-weighted
and DW images. This technique should be
investigated in future studies.
In patients with mucinous adeno-
carcinoma, cellular mucin can turn into pure
mucin without residual tumor cells after
neoadjuvant CRT. This condition manifests
as fluidlike signal intensity on T2-weighted
images [14]. However, when the pure mu-
cin pool is small and mixed with fibrosis, the
change in signal intensity may not be obvi-
ous, leading to overstaging of mrTRG.
Overstaging can also be caused by mis-
identification of the intestinal wall as resid-
ual tumor, as muscularis propria, edematous
mucosa and submucosa adjacent to the tu-
mor, and residual tumor itself, all appearing
as intermediate signal intensity.
In cases of understaged disease, we found
that the scattered tumor cells in fibrotic areas
were not accurately identified at MRI. Sim-
ilarly, micrometastasis within lymph nodes
could not be accurately identified on MR im-
ages, even when signal intensity on DW im-
ages was considered. Using a slice thickness
of at least 3 mm may have also led to the
omission of small positive lymph nodes.
Tumor Regression Grade
The accuracy of mrTRG in our study was
59.6%, which was higher than the accuracy
reported in recent studies (28–34%) [9, 10]. In
the previous studies, the interval between re-
staging MRI and surgery ranged from 2.5 to
17 weeks. During this time, the proportion of
fibrosis can change, causing discrepancies be-
tween MRI and pathologic results [26]. In our
study, the median interval between MRI and
surgery was 1 week, which may partially ex-
plain the higher accuracy we observed. In ad-
dition, pure mucin was considered evidence
of tumor response equivalent to fibrosis in the
evaluation of regression in our study, which
may have improved the accuracy of MRI.

1088 AJR:213, November 2019


When dichotomous classification was used in
this study, the accuracy of mrTRG was 77.2%,
suggesting that this marker could be a useful
prognostic indicator.
T and N Categories
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In many previous studies, pT0–pT2 or
pT0–pT3a has been classified as responders
(i.e., favorable prognosis) [3, 27, 28]. In our
study, restaging MRI had favorable specifici-
ty for predicting pCR, pT0–T2, and pT0–T3a
(93.9–100%), but the sensitivity was much
lower (25.0–66.7%). Restaging MRI and
pathologic analysis were consistent in as-
sessing N category in 71.9% of cases. Over-
staging was the main cause of discrepancy, a
result that is in accordance with those of pre-
vious studies [26, 29].
Circumferential Resection Margin
The sensitivity and specificity of ­ymrCRM
reached as high as 87.5% and 85.7% in our
study. These values are consistent with re-
sults of a previous meta-analysis (sensitiv-
ity, 85.4%; specificity, 80%) [26]. In some
cases, the rectum abutted the MRF anteri-
orly, and the low rectum abutted the levator
ani posteriorly, which resulted in overstag-
ing. Nevertheless, ymrCRM had a negative
predictive value of 97.7% in our analysis, a
result similar to that in the Magnetic Reso-
nance Imaging and Rectal Cancer European
Equivalence (MERCURY) study [30], which
showed the utility of ymrCRM for predicting
the possibility of radical resection after neo-
adjuvant treatment.
Extramural Vascular Invasion
EMVI has been identified as an inde-
pendent predictor of disease-free survival,
whether assessed with pathologic analysis or
MRI [31]. In our study, ymrEMVI had mod-
erate specificity of 64.4%. In addition to fi-
brosis misidentified as invaded vessels, an-
other cause of overstaging may have involved
tumor cells growing along vessels without in-
vasion into the lumen, a finding that was dif-
ficult to detect with MRI. Some patients, on
the other hand, appeared to have MRI evi-
dence of invasion of large vessels, but these
results were unsupported by pathologic re-
sults. We believe that these discrepancies
may have been caused by false-negative find-
ings of pEMVI. In our study, pathologic anal-
ysis using H and E staining revealed EMVI
in only 21.1% of patients, which was less than
the rate of 31% reported in a previous study in
which elastic staining was used [32]. Tumor
AJR:213, November 2019 1089
MRI of Rectal Cancer
infiltration may also have destroyed the vas-
cular structure beyond recognition, leading to
false-negative pathologic results [33].
