Introduction
Coexistence of colorectal tumors and diverticulum has been reported [1]
[2]. Because a colonic diverticulum is a false diverticulum without a muscular layer,
tumors involving diverticulum may be diagnosed at advance stages, despite their small
size, and may be more rapidly exposed to the serosal surface, possibly contributing
to their low survival rate [3].
On the other hand, because they are associated with a negligible risk of lymph node
metastasis, colorectal tumors confined to the mucosal layer can be successfully managed
by endoscopic treatments such as endoscopic mucosal resection (EMR) or endoscopic
submucosal dissection (ESD) [4]. However, EMR is considered dangerous in cases of diverticula-associated colorectal
tumors due to absence of a muscular layer in diverticulum and the consequent increased
risk of perforation [5].
ESD allows en-bloc resection of colorectal tumors using electrosurgical knives under
direct visualization [6]. ESD also allows precise pathological diagnosis of the resected specimen. These
are beneficial factors in management of colorectal tumors associated with a diverticulum
because tumors can directly invade the serosa in this uncommon location [3]
[7]. Although several individual cases of ESD treatment of such colonic tumors have
been reported [8]
[9]
[10]
[11]
[12]
[13]
[14], use of ESD for treating a colonic tumor found near or involving a diverticulum
remains controversial. Here, we report on a series of 12 consecutive patients with
colorectal tumors near or involving a diverticulum treated by ESD.
Patients and methods
From December 2004 to February 2017, we performed ESD in 12 consecutive patients who
had colorectal tumors near or involving a diverticulum. The procedures were performed
at the National Cancer Center Hospital, Tokyo, Japan, and at the National Cancer Center
Hospital East, Chiba, Japan. We retrospectively analyzed patients’ clinicopathological
features and clinical outcomes. This case series was approved by the Institutional
Review Board of the National Cancer Center.
Classification of colorectal tumors related to the diverticular orifice
All tumors were divided into two groups ([Fig. 1]):
-
Near type – The tumor reached the diverticular border, but did not enter the diverticular
orifice.
-
Involving type – The tumor reached and entered the diverticular orifice; when the
lesion fully covered the diverticulum, the diverticulum was unrecognized before ESD
was performed.
Fig. 1 Classification of tumors related to the diverticular orifice. a Near type: the tumor reached the diverticular border, but did not enter the diverticular
orifice. b Involving type: the tumor reached and entered the diverticular orifice; when the
lesion fully covered the diverticulum, the diverticulum was unrecognized before ESD
was performed.
Endoscopic diagnosis
All diagnostic colonoscopies were performed using magnifying colonoscopes (CF-HQ290AZI,
CF-H260AZI, CF-FH260AZI, PCF-Q260AZI or PCF-Q240ZI, Olympus, Tokyo, Japan).
After white-light observation, narrow-band imaging (NBI) with magnification and chromoendoscopy
was performed to determine the pit pattern of the tumor [15] to assess whether it was suitable for ESD. If a diverticulum was detected, careful
examination was performed to determine the size of the diverticulum and the pit pattern
of the tumor involving the diverticulum. A short-type ST hood (DH-28GR Fujifilm Medical
Co., Tokyo, Japan) was used to measure the size of diverticulum. Biopsy was not performed
before ESD because that could cause fibrosis, which might interfere with submucosal
lifting.
ESD procedure
Details of the ESD technique have been described previously [6]. All procedures were performed using a therapeutic endoscope with a water-jet function
and carbon dioxide insufflations. A short-type ST hood (DH-28GR Fuji film Medical
Co., Tokyo, Japan) was used for traction and to obtain good field visualization for
cutting the submucosal layer. An electrosurgical knife (Ball-tip bipolar needle knife
[B-knife or jet B-knife; XEMEX Co, Tokyo Japan]), a Dual knife (Olympus Optical Co,
Tokyo, Japan) and/or an insulation-tipped knife nano (IT-Knife nano, Olympus Optical
Co, Tokyo, Japan) was used during ESD procedures. Glyceol (Chugai Pharmaceutical Co.,
Tokyo, Japan) and MucoUp (Johnson and Johnson, Tokyo, Japan) were used for submucosal
injection.
