Advanced feasibility of endoscopic submucosal dissection for the treatment of gastric tube cancer after esophagectomy Shin Tawaraya, MD,* Mario Jin, MD, PhD,* Tamotsu Matsuhashi, MD, PhD,* Yusato Suzuki, MD, Masayuki Sawaguchi, MD, Noboru Watanabe, MD, Kengo Onochi, MD, Shigeto Koizumi, MD, PhD, Natsumi Hatakeyama, MD, PhD, Reina Ohba, MD, PhD, Hirosato Mashima, MD, PhD, Hirohide Ohnishi, MD, PhD Akita, Japan
The incidence of esophageal cancer is increasing worldwide.1 However, progress in surgical techniques and the development of novel therapeutic modalities such as adjuvant chemoradiation therapy combined with surgery have improved the postoperative survival up to 34% to 51% at 5 years.2,3 Therefore, long-term survival cases are no longer rare. Generally, gastric tubes are substituted for the reconstitution after the esophagectomy for the treatment of esophageal cancer.1,3 In association with the increase in the number of long-term follow-up cases after esophagectomy, the occurrence of secondary malignancies such as adenocarcinoma arising in gastric tubes has been reported.4-7 Until a decade ago, repeat surgery was considered for the treatment of adenocarcinoma in gastric tubes. However, this did not achieve satisfactory clinical outcomes because of its high operative risks.6,7 Recently, the use of EMR has been emphasized for treatment in patients with superficial lesions.6-8 Although the clinical risks of EMR associated with gastric tube cancer (GTC) treatment are significantly lower than those associated with surgery, EMR cannot always be used to resect GTC completely because of its technical limitations regarding the tumor sizes. Therefore, endoscopic submucosal dissection (ESD) is currently used as a therapeutic option for treating GTC. However, ESD for GTC also carries limitations with respect to the anatomical features of gastric tubes, particularly the suture line and staples with the possibility of fibrosis.9,10 We therefore investigated the feasibility of
ESD for the treatment of GTC by evaluating our experience with 15 cases of 16 GTCs, including 4 GTCs located on the suture lines.
PATIENTS AND METHODS Patients We evaluated a total of 22 patients with 23 GTCs at Akita University Graduate School of Medicine between January 2004 and December 2012. All GTCs were adenocarcinomas. The original esophageal tumor in all 22 cases was squamous cell carcinoma (SCC), which was treated by radical esophagectomy with gastric tube reconstitution. Endoscopic observation in detail with biopsy and contrastenhanced CT revealed that 7 GTCs were unresectable by ESD according to the criteria for the endoscopic curative resection of gastric cancer described in the following. We excluded these 7 GTCs in 7 patients from the analysis. Therefore, we enrolled 16 GTCs in 15 patients in this study.
Method of ESD
Reprint requests: Dr Mario Jin, Akita University Graduate School of Medicine, Department of Gastroenterology, 1-1-1 Hondo, Akita City, Akita 010-8543 Japan.
Written informed consent was obtained from all patients before ESD. The study was carried out in accordance with the Declaration of Helsinki. During the ESD procedure, patients were sedated via intravenous administration of flunitrazepam under blood pressure, electrocardiograph, and oxygen saturation monitoring. ESD was typically carried out by using a GIF-Q260J endoscope (Olympus, Tokyo, Japan) with a transparent hood (D-201-11804; Olympus) attached to the tip. The electrosurgical generator used for ESD was an ICC 200 device (ERBE, Tübingen, Germany) or VIO300D device (ERBE). After the tumor outline was delineated on chromoendoscopy (Fig. 1A and B), marker dots were circumferentially placed 5 mm outside the tumor margin by using a needle-knife (KD1L-1; Olympus). Then, a mixture of 30% hyaluronic acid, 70% saline solution, and a small amount of indigo carmine was injected into the submucosa to lift the lesion. The injection was repeated if necessary during ESD to keep the lesion lifted. Then, after performing precutting with a needle-knife, we made a circumferential incision around the lesion with an insulated-tip (IT), diathermic knife (KD-610L or KD-611L; Olympus) outside the marking
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Volume 79, No. 3 : 2014 GASTROINTESTINAL ENDOSCOPY 525
Abbreviations: ESD, endoscopic submucosal dissection; GTC, gastric tube cancer; IT, insulated-tip; SCC, squamous cell carcinoma. DISCLOSURE: All authors disclosed no financial relationships relevant to this publication. *Drs Tawaraya, Jin, and Matsuhashi contributed equally to the article. Copyright ª 2014 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2013.10.007 Received September 3, 2013. Accepted October 2, 2013. Current affiliations: Department of Gastroenterology, Akita University Graduate School of Medicine, Akita City, Akita, Japan.
