Innovations and brief communications
529
Authors
Kenichiro Imai1, Kinichi Hotta1, Yuichiro Yamaguchi1, Tomoaki Shinohara2, Shohei Ooka3, Kei Shinoki3, Naomi Kakushima1, Masaki Tanaka1, Kohei Takizawa1, Hiroyuki Matsubayashi1, Takuma Oishi4, Hiroyuki Ono1
Institutions
Institutions are listed at the end of article.
submitted 26. December 2013 accepted after revision 30. September 2014
Background and study aims: Unique anatomical features render endoscopic resection for rectal tumors extending to the dentate line (RTDL) technically challenging. The aim of this study was to evaluate the feasibility of endoscopic submucosal dissection (ESD) for RTDLs. Patients and methods: This retrospective study compared ESD for RTDLs with proximal rectal tumors between September 2002 and June 2012. En bloc resection rate, R0 resection rate, complications, and tumor recurrences were assessed. Results: A total of 45 RTDLs (median age 69 years; 15 males; median lesion size 38.4 mm) and 94 proximal rectal tumors were identified. En bloc re-
section and R0 resection rates were 95.6 % (43/45) and 53.3 % (24/45), respectively. The perforation rate was 4.4 %. Compared with proximal rectal ESD, ESD for RTDLs showed longer procedure time (104 vs. 60 minutes; P < 0.001), lower R0 resection rate (53.3 % vs. 70.2 %; P = 0.019), and more frequent high grade fever (22.2 % vs. 4.3 %; P = 0.002). No residual adenoma was observed at the first surveillance colonoscopy. Recurrence rate did not differ significantly between the two groups. Conclusions: ESD for RTDLs demonstrated safety and effectiveness comparable to ESD in proximal rectal lesions.
Introduction
tients. Study approval was obtained from the Institutional Review Board of Shizuoka Cancer Center. The inclusion criterion was intraepithelial neoplasm involving the dentate line, which was diagnosed endoscopically to extend no deeper than the shallow submucosal layer. High risk for recurrence was defined based on the following histological conditions: positive margins; a deep submucosal cancer (> 1000 µm); or lymphovascular permeation or poor differentiated-type histology. R0 resection was defined as a pathologically negative margin resection. Rx resection occurred when the tumor infiltration at the margin could not be determined. Patients with R0 or Rx resection underwent follow-up colonoscopy 12 or 6 months after ESD, respectively. En bloc resection rate, R0 resection rate, complications, pathological diagnoses, and tumor recurrence were assessed. To clarify the procedural features in RTDL, the characteristics and ESD outcomes of RTDL were compared with those of consecutive proximal rectal lesions treated with ESD at one of the three participating institutions during the same period.
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1391078 Published online: 11.12.2014 Endoscopy 2015; 47: 529–532 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0013-726X Corresponding author Kenichiro Imai, MD Division of Endoscopy Shizuoka Cancer Center 1007 Shimonagakubo Nagaizumicho Suntougun Shizuoka 411-8777 Japan Fax: 81-55-989-5634 [email protected]
!
Rectal tumors extending to the dentate line (RTDL) are considered difficult to remove endoscopically because of the narrow lumen, the risk of bleeding from the rectal venous plexus, and anal pain through sensory nerves in the anoderm [1, 2]. There is also the theoretical risk of systemic bacteremia because of direct drainage to the systemic circulation. Therefore, modified procedures may be needed for endoscopic resection in this region. Endoscopic submucosal dissection (ESD) has been introduced as an effective treatment with high en bloc resection rates that provides complete tumor elimination and precise histological assessment [3]. However, few data for ESD of RTDLs are available [4]. This multicenter cohort study aimed to evaluate the feasibility of ESD for RTDLs.
Patients and methods !
ESD for RTDLs was performed in patients at three institutions between September 2002 and June 2012. Written consent was obtained from all pa-
Imai Kenichiro et al. Endoscopic resection of rectal tumors … Endoscopy 2015; 47: 529–532
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Safety and efficacy of endoscopic submucosal dissection of rectal tumors extending to the dentate line
Innovations and brief communications
ESD procedures Midazolam (mean 3.19 ± 3.04 mg) and pethidine (fixed dose 35 mg) were administered intravenously. Carbon dioxide insufflation was used. A gastroscope with a water-jet system (GIFQ260J; Olympus Medical Systems Corp., Tokyo, Japan), a standard electrosurgical generator (ICC200 or VIO300D; ERBE, Tübingen, Germany), and one or two knives, including a revised insulation-tipped knife (ITknife 2), ITknife nano, Flex knife, Dual knife, and Hook knife (Olympus) were used [5]. Hemostatic forceps (Coagrasper; Olympus) were used for hemostasis of bleeding.