In the near type group, submucosal injection and mucosal incision were started nearest
to the diverticulum, where the tumor and diverticulum were closest together. Then,
ESD was continued from the periphery of the diverticulum to the opposite side to complete
the procedure.
In the involving type group, submucosal injection and mucosal incision were started
with a standard approach. We tried to dissect the submucosal layer early in the procedure
for easier lifting. However, in cases in which the tumor completely covered the diverticulum,
it was not recognized before ESD. A traction device, a silk line tied to the arm of
a clip, was used as required [16]
[17]. The submucosal side of the targeted specimen was grasped under clear visualization
and the line was pulled very gently. Polypectomy, strip biopsy [18], argon plasma and elastic band ligation (EBL) were used as required to complete
resection in the intradiverticular area. Experienced endoscopists performed the procedures
(MY, HI, HT, SA, TS, TN, TM and YS).
Histopathological evaluation
Resected specimens were stretched and fixed in 10 % formalin and then cut into 2-mm
slices. Histological type, depth of invasion, and lymphovascular invasion were evaluated
according to World Health Organization classification [19]. R0 resection was defined histopathologically as tumor-free lateral and vertical
margins. R1 resection was defined by presence of tumor cells in the resection margin.
Complete resection was defined as en-bloc R0 resection. Patients whose specimens did
not fulfill the criteria for complete resection were classified as incomplete resection.
Follow-up
Patients with incomplete resection after ESD had intensive follow-up with colonoscopy
and computed tomography (CT) scans as required every 3 to 6 months. Patients with
complete resection post-ESD were followed up with annual colonoscopy and CT scans
as required.
Results
Clinicopathological characteristics and ESD procedure technical outcomes for the 12
patients with colorectal tumors near or involving diverticulum are summarized in [Table 1].
Table 1
Clinicopathological features and clinical outcomes of ESD for colonic tumors near
or involving a diverticulum.
Patient
|
Tumor location
|
Tumor Size (mm)
|
Morphology
|
Diverticulum size (mm)[1]
|
Treatment
|
Traction
|
Adverse events[2]
|
Complete resection[3]
|
Histology
|
Depth of tumor
|
Follow-up (m)
|
Residual or recurrent tumor
|
Near diverticulum type tumors
|
1
|
Sigmoid
|
40
|
IIa (LST-NG)
|
3
|
ESD
|
No
|
No
|
Yes
|
HGD
|
M
|
12
|
No
|
2
|
Sigmoid
|
23
|
IIa (LST-NG)
|
5
|
ESD
|
No
|
No
|
Yes
|
HGD
|
M
|
13
|
No
|
3
|
Sigmoid
|
15
|
IIa (LST-NG)
|
4
|
ESD
|
No
|
No
|
Yes
|
HGD
|
M
|
40
|
No
|
4
|
T/C
|
16
|
Recurrent
|
4
|
ESD
|
No
|
No
|
Yes
|
HGD
|
M
|
60
|
No
|
5
|
A/C
|
21
|
IIa (LST-NG)
|
5
|
ESD
|
No
|
No
|
Yes
|
LGD
|
M
|
20
|
No
|
6
|
Cecum
|
30
|
IIa (LST-G)
|
5
|
ESD
|
No
|
No
|
Yes
|
Adeno-carcinoma
|
SM
|
13
|
No
|
Involving diverticulum type tumors
|
7
|
Sigmoid
|
80
|
Is + IIa (LST-G)
|
4
|
ESD
|
Yes
|
Perforation
|
Yes
|
Adeno-carcinoma
|
SM
|
12
|
No
|
8
|
Sigmoid
|
30
|
IIa (LST-G)
|
6
|
Hybrid ESD & band ligation
|
No
|
No
|
No
|
HGD
|
M
|
12
|
Yes
|
9
|
Sigmoid
|
40
|
Is + IIa (LST-G)
|
6
|
Hybrid ESD & polypectomy
|
No
|
No
|
No
|
HGD
|
M
|
12
|
Yes
|
10
|
A/C
|
30
|
Is + IIa (LST-G)
|
10
|
ESD, polypectomy & APC
|
No
|
No
|
No
|
HGD
|
M
|
3
|
No
|
11
|
Cecum
|
20
|
IIa (LST-NG)
|
6
|
Hybrid ESD & strip biopsy
|
No
|
No
|
No
|
HGD
|
M
|
12
|
No
|
12
|
Cecum
|
20
|
IIa (LST-NG)
|
3
|
ESD
|
No
|
No
|
Yes
|
HGD
|
M
|
12
|
No
|
ESD, endoscopic submucosal dissection; LST, laterally spreading tumor; G, granular;
NG, non-granular; HGD, high-grade dysplasia; LGD, low-grade dysplasia; SM, submucosal
invasive cancer; M, mucosa; T/C transverse colon; A/C, ascending colon; PC, argon
plasma coagulation.