ESD for gastric tube cancer
Tawaraya et al
Figure 1. Endoscopic submucosal dissection procedure for treating gastric tube cancer (GTC) localized on the suture line (case 10). A, B, Endscopy revealed a 0-IIc type GTC localized on the suture line. The white arrows indicate the GTC, and the black arrows indicate the suture line. B, Chromoendoscopy with indigo carmine of the same lesion. C, D, When metallic staples in the suture line disturbed the ability to perform submucosal dissection (C), they were removed with a hook knife (D). E, En bloc resection was achieved, with negative margins. The red lines indicate the cancerous lesion, and the black arrows indicate the suture line.
spots, with a sufficient distance remaining outside the marking spots to allow for the submucosal fibrosis caused by the gastric tube creation. Finally, submucosal dissection was carried out with an IT knife, concomitantly using hemostatic instruments, such as the Coagrasper (Olympus),
to treat hemorrhage. When the tissue was too hard to cut with the IT knife because of the presence of submucosal fibrosis along the suture line accompanied by staples created during the previous surgery for esophageal SCC, a needle-knife or hook knife (KD-620QR; Olympus) was
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ESD for gastric tube cancer
TABLE 1. Characteristics of the 16 GTCs in the 15 patients
Age
Sex
Reconstruction route
Time between esophagectomy and GTC development, mo
Location of GTC
GTC on suture line
Type of GTC
1/1
63
Male
Posterior-mediastinal
39
L
No
II c
2/2
76
Male
Posterior-mediastinal
72
L
No
II c
3/3
74
Male
Posterior-mediastinal
65
M
No
II c
4/4
66
Female
Posterior-mediastinal
49
M
Yes
II a
5/5
74
Male
Posterior-mediastinal
72
M
Yes
II c
6/6
79
Male
Retrosternal
236
M
No
II c
7/7
71
Male
Ante-sternal
42
M
No
II a
8/8
70
Male
Posterior-mediastinal
174
M
No
II c
9/9
65
Male
Ante-sternal
31
M
No
II a þ I
10/10
73
Male
Posterior-mediastinal
99
M
Yes
II c
11/11
61
Male
Ante-sternal
15
M
No
II a
12/12
74
Male
Posterior-mediastinal
216
L
Yes
II c
13/13
68
Female
Posterior-mediastinal
58
L
No
II a
14/14
71
Male
Posterior-mediastinal
122
L
No
II c
122
L
No
II c
78
L
No
II c
Case/lesion
14/15 15/16
69
Male
Posterior-mediastinal
GTC, Gastric tube cancer; L, lower third of the gastric tube; M, middle third of the gastric tube.
appropriately used. Furthermore, when metallic staples in the suture line prevented our ability to perform en bloc dissection, the staples were removed endoscopically with the hook knife by hanging the tip on staples (Fig. 1C and D). Intravenous administration of a full dose of proton pump inhibitor (omeprazole or lansoprazole) for 2 days was started on the day of the procedure, and the proton pump inhibitor was orally administered for 2 months thereafter.
Histopathology assessment The specimens resected during ESD were cut into 2-mm slices, stained with hematoxylin and eosin, and evaluated by a pathologist (Fig. 1E). The tumor size, depth of vertical tumor invasion, lymphovascular invasion, presence of ulceration, and horizontal and vertical margin involvement were evaluated. Complete resection was defined as resection of the specimen en bloc with tumor-free horizontal and vertical margins. Then, the curability of the specimens in the cases of complete resection was evaluated. According to the criteria for the endoscopic curative resection of gastric cancer described in the Japanese Gastric Cancer Treatment Guidelines 2010,11 we judged the resection to be curative when the complete resection specimens were without lymphovascular infiltration and www.giejournal.org
fulfilled 1 of the 5 following categories: (1) tumor size %2 cm, histologically differentiated type, pT1a; (2) tumor size O2 cm, histologically differentiated type, pT1a, ulceration (-); (3) tumor size %3 cm, histopathologically differentiated type, pT1a, ulceration (þ); (4) tumor size %2 cm, histopathologically of undifferentiated type, pT1a, ulceration (-); or (5) tumor size %3 cm, histopathologically differentiated type, pT1b (SM1,!500 mm from the muscularis mucosae).11
Follow-up after ESD Follow-up endoscopy was performed 2 months after ESD. The examinations were conducted every 6 months or every year thereafter. The patients were followed-up with CT to detect the recurrence of the original esophageal cancer and GTC every 6 months or every year after ESD. The latest follow-up examination was conducted in July 2013.