Modified ESD techniques for RTDLs
" Video 1). ESD techniques were modified for RTDLs as follows (● 1. A transparent hood was attached to the tip of the gastroscope to maintain good visualization and obtain good scope oper" Fig. 1 a). ability in the narrow space at the anal canal (● 2. To prevent pain, 1 % lidocaine (100 mg/10 mL) was injected into the submucosa, as previously reported [6]. A nonsteroidal anti-inflammatory drug (NSAID) was administered for postoperative persistent anal pain. 3. It was necessary to employ a horizontal approach with the ESD knives to minimize thermal damage to the muscular layer. This approach was accomplished by positioning the lesion in line with the gastroscope device port. 4. A resection line at the anal side was defined under direct visualization of the tumor margin. After a shallow mucosal incision, direct visualization of the submucosa enabled ade" Fig. 1 b). When thick, swollen quate handling of the vessels (● hemorrhoidal columns were observed, preventive hemostasis was performed.
Statistical analysis The Mann–Whitney U test was used for continuous variables, and the chi-squared test or Fisher’s exact test, as appropriate, was used for categorical variables. All tests were two tailed. A P value of < 0.05 was considered to be statistically significant using JMP software (version 8.0; SAS Institute Inc., Cary, North Carolina, USA).
Results !
From 1019 patients undergoing ESD at the three centers, 45 (median age 69 years) were included in the study. A total of 94 consecutive proximal rectal lesions were also treated with ESD at the participating institutions during the same period. Institutional volumes of colorectal ESD at the three institutions were 140, 40, and 30 cases per year, respectively.
Video 1
Endoscopic submucosal dissection of Online content including rectal tumors extending to the den- video sequences viewable at: www.thieme-connect.de tate line.
Fig. 1 Endoscopic submucosal dissection of rectal tumors extending to the dentate line. a This front-facing view demonstrates that the tumor margin at the anal side of the lesion extends to the dentate line. b Vessels in the submucosal layer were visible after mucosal incision at the anal side of the lesion.
" Table 1. ESD Patient and lesion characteristics are shown in ● " Table 2. The median lesion size outcomes are presented in ● was 38.4 mm. The median procedure time was 104 minutes (range 25 – 420 minutes). The en bloc resection rate and R0 resection rate were 95.6 % (43/45) and 53.3 % (24/45), respectively " Table 2, ● " Fig. 2). (● Perforation occurred in two patients (4.4 %) and postoperative bleeding occurred in one patient (2.2 %). Both complications were successfully managed endoscopically. No association between the presence of hemorrhoid and perioperative bleeding was observed. Although 10 patients (22.2 %) experienced postoperative high grade fever (> 38 °C), they recovered without clinical symptoms of septic disease after the administration of antibiotics for a few days. Antibiotics were used prophylactically in 16 cases. High grade fever occurred in 18.8 % (3/16) or 24.1 % (7/29) of patients with or without prophylactic antibiotics use, respectively. No significant association between prophylactic antibiotic administration and high grade fever was observed (P = 0.68).
Imai Kenichiro et al. Endoscopic resection of rectal tumors … Endoscopy 2015; 47: 529–532
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
530
Innovations and brief communications
Patient and lesion characteristics.
Age, median (range), years
RTDL
Proximal rectal
(n = 45)
(n = 94)
69 (30 – 85)
69 (34 – 88)
0.47
Sex, n (%)
0.0002
Male
15 (33.3)
63 (67.0)
Female
30 (66.7)
31 (33.0)
38.4 (9 – 80) 1
34 (5 – 85)
LST
34 (75.6)
71 (75.5)
Protruding
9 (20.0)
15 (16.0)
Depressed
0
3 (3.2)
Scar lesion 2
2 (4.4)
5 (5.3)
17 (37.8)
18 (19.1)
Tumor size, median (range), mm
0.37
Macroscopic type, n (%)
0.62
Histology, n (%) Adenoma
0.07
Tis (M)
21 (46.7)
57 (60.6)
T1 (SM)
7 (15.6)
26 (27.7)
Incidence of hemorrhoid, n (%)
P
Discussion !
11 (24.4)
RTDL, rectal tumor extending to the dentate line; LST, laterally spreading tumor; Tis (M), mucosal cancer without invasion into the submucosal layer; T1 (SM), submucosal invasive cancer. 1 Even small tumors 9 mm in size were resected by ESD because of concomitant scar after previous treatments. 2 A scar lesion was defined as an intraepithelial tumor with submucosal fibrosis showing nonlifting signs caused by previous endoscopic treatment.
