Introduction
The therapeutic strategy for superficial duodenal neoplasms (SDNs) remains unestablished.
Although endoscopic resection can be a curative procedure for such lesions [1], it still remains technically challenging because of the high risk of severe adverse
events (SAEs) including delayed perforation [2]. On the other hand, surgical treatment of such lesions often results in extensive
resections, causing significant morbidity. Recently, laparoscopic and/or endoscopic
full-thickness resection (FTR) has been reported to be a useful technique for the
treatment of nonampullary SDNs [3]
[4]
[5]. Despite their minimally invasive nature, all FTR procedures are associated with
the possibility of intraperitoneal tumor dissemination. Therefore, we developed an
alternative FTR method, which we call laparoscopy-assisted endoscopic full-thickness
resection with ligation device (LAEFTR-L). Herein we report on resection of nonampullary
SDNs using LAEFTR-L in 5 consecutive patients and an evaluation of the efficacy and
safety of these procedures.
Case reports
Patients
From June 2015 to September 2015, 5 patients underwent resection of nonampullary SDNs
using LAEFTR-L. Written informed consent was obtained from each patient. This study
was approved by the ethics committee of the NTT Medical Center.
LAEFTR-L procedure
The LAEFTR-L procedure was performed under general anesthesia. The set up for the
LAEFTR-L procedure was previously described [3]. After mobilizing the duodenum from the retroperitoneum, a forward-viewing endoscope
(GIF260J; Olympus, Medical Systems Corp., Tokyo, Japan) was inserted into the duodenum
and the target lesion was identified ([Fig. 1a]). Endoscopic light was used to help the surgeon identify the tumor location. Using
an endoclip as a marker, the tumor (including the seromuscular layer) was ligated
using a ligation device (PNEUMO-ACTIVATE EVL DEVICE; Sumitomo Bakelite Corp., Ltd.
Tokyo, Japan) ([Fig. 1b]). The laparoscopist then temporarily sutured the seromuscular layer, after confirming
the presence of a full-thickness aspirated sign ([Fig. 2a]). Then, an endoscopist resected the targeted lesion under the ligation band using
snare technique ([Fig. 1c], [Fig. 1d], [Fig. 1e]). Consequently, the presutured site was reinforced laparoscopically ([Fig. 2b]). Finally, the specimen was retrieved intraluminally using the endoscope ([Fig. 1f]). Despite the lack of a seromuscular layer, the provisional and additional sutures
prevented exposure of the abdominal cavity to malignant cells. In addition, vessels
were ligated during the closure of the defect in the duodenal wall. Therefore, the
LAEFTR-L procedure was completed in a closed manner without complications.
Fig. 1 Endoscopic findings of laparoscopy-assisted endoscopic full-thickness resection with
ligation device for superficial duodenal neoplasm. a A flat elevated lesion, measuring 15 mm in diameter, located at the opposite side
of the ampulla of Vater. b Using an endoclip as a marker, the targeted lesion was ligated with a ligation device.
c The tissue including the target lesion was resected with a snare technique. d Resection site. e Laparoscopic temporary suture secures patency of the duodenal wall. f Resected lesion after administration of 0.1 % indigo carmine solution.
Fig. 2 Laparoscopic findings of laparoscopy-assisted endoscopic full-thickness resection
with ligation device for superficial duodenal neoplasm. a Full-thickness aspirated sign, which helps the surgeon accurately identify the tumor
location. b The presutured site was reinforced to prevent delayed perforation and/or bleeding.
Inhibitors of gastric acid and protease secretion were administered to the patients
during their hospitalizations. A normal diet was resumed approximately 2 days after
the procedure, and the patients were discharged after a 1-week hospital stay.
Clinical outcomes
All lesions were successfully resected with the LAEFTR-L procedure. Clinicopathological
characteristics are shown in [Table 1]. Two of the 5 tumors were located at the duodenal bulb, and the others at the second
part of the duodenum (opposite to the ampulla of Vater). The mean operative time was
173 minutes (range 138 – 217 minutes). Mean diameter of the resected specimen was
24 mm (range 18 – 32 mm), and the mean tumor size was 9 mm (range 7 – 11 mm). Complete
resection was achieved, and full-thickness resection was histologically confirmed
in all cases ([Fig. 3]). Two of the 5 lesions were intramucosal carcinoma. No AEs were observed. Importantly,
all the procedures were completed without the tumors contacting the peritoneum.