RESULTS The characteristics of the 15 patients and the endoscopic findings of the GTCs are shown in Table 1. The average age of the patients was 70 years (range 61-79 years) at the time of detection of GTC. A synchronous GTC was detected in one case (case 14). The median interval between the Volume 79, No. 3 : 2014 GASTROINTESTINAL ENDOSCOPY 527
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Tawaraya et al
TABLE 2. Clinicopathologic features and adverse events of the 16 GTCs in the 15 patients* Case/ lesion
GTC size, mm
Size of resected specimen, mm
Procedure time, min
Pathology of GTC
Depth of invasion
Lymphovascular invasion
UL
ESD curability
Adverse event
1/1
5
20
24
tub1
pT1a
No
Curative
None
2/2
19
44
42
pap
pT1a
No
Curative
None
3/3
23
42
45
tub2
pT1a
No
Curative
None
4/4
22
37
100
tub1
pT1a
Yes
Curative
Aspiration pneumonia
5/5
24
40
121
tub1
pT1b (SM2)
Yes
＋
Non-curative
None
6/6
42
58
106
tub1
pT1a
No
＋
Non-curative
None
7/7
12
30
41
tub1
pT1a
No
Curative
None
8/8
8
24
116
sig
pT1a
No
Curative
None
9/9
24
39
129
tub1
pT1a
No
Curative
None
10/10
9
36
252
tub1
pT1b (SM1)
Yes
Curative
None
11/11
30
55
61
tub1
pT1a
No
Curative
None
12/12
22
47
78
tub1
pT1b (SM1)
Yes
Curative
None
13/13
15
35
58
tub1
pT1a
No
Curative
Delayed hemorrhage
14/14
26
80
165
tub1
pT1a
No
Curative
None
14/15
7
tub1
pT1a
No
Curative
None
15/16
10
tub2
pT1a
No
Curative
None
43
55
GTC, Gastric tube cancer; UL, ulceration; ESD, endoscopic submucosal dissection. *En bloc and complete resection were achieved in all cases and all patients. yTwo lesions were resected en bloc in 1 patient.
esophagectomy procedure and the detection of GTC was 72 months (range 15-236 months). No recurrence of the original SCC or metastasis of GTC was observed on CT in any case. We thus performed ESD for the treatment of all 16 GTCs. The outcomes of the ESD procedures are shown in Table 2. In all 15 cases, ESD of the GTC was performed without serious adverse events, including perforation or uncontrollable bleeding. Furthermore, no gastric tube stricture occurred after ESD. However, minor delayed adverse events related to the ESD procedure were observed in 2 cases. In 1 case, bleeding from the artificial ulcer because of ESD occurred 8 days after the procedure. The patient was successfully treated with endoscopic hemostasis and did not require a blood transfusion. In another case, aspiration pneumonia was induced by the ESD procedure. The patient’s condition promptly improved with conservative therapy with antibiotics. The average diameter of the major axis of the GTCs was 18.6 mm (range 5-42 mm). All 16 GTCs in all 15 cases (100%) were resected en bloc. The results of the pathology examinations of the specimens resected via ESD showed all 16 GTCs in all 15 cases to have been treated with complete
resections (100%). Furthermore, 12 GTCs in 11 cases were judged to be curative resection (13/15 cases, 86.7%: 14/16 GTCs, 87.5%). The prognoses of the patients after ESD are shown in Table 3. Of the two non-curative cases, one patient underwent chemotherapy for 12 months with S-1, which is an oral combination drug consisting of tegafur, gemeracil, and oteracil potassium at a molar ratio of 1:0.4:1 (case 5). Another patient was followed without any additional treatment because of comorbidities (case 6). Fourteen patients, including all patients treated with noncurative resection, were alive at the latest follow-up without recurrence or metastasis of esophageal SCC or GTC (14/15: 93.3%). One patient died because of pneumonia unrelated to SCC or GTC 48 months after undergoing ESD (case 3). In two cases, metachronous GTC was detected on follow-up endoscopy during the follow-up period after the first ESD procedure (cases 2 and 3). The pathological type of metachronous GTC differed from that of the original lesions, indicating that the metachronous GTCs were not recurrent tumors. Both metachronous GTCs were treated by using ESD, achieving complete resection. Unfortunately, however, the pathology examination of the resected specimens
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ESD for gastric tube cancer
TABLE 3. Results after ESD of the 16 GTCs in the 15 patients Additional treatment
Result
Survival, mo
Metachronous GTCs
1
Patient
None
Alive
105
–
2
None
Alive
84
þ (tub1, SM2)
3
None
Dead*
48
þ (por2, M)
4
None
Alive
62
–
5
Chemotherapy
Alive
60
–
6
None
Alive
56
–
7
None
Alive
51
–
8
None
Alive
40
–
9
None
Alive
39
–
10
None
Alive
37
–
11
None
Alive
37
–
12
None
Alive
20
–
13
None
Alive
17
–
14
None
Alive
14
–
15
None
Alive
8
–
ESD, Endoscopic submucosal dissection; GTC, gastric tube cancer. *Death due to pneumonia.
showed findings of non-curative resection in both cases. Because of age (case 2) and the presence of comorbidities (case 3), the two patients were followed without additional treatment. Thereafter, one patient died because of pneumonia, as described earlier, whereas the other remained alive and tumor free at the latest follow-up. Consequently, the medial survival time after the first ESD for GTC among all cases was 40 months (range 8-105 months), whereas that of the 14 patients who remain alive was 39.5 months (range 8-105 months).