No patients complained of anal pain during the procedures. Postoperative anal pain was observed in 12 patients (26.7 %); however, pain improved when an NSAID was administered for a few days after ESD. One (2.2 %) symptomatic proctostenosis was observed, but the patient recovered following incidental colonoscopic bougie dilation at the first surveillance colonoscopy. Of the five patients at high risk for recurrence, two underwent additional surgery (intersphincteric resection) with lymph node dissection, and pathology revealed no residual cancer in the surgical specimens and no metastasis. Two patients developed metastatic diseases, and the remaining patient had no evidence of recurrence. Of the remaining 40 patients with no high risk for
Table 2
recurrence, 38 underwent surveillance colonoscopy, and no residual adenoma was observed at the ESD scar during a median follow-up period of 17.8 months (range 6 – 77 months). Comparison of characteristics between RTDLs and proximal rec" Table 1. There were no significant diftal lesions are shown in ● ferences in the parameters except for patient sex. ESD for RTDLs was characterized by a significantly longer procedure time (104 vs. 60 minutes; P < 0.001) and lower R0 resection rate (53.3 % vs. 70.2 %; P = 0.019) compared with ESD for proximal rectal lesions. However, the procedures did not differ significantly regarding recurrence rates. Complications were frequent in the RTDL group because of a higher incidence of high grade fever (22.2 % vs. 4.3 %; P = 0.002), postoperative anal pain (26.7 % vs. 0 %; P < 0.001), and proctostenosis (2.2 % vs. 0 %; P = 0.32).
Endoscopic resection of RTDLs is limited because of the pain associated with injury at the anoderm. Previously, we reported effectiveness of local lidocaine injection in preventing intraoperative pain in a patient with RTDL. By accumulating cases, prolonged anal pain for a few days after ESD has emerged in 27 % of our series. Although use of a long-acting local anesthetic has been proposed, it could not address pain lasting a few days [7]. In our experience, the safety and efficacy of combined local lidocaine injection and NSAID administration for perioperative anal pain has been verified. The profuse fibrovascular submucosa at the anal canal required frequent hemostasis or submucosal injections in the current series. These procedures may increase the risk of bacteremia owing to the unique direct drainage system via the venous plexus into the systemic circulation. High grade fever was significantly more frequent in patients with RTDLs than in those with proximal rectal lesions. Thus, prophylactic antibiotics should be considered in ESD for RTDLs. Although no association was observed between high grade fever and prophylactic antibiotic use, further study in large series will be required on this issue. The rich vascularity in the submucosa or the presence of submucosal hemorrhage may cause intraoperative bleeding. During
Comparison of endoscopic submucosal dissection outcomes between rectal tumors extending to the dentate line and proximal rectal lesions.
RTDL (n = 45)
Procedure time, median (range), minutes
Proximal rectal (n = 94)
P
Frequency
95 %CI
Frequency
95 %CI
104 (25 – 420)
109 – 171
60 (20 – 326)
69.3 – 94.3
< 0.001
Resection rates, n (%) En bloc
43 (95.6)
85.1 – 98.8
85 (90.4)
82.8 – 94.9
0.50
R0
24 (53.3)
39.1 – 67.1
60 (63.8)
60.3 – 78.5
0.019
R1
1 (2.2)
0.4 – 11.6
11 (11.7)
6.7 – 19.8
Rx
20 (44.4)
30.9 – 58.8
17 (18.1)
11.6 – 27.1
2 (4.4)
1.3 – 15.4
1 (1.1)
0.2 – 5.8
0.26
Recurrence rate, n (%) Local residual disease Metastatic disease
0
1 (1.1)
2 (4.4)
0
Perforation, n (%)
2 (4.4)
1.2 – 14.8
2 (2.1)
5.9 – 7.4
0.59
Postoperative bleeding, n (%)
1 (2.2)
0.4 – 11.5
1 (1.1)
1.9 – 5.8
0.24
High grade fever (> 38 °C), n (%)
10 (22.2)
12.5 – 36.3
4 (4.3)
1.7 – 10.4
0.002
Postoperative anal pain, n (%)
12 (26.7)
15.9 – 41.0
0
< 0.001
1 (2.2)
0.4 – 11.5
0
0.32
Proctostenosis, n (%)
RTDL, rectal tumors extending to the dentate line; CI, confidence interval.