Understaging of EMVI was seen in only
one patient: the pathologic finding of com-
plete mucinous change in an invaded large
vessel was interpreted on MRI as a response
of the primary tumor. Recognizing the vas-
cular structure on MR images was difficult,
because the mucinous high signal inten-
sity did not extend far into the vascular lu-
men. Overall, although we found only mod-
erate agreement with pathologic results in
this study, the negative predictive value of
ymrEMVI was favorable, suggesting that the
absence of ymrEMVI may serve as a useful
predictor of good prognosis.
Although the causes of MRI misinterpre-
tations of residual tumor often exist at the
microscopic level, some suggestions for im-
proving the assessment of tumor response at
MRI can still be implemented. First, DWI
can be used as a supplement to T2-weighted
imaging for many indicators of tumor re-
sponse. Because of the high sensitivity of
DWI in detecting residual tumor, the ab-
sence of high signal intensity in fibrotic ar-
eas on DW images could help to confirm
cases of pCR. Muscularis propria and nor-
mal mucosa and submucosa adjacent to the
tumor could appear as intermediate signal
intensity on T2-weighted images and ab-
sence of high signal intensity on DW imag-
es, which might be differentiated from resid-
ual tumor. DWI can also be used to assess
the infiltration level of the residual tumor.
When areas of fibrosis (low signal intensi-
ty) are mixed with residual tumor (interme-
diate signal intensity) adjacent to the MRF
or adjacent organs on T2-weighted images,
the absence of high signal intensity abutting
the MRF or adjacent organs on DW images
could confirm the absence of invasion. Sec-
ond, suspected invasion of vessels with a di-
ameter smaller than 3 mm on MR images is
more likely to be fibrosis. Therefore, caution
must be used when assessing the presence
of EMVI in these smaller vessels. Third, the
presence of pure mucin (fluidlike high signal
intensity on T2-weighted images) after treat-
ment may indicate the absence of viable tu-
mor and could therefore be used as a marker
of tumor response.
This study had several limitations. First,
although pathologic analysis was the only
method used to confirm the morphologic
findings from preoperative imaging exami-
nations, it was impossible to process all tu-
mor-bearing slices into pathologic sections.
Thus, mrTRG and T category may have been
misinterpreted, and EMVI may have been
missed once the sample was cross-sectioned.
Second, the inclusion of patients with muci-
nous adenocarcinoma and those treated with
neoadjuvant chemotherapy alone or radio-
therapy alone could influence the accuracy
and the interobserver agreement of restaging
MRI results. Tumor responses in these pa-
tients may differ from those of patients with
adenocarcinoma or those treated with neoad-
juvant CRT. Third, the routine use of H and E
staining and the destruction of vascular struc-
ture during sampling may have resulted in a
low EMVI detection rate. In addition, not all
slices of the sample were processed as whole-
mount sections. Fourth, several patients
lacked baseline MR images, which may have
altered the interpretation of restaging MRI
results. Finally, the sample size for this study
was small. Further studies conducted with
special staining and larger sample sizes are
needed to investigate the accuracy of MRI in-
dicators, especially EMVI, and to assess dif-
ferences in tumor response among patients
treated with various neoadjuvant strategies.
Conclusion
Restaging MRI was prone to overstaging
of residual tumor after neoadjuvant treat-
ment in the patient population studied. The
discrepancies between MRI and pathologic
results were mainly caused by misinterpre-
tation of fibrosis. Inflammatory cell infil-
tration, pure mucin, edematous mucosa and
submucosa adjacent to the tumor, and mus-
cularis propria could also be misinterpreted
as residual tumor.
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