The number of patients with advanced esophageal SCC exhibiting long-term survival after undergoing radical esophagectomy has been increasing.3,12 In these cases, especially those in which the patient underwent radical esophagectomy with gastric tube reconstitution for advanced esophageal SCC, the development of GTC has been a major problem affecting survival for more than a decade.4-8 Because surgical resection of GTC is highly invasive and complicated,5 EMR is used to treat GTC when the lesion is superficial.6-8 Although EMR is safer and associated with fewer adverse events than surgical resection in patients with GTC,6 EMR cannot be applied in the treatment of large GTCs.13 Therefore, endoscopists have begun
to use ESD to treat GTC.9,10,14 Bamba et al14 recently reported the results of a comparison between ESD and EMR in patients with GTC, particularly the rates of en bloc resection. In that study, 7 and 10 GTCs were treated with EMR and ESD, and the complete resection rates of EMR and ESD were 14.3% and 90.0%, respectively.14 These data demonstrated that ESD is superior to EMR, at least with respect to the complete resection rate. Osumi et al10 also reported their experience with ESD in 7 GTC cases. In that study, the rate of en bloc resection was 7 of 8 lesions (87.5%) and 6 of 7 cases (85.7%). In 1 case, ESD resulted in piecemeal dissection because of the localization of the GTC on the suture line. In contrast, the current study demonstrated both en bloc and complete resection rates of ESD for GTC of 100% (16/16 lesions, 15/15 cases), with a curative resection rate of 14 of 16 lesions (87.5%) and 13 of 15 cases (86.7%). The perfect en bloc and complete resection rates observed in our study, including the 4 GTCs localized on the suture line, may be attributed to the removal of metallic staples at suture lines. Consistent with this speculation, Nishide et al9 suggested that surgical sutures and anastomosis decrease the en bloc rate of ESD for early gastric cancer arising in the remnant stomach or gastric tube. Therefore, performing a careful ESD procedure and removing metallic staples during GTC treatment is required to improve the clinical outcomes of ESD for GTC. In the present study, which
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Volume 79, No. 3 : 2014 GASTROINTESTINAL ENDOSCOPY 529
DISCUSSION
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1. Mariette C, Piessen G, Triboulet JP. Therapeutic strategies in oesophageal carcinoma: role of surgery and other modalities. Lancet Oncol 2007;8:545-53. 2. Birkmeyer JD, Sun Y, Wong SL, et al. Hospital volume and late survival after cancer surgery. Ann Surg 2007;245:777-83. 3. Altorki N, Kent M, Ferrara C, et al. Three-field lymph node dissection for squamous cell and adenocarcinoma of the esophagus. Ann Surg 2002;236:177-83.
4. Suzuki H, Kitamura M, Saito R, et al. Cancer of the gastric tube reconstructed through the posterior mediastinal route after radical surgery for esophageal cancer. Jpn J Thorac Cardiovasc Surg 2001;49:466-9. 5. Shigemitsu K, Naomoto Y, Shirakawa Y, et al. Five cases of early gastric cancer in the reconstructed gastric tube after radical resection for esophageal cancer. Jap J Clin Oncol 2002;32:425-9. 6. Sugiura T, Kato H, Tachimori Y, et al. Second primary carcinoma in the gastric tube constructed as an esophageal substitute after esophagectomy. J Am Coll Surg 2002;194:578-83. 7. Kuwabara S, Nishimaki T, Kanda T, et al. Second primary cancer developing in the reconstructed gastric tube after esophagectomy for esophageal cancer: clinicopathological analyses of 14 cases. Acta Medica et Biologica 2002;50:91-6. 8. Okamoto N, Ozawa S, Kitagawa Y, et al. Metachronous gastric carcinoma from a gastric tube after radical surgery for esophageal carcinoma. Ann Thorac Surg 2004;77:1189-92. 9. Nishide N, Ono H, Kakushima N, et al. Clinical outcomes of endoscopic submucosal dissection for early gastric cancer in remnant stomach or gastric tube. Endoscopy 2012;44:577-83. 10. Osumi W, Fujita Y, Hiramatsu M, et al. Endoscopic submucosal dissection allows less-invasive curative resection for gastric tube cancer after esophagectomyda case series. Endoscopy 2009;41: 777-80. 11. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer 2011;14:113-23. 12. Ng T, Vezeridis MP. Advances in the surgical treatment of esophageal cancer. J Surg Oncol 2010;101:725-9. 13. Oka S, Tanaka S, Kaneko I, et al. Advantage of endoscopic submucosal dissection compared with EMR for early gastric cancer. Gastrointest Endosc 2006;64:877-83. 14. Bamba T, Kosugi S, Takeuchi M, et al. Surveillance and treatment for second primary cancer in the gastric tube after radical esophagectomy. Surg Endosc 2010;24:1310-7.
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included 2 noncurative cases, no recurrence or metastasis of GTC was observed during follow-up. Previous reports with shorter follow-up periods also reported that no recurrence of GTC was detected.10,14 The present study as well as previous studies indicate that patients with GTCs after ESD treatment, even those treated with non-curative resection concerning the presence of lymph node metastasis, rarely develop lymph node recurrence or other organ metastasis. One may speculate that performing lymphadenectomy during surgery for esophageal SCC contributes to the rarity of recurrence and metastasis of GTC.14 Nevertheless, there are some limitations to the current study. For example, this is a retrospective study from a single institution. In conclusion, performing ESD by using measures to address the presence of metallic staples along the suture line is feasible and safe, promising good curability and an improved prognosis in patients who develop GTC after esophagectomy for advanced SCC.