Imai Kenichiro et al. Endoscopic resection of rectal tumors … Endoscopy 2015; 47: 529–532
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Table 1
531
Innovations and brief communications
Patients with RTDL (n = 60) Excluded (n = 15) Deeper submucosal invasion (n = 11) Combined surgery* (n = 4) Patients with RTDL underwent ESD (n = 45)
En bloc resection (n = 43)
R0/Rx resection (n = 24 /18)
R1 resection (n = 1)
Low-risk for recurrence (n = 38)
High-risk for recurrence† (n = 5)
Follow-up (n = 38)
Follow-up (n = 3)
No recurrence n = 38
Recurrence n=2
Procedure failure (n = 2)
Re-EMR (n = 1)
Additional surgery (n = 3)
Fig. 2 Flow chart of patients who underwent endoscopic submucosal dissection for rectal tumors extending to the dentate line. * Until local lidocaine injection was developed, rectal tumors extending to the dentate line were mainly treated with combined endoscopy and surgical resection under spinal anesthesia: endoscopic submucosal dissection at the oral side of each lesion and perianal surgical resection at the anal side of each lesion. †The main reasons for high risk for recurrence were shallow submucosal invasive cancer within 1000 µm with lymphovascular permeation (n = 1), and submucosal invasive cancer deeper than 1000 µm with lymphovascular permeation (n = 1) or without lymphovascular permeation (n = 3). RTDL, rectal tumors extending to the dentate line; ESD, endoscopic submucosal dissection; EMR, endoscopic mucosal resection.
Follow-up (n = 1)
No recurrence n=5
ESD, the submucosal layer can be directly visualized after mucosal incision. Consequently, the vessels can be managed appropriately while viewing the submucosa directly. The R0 resection rate was lower when ESD was employed to treat RTDL than proximal rectal lesions, mainly because of high Rx resection rates in RTDL owing to burning artifacts at the anal side of the specimens. Thermal damage from ESD knives easily passes through the muscularis mucosa because the submucosa is thin in the anal canal. Because no residual adenoma was observed after surveillance endoscopy, careful observation may be a choice for Rx resection in RTDL cases. In contrast, two metastases occurred in cases predicted to have high risk for recurrence. We suggest that additional surgery may be required for these cases in order to achieve complete cure. Although rare in the proximal rectum, postoperative complications, including high grade fever, persistent anal pain, and proctostenosis, were common in RTDLs. ESD for RTDL required careful postoperative observation and management. The effectiveness of modified endoscopic mucosal resection (EMR) for RTDL was reported recently [7]. ESD has several advantages over EMR. First, EMR was based on piecemeal resection, and multiple piecemeal resections can lead to insufficient tumor staging. In contrast, accurate staging by en bloc resection enables the application of ESD for possible invasive lesions. ESD also enables flexible setting of the resection line close to the tumor margin. This means that mucosal defects can be minimized, which may reduce the risk of stricture in semi-circumferential lesions. Transanal endoscopic microsurgery has been introduced for distal rectal lesions, with lower recurrence rates, which are favorable [8]. However, it requires general anesthesia, and severe complications are problematic [9]. In conclusion, ESD for RTDLs requires strict surveillance tests for Rx resection and attentive management for increased minor complications. However, ESD for RTDLs is feasible, with high rates
of complete tumor removal and en bloc resection for accurate staging that are comparable to ESD of proximal rectal lesions. Competing interests: None Institutions 1 Division of Endoscopy, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan 2 Department of Gastroenterology, Saku Central Hospital, Saku, Nagano, Japan 3 Division of Gastroenterology, Toshiba Rinkan Hospital, Sagamihara, Kanagawa, Japan 4 Division of Pathology, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan
References 1 Standring S. Gray’s anatomy: the anatomical basis of clinical practice. London: Churchill Livingstone; 2008 2 Duthie HL, Gairns FW. Sensory nerve-endings and sensation in the anal region of man. Br J Surg 1960; 47: 585 – 595 3 Saito Y, Uraoka T, Yamaguchi Y et al. A prospective, multicenter study of 1111 colorectal endoscopic submucosal dissections (with video). Gastrointest Endosc 2010; 72: 1217 – 1225 4 Nakadoi K, Tanaka S, Hayashi N et al. Clinical outcomes of endoscopic submucosal dissection for rectal tumor close to the dentate line. Gastrointest Endosc 2012; 76: 444 – 450 5 Hotta K, Yamaguchi Y, Saito Y et al. Current opinions for endoscopic submucosal dissection for colorectal tumors from our experiences: indications, technical aspects and complications. Dig Endosc 2012; 24: 110 6 Sanchez-Yague A, Yamaguchi Y, Takao T et al. Endoscopic submucosal dissection of a lower rectal polyp proximal to the dentate line by using local lidocaine injection. Gastrointest Endosc 2011; 73: 405 – 407 7 Holt BA, Bassan MS, Sexton A et al. Advanced mucosal neoplasia of the anorectal junction: endoscopic resection technique and outcomes (with videos). Gastrointest Endosc 2014; 79: 119 – 126 8 Barendse RM, van den Broek FJC, Dekker E et al. Systematic review of endoscopic mucosal resection versus transanal endoscopic microsurgery for large rectal adenomas. Endoscopy 2011; 43: 941 – 955 9 Bretagnol F, Merrie A, George B et al. Local excision of rectal tumours by transanal endoscopic microsurgery. Br J Surg 2007; 94: 627 – 633
Imai Kenichiro et al. Endoscopic resection of rectal tumors … Endoscopy 2015; 47: 529–532
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529
Authors
Kenichiro Imai1, Kinichi Hotta1, Yuichiro Yamaguchi1, Tomoaki Shinohara2, Shohei Ooka3, Kei Shinoki3, Naomi Kakushima1, Masaki Tanaka1, Kohei Takizawa1, Hiroyuki Matsubayashi1, Takuma Oishi4, Hiroyuki Ono1
Institutions
Institutions are listed at the end of article.