1 Diverticular size was measured by comparing the top of the attachment to the diameter
of the diverticular opening.
2 Adverse events were bleeding and perforation.
3 Complete resection was defined as en-bloc resection with tumor-free margins on pathological
assessment (R0).
None of the patients had a previous history of diverticulitis. Of the 12 patients,
in six patients, the tumor was near a diverticulum and in the other six patients the
tumor was involving a diverticulum. Pre-ESD endoscopic depth diagnosis showed dysplasia
in 12 patients, with a median tumor size of 26.5 mm (range, 15 – 80 mm). The tumors
were all classified as type 2 according to the NBI International Colorectal Endoscopic
(NICE) classification [20]
[21]. Kudo’s pit pattern classification identified two tumors as type IIIL, one as type
IV with serration features, two as type IV without serration features and seven as
type VI. In four patients, the diverticulum was not detected in the tumors prior to ESD.
Median procedure time for ESD was 110 minutes (range, 50 – 220 minutes). En-bloc R0
resection was achieved in eight of 12 patients (67 %). In the near type group, all
the diverticula were recognized before ESD; whereas, in the involving type group,
diverticulum were recognized in only two cases prior to ESD.
In the near type group, median procedure time was 110 minutes (range, 60 – 220 minutes)
and en-bloc resection was achieved in 6/6 patients (100 %). There were no adverse
events (AEs) and no residual/recurrent tumor was detected during the follow-up period
(median, 16.5 months; range, 12 – 60 months). In contrast, among the involving type
group, median procedure time was 90 minutes (range, 50 – 210 minutes) and en-bloc
resection was achieved in 2/6 patients (33 %). In the other four patients, resection
had to be performed peacemeal because of intradiverticular tumor extension; strip
biopsy ([Fig. 2]), band ligation, polypectomy and/or argon plasma coagulation were required in these
cases. In all but one case, intradiverticular extension was 100 %. Therefore, we used
traction with the “clip with line method” [16] in that patient to achieve complete resection ([Fig. 3]).
Fig. 2 a A 20-mm LST-NG tumor was detected in the cecum. b Characterized as tumor type VI Kudoʼs pit pattern, the tumor was resected initially by ESD. c During the ESD procedure, it was observed that the tumor was involving completely
a diverticulum. d Hybrid ESD with strip biopsy was necessary. e Finally, the lesion was resected in piecemeal. f Resected specimen (mucosal side). g Resected specimen (submucosal side). ESD, endoscopic submucosal dissection; LST-NG,
laterally spreading tumor-non-granular.
Fig. 3 a An 80-mm LST-mixed tumor, Sano type 2, was detected in the sigmoid colon. b Characterized as tumor type IV Kudo's pit pattern with serrated features, the tumor
was resected by ESD. c,d During the procedure, it was observed that the lesion was involving a diverticulum
(black arrow), and in addition, a pin-hole perforation was detected (white arrow).
e A traction technique was used with a clip and silk line. f Finally, the lesion was resected en-bloc. ESD, endoscopic submucosal dissection;
LST, laterally spreading tumor.
To prevent delayed perforation, the diverticulum was closed in five of the 12 patients
and excision sites were completely closed with endoclips in two cases. Tattoo was
performed in one case in the involving type group due to a suspicion of submucosal
invasion.