Table 1
Characteristics and therapeutic results of the enrolled patients.
Case
|
Age
|
Sex
|
Location
|
Total operative (endoscopic resection) time (min)
|
Size of resected specimen (mm)
|
Tumor size (mm)
|
Macroscopic classification
|
Pathological diagnosis
|
R0 resection
|
Hospital stay, day
|
Adverse events
|
1
|
60
|
M
|
Second part of duodenum Opposite the papilla of Vater
|
180 (5)
|
20
|
9
|
depressed
|
Cancer
|
Yes
|
8
|
None
|
2
|
50
|
F
|
Second part of duodenum Opposite the papilla of Vater
|
143 (4)
|
18
|
11
|
Depressed
|
Adenoma
|
Yes
|
7
|
None
|
3
|
52
|
M
|
Third part of duodenum Anterior wall
|
187 (4)
|
26
|
7
|
Flat-elevated
|
Adenoma
|
Yes
|
6
|
None
|
4
|
65
|
M
|
Second part of duodenum Opposite the papilla of Vater
|
138 (3)
|
32
|
7
|
Depressed
|
Adenoma
|
Yes
|
8
|
None
|
5
|
68
|
M
|
Duodenal bulb, Posterior wall
|
217 (5)
|
24
|
11
|
Flat-elevated
|
Cancer
|
Yes
|
7
|
None
|
Fig. 3 Pathological findings. HE staining of resected specimen (Case 1). Intraepithelial
adenocarcinoma was completely resected with the muscular layer. a Low magnification. b High magnification.
Discussion
Because the malignant potential of SDN is difficult to define from the preoperative
endoscopic diagnosis [6], complete en-bloc resection is necessary to achieve appropriate pathological evaluation and treatment.
Although conventional endoscopic mucosal resection (EMR) could be a curative strategy
for SDNs, complete resection is challenging, especially for flat or non-lifting lesions.
In recent years, the indications for ESD have been expanded to SDNs [7]. However, delayed perforation in the duodenum, in particular, may cause potentially
fatal peritonitis or retroperitoneal complications, requiring emergency open surgery
to counter leakage of bile and pancreatic juices [8]. Moreover the technical difficulty of this procedure is extremely high, due to the
poor maneuverability of the endoscope and the thin wall. Therefore, duodenal ESD is
not a standard clinical procedure. On the other hand, laparoscopic FTR procedures
reportedly achieve higher complete resection rates without SAEs [3]
[4]. Although short-term clinical outcomes were preferable, we need to consider the
risk of intraperitoneal tumor dissemination, given the lack of data on long-term outcomes
in patients undergoing conventional FTR procedures.
Compared with conventional FTR procedures, LAEFTR-L has two advantages. Most importantly,
the resected specimen can be collected intraluminally, avoiding contact with the peritoneum.
Shen et al. conducted an animal model study and revealed that pneumoperitoneum from laparoscopic
surgery could be a risk factor for peritoneal dissemination of tumor cells [9]. Because long-term outcomes of SDNs treated with the conventional FTR method rarely
have been investigated, peritoneal exposure of tumor cells should be avoided as far
as possible. Moreover, LAEFTR-L does not require proficient experience in ESD. The
simplicity of this procedure enables endoscopists to resect target lesions easily.
Indeed, total operative time was not different from previous reports on conventional
FTR for SDNs [3]
[4], and endoscopic resection time was even significantly shorter.
Tumor size is a major limiting factor when considering the indication for LAEFTR.
In the current study, mean specimen size was 24 mm. Lee et al. reported that esophageal
subepithelial lesions no larger than 13 mm could be successfully resected by EMR with
a ligation device [10]. Considering the size of the ligation device, lesions smaller than 15 mm in diameter
may be candidates for this procedure. Although additional studies are needed, application
of a large oblique cap may enable en-bloc resection of larger lesions. In addition, tumor location is also important to decisions
about the indication for LAEFTR-L. LAEFTR-L cannot to be applied to lesions close
to the ampulla of Vater, because mobilization of these portions is technically difficult
with laparoscopic procedures.
In conclusion, LAEFTR-L may be a promising technique for the treatment of nonampullary
SDNs which can achieve complete resection without peritoneal exposure of tumor cells
or SAEs. Prospective studies are needed to further evaluate the efficacy and safety
of LAEFTR-L procedures.