submitted 26. December 2013 accepted after revision 30. September 2014
Background and study aims: Unique anatomical features render endoscopic resection for rectal tumors extending to the dentate line (RTDL) technically challenging. The aim of this study was to evaluate the feasibility of endoscopic submucosal dissection (ESD) for RTDLs. Patients and methods: This retrospective study compared ESD for RTDLs with proximal rectal tumors between September 2002 and June 2012. En bloc resection rate, R0 resection rate, complications, and tumor recurrences were assessed. Results: A total of 45 RTDLs (median age 69 years; 15 males; median lesion size 38.4 mm) and 94 proximal rectal tumors were identified. En bloc re-
section and R0 resection rates were 95.6 % (43/45) and 53.3 % (24/45), respectively. The perforation rate was 4.4 %. Compared with proximal rectal ESD, ESD for RTDLs showed longer procedure time (104 vs. 60 minutes; P < 0.001), lower R0 resection rate (53.3 % vs. 70.2 %; P = 0.019), and more frequent high grade fever (22.2 % vs. 4.3 %; P = 0.002). No residual adenoma was observed at the first surveillance colonoscopy. Recurrence rate did not differ significantly between the two groups. Conclusions: ESD for RTDLs demonstrated safety and effectiveness comparable to ESD in proximal rectal lesions.
Introduction
tients. Study approval was obtained from the Institutional Review Board of Shizuoka Cancer Center. The inclusion criterion was intraepithelial neoplasm involving the dentate line, which was diagnosed endoscopically to extend no deeper than the shallow submucosal layer. High risk for recurrence was defined based on the following histological conditions: positive margins; a deep submucosal cancer (> 1000 µm); or lymphovascular permeation or poor differentiated-type histology. R0 resection was defined as a pathologically negative margin resection. Rx resection occurred when the tumor infiltration at the margin could not be determined. Patients with R0 or Rx resection underwent follow-up colonoscopy 12 or 6 months after ESD, respectively. En bloc resection rate, R0 resection rate, complications, pathological diagnoses, and tumor recurrence were assessed. To clarify the procedural features in RTDL, the characteristics and ESD outcomes of RTDL were compared with those of consecutive proximal rectal lesions treated with ESD at one of the three participating institutions during the same period.
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1391078 Published online: 11.12.2014 Endoscopy 2015; 47: 529–532 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0013-726X Corresponding author Kenichiro Imai, MD Division of Endoscopy Shizuoka Cancer Center 1007 Shimonagakubo Nagaizumicho Suntougun Shizuoka 411-8777 Japan Fax: 81-55-989-5634 [email protected]
!
Rectal tumors extending to the dentate line (RTDL) are considered difficult to remove endoscopically because of the narrow lumen, the risk of bleeding from the rectal venous plexus, and anal pain through sensory nerves in the anoderm [1, 2]. There is also the theoretical risk of systemic bacteremia because of direct drainage to the systemic circulation. Therefore, modified procedures may be needed for endoscopic resection in this region. Endoscopic submucosal dissection (ESD) has been introduced as an effective treatment with high en bloc resection rates that provides complete tumor elimination and precise histological assessment [3]. However, few data for ESD of RTDLs are available [4]. This multicenter cohort study aimed to evaluate the feasibility of ESD for RTDLs.