In regards to AEs, only one patient in the involving type group (1/6, 17 %) developed
a pin-hole perforation in the diverticulum during the procedure, which was immediately
successfully closed using endoclips (HX-610-090; Olympus Medical Systems Corp., Tokyo,
Japan), and only in that case was the serosa visualized. After clip closure, the patient had no fever or abdominal pain. There were no other
AEs and no cases required emergency surgery.
All ESD scars were clearly recognized during follow-up. Residual tumors were detected
in two patients (2/6, 33 %; patients 8 and 9) during the follow-up period (median,
12 months; range, 3 – 12 months). In patient 8, the tumor was tiny and was successfully
ablated by hot biopsy. Patient 9 required additional surgery because residual tumor
at the diverticulum had become large by the time of the 12-month surveillance colonoscopy.
No stricture was detected in the area of endoscopic treatment during follow-up and
all the diverticula had disappeared within the scars.
Discussion
This is the first referral center case series of colorectal tumors arising near or
involving a diverticulum treated using ESD. The overall en-bloc R0 resection rate
in this series of 12 patients was 67 %, with a clear dichotomy between the rate for
tumors near a diverticulum (100 %) and those involving a diverticulum (33 %). Therefore,
ESD is considered a feasible treatment for colorectal tumors near a diverticulum.
Indeed, there were no cases of delayed perforation or bleeding and no emergency surgeries
were required. In contrast, in addition to the low en-bloc resection rate in tumors
involving a diverticulum, two of these patients were found to have residual tumor
at the time of first surveillance colonoscopies. Therefore, ESD may be considered
more challenging as a treatment in this group.
ESD has resulted in high en-bloc resection rates in previous studies with accurate
pathological evaluations (88 % – 95 %) [6]
[22]
[23]. In addition, long-term clinical outcome studies have shown near-zero recurrence
rates if ESD achieved complete resection without unfavorable histological features
[24]
[25]. In line with previous studies, our en-bloc R0 resection rate was 100 % in patients
with tumors near diverticulum, with no recurrences. In contrast, the en-bloc resection
rate was low (33 %), and incidence of residual/recurrent tumor was high (33 %) in
patients with tumors involving diverticulum. Furthermore, difficult recognition of
tumor within diverticulum before ESD is a very serious problem. Indeed, all but one
diverticulum was unrecognized before ESD. In those cases, we suggest that ESD combined
with other techniques, such as traction devices, endoscopic band ligation (EBL) and
endoscopic full-thickness resection using over-the-scope clip (EFTR-OTSC), may improve
treatment outcomes [10]
[14]
[26]. Indeed, good visualization and traction in the submucosal layer can be obtained
with use of traction devices [16]
[17]. In the current study, a traction device helped us achieve en-bloc resection in
one patient with a tumor involving diverticulum. Three isolated reports also suggested
that traction devices were successful in facilitating the procedure. [8]
[11]
[14]. In addition to near and involving type, diverticulum size also was considered as
a potentially an important factor in achieving en-bloc resection. All four patients
with incomplete resection had tumors involving a diverticulum. In all of the incomplete
resection cases, diverticulum size was ≥ 6 mm, larger than in the complete resection
cases (range, 3 – 5 mm; [Table 1]).
To prevent delayed perforation, the diverticulum was closed in three of the six involving-type
cases. All ESD scars were clearly recognized during follow-up and all diverticula
had disappeared within the scars. Residual lesions were detected in two patients whose
diverticulum had not closed. Therefore, if there is a possibility of residual tumor,
it is better to not close the diverticulum. In such cases, EBL and EFTR-OTSC might
be applied. Intensive follow-up of these patients with colonoscopy and computed tomography
scans is necessary.