REFERENCES
The incidence of esophageal cancer is increasing worldwide.1 However, progress in surgical techniques and the development of novel therapeutic modalities such as adjuvant chemoradiation therapy combined with surgery have improved the postoperative survival up to 34% to 51% at 5 years.2,3 Therefore, long-term survival cases are no longer rare. Generally, gastric tubes are substituted for the reconstitution after the esophagectomy for the treatment of esophageal cancer.1,3 In association with the increase in the number of long-term follow-up cases after esophagectomy, the occurrence of secondary malignancies such as adenocarcinoma arising in gastric tubes has been reported.4-7 Until a decade ago, repeat surgery was considered for the treatment of adenocarcinoma in gastric tubes. However, this did not achieve satisfactory clinical outcomes because of its high operative risks.6,7 Recently, the use of EMR has been emphasized for treatment in patients with superficial lesions.6-8 Although the clinical risks of EMR associated with gastric tube cancer (GTC) treatment are significantly lower than those associated with surgery, EMR cannot always be used to resect GTC completely because of its technical limitations regarding the tumor sizes. Therefore, endoscopic submucosal dissection (ESD) is currently used as a therapeutic option for treating GTC. However, ESD for GTC also carries limitations with respect to the anatomical features of gastric tubes, particularly the suture line and staples with the possibility of fibrosis.9,10 We therefore investigated the feasibility of
ESD for the treatment of GTC by evaluating our experience with 15 cases of 16 GTCs, including 4 GTCs located on the suture lines.
PATIENTS AND METHODS Patients We evaluated a total of 22 patients with 23 GTCs at Akita University Graduate School of Medicine between January 2004 and December 2012. All GTCs were adenocarcinomas. The original esophageal tumor in all 22 cases was squamous cell carcinoma (SCC), which was treated by radical esophagectomy with gastric tube reconstitution. Endoscopic observation in detail with biopsy and contrastenhanced CT revealed that 7 GTCs were unresectable by ESD according to the criteria for the endoscopic curative resection of gastric cancer described in the following. We excluded these 7 GTCs in 7 patients from the analysis. Therefore, we enrolled 16 GTCs in 15 patients in this study.
Method of ESD
Reprint requests: Dr Mario Jin, Akita University Graduate School of Medicine, Department of Gastroenterology, 1-1-1 Hondo, Akita City, Akita 010-8543 Japan.
Written informed consent was obtained from all patients before ESD. The study was carried out in accordance with the Declaration of Helsinki. During the ESD procedure, patients were sedated via intravenous administration of flunitrazepam under blood pressure, electrocardiograph, and oxygen saturation monitoring. ESD was typically carried out by using a GIF-Q260J endoscope (Olympus, Tokyo, Japan) with a transparent hood (D-201-11804; Olympus) attached to the tip. The electrosurgical generator used for ESD was an ICC 200 device (ERBE, Tübingen, Germany) or VIO300D device (ERBE). After the tumor outline was delineated on chromoendoscopy (Fig. 1A and B), marker dots were circumferentially placed 5 mm outside the tumor margin by using a needle-knife (KD1L-1; Olympus). Then, a mixture of 30% hyaluronic acid, 70% saline solution, and a small amount of indigo carmine was injected into the submucosa to lift the lesion. The injection was repeated if necessary during ESD to keep the lesion lifted. Then, after performing precutting with a needle-knife, we made a circumferential incision around the lesion with an insulated-tip (IT), diathermic knife (KD-610L or KD-611L; Olympus) outside the marking
www.giejournal.org
Volume 79, No. 3 : 2014 GASTROINTESTINAL ENDOSCOPY 525
Abbreviations: ESD, endoscopic submucosal dissection; GTC, gastric tube cancer; IT, insulated-tip; SCC, squamous cell carcinoma. DISCLOSURE: All authors disclosed no financial relationships relevant to this publication. *Drs Tawaraya, Jin, and Matsuhashi contributed equally to the article. Copyright ª 2014 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2013.10.007 Received September 3, 2013. Accepted October 2, 2013. Current affiliations: Department of Gastroenterology, Akita University Graduate School of Medicine, Akita City, Akita, Japan.