Patients and methods !
ESD for RTDLs was performed in patients at three institutions between September 2002 and June 2012. Written consent was obtained from all pa-
Imai Kenichiro et al. Endoscopic resection of rectal tumors … Endoscopy 2015; 47: 529–532
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Safety and efficacy of endoscopic submucosal dissection of rectal tumors extending to the dentate line
Innovations and brief communications
ESD procedures Midazolam (mean 3.19 ± 3.04 mg) and pethidine (fixed dose 35 mg) were administered intravenously. Carbon dioxide insufflation was used. A gastroscope with a water-jet system (GIFQ260J; Olympus Medical Systems Corp., Tokyo, Japan), a standard electrosurgical generator (ICC200 or VIO300D; ERBE, Tübingen, Germany), and one or two knives, including a revised insulation-tipped knife (ITknife 2), ITknife nano, Flex knife, Dual knife, and Hook knife (Olympus) were used [5]. Hemostatic forceps (Coagrasper; Olympus) were used for hemostasis of bleeding.
Modified ESD techniques for RTDLs
" Video 1). ESD techniques were modified for RTDLs as follows (● 1. A transparent hood was attached to the tip of the gastroscope to maintain good visualization and obtain good scope oper" Fig. 1 a). ability in the narrow space at the anal canal (● 2. To prevent pain, 1 % lidocaine (100 mg/10 mL) was injected into the submucosa, as previously reported [6]. A nonsteroidal anti-inflammatory drug (NSAID) was administered for postoperative persistent anal pain. 3. It was necessary to employ a horizontal approach with the ESD knives to minimize thermal damage to the muscular layer. This approach was accomplished by positioning the lesion in line with the gastroscope device port. 4. A resection line at the anal side was defined under direct visualization of the tumor margin. After a shallow mucosal incision, direct visualization of the submucosa enabled ade" Fig. 1 b). When thick, swollen quate handling of the vessels (● hemorrhoidal columns were observed, preventive hemostasis was performed.
Statistical analysis The Mann–Whitney U test was used for continuous variables, and the chi-squared test or Fisher’s exact test, as appropriate, was used for categorical variables. All tests were two tailed. A P value of < 0.05 was considered to be statistically significant using JMP software (version 8.0; SAS Institute Inc., Cary, North Carolina, USA).
Results !
From 1019 patients undergoing ESD at the three centers, 45 (median age 69 years) were included in the study. A total of 94 consecutive proximal rectal lesions were also treated with ESD at the participating institutions during the same period. Institutional volumes of colorectal ESD at the three institutions were 140, 40, and 30 cases per year, respectively.
Video 1
Endoscopic submucosal dissection of Online content including rectal tumors extending to the den- video sequences viewable at: www.thieme-connect.de tate line.
Fig. 1 Endoscopic submucosal dissection of rectal tumors extending to the dentate line. a This front-facing view demonstrates that the tumor margin at the anal side of the lesion extends to the dentate line. b Vessels in the submucosal layer were visible after mucosal incision at the anal side of the lesion.
" Table 1. ESD Patient and lesion characteristics are shown in ● " Table 2. The median lesion size outcomes are presented in ● was 38.4 mm. The median procedure time was 104 minutes (range 25 – 420 minutes). The en bloc resection rate and R0 resection rate were 95.6 % (43/45) and 53.3 % (24/45), respectively " Table 2, ● " Fig. 2). (● Perforation occurred in two patients (4.4 %) and postoperative bleeding occurred in one patient (2.2 %). Both complications were successfully managed endoscopically. No association between the presence of hemorrhoid and perioperative bleeding was observed. Although 10 patients (22.2 %) experienced postoperative high grade fever (> 38 °C), they recovered without clinical symptoms of septic disease after the administration of antibiotics for a few days. Antibiotics were used prophylactically in 16 cases. High grade fever occurred in 18.8 % (3/16) or 24.1 % (7/29) of patients with or without prophylactic antibiotics use, respectively. No significant association between prophylactic antibiotic administration and high grade fever was observed (P = 0.68).
Imai Kenichiro et al. Endoscopic resection of rectal tumors … Endoscopy 2015; 47: 529–532
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
530
Innovations and brief communications
Patient and lesion characteristics.
