Patient characteristics and ESD procedure-related outcomes
Patient characteristics and procedure-related outcomes are shown in Table 1. A total of 31 consecutive patients (29 men and 2 women) with 45 GTC cases were treated using ESD. The median age of the patients was 73 years (range, 58-84 years) at the time of ESD. Six patients had multiple lesions with synchronous occurrence, and nine patients had multiple lesions with metachronous occurrence. The median period from esophagectomy to ESD after the initial GTC was 10.6 years (range, 0.8-18.2 years). The route of reconstruction was retrosternal for 16 cases and the posterior mediastinum for 15 cases. In our series, all patients with GTC had Helicobacter pylori-related atrophic gastritis.
Table 1: Patient characteristics and ESD procedure-related outcomes (n=31)
Patient characteristics
|
Sex ratio (%)
|
|
Male
|
29 (93.5)
|
Female
|
2 (6.5)
|
Median age, years (range)
|
73 (58-84)
|
Synchronous/metachronous occurrence
|
6/9
|
Period from onset to esophagectomy, years (range)
|
10.6 (0.8-18.2)
|
Reconstruction route
|
|
Retrosternal
|
16
|
Posterior mediastinum
|
15
|
Atrophic gastritis
|
|
Positive
|
31
|
Negative
|
0
|
ESD procedure-related outcomes
|
Adverse events (%)
|
|
Bleeding
|
2 (6.5)
|
Perforation
|
0
|
Complete resection (%)
|
25 (80.6)
|
Curative resection (%)
|
15 (48.4)
|
ESD, endoscopic submucosa dissection.
The only adverse event due to ESD was bleeding (2 patients: 6.5%). Fatal complications, including perforation, were not observed. The rates of complete resection and curative resection were 80.6%, and 48.4%, respectively.
Clinical and histopathological findings
Histopathological findings are shown in Table 2. In terms of tumor location, there were 26 lesions in the lower gastric tube, 17 lesions in the middle gastric tube, and 2 lesions in the upper gastric tube. Four lesions were on the suture line. Macroscopically, 34 lesions were diagnosed as 0-IIc (slightly depressed type), 10 lesions were diagnosed as 0-IIa (slightly elevated type), and one lesion was diagnosed as 0-I (elevated type). The median tumor size was 17.5 mm (range, 5-53 mm), with 33 differentiated, 2 undifferentiated, and 10 mixed-type adenocarcinomas. The depth of tumor invasion was pT1a (mucosa [M]) in 29 lesions, pT1b (SM1: <500 μm below the muscularis mucosa in the SM) in 3 lesions, pT1b (SM2: 500 μm or deeper invasion from the SM) in 12 lesions, and pT2 (muscularis propria [MP]) in one lesion. Lymphovascular invasion was observed with seven lesions. The horizontal margin was positive in one lesion and the vertical margin was positive in five lesions. The positive horizontal margin was misdiagnosed when there was a poorly differentiated lesion. The positive vertical margin was diagnosed because of its invasion deeper than SM2.
Table 2: Clinical and histological findings of gastric tube carcinomas (n=45)
Location
|
|
Upper
|
2
|
Middle
|
17
|
Lower
|
26
|
On the suture line
|
4
|
Macroscopic types
|
|
0-I
|
1
|
0-IIa
|
10
|
0-IIc
|
34
|
Median size of the tumors, mm
|
17.5 (5-53)
|
Histological type
|
|
Differentiated (tub1, tub2)
|
33
|
Undifferentiated (por, sig)
|
2
|
Mixed
|
10
|
Depth of invasion
|
|
pT1a (M)
|
29
|
pT1b (SM1)
|
3
|
pT1b (SM2)
|
12
|
pT2 (MP)
|
1
|
Lymphovascular invasion
|
|
Positive
|
7
|
Negative
|
38
|
Horizontal margin
|
|
Positive
|
1
|
Negative
|
44
|
Vertical margin
|
|
Positive
|
5
|
Negative
|
40
|
tub1, well-differentiated adenocarcinoma; tub2, moderately-differentiated adenocarcinoma; por, poorly-differentiated adenocarcinoma; sig, signet-ring cell carcinoma; M, mucosal; SM1, <500 μm below the muscularis mucosa into the submucosa; SM2, 500 μm or deeper invasion from the muscularis mucosa into the submucosa.
Clinical course after ESD and long-term outcomes
All patients were followed-up for a median of 50 months (range, 2-168 months). Twenty-nine patients were followed-up during this study (93.5%; 29/31). The clinical course details are shown in Fig. 4. Fourteen patients (48.3%) had curative resection and 15 patients (51.7%) had non-curative resection. Among the 14 patients with curative resection, 8 patients were alive, and 6 patients died of another disease (pneumonia, 3; hypopharyngeal cancer, 1; cervical esophageal cancer, 1; sepsis due to psoas abscess, 1). Metachronous occurrence was diagnosed in three patients (21.2%; 3/14) and curative ESD was performed for all patients. No patients with curative resection died of GTC.
Of the 15 patients with non-curative resection, one had an undifferentiated mucosal lesion, five had positive vertical margins, one had only a positive horizontal margin, and eight had negative tumor margins with lymphovascular invasion or invasion more than SM2. All were followed-up without additional surgery. The patient with an undifferentiated mucosal lesion larger than 20 mm was alive. Of the five patients with positive vertical margins, four patients had SM2 invasion, and one had MP invasion. Two patients with SM2 invasion were alive, including one patient who had local recurrence and underwent additional radiation. The other two patients with SM2 invasion died of intrahepatic cholangiocarcinoma and heart failure, respectively. The patient with MP invasion died of local recurrence, despite chemotherapy (5-fluorouracil and cisplatin) after ESD. The one patient with only a positive horizontal margin died of pancreatic cancer. Three patients among the eight patients who had negative tumor margins with lymphovascular invasion or invasion more than SM2 were alive, including one patient who was treated with curative ESD for metachronous lesions after non-curative ESD. The other five patients died of another disease (pneumonia, 2; hypopharyngeal cancer, 1; malignant lymphoma, 1; heart failure, 1).
The 3-year and 5-year overall survival rates were 67.6% and 47.7%, respectively. The 3-year and 5-year disease-specific survival rates were 100% and 92.9%, respectively (Fig. 5). Only one patient died of GTC resected with non-curative ESD. Of the 14 deaths due to other causes, 5 were other primary carcinomas (hypopharyngeal cancer, 2; cervical esophageal cancer, 1; pancreatic cancer, 1; malignant lymphoma, 1).