ESD for gastric tube cancer
Tawaraya et al
Figure 1. Endoscopic submucosal dissection procedure for treating gastric tube cancer (GTC) localized on the suture line (case 10). A, B, Endscopy revealed a 0-IIc type GTC localized on the suture line. The white arrows indicate the GTC, and the black arrows indicate the suture line. B, Chromoendoscopy with indigo carmine of the same lesion. C, D, When metallic staples in the suture line disturbed the ability to perform submucosal dissection (C), they were removed with a hook knife (D). E, En bloc resection was achieved, with negative margins. The red lines indicate the cancerous lesion, and the black arrows indicate the suture line.
spots, with a sufficient distance remaining outside the marking spots to allow for the submucosal fibrosis caused by the gastric tube creation. Finally, submucosal dissection was carried out with an IT knife, concomitantly using hemostatic instruments, such as the Coagrasper (Olympus),
to treat hemorrhage. When the tissue was too hard to cut with the IT knife because of the presence of submucosal fibrosis along the suture line accompanied by staples created during the previous surgery for esophageal SCC, a needle-knife or hook knife (KD-620QR; Olympus) was
526 GASTROINTESTINAL ENDOSCOPY Volume 79, No. 3 : 2014
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Tawaraya et al
ESD for gastric tube cancer
TABLE 1. Characteristics of the 16 GTCs in the 15 patients
Age
Sex
Reconstruction route
Time between esophagectomy and GTC development, mo
Location of GTC
GTC on suture line
Type of GTC
1/1
63
Male
Posterior-mediastinal
39
L
No
II c
2/2
76
Male
Posterior-mediastinal
72
L
No
II c
3/3
74
Male
Posterior-mediastinal
65
M
No
II c
4/4
66
Female
Posterior-mediastinal
49
M
Yes
II a
5/5
74
Male
Posterior-mediastinal
72
M
Yes
II c
6/6
79
Male
Retrosternal
236
M
No
II c
7/7
71
Male
Ante-sternal
42
M
No
II a
8/8
70
Male
Posterior-mediastinal
174
M
No
II c
9/9
65
Male
Ante-sternal
31
M
No
II a þ I
10/10
73
Male
Posterior-mediastinal
99
M
Yes
II c
11/11
61
Male
Ante-sternal
15
M
No
II a
12/12
74
Male
Posterior-mediastinal
216
L
Yes
II c
13/13
68
Female
Posterior-mediastinal
58
L
No
II a
14/14
71
Male
Posterior-mediastinal
122
L
No
II c
122
L
No
II c
78
L
No
II c
Case/lesion
14/15 15/16
69
Male
Posterior-mediastinal
GTC, Gastric tube cancer; L, lower third of the gastric tube; M, middle third of the gastric tube.
appropriately used. Furthermore, when metallic staples in the suture line prevented our ability to perform en bloc dissection, the staples were removed endoscopically with the hook knife by hanging the tip on staples (Fig. 1C and D). Intravenous administration of a full dose of proton pump inhibitor (omeprazole or lansoprazole) for 2 days was started on the day of the procedure, and the proton pump inhibitor was orally administered for 2 months thereafter.
Histopathology assessment The specimens resected during ESD were cut into 2-mm slices, stained with hematoxylin and eosin, and evaluated by a pathologist (Fig. 1E). The tumor size, depth of vertical tumor invasion, lymphovascular invasion, presence of ulceration, and horizontal and vertical margin involvement were evaluated. Complete resection was defined as resection of the specimen en bloc with tumor-free horizontal and vertical margins. Then, the curability of the specimens in the cases of complete resection was evaluated. According to the criteria for the endoscopic curative resection of gastric cancer described in the Japanese Gastric Cancer Treatment Guidelines 2010,11 we judged the resection to be curative when the complete resection specimens were without lymphovascular infiltration and www.giejournal.org
fulfilled 1 of the 5 following categories: (1) tumor size %2 cm, histologically differentiated type, pT1a; (2) tumor size O2 cm, histologically differentiated type, pT1a, ulceration (-); (3) tumor size %3 cm, histopathologically differentiated type, pT1a, ulceration (þ); (4) tumor size %2 cm, histopathologically of undifferentiated type, pT1a, ulceration (-); or (5) tumor size %3 cm, histopathologically differentiated type, pT1b (SM1,!500 mm from the muscularis mucosae).11
Follow-up after ESD Follow-up endoscopy was performed 2 months after ESD. The examinations were conducted every 6 months or every year thereafter. The patients were followed-up with CT to detect the recurrence of the original esophageal cancer and GTC every 6 months or every year after ESD. The latest follow-up examination was conducted in July 2013.