Age, median (range), years
RTDL
Proximal rectal
(n = 45)
(n = 94)
69 (30 – 85)
69 (34 – 88)
0.47
Sex, n (%)
0.0002
Male
15 (33.3)
63 (67.0)
Female
30 (66.7)
31 (33.0)
38.4 (9 – 80) 1
34 (5 – 85)
LST
34 (75.6)
71 (75.5)
Protruding
9 (20.0)
15 (16.0)
Depressed
0
3 (3.2)
Scar lesion 2
2 (4.4)
5 (5.3)
17 (37.8)
18 (19.1)
Tumor size, median (range), mm
0.37
Macroscopic type, n (%)
0.62
Histology, n (%) Adenoma
0.07
Tis (M)
21 (46.7)
57 (60.6)
T1 (SM)
7 (15.6)
26 (27.7)
Incidence of hemorrhoid, n (%)
P
Discussion !
11 (24.4)
RTDL, rectal tumor extending to the dentate line; LST, laterally spreading tumor; Tis (M), mucosal cancer without invasion into the submucosal layer; T1 (SM), submucosal invasive cancer. 1 Even small tumors 9 mm in size were resected by ESD because of concomitant scar after previous treatments. 2 A scar lesion was defined as an intraepithelial tumor with submucosal fibrosis showing nonlifting signs caused by previous endoscopic treatment.
No patients complained of anal pain during the procedures. Postoperative anal pain was observed in 12 patients (26.7 %); however, pain improved when an NSAID was administered for a few days after ESD. One (2.2 %) symptomatic proctostenosis was observed, but the patient recovered following incidental colonoscopic bougie dilation at the first surveillance colonoscopy. Of the five patients at high risk for recurrence, two underwent additional surgery (intersphincteric resection) with lymph node dissection, and pathology revealed no residual cancer in the surgical specimens and no metastasis. Two patients developed metastatic diseases, and the remaining patient had no evidence of recurrence. Of the remaining 40 patients with no high risk for
Table 2
recurrence, 38 underwent surveillance colonoscopy, and no residual adenoma was observed at the ESD scar during a median follow-up period of 17.8 months (range 6 – 77 months). Comparison of characteristics between RTDLs and proximal rec" Table 1. There were no significant diftal lesions are shown in ● ferences in the parameters except for patient sex. ESD for RTDLs was characterized by a significantly longer procedure time (104 vs. 60 minutes; P < 0.001) and lower R0 resection rate (53.3 % vs. 70.2 %; P = 0.019) compared with ESD for proximal rectal lesions. However, the procedures did not differ significantly regarding recurrence rates. Complications were frequent in the RTDL group because of a higher incidence of high grade fever (22.2 % vs. 4.3 %; P = 0.002), postoperative anal pain (26.7 % vs. 0 %; P < 0.001), and proctostenosis (2.2 % vs. 0 %; P = 0.32).
Endoscopic resection of RTDLs is limited because of the pain associated with injury at the anoderm. Previously, we reported effectiveness of local lidocaine injection in preventing intraoperative pain in a patient with RTDL. By accumulating cases, prolonged anal pain for a few days after ESD has emerged in 27 % of our series. Although use of a long-acting local anesthetic has been proposed, it could not address pain lasting a few days [7]. In our experience, the safety and efficacy of combined local lidocaine injection and NSAID administration for perioperative anal pain has been verified. The profuse fibrovascular submucosa at the anal canal required frequent hemostasis or submucosal injections in the current series. These procedures may increase the risk of bacteremia owing to the unique direct drainage system via the venous plexus into the systemic circulation. High grade fever was significantly more frequent in patients with RTDLs than in those with proximal rectal lesions. Thus, prophylactic antibiotics should be considered in ESD for RTDLs. Although no association was observed between high grade fever and prophylactic antibiotic use, further study in large series will be required on this issue. The rich vascularity in the submucosa or the presence of submucosal hemorrhage may cause intraoperative bleeding. During
Comparison of endoscopic submucosal dissection outcomes between rectal tumors extending to the dentate line and proximal rectal lesions.
RTDL (n = 45)
Procedure time, median (range), minutes
Proximal rectal (n = 94)
P
Frequency
95 %CI
Frequency
95 %CI
104 (25 – 420)
109 – 171
60 (20 – 326)
69.3 – 94.3
< 0.001
Resection rates, n (%) En bloc
43 (95.6)
85.1 – 98.8
85 (90.4)
82.8 – 94.9
0.50
R0
24 (53.3)
39.1 – 67.1
60 (63.8)
60.3 – 78.5
0.019
R1
1 (2.2)
0.4 – 11.6
11 (11.7)
6.7 – 19.8
Rx
20 (44.4)
30.9 – 58.8
17 (18.1)
11.6 – 27.1
2 (4.4)
1.3 – 15.4
1 (1.1)
0.2 – 5.8
0.26
Recurrence rate, n (%) Local residual disease Metastatic disease
0
1 (1.1)
2 (4.4)
0
Perforation, n (%)
2 (4.4)
1.2 – 14.8
2 (2.1)
5.9 – 7.4
0.59
Postoperative bleeding, n (%)
1 (2.2)
0.4 – 11.5
1 (1.1)
1.9 – 5.8
0.24
High grade fever (> 38 °C), n (%)
10 (22.2)
12.5 – 36.3
4 (4.3)
1.7 – 10.4
0.002
Postoperative anal pain, n (%)
12 (26.7)
15.9 – 41.0
0
< 0.001
1 (2.2)
0.4 – 11.5
0
0.32
Proctostenosis, n (%)
RTDL, rectal tumors extending to the dentate line; CI, confidence interval.