There have been seven isolated case reports describing ESD for colorectal tumors associated
with diverticulum; in six cases the tumors involved a diverticulum and in one case
the tumor was near a diverticulum [8]
[9]
[10]
[11]
[12]
[13]
[14]. In only one of these cases was failure to achieve en-bloc resection reported, and
that was in a patient with a tumor involving a diverticulum. Also, local peritonitis
was reported in one case within a diverticulum and improved 3 days after ESD with
conservative management. Conventional EMR is a promising strategy for colorectal dysplasia
[27]. However, if there is a diverticulum, EMR has risk of perforation or incomplete
resection [5]
[7]
[13]. It is difficult to see the cutting point during EMR. Notably, four of the six cases
of near type were smaller than 25 mm in the current study. However, five of six were
lateral spreading tumors-non-granular type (LST-NG) and the remaining 16-mm case was
a recurrent tumor after incomplete EMR. It has been reported that LST-NG lesions have
a higher rate of submucosal invasion [28]. Given the possibility of increased fibrosis, EMR would not have been an effective
alternative [29]. Therefore, we believe that ESD is a safer option, as long as the cutting point
can be directly visualized.
“Non-ESD” techniques for resection of tumors arising in diverticulum have been reported
[30]
[31]
[32]
[33]
[34] ([Table 2]). EBL is a minimally invasive procedure that may be safe and effective for treating
tumors involving a diverticulum, but tumor size no doubt is a limitation, and no specimen
is obtained for histopathological analysis. The ligate-and-let-go-technique using
an endoloop has been described mainly for treating lipomas in the small bowel and
colon; however, as with EBL, a specimen is not obtained for histopathological study.
Laparoscopic-assisted colorectal (LAC) surgery is one option for tumors involving
a diverticulum. However, when we compared incidence of AEs (e. g., wound infection,
leakage, ileus), procedure time, procedure invasiveness, hospitalization length, and
cost for LAC procedures versus ESD procedures, the improved safety profile and the
possibility of curative treatment with ESD provided advantageous in treating dysplasia
[35].
Table 2
Non-ESD techniques reported for resection of involving-diverticulum type tumors.
Author
|
Tumor location
|
Tumor size (mm)
|
Diverticulum size (mm)
|
Diverticulum identified before treatment
|
Treatment
|
Adverse events
|
Complete resection[1]
|
Diverticulum closure
|
Follow-up
|
Residual or recurrent tumor
|
Mori H, et al.[30]
|
Sigmoid
|
25
|
N/E
|
No
|
EMR + OTSC
|
No
|
Yes
|
Yes
|
No
|
No follow-up
|
Carmo J, et al.[31]
|
Sigmoid
|
6
|
N/E
|
Yes
|
EBL
|
No
|
[2]
|
No
|
2 weeks
|
No
|
Pinho R, et al.[32]
|
Sigmoid
|
10
|
N/E
|
Yes
|
Endoloop
|
No
|
[2]
|
Yes
|
2 months
|
No
|
Shakhatreh M, et al. [33]
|
T/C
|
10
|
N/E
|
Yes
|
EBL + OTSC
|
No
|
Yes
|
Yes
|
No
|
No follow-up
|
Valli P, et al.[34]
|
A/C
|
13
|
N/E
|
Yes
|
OTSC
|
No
|
Yes
|
Yes
|
3 months
|
No
|
ESD, endoscopic submucosal dissection; T/C transverse colon; A/C, ascending colon;
N/E, not specified; EMR, endoscopic mucosal resection; OTSC, over-the-scope clip;
EBL, elastic band ligation.
1 Complete resection was defined as en-bloc resection with tumor-free margins on pathological
assessment (R0).
2 Specimen not obtained.
This study had some limitations. First, it was retrospective and observational, performed
in two referral centers and lacking in a control group. Second, all procedures were
performed by experienced Japanese endoscopists, which could be a limitation. However,
use of ESD has been spreading worldwide and good outcomes with it have been reported.
Results of this study with use of ESD for tumor near the diverticulum are generalizable.
Regarding ESD for tumor involving diverticulum, accumulation of traction-assisted
ESD cases is expected.
Conclusion
The case series presented here indicates that ESD is safe and feasible for treatment
of colorectal tumors near a diverticulum and might be feasible for tumors involving
a diverticulum smaller than 6 mm. Small diverticulum size may be a predictor of better
outcome for ESD treatment of tumors involving a diverticulum.