RESULTS The characteristics of the 15 patients and the endoscopic findings of the GTCs are shown in Table 1. The average age of the patients was 70 years (range 61-79 years) at the time of detection of GTC. A synchronous GTC was detected in one case (case 14). The median interval between the Volume 79, No. 3 : 2014 GASTROINTESTINAL ENDOSCOPY 527
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TABLE 2. Clinicopathologic features and adverse events of the 16 GTCs in the 15 patients* Case/ lesion
GTC size, mm
Size of resected specimen, mm
Procedure time, min
Pathology of GTC
Depth of invasion
Lymphovascular invasion
UL
ESD curability
Adverse event
1/1
5
20
24
tub1
pT1a
No
Curative
None
2/2
19
44
42
pap
pT1a
No
Curative
None
3/3
23
42
45
tub2
pT1a
No
Curative
None
4/4
22
37
100
tub1
pT1a
Yes
Curative
Aspiration pneumonia
5/5
24
40
121
tub1
pT1b (SM2)
Yes
＋
Non-curative
None
6/6
42
58
106
tub1
pT1a
No
＋
Non-curative
None
7/7
12
30
41
tub1
pT1a
No
Curative
None
8/8
8
24
116
sig
pT1a
No
Curative
None
9/9
24
39
129
tub1
pT1a
No
Curative
None
10/10
9
36
252
tub1
pT1b (SM1)
Yes
Curative
None
11/11
30
55
61
tub1
pT1a
No
Curative
None
12/12
22
47
78
tub1
pT1b (SM1)
Yes
Curative
None
13/13
15
35
58
tub1
pT1a
No
Curative
Delayed hemorrhage
14/14
26
80
165
tub1
pT1a
No
Curative
None
14/15
7
tub1
pT1a
No
Curative
None
15/16
10
tub2
pT1a
No
Curative
None
43
55
GTC, Gastric tube cancer; UL, ulceration; ESD, endoscopic submucosal dissection. *En bloc and complete resection were achieved in all cases and all patients. yTwo lesions were resected en bloc in 1 patient.
esophagectomy procedure and the detection of GTC was 72 months (range 15-236 months). No recurrence of the original SCC or metastasis of GTC was observed on CT in any case. We thus performed ESD for the treatment of all 16 GTCs. The outcomes of the ESD procedures are shown in Table 2. In all 15 cases, ESD of the GTC was performed without serious adverse events, including perforation or uncontrollable bleeding. Furthermore, no gastric tube stricture occurred after ESD. However, minor delayed adverse events related to the ESD procedure were observed in 2 cases. In 1 case, bleeding from the artificial ulcer because of ESD occurred 8 days after the procedure. The patient was successfully treated with endoscopic hemostasis and did not require a blood transfusion. In another case, aspiration pneumonia was induced by the ESD procedure. The patient’s condition promptly improved with conservative therapy with antibiotics. The average diameter of the major axis of the GTCs was 18.6 mm (range 5-42 mm). All 16 GTCs in all 15 cases (100%) were resected en bloc. The results of the pathology examinations of the specimens resected via ESD showed all 16 GTCs in all 15 cases to have been treated with complete
resections (100%). Furthermore, 12 GTCs in 11 cases were judged to be curative resection (13/15 cases, 86.7%: 14/16 GTCs, 87.5%). The prognoses of the patients after ESD are shown in Table 3. Of the two non-curative cases, one patient underwent chemotherapy for 12 months with S-1, which is an oral combination drug consisting of tegafur, gemeracil, and oteracil potassium at a molar ratio of 1:0.4:1 (case 5). Another patient was followed without any additional treatment because of comorbidities (case 6). Fourteen patients, including all patients treated with noncurative resection, were alive at the latest follow-up without recurrence or metastasis of esophageal SCC or GTC (14/15: 93.3%). One patient died because of pneumonia unrelated to SCC or GTC 48 months after undergoing ESD (case 3). In two cases, metachronous GTC was detected on follow-up endoscopy during the follow-up period after the first ESD procedure (cases 2 and 3). The pathological type of metachronous GTC differed from that of the original lesions, indicating that the metachronous GTCs were not recurrent tumors. Both metachronous GTCs were treated by using ESD, achieving complete resection. Unfortunately, however, the pathology examination of the resected specimens
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ESD for gastric tube cancer
TABLE 3. Results after ESD of the 16 GTCs in the 15 patients Additional treatment
Result
Survival, mo
Metachronous GTCs
1
Patient
None
Alive
105
–
2
None
Alive
84
þ (tub1, SM2)
3
None
Dead*
48
þ (por2, M)
4
None
Alive
62
–
5
Chemotherapy
Alive
60
–
6
None
Alive
56
–
7
None
Alive
51
–
8
None
Alive
40
–
9
None
Alive
39
–
10
None
Alive
37
–
11
None
Alive
37
–
12
None
Alive
20
–
13
None
Alive
17
–
14
None
Alive
14
–
15
None
Alive
8
–
ESD, Endoscopic submucosal dissection; GTC, gastric tube cancer. *Death due to pneumonia.
showed findings of non-curative resection in both cases. Because of age (case 2) and the presence of comorbidities (case 3), the two patients were followed without additional treatment. Thereafter, one patient died because of pneumonia, as described earlier, whereas the other remained alive and tumor free at the latest follow-up. Consequently, the medial survival time after the first ESD for GTC among all cases was 40 months (range 8-105 months), whereas that of the 14 patients who remain alive was 39.5 months (range 8-105 months).