Imai Kenichiro et al. Endoscopic resection of rectal tumors … Endoscopy 2015; 47: 529–532
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Table 1
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Innovations and brief communications
Patients with RTDL (n = 60) Excluded (n = 15) Deeper submucosal invasion (n = 11) Combined surgery* (n = 4) Patients with RTDL underwent ESD (n = 45)
En bloc resection (n = 43)
R0/Rx resection (n = 24 /18)
R1 resection (n = 1)
Low-risk for recurrence (n = 38)
High-risk for recurrence† (n = 5)
Follow-up (n = 38)
Follow-up (n = 3)
No recurrence n = 38
Recurrence n=2
Procedure failure (n = 2)
Re-EMR (n = 1)
Additional surgery (n = 3)
Fig. 2 Flow chart of patients who underwent endoscopic submucosal dissection for rectal tumors extending to the dentate line. * Until local lidocaine injection was developed, rectal tumors extending to the dentate line were mainly treated with combined endoscopy and surgical resection under spinal anesthesia: endoscopic submucosal dissection at the oral side of each lesion and perianal surgical resection at the anal side of each lesion. †The main reasons for high risk for recurrence were shallow submucosal invasive cancer within 1000 µm with lymphovascular permeation (n = 1), and submucosal invasive cancer deeper than 1000 µm with lymphovascular permeation (n = 1) or without lymphovascular permeation (n = 3). RTDL, rectal tumors extending to the dentate line; ESD, endoscopic submucosal dissection; EMR, endoscopic mucosal resection.
Follow-up (n = 1)
No recurrence n=5
ESD, the submucosal layer can be directly visualized after mucosal incision. Consequently, the vessels can be managed appropriately while viewing the submucosa directly. The R0 resection rate was lower when ESD was employed to treat RTDL than proximal rectal lesions, mainly because of high Rx resection rates in RTDL owing to burning artifacts at the anal side of the specimens. Thermal damage from ESD knives easily passes through the muscularis mucosa because the submucosa is thin in the anal canal. Because no residual adenoma was observed after surveillance endoscopy, careful observation may be a choice for Rx resection in RTDL cases. In contrast, two metastases occurred in cases predicted to have high risk for recurrence. We suggest that additional surgery may be required for these cases in order to achieve complete cure. Although rare in the proximal rectum, postoperative complications, including high grade fever, persistent anal pain, and proctostenosis, were common in RTDLs. ESD for RTDL required careful postoperative observation and management. The effectiveness of modified endoscopic mucosal resection (EMR) for RTDL was reported recently [7]. ESD has several advantages over EMR. First, EMR was based on piecemeal resection, and multiple piecemeal resections can lead to insufficient tumor staging. In contrast, accurate staging by en bloc resection enables the application of ESD for possible invasive lesions. ESD also enables flexible setting of the resection line close to the tumor margin. This means that mucosal defects can be minimized, which may reduce the risk of stricture in semi-circumferential lesions. Transanal endoscopic microsurgery has been introduced for distal rectal lesions, with lower recurrence rates, which are favorable [8]. However, it requires general anesthesia, and severe complications are problematic [9]. In conclusion, ESD for RTDLs requires strict surveillance tests for Rx resection and attentive management for increased minor complications. However, ESD for RTDLs is feasible, with high rates
of complete tumor removal and en bloc resection for accurate staging that are comparable to ESD of proximal rectal lesions. Competing interests: None Institutions 1 Division of Endoscopy, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan 2 Department of Gastroenterology, Saku Central Hospital, Saku, Nagano, Japan 3 Division of Gastroenterology, Toshiba Rinkan Hospital, Sagamihara, Kanagawa, Japan 4 Division of Pathology, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan
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Imai Kenichiro et al. Endoscopic resection of rectal tumors … Endoscopy 2015; 47: 529–532
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