The number of patients with advanced esophageal SCC exhibiting long-term survival after undergoing radical esophagectomy has been increasing.3,12 In these cases, especially those in which the patient underwent radical esophagectomy with gastric tube reconstitution for advanced esophageal SCC, the development of GTC has been a major problem affecting survival for more than a decade.4-8 Because surgical resection of GTC is highly invasive and complicated,5 EMR is used to treat GTC when the lesion is superficial.6-8 Although EMR is safer and associated with fewer adverse events than surgical resection in patients with GTC,6 EMR cannot be applied in the treatment of large GTCs.13 Therefore, endoscopists have begun
to use ESD to treat GTC.9,10,14 Bamba et al14 recently reported the results of a comparison between ESD and EMR in patients with GTC, particularly the rates of en bloc resection. In that study, 7 and 10 GTCs were treated with EMR and ESD, and the complete resection rates of EMR and ESD were 14.3% and 90.0%, respectively.14 These data demonstrated that ESD is superior to EMR, at least with respect to the complete resection rate. Osumi et al10 also reported their experience with ESD in 7 GTC cases. In that study, the rate of en bloc resection was 7 of 8 lesions (87.5%) and 6 of 7 cases (85.7%). In 1 case, ESD resulted in piecemeal dissection because of the localization of the GTC on the suture line. In contrast, the current study demonstrated both en bloc and complete resection rates of ESD for GTC of 100% (16/16 lesions, 15/15 cases), with a curative resection rate of 14 of 16 lesions (87.5%) and 13 of 15 cases (86.7%). The perfect en bloc and complete resection rates observed in our study, including the 4 GTCs localized on the suture line, may be attributed to the removal of metallic staples at suture lines. Consistent with this speculation, Nishide et al9 suggested that surgical sutures and anastomosis decrease the en bloc rate of ESD for early gastric cancer arising in the remnant stomach or gastric tube. Therefore, performing a careful ESD procedure and removing metallic staples during GTC treatment is required to improve the clinical outcomes of ESD for GTC. In the present study, which
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1. Mariette C, Piessen G, Triboulet JP. Therapeutic strategies in oesophageal carcinoma: role of surgery and other modalities. Lancet Oncol 2007;8:545-53. 2. Birkmeyer JD, Sun Y, Wong SL, et al. Hospital volume and late survival after cancer surgery. Ann Surg 2007;245:777-83. 3. Altorki N, Kent M, Ferrara C, et al. Three-field lymph node dissection for squamous cell and adenocarcinoma of the esophagus. Ann Surg 2002;236:177-83.
4. Suzuki H, Kitamura M, Saito R, et al. Cancer of the gastric tube reconstructed through the posterior mediastinal route after radical surgery for esophageal cancer. Jpn J Thorac Cardiovasc Surg 2001;49:466-9. 5. Shigemitsu K, Naomoto Y, Shirakawa Y, et al. Five cases of early gastric cancer in the reconstructed gastric tube after radical resection for esophageal cancer. Jap J Clin Oncol 2002;32:425-9. 6. Sugiura T, Kato H, Tachimori Y, et al. Second primary carcinoma in the gastric tube constructed as an esophageal substitute after esophagectomy. J Am Coll Surg 2002;194:578-83. 7. Kuwabara S, Nishimaki T, Kanda T, et al. Second primary cancer developing in the reconstructed gastric tube after esophagectomy for esophageal cancer: clinicopathological analyses of 14 cases. Acta Medica et Biologica 2002;50:91-6. 8. Okamoto N, Ozawa S, Kitagawa Y, et al. Metachronous gastric carcinoma from a gastric tube after radical surgery for esophageal carcinoma. Ann Thorac Surg 2004;77:1189-92. 9. Nishide N, Ono H, Kakushima N, et al. Clinical outcomes of endoscopic submucosal dissection for early gastric cancer in remnant stomach or gastric tube. Endoscopy 2012;44:577-83. 10. Osumi W, Fujita Y, Hiramatsu M, et al. Endoscopic submucosal dissection allows less-invasive curative resection for gastric tube cancer after esophagectomyda case series. Endoscopy 2009;41: 777-80. 11. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer 2011;14:113-23. 12. Ng T, Vezeridis MP. Advances in the surgical treatment of esophageal cancer. J Surg Oncol 2010;101:725-9. 13. Oka S, Tanaka S, Kaneko I, et al. Advantage of endoscopic submucosal dissection compared with EMR for early gastric cancer. Gastrointest Endosc 2006;64:877-83. 14. Bamba T, Kosugi S, Takeuchi M, et al. Surveillance and treatment for second primary cancer in the gastric tube after radical esophagectomy. Surg Endosc 2010;24:1310-7.
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included 2 noncurative cases, no recurrence or metastasis of GTC was observed during follow-up. Previous reports with shorter follow-up periods also reported that no recurrence of GTC was detected.10,14 The present study as well as previous studies indicate that patients with GTCs after ESD treatment, even those treated with non-curative resection concerning the presence of lymph node metastasis, rarely develop lymph node recurrence or other organ metastasis. One may speculate that performing lymphadenectomy during surgery for esophageal SCC contributes to the rarity of recurrence and metastasis of GTC.14 Nevertheless, there are some limitations to the current study. For example, this is a retrospective study from a single institution. In conclusion, performing ESD by using measures to address the presence of metallic staples along the suture line is feasible and safe, promising good curability and an improved prognosis in patients who develop GTC after esophagectomy for advanced SCC.
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